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Evaluation of a peritoneal dialysis (PD) program in a nephrology center involve qualitative and quantitative indicators on clinical outcomes. International guidelines recommend monitoring outcomes of peritoneal catheter implantation, catheter-related infections, peritonitis and purification adequacy. However, none of these parameters can determine the organizational efficiency of a peritoneal dialysis (PD) program. It is desirable that centers with PD programs serving ≤14 patients, once capable of performing the peritoneal equilibration test, either safeguard their expertise or establish collaborations with nephrology units that have well-established PD programs.

Keywords: quality, peritoneal dialysis (PD), peritoneal equilibration test (PET), intraperitoneal pressure (IPP), telemedicine, staff

Cool dialysate has variable impact on hemodynamic stability and dialysis adequacy.  Hemodynamic stability and dialysis adequacy are crucial indicators for better life expectancy and cardiovascular mortality. This research aims to evaluate the impact of cool dialysate temperature (35.5°C) compared to standard dialysate temperature (37°C) on blood pressures, pulse rate, and dialysis adequacy (Urea reduction ratio and online Kt/V) in a cross over design.
Material and Methods. Consenting ESRD patients on maintenance haemodialysis (HD) with minimum 3 months dialysis vintage and functioning permanent vascular access are included for the study. Each participant had two sessions of HD at 37°C followed by two sessions at 35.5° C on a Fresenius 4008S HD machine. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and Pulse rate are measured pre-HD, every hourly and post dialysis. Pre-HD Blood urea nitrogen (BUN) and post-HD BUN are measured, and Urea reduction rate was calculated for each HD session. Kt/V was calculated by ionic conductance by HD machine for each session.
Results. 25 patients (5 females and 20 males) were enrolled. The mean age was 54 ± 9.58 years. Dialysis vintage was 21.48 ± 6.9 months for study participants 10 patients (40%) were diabetic nephropathy, 9 patients (36%) were presumed chronic glomerulonephritis, 2 patients (8%) were lupus nephritis and 4 patients (16%) were chronic interstitial nephritis. There was statistically no difference between pre-HD BUN (p = 0.330), post-HD BUN (p = 0.776), URR (p = 0.718) and Kt/V (p = 0.534) among the dialysis sessions done at 37°C and 35.5°C.
SBP variability in the low temperature (35.5°C) group at 4^th hour and post dialysis assumed statistical significance with p = 0.05 and p = 0.025 respectively. DBP variability in the low temperature (35.5°C) group at 3^rd hour, 4^th hour and post-dialysis demonstrated statistical significance with p = 0.027, p = 0.36 and p = 0.016 respectively. Pulse rate variability was more in the low temperature (35.5°C) group at 3^rd hour and 4^th hour which showed statistical significance with p = 0.037 and p = 0.05 respectively.
Conclusion. Cool dialysate is non inferior to standard dialysate temperature in terms of dialysis adequacy and is associated with less variability in diastolic blood pressure, systolic blood pressure and more pulse rate variability thereby contributing to better hemodynamic stability.

Keywords: Cool dialysate, Dialysis adequacy, Hemodynamic stability, Pulse rate variability

The arteriovenous fistula constitutes the vascular access of first choice in hemodialysis. We present three clinical cases that highlight the resolution in interventional radiology of venous stenosis, one of the major complications.
Clinical monitoring and instrumental diagnostics with color Doppler ultrasound have prevented the failure of the AVF due to high risk of thrombosis.
The angiographic interventions, thanks to the collaboration between Spoke and Hub, were completed without complications.

Keywords: hemodialysis, stenosis, AVF, interventional radiology, color Doppler ultrasound, PTA

Bacteremia caused by Lactobacillus is rare, data on its clinical significance are based only on case reports and a limited number of studies, often difficult to interpret.
Lactobacillus species is a commensal colonizer of the mouth, gastrointestinal and genitourinary tract. Its significance as a pathogen is overlooked frequently.  The diagnosis of these infections requires a mutual relationship between the physician and the microbiologist to rule out contamination risk.
Most patients with Lactobacillus bacteremia are immunosuppressed or patients at increased risk of symptomatic bacteremia with comorbidities, treated with broad-spectrum antibiotics and have indwelling venous catheters.
Risk factors related to Lactobacillus bacteremia include impaired host defenses and severe underlying diseases, as well as prior surgery and prolonged antibiotic therapy ineffective for lactobacilli.
We describe an unusual case of a woman, on chronic hemodialysis treatment, with a sepsis due to Lactobacillus casei and review the literature.

Keywords: Lactobacillus, bacteremia, hemodialysis, immunocompromised patients

Introduction. Renal functional reserve (RFR) is the kidney capability of increasing its basal glomerular filtration rate (GFR) at least 20% after an adequate stimulus. Renal disorders have been reported in seropositive HIV patients, particularly the decrease in glomerular filtration rate (eGFR), nephrotic syndrome, and proximal tubular deficiency associated with the disease itself or the use of some anti-retroviral treatments. Thus, it was decided to carry out a prospective study in order to evaluate if RFR test was preserved in naive HIV patients.
Material and Method. GFR was measured by using cimetidine-aided creatinine clearance (CACC), and RFR as described Hellerstein et al. in seropositive naive HIV patients and healthy volunteers.
Results. RFR was evaluated in 12 naïve HIV patients who showed positive RFR (24.8±2%), but significantly lower compared to RFR in 9 control individuals (90.3 ± 5%).
Conclusion. In this study was found that renal functional reserve was positive in naïve HIV patients, but significantly lower compared to renal functional reserve achieved by seronegative healthy individuals.

Keywords: renal reserve, HIV, renal physiology

The arteriovenous fistula (AVF) represents the favorite vascular access in individuals with chronic kidney disease (CKD). Because AVF is a guarantee of survival for these patients, proper surgical packing and a timely follow-up program is crucial.
Although a good objective examination of the limb site of FAV provides useful information both in planning the fistula surgery and in its surveillance and monitoring, it is now well established that the advent of instrumental diagnostics (ultrasonography, digital angiography, Angio-TC, MRI) has contributed significantly to improving primary and secondary patency of FAV and early diagnosis of vascular access complications.
In this area, clinical thermography, a noninvasive and nondestructive diagnostic technique for assessing minute surface temperature differences, has shown good potential for the assessment of AVF. In fact, thermographic analysis of a limb site of AVF shows an increase in temperature at the site of the anastomosis and along the course of the arterialized vein.
In this article we report our experience on the use of thermography in preoperative evaluation and postoperative surgical packing of an AVF.
Further studies could validate the use of clinical thermography as a diagnostic technique to be used in the field of hemodialysis vascular accesses.

Keywords: Thermography, Haemodialysis, Arteriovenous Fistula (AVF),   AVF Pre-Postoperative Examination, Post-Operative AVF Management

Rhabdomyolysis is one of the principal causes of acute kidney disease. Multiple endogenous and exogenous causes could start this process: cocaine addiction, a social phenomenon present in our Country among young adults, is one exogenous causes. Natural stimulating alkaloid cocaine has toxic action on multiple systems, principally central nervous system and cardiovascular system. Etiopathogenesis is related either to changes in local and systemic hemodynamics, or to direct damage caused by myofibril accumulation, or to immunological events leading to vasculitis or thrombotic microangiopathies. Scientific evidences describe different therapeutic approaches: supportive therapy, extracorporeal treatments and possible removal of the pathogenic noxa, and the therapeutic apheresis plays a role yet to be confirmed in this field.

We describe the case of a 52-year-old man, hospitalized in the Cardiological Intensive Care Unit of our hospital, due to serious alterations in the indices of myocardiocytonecrosis and liver function, following cocaine abuse. During hospitalization, renal function indices worsened associated to diuresis contraction and onset of metabolic acidosis, not responsive to medical therapy. Also in consideration of myoglobin high circulating levels, related to rhabdomyolysis, the patient went under a cycle of selective apheresis using adsorption with a TR350 cartridge associated to hemodialysis: after two adsorption sessions, the patient resumed spontaneous diuresis with progressive normalization of the blood indices.

Keywords: Cocaine, Rhabdomyolysis, Apheresis, Adsorption

Familial Hypocalciuria Hypercalcemia (FHH) is an inherited disease with autosomal dominant transmission characterized by the presence of usually mild-to-moderate hypercalcemia, hypophosphatemia, hypocalciuria, and normal or moderately increased PTH values. Generally, FFH is asymptomatic although symptoms related to elevated plasma calcium values such as asthenia, intense thirst, polyuria, polydipsia or confusional state may occur.
Three types of FHH, which differ in the genetic alterations underlying the condition, are described.
The majority of FHH cases are classified as type 1 (about 65 percent of cases), due to mutation in the gene for the calcium-sensitive receptor CASR, expressed on chromosome (Chr) 3q13.3-21, which encodes for a calcium-sensitive receptor G-protein-coupled protein of the plasma membrane.
FHH types 2 and 3 are due to GNA11 and AP2S1 mutations, respectively, and other genes involved in the pathogenesis of the disease have likely yet to be identified.
Rarely, familial hypocalciuric hypercalcemia may not recognize a genetic cause but be caused by autoantibodies directed against CASR.
The frequency of the disease is not known and is estimated, probably by default, because of paucisymptomatic presentation of the disease, to be around 1:80000 cases.
Recognition of FHH is especially important for differential diagnosis with primary hyperparathyroidism, which has a much higher incidence, about 1:1000 cases. This allows for the identification of patients at risk for chondrocalcinosis and/or pancreatitis. Clinical suspicion must be raised in cases of hypercalcaemia associated with hypocalciuria, and genetic analysis is fundamental in the differential diagnosis toward forms of primary hyperparathyroidism that might result in unnecessary surgical interventions.
We describe a clinical case in which a novel inactivating mutation of CASR leading to FHH type 1 was found.

Keywords: Familial Hypocalciuric Hypercalcemia, CASR, Gene, Parathyroid, Calcium

This article constitutes a review of the existing literature on the potential correlation between autosomal dominant polycystic kidney disease (ADPKD) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Additionally, it presents a clinical case where familiarity for both pathologies was observed, derived from the direct experience of our clinic, reinforcing the hypothesis of a possible common pathogenetic pathway. The review focuses on the potential genetic correlation between these two pathologies within the realm of ciliopathies, emphasizing the importance of targeted screening and monitoring strategies to detect pancreatic complications early in patients with ADPKD. Furthermore, it highlights the complexity in the clinical management of these rare conditions and underscores the importance of early diagnosis in optimizing clinical outcomes.

Keywords: ADPKD, IPMN, ciliopathies, polycystic diseases

Introduction. Eighty percent of children with primitive nephrotic syndrome (NS) will have at least one relapse in their life. Specific risk factors could be associated with a higher incidence of relapses and a worse prognosis. This study aims to deepen the demographic and onset-related risk factors in children with known diagnosis of primitive NS attending the Pediatric Nephrology Unit of the University Hospital of Padua.
Methods. Observational, descriptive study of all children (1-11 years old) with a known diagnosis of Primitive NS who attended our Pediatric Nephrology Unit between 1 January 2002 and 31 March 2023.
Results. 49 patients were involved. 79.5% had at least one episode of NS relapse during their lifetime. 69.4% were classified as frequently relapsing or steroid-dependent NS. The relapse risk factor “non-Western ethnicity” was related to a worse prognosis and steroid-dependent NS classification (p = 0.041). The onset-related risk factor “thrombocytosis” appears to be related to a better prognosis (p = 0.03).
Conclusion. The relapse risk factors “non-Western ethnicity” and “thrombocytosis” are characterized by worse and better prognosis, respectively. This evidence could support the follow-up of primitive NS in pediatric age.

Keywords: nephrotic syndrome relapse, risk factors, ethnicity, thrombocytosis

Phosphorus is a macroelement found in the body, mostly in the bones as crystals of hydroxyapatite. Higher levels are found in patients affected by chronic kidney disease (CKD). Since the early stage of CKD phosphorous excretion is impaired, but the increase of PTH and FGF23 maintains its level in the normal range. In the last decades, the role of FGF23 in erythropoiesis was studied, and now it is well known for its role in anemia genesis in patients affected by conservative CKD. Both Hyperphosphatemia and anemia are two manifestations of CKD, but many studies showed a direct association between serum phosphorous and anemia. Phosphorus can be considered as the common point of more pathogenetic ways, independent of renal function: the overproduction of FGF23, the worsening of vascular disease, and the toxic impairment of erythropoiesis, including the induction of hemolysis.

Keywords: Phosphorus, Hemoglobin, Anemia, Chronic Kidney Disease, FGF23

The prevalence of chronic kidney disease (CKD) continues to rise globally, paralleled by an increase in associated morbidity and mortality, as well as significant implications for patient quality of life and national economies. Chronic kidney disease often progresses unrecognized by patients and physicians, despite diagnosis relying on two simple laboratory measures: estimated glomerular filtration rate (eGFR) and urine analysis. GFR measurement has been grounded in renal physiology, specifically the concept of clearance, with creatinine identified as a suitable endogenous marker for estimating creatinine clearance (CrCl). On this foundation, various equations have been developed to calculate CrCl or estimated GFR (eGFR) using four variables that incorporate creatinine and certain demographic information, such as sex and age. However, creatinine measurement requires standardization to minimize assay variability across laboratories. Moreover, the accuracy of these equations remains contentious in certain patient subgroups. For these reasons, additional mathematical models have been devised to enhance CrCl estimation, for example, when urine collection is impractical, in elderly or debilitated patients, and in individuals with trauma, diabetes, or obesity. Presently, eGFR in adults can be immediately measured and reported using creatinine-based equations traceable through isotope dilution mass spectrometry. In conclusion, leveraging insights from renal physiology, eGFR can be employed clinically for early diagnosis and treatment of CKD, as well as a public health tool to estimate its prevalence.

Keywords: renal function markers, creatinine, cystatin C, inulin, iohexol

Viral infections are one of the most common triggers of Systemic Lupus Nephritis (SLE) flare-ups. COVID-19 pneumonia can be severe in patients affected by SLE representing a risk factor for lupus nephritis flare. We report the case of a 28-year-old woman with a history of lupus nephritis (LN), who relapsed with severe nephritic-nephritic syndrome after the resolution of COVID-19 pneumonia.

In addition, we conducted a literature review to analyze all described cases of LN, vaccinated and unvaccinated, in COVID-19 showing that the course of COVID-19 is more severe in SLE patients with renal involvement, especially in those who have not been vaccinated. Vaccination is the most important measure for preventing COVID-19 in people with rheumatic diseases such as SLE.

The case and data we present suggests that LN relapses can occur even after the infection has resolved and illustrates the benefit of vaccination, the role of modulation of immunosuppression during COVID-19 and the specific risk of disease relapse during SARS-CoV-2 infection.

Keywords: SARS-CoV-2, SLE, flare, lupus nephritis, vaccination, COVID-19

Thrombotic microangiopathies represent a group of particularly serious pathologies that can cause a rapid worsening of renal function, especially in young subjects. Through the clinical case described, we will focus our attention on the clinical and laboratory manifestations of the pathology, on the diagnostics and on the therapies to be used. Recent therapeutic innovations for the treatment of this pathology will also be analysed.

Keywords: Thrombotic microangiopathies, Hemolytic Uremic Syndrome

Background. Data on the prevalence of cardiac failure with preserved ejection in the haemodialysis population, which impacts treatment strategy, mortality, and morbidity, are scarce.
Aims and Objectives. 

• Estimate the prevalence of heart failure with preserved ejection fraction (HFpEF) in haemodialysis patients
• Classify cardiac failure and ascertain the risk factors influencing HFpEF in haemodialysis patients.

Methods. All consenting individuals on haemodialysis over 18 years of age were included. Lung ultrasound was performed as per the LUST study protocol, and the labs were documented. Echocardiographic parameters were measured using two-dimensional (2D ECHO).
Results. A total of 102 patients consented to participate in the study, which included 63 males (61.8%) and 39 females (38.2%). The mean patient age was 53 ± 13.1 years. The dialysis vintage of the participants was 38.92 ± 6.947 months. 47 (46.1%) patients had diabetes and 88 (80.4%) had hypertension. ECG findings included sinus rhythm (51/102, 50%), sinus tachycardia (22/102, 21.6%), ST-T wave abnormalities (18/102, 17.6%), and atrial fibrillation (11/102, 10.8%). Heart failure with preserved ejection fraction (HFpEF) was present in 44/102 (43.14%), heart failure with mid-range EF in 14/102 (13.72%), and heart failure with reduced EF in 13/102 (12.7%) patients. The ejection fraction was positively associated with haemoglobin (r = 0.23; p = 0.044), and calcium levels (r = 0.25; p =0 .03). E/lateral e′ ratio was positively correlated with NT pro-BNP (r = 0.63; p < 0.001), systolic blood pressure (r = 0.44; p = 0.003) and age (r = 0.353; p = 0.003) and negatively correlated with transferrin saturation (r = -0.353; p = 0.027) and diastolic blood pressure (r = -0.31; p = 0.040). Binary logistic regression analysis revealed that the odds of diastolic dysfunction increased by 2.3 times with each unit increase of creatinine, and diabetics have 7.66 times higher risk for diastolic dysfunction. Binary logistic regression involving ejection fraction (EF) and all laboratory and clinical parameters revealed odds of HFpEF increased by 1.93 times with each unit increase in age, odds of HFpEF increases by 1.53 times with each unit increase in phosphorous and odds of HFpEF increased by 1.1 times with a unit increase of systolic blood pressure. Conclusion. HFpEF is the predominant form of heart failure in haemodialysis patients. Haemoglobin and calcium were positively associated with ejection fraction. Advancing age, elevated creatinine and diabetes mellitus levels are independent predictors of diastolic dysfunction in haemodialysis patients.

Keywords. HFpEF, E/ Lateral e, E/A ratio, 2D ECHO, hemodialysis, cardiac failure

Chronic Kidney Disease (CKD) is a clinical condition characterized by the progressive loss of kidney function. 10% of the world’s population is affected by this condition, which represents the fifth leading cause of death globally. Furthermore, CKD is associated with increased risk of fatal and non-fatal cardiovascular events, and progression to end-stage renal disease. Over the last twenty years, an exponential growth in its prevalence and incidence has been observed. For this reason, various drugs have been developed and implemented in clinical practice, with various mechanisms, with the aim of reducing and minimizing this dramatic “cardio-renal” risk. These include SGLT2 inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists. However, a large proportion of CKD patients do not respond sufficiently to these treatments. GLP-1 receptor agonists represent a class of antidiabetic and nephroprotective drugs that are very promising in improving the prognosis of patients with CKD, especially if associated with one of the above-mentioned classes. In this article, we discuss the direct and indirect mechanisms through which one of the GLP-1 agonists, semaglutide, ensures nephro- and cardioprotection in patients with CKD and type 2 diabetes.

Keywords:  chronic kidney disease, epidemiology CKD, semaglutide

Roxadustat, recently approved, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favorable safety and efficacy in the treatment of renal anemia. This article reviews main features and possible effects by activation of pathway sequences HREs.

Keywords: Roxadustat, EPO, hypoxia-inducible factor, fibrosis, inflammation, oxidative stress

The development of acute kidney injury (AKI) in polytrauma patients is a common and serious complication, with an incidence ranging from 6% to 50%.
Polytrauma is a complex pathological condition that involves the collaboration of various specialists. On one hand, hemodynamic stabilization through fluid therapy and aminic support, with specific attack protocols, managed by anesthetists.
On the other hand, if necessary, the initiation of renal replacement therapy such as Continuous Renal Replacement Therapy (CRRT), managed by nephrologists.
CRRT is chosen both for managing fluid balance and ensuring the removal of toxic substances, as well as for proper control of electrolytes and acid-base balance.

Keywords: Acute Kidney Injury, Polytrauma, Continuous Renal Replacement Therapy

Background/Objectives. Peritoneal dialysis stands as an established form of renal replacement therapy; yet peritonitis remains a major complication associated with it. This study, analyzing two decades of data from the Nephrology, Dialysis, and Hypertension Division of the University-Hospital IRCCS in Bologna, aimed to identify prognostic factors linked to peritonitis events. It also sought to evaluate the suitability of different peritoneal dialysis techniques, with a focus on Automated Peritoneal Dialysis (APD) and Continuous Ambulatory Peritoneal Dialysis (CAPD). Additionally, the study assessed the impact of an educational program introduced in 2005 on peritonitis frequency.
Methods. Conducting an observational, retrospective, single-center study, 323 patients were included in the analysis, categorized based on their use of APD or CAPD.
Results. Despite widespread APD usage, no significant correlation was found between the dialysis technique (APD or CAPD) and peritonitis onset. The analysis of the educational program’s impact revealed no significant differences in peritonitis occurrence. However, a clear relationship emerged between regular patient monitoring at the reference center and the duration of peritoneal dialysis.
Conclusions. Despite the absence of a distinct association between peritonitis onset and dialysis technique, regular patient monitoring at the reference center significantly correlated with prolonged peritoneal dialysis duration.

Keywords: end-stage renal disease, peritoneal dialysis, peritonitis, peritoneal catheter

Introduction and aim of the study. The centralized preparation and distribution system of acidic concentrate represents a true innovation in hemodialysis, when compared to acid bags, in terms of convenience and eco-sustainability. The aim of this study is to compare the use of traditional acid bags with the centralized distribution system of acidic concentrate, with particular attention to differences in terms of eco-sustainability and convenience.
Methods. At the Nephrology Dialysis and Renal Transplantation Unit of the University Hospital of Modena was installed the Granumix system® (Fresenius Medical Care, Bad Homburg, Germany). Data collected before the introduction of the Granumix® system (including the used acid bags, boxes and pallets used for their packaging, liters of acid solution used and kilograms of waste generated from wood, plastic, cardboard and residual acid solution) were compared with those collected after the implementation of the Granumix® system. Factors such as material consumption, volume of waste generated, unused and wasted products, time required for dialysis session preparation and nurses’ satisfaction were analyzed to document which system was more environmentally sustainable.
Results. Data collected in 2019 at our Dialysis Center showed a consumption of 30,000 acid bags, which generated over 20,000 kg of waste from wood, plastic and cardboard, and approximately 12,000 liters of residual acid solution to be disposed of, with a handling weight by operators reaching nearly 160,000 kg. The use of the centralized distribution system of acidic concentrate resulted in a significant reduction in waste generated (2,642 kg vs 13,617 kg), residual acid solution to be disposed of (2,351 liters vs 12,100 liters) and weights handled by operators (71,522 kg vs 158,117 kg).
Conclusions. The acidic concentrate appears to be better suited to the sustainability challenge that dialysis must faces today, particularly due to the significant increase in the number of patients, which leads to a higher number of treatments and, therefore, a growing demand for eco-sustainable products.

Keywords: Hemodialysis, Innovation, Sustainability, Acidic Concentrate, Central Dialysis Fluid Delivery System

IgA nephropathy (IgAN) is a fairly common association with alcoholic liver disease. However, IgA vasculitis (IgAV) is quite an uncommon association with alcoholic liver cirrhosis and only a handful of cases have been reported in literature. Secondary IgAN usually presents in a docile manner, progressing slowly in about 5-25 years. It is usually responsive to steroid therapy, very rarely progressing to End-Stage Renal Disease.

Here, we present a man in his late 50s, a known hypertensive and alcohol related liver-cirrhotic, who presented to our hospital with rash and rapidly progressive renal failure (RPRF). He was diagnosed with IgA nephritis with IgA vasculitis (IgAVN). His diagnosis was confirmed with skin and renal biopsy.

He was started on renal replacement therapy for his renal failure and began oral steroid therapy. After administration of steroid therapy for 6 months, the patient recovered and was dialysis independent with stable renal parameters.

Keywords: IgA nephropathy, Alcoholic Liver disease, rapidly progressive glomerulonephritis, IgA vasculitis

Background. Patients with chronic kidney disease (CKD) can be successfully treated with sodium-glucose cotransporter-2 inhibitors (SGLT2-Is), regardless of diabetes. Fondazione Ricerca e Salute’s (ReSD) administrative and Health Search’s (HSD) primary care databases were combined in the Database Consortium ReS-HS to quantify and describe patients with CKD potentially eligible for SGLT2-Is and assess costs charged to the Italian National Health Service (SSN).
Methods. Patients aged ≥18 with CKD and estimated glomerular filtration rate (eGFR) <60 ml/min in 2018, without dialysis and/or renal transplantation, were included. HSD was used to develop and validate algorithms for estimating eGFR, based on covariates, within the ReSD. Comorbidities, dispensed drugs, and direct healthcare costs were assessed.
Results. In 2018, 66,297 (5.0% of HSD population) and 211,494 (4.4% of ReSD population) patients with CKD potentially eligible for SGLT2-Is were identified (females ≥58%). Prevalence increased with age with a peak at 75-84 years. Within HSD and ReSD cohorts, respectively: 31.0% and 41.5% had diabetes; in the observation periods, >82% and >96% received ≥1 pharmacological treatment, of which ≥50% and ≥25% received cardiovascular/blood agents and antidiabetics, respectively. From ReSD, mean per capita direct SSN cost was € 3,825 (CI 95%, € 3,655-€ 4,000): 50.1% due to hospitalizations, and 40.2% to pharmaceuticals (31.6% to cardiovascular drugs and 10.1% to antidiabetics).
Conclusion. The Database Consortium ReS-HS methodology found 5% of adult SSN beneficiaries with CKD potentially eligible for SGLT2-Is bringing with them a high cardio-metabolic burden which increases the risk of CKD progression.

Keywords: Sodium-Glucose Transporter 2 Inhibitors, Chronic Kidney Diseases, Primary Care, Health Care Costs, National Healthcare System

Cystic fibrosis is a multisystem disease with extremely variable onset, symptoms and course. One of the onset modality but also a complication of the disease is the pseudo-Bartter syndrome, characterized by hyponatremia, hypochloremic dehydration and metabolic alkalosis in absence of any renal disease. This syndrome occurs more frequently in the first year of life and has a peak in the summer.

In this article, we describe two cases of cystic fibrosis associated with pseudo-Bartter syndrome in childhood. Excluding every possible cause of metabolic alkalosis associated with hyponatremia was crucial for our diagnostic pathway, and the experience gained with the first case helped a lot with the second one.

Keywords: cystic fibrosis, pseudo-Bartter syndrome, metabolic alkalosis, hyponatremia, pediatrics

Immunoglobulin A (IgA) nephropathy is a common glomerulonephritis, but its treatment remains matter of debate. Recommendation for corticosteroids has been supported, but renin-angiotensin inhibitors, RAAS, and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are increasingly used because of a better benefit/safety balance in comparison with systemic steroids and immunosuppressive treatments. In this case report, a patient with type 2 diabetes (T2DM) and biopsy-proven nephrotic IgA-related nephropathy documented a rapid meaningful reduction of proteinuria and the effect was persistent for 2 years, after receiving the treatment with a GLP1-RA on top of the previous treatment with ACE-inhibitors and SGLT2-i. Considering the beneficial effects of GLP1-RA in diabetes related chronic kidney disease, the present case report supports the notion that these drugs could also represent a beneficial treatment option in IgA nephropathy.

Keywords: IgA nephropathy, Dulaglutide, Empagliflozin, DAPA-CKD, Empa-Kidney

Standard ultrasound (US) finds wide use in renal diseases as a screening procedure, but it is not always able to characterize lesions, especially in differential diagnosis between benign and malignant lesions. In contrast, contrast-enhanced ultrasonography (CEUS) is appropriate in differentiating between solid and cystic lesions as well as between tumors and pseudotumors. We show the case of a nephropathic patient who showed a complex, large, growing renal mass, characterized through a CEUS. This seventy-five-year-old diabetic heart patient showed a 6 cm-complex and plurisected cyst on ultrasound of left kidney. Laboratory data showed the presence of stage IIIb chronic renal failure with GFR 30 ml/min, creatinine 2.33 mg/dl, azotemia 88 mg/dl. The patient performed abdominal CT without contrast medium, showing at the level of the left upper pole, a roundish formation with the dimensions of approximately 70x53x50 mm. At the semiannual checkup, the nephrology examination showed a slight rise in creatinine and, therefore, after six months, it was decided to perform a CT scan without contrast medium again. CT showed a slight increase in the size of the mass located at the left kidney (74x56x57 mm). Given the increased size of the left mass, albeit modest, a CEUS was performed to reach a diriment diagnosis. CEUS concluded for complex cystic formation with presence of intraluminal solid-corpuscular material, with thrombotic-hemorrhagic etiology, in progressive phase of organization, classifiable as Bosniak type II cyst. CEUS in the kidneys is a cost-effective and valuable imaging technique; it is accurate in the characterization of indeterminate lesions and complex cysts.

Keywords: Contrast-Enhanced Ultrasound, CEUS, Renal Cyst, Indeterminate Renal Mass

Introduction. The Triveneto Peritoneal Dialysis (PD) Network aims to bring together doctors and nurses who deal with PD in a collaborative network in which to exchange mutual knowledge and optimize the use of this method of replacing renal function. A topic of particular interest was the management of peritoneal catheter exit-site infection, given the recent publication of the new guidelines of the International Society of Peritoneal Dialysis (ISPD).
Materials and methods. The survey concerned the criteria for carrying out nasal swab and exit-site, management of exuberant granulation tissue “Proud Flesh”, treatment of exit-site infection (ESI), use of silver dressings, the role of subcutaneous tunnel ultrasound and cuff shaving.
Results. All PD centers in the North-East Italy area have joined the survey with at least one operator per centre. There was a wide variability between the indications for performing the exit-site swab. In the presence of ESI, the prevalent approach is that of oral systemic empiric therapy associated (20.0%) or less (28.9%) with topical therapy, and then adapting it in a targeted manner to the culture examination.
Discussion. From the discussion of the survey emerged the importance of the ESI as an outcome indicator, which allows us to verify whether our clinical practice is in line with the reference standards. It is essential to know and base our activity on what is indicated in national and international guidelines and to document the events that occur in the patient population of each dialysis unit.

Keywords: Peritoneal Dialysis, Exit-site management, Catheter-related Infections, Survey

Reflecting on the inappropriateness (medical overuse) and on defensive medicine, the Authors wonder whether the new Italian reform of professional guilt, desired at all institutional levels, will actually contain the high economic costs produced by these large and widespread phenomena. After having characterized the medical overuse and the defensive medicine indicating the common traits and main differences, the reflection is conducted by exploring the many scientific evidence that does not document any causal link between the decriminalization of professional conduct and the containment of the costs produced by the prescriptive inappropriateness. They conclude by stating that, for their containment, a third reform of professional liability will not be helpful. Instead, it must focus on other issues, mainly addressing the excessive reliance on judicial recourse. It should provide for mandatory out-of-court conciliatory mechanisms and clarifying the protective umbrella of the doctor’s non-criminality.

Keywords: medical overuse, diagnostic inappropriateness, defensive medicine, malpractice

Introduction. Patients undergoing chronic haemodialysis (HD) treatment have an 8-10 times higher risk of experiencing stroke events and developing cognitive impairment. The high vascular stress they are subjected to may be the basis for the development of vascular dementia (VaD).
Objective. The aim of the study is to investigate the executive functions, typically impaired in VaD, of patients undergoing chronic haemodialysis treatment.
Method. HD patients were recruited from the U.O.C. of Nephrology and Dialysis (ASP Ragusa). Risk factors for VaD were collected and then the Frontal Assessment Battery (FAB) was administered.
Results. 103 HD patients were included (males = 63%, age 66 ± 14 years). Risk factors for VaD included a high percentage of patients with anaemia (93%), hypertension (64%) and coronary artery disease (68%).  The cognitive data obtained via FAB show a percentage of 55% deficit scores. All risk factors found a significant association with cognitive scores. Anemia, hypertension, intradialytic hypotension, coronary artery disease, and homocysteine are negative predictors of executive function integrity.
Conclusions. More than half of the patients had deficit scores on the FAB. Reduced cognitive flexibility, high sensitivity to interference, poor inhibitory control and impaired motor programming with the dominant hand were evident. In conclusion, a marked impairment of the executive functions, generally located in the frontal lobes of the brain, was detected in the HD patient, which could be a symptom of a dementia of a vascular nature.

Keywords: hemodialysis, cognitive, impairment, vascular, dementia

Introduction. The clinical implications of serum anti-PLA2R with glomerular PLA2R deposits in primary membranous nephropathy (PMN) is scarcely reported. Hence the study was designed to demonstrate the prevalence of serum anti-PLA2R levels and PLA2R staining in glomeruli in PMN and the clinical implications of the two parameters.
Objectives.

1. Investigate the prevalence of anti PLA2R positivity in PMN.
2. Ascertain correlation between serum anti-PLA2R levels and glomerular staining for PLA2R with clinical and lab parameters in PMN.

Patients and Methods. Fifty PMN patients during the period from October 2017 to December 2018 were included. Labs were done and eGFR was calculated as per MDRD 6. Anti-PLA2R titres were done in all patients. Titres more than 20 RU/ml were considered positive. Glomerular staining for PLA2R was graded on fresh frozen tissue by immunofluorescence technique.
Results. Anti-PLA2R antibody positivity and glomerular PLA2R deposition was observed in 42% (21/50) and 86% (43/50) patients respectively. 79.3% (23/29) had positive glomerular PLA2R deposition with negative serum anti PLA2R. Positive correlation were observed between serum PLA2R antibody and serum creatinine (p = 0.0001) and urine protein-creatinine ratio levels with tissue PLA2R staining grades (p = 0.04). Negative association was found between serum albumin (p = 0.026) and tissue PLA2R staining grades.
Conclusion. Serum anti-PLA2R wasn’t a sensitive marker of primary membranous nephropathy in our study group emphasising the need to consider a compendium of serological markers for diagnosis of primary membranous nephropathy and to rely more on glomerular deposition of PLA2R as a better clinical indicator for PMN.

Keywords: anti-PLA2R, Membranous Nephropathy, Glomerular PLA2R deposits, Tissue PLA2R staining, Nephrotic Syndrome

Background. Neonatal high blood pressure has been diagnosed more frequently in recent years, and its impact extends to adulthood. However, the knowledge gaps on associated factors, diagnosis, and treatment are challenging for medical personnel. The incidence of this condition varies depending on neonatal conditions. Patients in the Newborn Unit are at increased risk of developing high blood pressure. The persistence of this condition beyond the neonatal stage increases the risk of cardiovascular disease and chronic kidney disease in childhood and adulthood.
Methodology. A case-control study was carried out. It included hospitalized patients with neonatal hypertension as cases. Three controls were randomly selected for each case and matched by gestational age. The variables were analyzed based on their nature. Multivariate analysis was performed using a multivariate conditional regression model to identify variables associated with the outcome. Finally, the model was adjusted for possible confounders.
Results. 37 cases were obtained and matched with 111 controls. In the univariate analysis, heart disease (OR 2.86; 95% CI 1.22-6.71), kidney disease (OR 7.24; 95% CI 1.92-28.28), bronchopulmonary dysplasia (OR 6.62; 95% CI 1.42-50.82) and major surgical procedures (OR 3.71; 95% CI 1.64-8.39) had an association with neonatal arterial hypertension. Only the latter maintained this finding in the multivariate analysis (adjusted OR 2.88; 95% CI 1.14-7.30). A significant association of two or more comorbidities with neonatal arterial hypertension was also found (OR 3.81; 95% CI 1.53-9.49).
Conclusions. The study analyzed the factors related to high blood pressure in hospitalized neonates, finding relevant associations in the said population. The importance of meticulous neonatal care and monitoring of risk factors such as birth weight and major surgeries is highlighted.

Keywords: Hypertension, Prematurity, Bronchopulmonary Dysplasia, Epigenetics, Neonate, Prematurity, Kidney Disease, Blood Pressure

In patients on peritoneal dialysis, the cutaneous emergency (exit-site) represents a potential access route to the peritoneum; consequently, it can become a site for microbial infections. These infections, initially localized to the exit-site, may spread to the peritoneum causing peritonitis, which is the most common cause of drop-out from peritoneal dialysis and transition to hemodialysis. Peritoneal catheters have dacron caps which have the function of counteracting the traction of the catheter itself and at the same time acting as a barrier for microorganisms, preventing the spread towards the peritoneum. Despite this, the same dacron cap can represent a sort of nest for microorganisms to colonize and, with the formation of a biofilm that facilitates their proliferation, make the same organisms impervious to antibiotic therapy and even resistance to them. The most effective tool for monitoring the health status of the exit-site is represented by the objective examination. This examination, through the use of well-defined scales, helps to provide a pathological score of the exit, facilitating the implementation of necessary precautions. In the presence of recurrent exit-site infections, from both Gram positive and Gram negative bacteria, minimally invasive surgical therapy is a valid approach to break this vicious circle. It helps avoid subjecting the patient to the removal of the peritoneal catheter, temporary transition to hemodialysis with the insertion of a central venous catheter, and subsequent repositioning of another peritoneal catheter. We propose the case of a recurrent Staphylococcus Aureus infection resolved after cuff shaving of the exit-site.

Keywords:  peritoneal dialysis, exit-site infection, cuff shaving

Patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed “worsening heart failure” (WHF). Although guideline-directed medical therapy is well established, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF with consequent higher risk of death and hospitalization than patients with “stable” HF. New drugs are emerging as cornerstones to reduce residual risk of both cardiovascular mortality and readmission for heart failure.
The following review will debate about emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the new therapeutic strategies in cardiorenal patients.

Keywords: Heart Failure, Worsening Heart Failure (WHF), Cardiorenal Syndrome, Vericiguat

“Palliative dialysis” is defined as the renal replacement therapy directed to patients living the most critical phases of illness and the end-of-life stage. Offering targeted dialysis prescriptions becomes imperative when health conditions, along with comorbidities, unfavorable prognosis and complications, do not allow standard dialysis to be started or continued. Management should also integrate adequate supportive care measures in both incident and prevalent patients.

This document summarizes nephrological recommendations and scientifical evidence regarding the palliative approach to dialysis, and proposes operative tools for a good clinical practice. After planning and sharing the route of care (“shared-decision-making”), which includes multidimensional evaluation of the patient, a pathway of treatment should be started, focusing on combining the therapeutical available options, adequacy and proportionality of care and patients’ preferences.

We propose a framework of indications that could help the nephrologist in practicing appropriate measures of treatment in patients’ frailest conditions, with the aim of reducing the burden of dialysis, improving quality of life, providing a better control of symptoms, decreasing the hospitalization rates in the end-of-life stage and promoting a home-centered form of care. Such a decisional pathway is nowadays increasingly needed in nephrology practice, but not standardized yet.

Keywords: palliative care, chronic kidney disease, end-of-life, palliative dialysis, hemodialysis, peritoneal dialysis, shared-decision-making

The law 219/2017 is the first Italian law about advanced care planning (ACP). ACP is an important part of the therapeutic relationship between patients and doctors: thanks to ACP patients can think and discuss about end of life decisions, considering clinical aspects, but also psychological, cultural, social and ethical issues. Patients prepare themselves in advance because of the possibility of future cognitive impairment, can identify a surrogate decision maker and make end-life decisions according to their goals and values.

End-stage kidney disease (ESRD) is often characterized by important symptoms, psychological suffering and social disadvantage, and patients affected by ESRD often have slow physical and cognitive decline. Despite this, access to palliative care is reduced for these patients as compared to patients affected by other end-stage organ failures. This is the reason why we want to explore the possibility of applying APC to ESRD patients.

This pilot study, regarding three patients from the Dialysis Unit of ASST Crema in Italy, has been conducted to verify the applicability of the law 219/2017 in Dialysis Units. It shows that we have to deeply investigate this issue from both sanitary workers’ and patients’ and families’ points of view. We need more studies with a larger number of patients and a longer period of follow-up, but we also need to teach sanitary workers how to approach APC and to teach people what APC is and why it’s so important for everyone.

Keywords: advanced care planning, end-stage kidney disease, dialysis

Background. The use of PD depends on economic, structural and organizational factors. The nephrologist’s opinion is that peritoneal dialysis is less used than it shold be. In Italy, PD is not carried out in private Centers, but neither is it in around one third of Public Centers. The aim of this study was to investigate the opinions of nephrologists on PD in Public Centers only, thereby nullifying the influence of the economic factors.
Materials and Methods. The investigation was carried out by means of an online questionnaire (Qs) via mail, and during meetings and Congresses in 2006-07. The Qs investigated the characteristics of the Centers, the nephrologists interviewed, and opinions on the various aspects of the choice of Renal Replacement Therapy Renal Replacement Therapy (RRT) (26 questions). Responses were received from 454 nephrologists in 270 public Centers. Among these, 205 centers (370 Qs) report PD (PD-YES), 36 (42 Qs) do not (PD-NO) and 29 (42 Qs) do not use it but send patients selected for PD to other Centers (PD-TRANSF).
Results. The PD-NO and PD-TRANSF Centers are significantly smaller, with greater availability of beds. In the PD-YES Centers the presence of a pre-dialysis pathway, early referral and nurses dedicated solely to PD are associated with a higher use of PD.
The nephrologists in the PD-NO Centers rate PD more negatively in terms of both clinical and non-clinical factors. The belief that more than 40% of patients can do either PD or HD differs among the nephrologists in the PD-YES (74.3%), PD-TRANSF (45.2%) and PD-NO (28.6%) Centers. Likewise, the belief that PD can be used as a first treatment in more than 30% of cases differs among the nephrologists in PD-YES (49.2%), PD-TRANSF (33.3%) and PD-NO (14.3%) Centers.
Conclusions. The use of PD in Public Centers is conditioned by both structural and organizational factors, and by the opinions of nephrologists on the use and effectiveness of the technique.

Graphical abstract

Keywords: Peritoneal Dialysis, Hemodialysis, Modality selection, Physicians opinion, Chronic Kidney Disease

Objectives. The results are presented of the 8^th National Census (Cs-22) of the Peritoneal Dialysis Project Group of the Italian Society of Nephrology relating to the characteristics of the Centers in Italy which used PD in 2022.
Materials and methods. The 227 non-pediatric centers which used Peritoneal Dialysis (PD) in 2022 took part. The data requested were sent in aggregate form. For the first time, the resources available and training were investigated as well as home visits. The Centers have been divided into Quartiles according to the number of prevalent PD patients at 31/12/2022.
Results. Centers with a smaller PD program (<9 pts) are characterized by 1. smaller overall size – 2. fewer personnel (doctors/nurses) dedicated to PD – 3. greater recourse to external personnel for training – 4. Less incremental prescription and evaluation of peritoneal permeability – 5. higher drop-out to HD in particular for choice/impossibility to continue and for adequacy/catheter-related issues. A lower peritonitis rate was recorded in Centers with a more extensive PD program (≥25 pts). Home visits are carried out regularly by a small minority of Centers. Conclusions. The analysis shows an association between size of Center PD program and available resources, PD modality and outcome.

Graphical abstract

Keywords: Peritoneal Dialysis, Center effect, technique failure

Therapeutic apheresis is an important hematological and nephrological method for conditions with altered plasma composition. It is also indicated for the removal of protein-bound molecules, such as bilirubin. Several techniques can remove these compounds, such as the extracorporeal circulation molecular adsorption system (MARS), plasma exchange (PEX), and plasma adsorption and perfusion (PAP). Here we report our experience in the comparison between MARS, PEX and PAP, since current guidelines do not specify which method is the most appropriate and under which circumstances it should be used.

The choice of technique cannot be based on the desired plasma bilirubin concentration, since these three techniques show similar results with a similar final outcome (exitus). In fact, PAP, PEX and MARS significantly reduce bilirubin levels, but the degree of reduction is not different among the three. Furthermore, the three techniques do not differ in the rate of cholinesterase change, while less reduction of liver transaminases was found by using PAP.

MARS should be preferred in the case of renal involvement (hepatorenal syndrome with hyperbilirubinemia). PAP has the advantage of being simple and inexpensive. PEX remains an option when emergency PAP is not available, but the risk of using blood products (plasma and albumin) must be considered.

Keywords: Molecular Adsorbent Recirculating System, MARS, Plasma Adsorption Perfusion, plasma exchange

Despite the rapidly growing area of onconephrology in the last decade, nephropathic patients have been rarely involved in clinical trials of cancer therapy, particularly in the case of chronic kidney disease (CKD) stage 4 (CKD4) or stage 5 (CKD5). We could offer better therapeutic opportunities to our patients thanks to the Onconephrology Clinic and the Multidisciplinary group, in which a dedicated team of specialists guarantees the highest level of possible care. In this paper, we analysed the activity of the first Italian OnconephrologyClinic, twelve years after its foundation. We studied retrospectively a cohort of 174 patients referred to our center in the last six months (from 11/01/2023 to 12/07/2023), with a total of 262 visits (40 first visits). We highlight a prevalence of moderated or advanced kidney disease, in contrast with the literature, which is probably the result of a transversal II level clinic with different specialists involved. Furthermore, in patients with a prolonged follow-up, we observed a progressive better attention to every kidney involvement, particularly in patients in active cancer therapy, by the oncologist colleagues. We observed a reduction of treatment withdrawals due to kidney toxicity, thanks to a multidisciplinary approach and experienced-based management. On the other side, we highlight also a delayed addressing of patients with acute kidney injury (AKI), which often results in chronic kidney damage. This could be related to a delayed identification of the reduced renal function, which is difficult to correctly value in patients with cancer.

Keywords: onconephrology, cancer therapy, nephrectomy, kidney function

The West Nile Virus (WNV), an RNA arbovirus, has been transmitted by wild birds and conveyed by ticks and mosquitoes, with wide diffusion all over the world; it is not transmitted from human to human. It can give clinical symptoms only in a minority of infected subjects such as fever, headache, muscle tiredness, visual disturbances, drowsiness, convulsions and muscle paralysis; in the most serious cases even potentially fatal encephalitis. In the literature there are few reports on WNV infection in patients with kidney diseases: here we report our experience on two patients on peritoneal dialysis infected by WNV with a revision of the literature.

Keywords: West Nile virus infection, chronic kidney disease, end-stage kidney failure, peritoneal dialysis, kidney transplant

The prevalence of central venous catheters (CVC) in hemodialysis patients is around 20-30%. In this scenario, complications related to the use of the CVC are commonly observed, requiring active management by nephrologists. These include infectious complications as well as those related to CVC malfunction. Among the latter, the formation of a fibrin sheath around the catheter linked to foreign body reaction could cause CVC malfunction in various ways. Even after the removal of the catheter, the fibrin sheath can remain inside the vascular lumen (ghost fibrin sheath) and rarely undergo calcification. We describe the clinical case of a hemodialysis patient who, following the removal of a malfunctioning, stuck CVC, presented a calcified tubular structure in the lumen of the superior vena cava, diagnosed as calcified fibrin sheath (CFS). This rare occurrence, described in the literature in 8 other cases, although rare, is certainly underdiagnosed and can lead to complications such as sepsis resulting from CFS, pulmonary embolisms, and vascular thrombosis. Therapeutic approaches should be considered only in symptomatic cases and involve an invasive surgical approach.

Keywords: CVC complication, fibrin sleeve, fibrin sheath, calcified fibrin sheath, stuck catheter, hemodialysis

47-year-old woman suffering from minimal lesion glomerulonephritis previously undergone high-dose steroid therapy and subjected to exacerbations of nephrotic syndrome after therapy discontinuation. It was decided to initiate off-label treatment with Rituximab at a dosage of 375 mg/m² administred at zero-time, one-month and three months with good therapeutic response and resolution of the clinical laboratory picture. The therapy was well tolerated and had no side effects. This scheme could be an alternative to the conventional therapeutic scheme with steroids or other classes of immunosuppressive drugs, especially in order to avoid problems related to prolonged exposure to steroid therapy.

Keywords: minimal change glomerulonephritis, Rituximab, steroid-dependent nephrotic syndrome

Renal involvement is very common in patients with HIV infection. The phenotype varies from the most frequently “collapsing” variant of focal and segmental glomerulosclerosis (FSGS) to “lupus-like HIV-immune complex kidney disease” (HIVICK). The latter is characterized by a histological picture that recalls lupus nephropathy.
Through a clinical case, we underline the importance of urinary sediment analysis in patients with suspected glomerulopathy. Findings such as the characteristic cells that show the typical appearance of Herpes virus (HSV) infection or LE cells have significantly supported the diagnosis of HIVICK. In light of the present observations, we suggest systematically carrying out a cytological examination of the urinary sediment to confirm diagnostic hypotheses of rare pathologies.

Keywords: HIV, HIVICK, HSV, LE cells, urinary sediment, cytology

Cystic fibrosis is an autosomal recessive disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most recent therapeutic approach to cystic fibrosis aims to correct structural and functional abnormalities of CFTR protein.
CFTR modulators including ivacaftor-tezacaftor-elexacaftor are used in patients with F508del mutation, with clinical improvement. To date, there are no experiences of CFTR modulator therapy in cystic fibrosis patients with organ transplantation and severe renal impairment.
We report the case of a patient diagnosed with cystic fibrosis with F508del mutation, who underwent liver transplantation at the age of 19 and started hemodialysis at the age of 24 due to end-stage renal disease secondary to membranous glomerulonephritis. She was treated with Kaftrio (ivacaftor-tezacaftor-elexacaftor) with clinical benefits on appetite, improvement of body mass index, and reduction of pulmonary exacerbations. A reduction of dosage to 75% of the standard dose was required due to alterations of the liver function.
Conclusions. Use of CFTR modulators in patient with cystic fibrosis, liver transplant and end-stage renal disease could be considered safe but a clinical and laboratoristic monitoring of hepatic function is needed.

Keywords: CFTR modulators, cystic fibrosis, ESRD, liver transplant

Although Randomized clinical trials (RCT) represent the gold standard to compare two or more treatments, the impact of observational studies cannot be ignored. Obviously, these latter are performed on unbalanced sample, and differences among the compared groups could be detected. These differences could have an impact on the estimated association between our allocation and our outcome. To avoid it, some methods should be applied in the analysis of observational cohort.
Propensity score (PS) can be considered as a value which sums up and balances the known variables. It aims to adjust or balance the probability of receiving a specific allocation group, and could be used to match, stratify, weight, and perform a covariate adjustment. PS is calculated with a logistic regression, using allocation groups as the outcome. Thanks to PS, we compute the probability of being allocated to one group and we can match patients obtaining two balanced groups. It avoids computing analysis in unbalanced groups.
We compared low protein diet (LPD) and the Mediterranean diet in CKD patients and analysed them using the PS methods. Nutritional therapy is fundamental for the prevention, progression and treatment of Chronic Kidney Disease (CKD) and its complications. An individualized, stepwise approach is essential to guarantee high adherence to nutritional patterns and to reach therapeutic goals. The best dietary regimen is still a matter of discussion.  In our example, unbalanced analysis showed a significant renal function preservation in LPD, but this correlation was denied after the PS analysis.
In conclusion, although unmatched analysis showed differences between the two diets, after propensity analysis no differences were detected. If RCT cannot be performed, balancing the PS score allows to balance the sample and avoids biased results.

Keywords: Chronic Kidney Disease, Low Protein Diet, Matching, Mediterranean Diet, Nutritional Therapy, Propensity Score, Randomized Clinical Trials

Case Report. C.S.T. (♂, 71 years old) is a patient with multiple and severe comorbidities, undergoing thrice-weekly chronic hemodialysis since 2008 due to the progression of post-lithiasic uropathy. Over the past 2 months, the patient had been experiencing progressive ptosis of the eyelids, muscle weakness, and ultimately dysphagia and dysarthria that emerged in the last few days. Urgently admitted to the Neurology department, electromyography (EMG) was performed, leading to a diagnosis of predominant cranial myasthenia gravis (with borderline anti-acetylcholine receptor antibody serology). Prompt treatment with pyridostigmine and steroids was initiated.
Considering the high risk of acute myasthenic decompensation, therapeutic plasma exchange (TPE) with centrifugation technique was promptly undertaken after femoral CVC placement. TPE sessions were alternated with hemodialysis. The patient’s condition complicated after the third TPE session, with septic shock caused by Methicillin-Sensitive Staphylococcus Aureus (MSSA). The patient was transferred to the Intensive Care Unit (ICU). Due to hemodynamic instability, continuous veno-venous hemodiafiltration (CVVHDF) with citrate anticoagulation was administered for 72 hours.
After resolving the septic condition, intermittent treatment with Acetate-Free Biofiltration (AFB) technique was resumed. The patient completed the remaining three TPE sessions and, once the acute condition was resolved, was transferred back to Neurology. Here, the patient continued the treatment and underwent a rehabilitation program, showing significant motor and functional recovery until discharge.
Conclusions. The multidisciplinary interaction among Nephrologists, Neurologists, Anesthesiologists, and experts from the Immunohematology and Transfusion Medicine Service enabled the management and treatment of a rare condition (MG) in a high-risk chronic hemodialysis patient.

Keywords: Myasthenia Gravis, Plasmapheresis, Therapeutic Plasma Exchange, Hemodialysis, Continuous Renal Replacement Therapy

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease. Its main feature is the progressive enlargement of both kidneys with progressive loss of kidney function. ADPKD is the fourth leading cause of terminal renal failure in the world. Even today there are still uncertainties and poor information. Patients too often have a renunciatory and passive attitude toward the disease. However, there are currently no internationally accepted clinical practice guidelines, and there are significant regional variations in approaches to the diagnosis, clinical evaluation, prevention, and treatment of ADPKD. Therefore, we believe it is important to point out the conduct of our specialist outpatient clinic for ADPKD, which from the beginning has developed a multidisciplinary approach (nephrologists, geneticists, psychologists, radiologists, nutritionists) to face the disease at 360° and therefore not only from a purely nephrological point of view. Such a strategy not only enables patients to receive a timely and accurate diagnosis of the disease, but also ensures that they will receive a thorough and focused follow-up over time, that can prevent or at least slow down the disease in its evolution providing patients with a serene awareness of their condition as much as possible.

Keywords: ADPKD, genetics, clinical psychology, clinical nutrition, multidisciplinary approach

Background. Estimated GFR (eGFR) is calculated using serum creatinine (SCr) based equations which have their own limitations. Novel biomarkers like beta trace protein (BTP) are studied for eGFR estimation. The aim of this study is to determine the serum levels of BTP in healthy controls and chronic kidney disease (CKD) cases and to find out the correlation of BTP levels with that of SCr and SCr-based eGFR formulas.
Methods. The control group comprised of 20 healthy adults. The cases comprised of 20 patients each in CKD stages 3, 4, and 5, categorized based on eGFR calculated using MDRD formula. Baseline characteristics of the study population were recorded. BTP was measured by ELISA (Enzyme Linked Immunosorbent Assay) method and SCr by modified Jaffe’s method. The statistical analyses were performed with the SPSS for Windows, version 16.0.
Results. The median value of blood urea nitrogen (BUN) in the cases was 26.50 mg/dL (IQR 19.25-37) and for control it was 9.5 mg/dL (IQR 8-12). The median value of SCr in the cases was 2.75 mg/dL (IQR 1.725-4.45) and in the controls, it was 0.7mg/dL (IQR 0.6 -0.8). The median value of BTP in cases was 6389.25 ng/ml (IQR 5610.875-10713.75) and in controls, it was 1089.5 ng/ml (IQR 900.5-1309.75).
Conclusion. Serum BTP levels correlated with SCr levels and renal function. We could establish the relationship between the two biomarkers, SCr and BTP, and derive a regression equation.

Keywords: Beta trace protein, estimated GFR, CKD, correlation

Kikuchi-Fujimoto disease (KFD), or Histiocytic Necrotizing Lymphadenitis, is a rare disease, with worldwide distribution but is best known in Japan and South Asia. The most common feature is cervical lymphadenopathy, accompanied by tenderness or high fever, with night sweats, but it can also be asymptomatic or with a very wide range of symptoms. The diagnosis is histopathological, on excisional biopsy. The Kikuchi-Fujmoto disease can mimic lymphoma but also tuberculosis and some autoimmune diseases, or be associated with them. Nephrologists need to be aware of it, considering the potential renal involvement. The association with systemic lupus erythematosus (SLE) is the most frequent but not the only one. Early diagnosis of this disease can prevent unnecessary investigations and aggressive therapies.

Keywords: Kikuchi-Fujimoto disease, Histiocytic Necrotizing Lymphadenitis, renal involvement, autoimmune disease, excisional biopsy, differential diagnosis

Hyperprolinemia is a rare genetic condition due to mutations in proline metabolic pathway. Type I Hyperprolinemia (HPI) typically causes neuropsychiatric disorders, and diagnosis is usually confirmed in pediatric population with suggestive neuropsychiatric involvement by elevated serum proline levels and elevated urinary proline, hydroxyproline, and glycine levels.
The possible coexistence of nephropathy in patients with HPI, often specified as malformative urinary disease, is often mentioned. However, reports of HPI diagnosis due to kidney impairment do not exist in scientific literature yet.
Here we present the case of a patient presenting with chronic kidney disease secondary to obstructive nephropathy who received a HPI diagnosis in adulthood.
Interestingly, the family study showed the same 22q11.21 deletion and elevated blood proline levels in the father, who had no clinical anomalies.
We therefore suggest, in light of the high frequency of mutations involving 22q11 and PRODH in the general population, to consider these rare alterations in patients with congenital urinary malformations, even in the presence of nuanced neurological symptoms and negative family history.

Keywords: hyperprolinemia, type I hyperprolinemia, genetic nephropathy, malformative urinary disease

In the last decades, our understanding of the genetic disorders of inherited podocytopathies has advanced immensely; this has been possible thanks to the development of next-generation sequencing technologies that offer the possibility to evaluate targeted genes at a lower cost than in the past. Identifying new genetic mutations has helped to recognize the key role of the podocyte in the health of the glomerular filter and to understand the mechanisms that regulate the cell biology and pathology of the podocyte. Here we describe a patient with congenital nephrotic syndrome due to a mutation in PODXL. This gene encodes podocalyxin, a podocyte-specific surface sialomucin known to maintain the characteristic architecture of the foot processes and the patency of the filtration slits.

Keywords: Proteinuria, Congenital nephrotic syndrome, Podocyte, PODXL, Podocalyxin

Mutations in the 24-hydroxylase gene CYP24A1 have been recognized as causes of childhood idiopathic hypercalcemia (IIH), a rare disease (incidence <1:1,000,000 live births) [1] characterized by increased vitamin D sensitivity [2], with symptomatic severe hypercalcemia.
IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis [3].
The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D [4], and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology [5].
The phenotypic spectrum of CYP24A1 mutation can be variable, manifesting predominantly with childhood onset and severe symptomatology (severe hypercalcemia, growth retardation, lethargy, muscle hypotonia, dehydration), but also with juvenile-adult onset forms with nephrolithiasis, nephrocalcinosis, and alterations in phosphocalcium homeostasis [6].
We describe the case of a patient in whom the diagnosis of IIH was made in adulthood, presenting with finding of nephrocalcinosis in childhood, and with subsequent onset of severe hypercalcemia with hypercalciuria, hypoparathyroidism, hypervitaminosis D, and recurrent renal lithiasis.
Genetic investigation revealed the presence in homozygosity of the c_428_430delAAG_p.Glu143del variant in the CYP24A1 gene with autosomal recessive transmission, a mutation not reported in the literature.

Keywords: CYP24A1, Hypercalcemia, Infantile Idiopatic Hypercalcemia, Vitamin D, Nephrocalcinosis

This article, written by several authors, describes the birth and early development of the nephrology at Molinette Hospital in Torino, Italy. In particular, it supplies important information on Antonio Vercellone, very motivated and innovative clinician and one of the fathers of Italian nephrology, and on Giuseppe Piccoli, his right-hand man and then his successor. This article also shows the strong professional and human engagement that was requested to the young doctors who, in the early Sixties and Seventies of the past century, had chosen to devote their professional lives to the patients with kidney diseases: from endless workdays without schedules to the anguish caused by the shortage of artificial kidneys to the cure of very fragile and unfortunate patients, and much more.

Keywords: History of Molinette Hospital, History of nephrology of Torino, History of Italian nephrology

Background. Polycystic kidney disease (ADPKD) is the most common monogenic cause of End Stage Renal Disease (ESRD), and, thus, of kidney transplantation and dialysis. Educational interventions aimed to improve adherence to therapy, physical performance, and adequate food intake in patients can slow down disease progression by developing self-care skills, which are useful to promote their autonomy while aligning their life plans and required treatments.
The aim of this review is to analyze the adherence of patients with polycystic kidney to pharmacological therapy, low-sodium diet, and physical activity, as evidenced in the clinical literature to guide structured educational interventions.
Methods. We conducted a literature review from 01/09/2021 to 30/12/2022 through the combination of free keywords and MeSH terms on the databases: PubMed, CINAHL and Cochrane.
Results. Findings in medical literature show that physical activity can improve blood pressure control and a low-sodium diet can slow down the progression towards ESRD. Furthermore, although patients may adhere to the complex drug therapy, unresolved educational demands concern choices and behaviors of daily life that, involving the sphere of feelings and emotions, can evolve into manifestations of anxiety and stress. Conclusion. Among ADPKD patients a personalized educational support, considering disease stage and psychological factors, may enable them to acquire knowledge, skills, and behaviors that can improve clinical outcomes.

Keywords: autosomal dominant polycystic kidney disease, patient education, disease management

The link between chronic renal failure and anemia has been known for more than 180 years, negatively impacting the quality of life, cardiovascular risk, mortality, and morbidity of patients with chronic kidney disease (CKD). Traditionally, the management of anemia in CKD has been based on the use of replacement martial therapy, vitamin therapy, and the use of erythropoiesis-stimulating agents (ESAs). In recent years, alongside these consolidated therapies, new molecules known as hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHIs) have appeared. The mechanism of action is expressed through an increased transcriptional activity of the HIF gene with increased erythropoietin production. The drugs currently produced are roxadustat, daprodustat, vadadustat, molidustat, desidustat, and enarodustat; among these only roxadustat is currently approved and usable in Italy. The possibility of oral intake, pleiotropic activity on martial and lipidic metabolism, and the non-inferiority compared to erythropoietins make these drugs a valid alternative to the treatment of anemia associated with chronic kidney disease in the nephrologist practice.

Keywords: CKD, Anemia, Erythropoietin, HIF, Roxadustat

Background. Catheter-related bloodstream infection (CRBSI) is defined as the presence of bacteremia originating from a venous catheter and is one of the most common and costly complications, often followed by death and septicemia.
Objectives. To evaluate the effectiveness of specific interventions on CRBSI reduction rates and other outcomes.
Materials and Methods. The review has been performed by consulting scientific evidence through the PUBMED/MEDLINE database using MeSh terms and Boolean operators. Studies related to the formulated hypothesis have been selected and included.
Results. The results showed that thanks to a series of interventions it was possible to decrease the risk of CRBSI and lowered the risk of catheter removal, hospitalization rate and morbidity rate.
Discussion and Conclusions. Proper catheter care and follow-up procedures are the first steps in preventing infection. Audit and education of dialysis unit personnel is essential.

Keywords: Catheter, Blood Stream Infection, Hemodialysis Catheter Management, Nurse, Central Lines, Rate of Infections

Intravenous iodinated contrast media are commonly used in clinical practice, ranging from medical imaging to interventional radiology (IR) procedures and endovascular interventions. Compared with patients with normal renal function, nephropathic patients have an increased risk of acute kidney injury (AKI). Nevertheless, this condition cannot represent a limit to diagnostics or endovascular interventions.
Despite the literature of the last five years, conflicting management and approaches for nephropathic patients persist, including the use of contrast agents and treatments replacing renal functions, which are often mistakenly considered as part of preventive strategies. Though the issue has been widely discussed, specialists often cope with uncertainty in handling properly the administration of contrast media and renal counselling requests. Furthermore, there is a general difficulty in distinguishing the Post-Contrast Acute Kidney Injury (PC-AKI) from the Contrast-Associated Acute Kidney Injury (CI-AKI).
The present review aims to provide an update on the issue and examine strategies to reduce the acute kidney injury risk after the administration of contrast media. These strategies include the early identification of high-risk individuals, the choice of the contrast media and the proper dosage, the suspension of nephrotoxic drugs, the follow-up of the high-risk individuals, and the early identification of AKI.

Keywords: Constrast Medium, Acute Kidney Injury, Prevention, Hydration

Introduction. Contrast Induced Encephalopathy (CIE) belongs to Major Adverse Renal and Cardiovascular Events (MARCE) after iodinated contrast medium (IOCM), especially for high-risk patients with several comorbidities such as hypertension, diabetes, heart failure, and Chronic Kidney Disease (CKD). We report a case of CIE in a Peritoneal Dialysis (PD)-patient.
Case report. A 78-year-old, affected by diabetes, hypertension, chronic heart failure, and End Stage Renal Disease (ESRD) treated with PD, underwent a carotid Percutaneous Angioplasty (PTA). Immediately after the exam, he developed mental confusion and aphasia. Encephalic CT scan and MRI excluded acute ischemia or hemorrhage but showed cerebral oedema.  Mannitol and steroids were administered and additional PD exchange was performed with depurative aim. Within 2 days the patient completely recovered.
Discussion. CIE mimics severe neurological diseases. It should be considered as a differential diagnosis if symptoms occur immediately after administration of IOCM, especially in high-risk patients and in case of intra-arterial injection. Clinical presentation includes transient cortical blindness, aphasia, focal neurological defects, and confusion. CIE is often a diagnosis of exclusion, and imaging plays a significant role. Symptoms generally resolve spontaneously within 24-48h, rarely in few days. Symptomatic therapy, including mannitol and steroids could be considered. In literature, CIE is reported only in a few patients affected by ESRD treated with chronic HD, and our is the first available case of a patient treated with chronic PD who developed this rare complication.

Keywords: Peritoneal Dialysis, Contrast-induced encephalopathy, contrast medium

Through a clinical case, we will describe the difficulties associated with providing transplantation opportunities to highly immunized patients. We will therefore focus on new desensitization therapies and their pharmacological effects with the consequent improvement in clinical outcomes. The main desensitization strategies in use and the main future therapeutic prospects will also be discussed.

Keywords: Imlifidase, Kidney Transplant, Hyperimmune Patients

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a low-prevalence pathology mainly associated with pathogenic variants of the UMOD gene. It is characterized by the progressive deterioration of renal function, associated with hyperuricemia and accompanied by a family history of gout or hyperuricemia. Often, clinical variability and a lack of molecular testing results in diagnostic failure to determine the ADTKD-UMOD association.

Case presentation: We describe the case of a 14-year-old male who presented to the nephrology service with hyperuricemia, renal ultrasonographic changes, and progression to chronic kidney disease in 4 years. He had a family history of hyperuricemia. A probable genetic disease with an autosomal dominant inheritance pattern was considered, confirmed by the presence of a probably pathogenic variant of the UMOD gene, not previously reported in the literature.

Conclusion: The investigation of this case led to the identification of a new variant in the UMOD gene, broadening the spectrum of known variants for ADTKD-UMOD. In addition, in this case, a comprehensive anamnesis, that takes into account family history, was the key point to carry out genetic tests that confirmed the diagnosis suspicion. Directed Genetic tests are currently an essential diagnostic tool and should be performed as long as they are available and there is an indication to perform them.

Keywords: UMOD, Uromodulin, hyperuricemia, Uric acid, Familial Juvenile Hyperuricemic Nephropathy, case report

The abuse of anabolic androgenic steroids (AAS) for competitive (and non-competitive) purposes for bodybuilding practice is increasingly common. The consequences of these substances on the various organs are only partially known. Cases of FSGS following the use of AAS have been reported in the literature, even with evolution to ESKD.
We describe three cases of bodybuilding athletes who presented alterations in renal function indices after taking AAS for a long time. Three renal biopsies were performed with histological diagnosis of FSGS collapsing variant. We examine the lesions observed on histological examination. Two athletes had rapid progression of renal disease requiring replacement therapy. The third one continues conservative treatment for chronic renal failure.
We discuss the risks related to the intake of doping substances and how bodybuilders are exposed to different causes of kidney damage: anabolic steroids, supplements, and a high-protein diet.

Keywords: anabolic-androgenic steroids, bodybuilding, FSGS, collapsing variant, chronic kidney disease

Myeloma cast nephropathy is the most common cause of acute kidney injury in patients affected by multiple myeloma. The mainstay of management of cast nephropathy is the clone-based therapy by reducing production and thereby precipitation of light chains. Adjuvant therapy consists of inducing high urine volume flow and alkalinisation, where possible. Extracorporeal removal of light chains is still debated and the advantages of these procedures are not established. The use of safe and low expensive membranes may encourage their use and address their utility.

Keywords: multiple myeloma, cast nephropathy, dialysis

Monoclonal Gammopathies of Renal Significance (MGRS) are a complex group of disorders characterized by the production of aberrant monoclonal proteins that interact with kidney structures, causing tissue damage. Unlike neoplastic forms, kidney damage in MGRS does not correlate with clone mass or circulating monoclonal protein levels, conferring unique pre-neoplastic or non-neoplastic properties to the responsible clones.

This manuscript explores the heterogeneity of monoclonal proteins involved, varying from full immunoglobulins to free light chains (FLC), and how they result in a spectrum of kidney lesions with differing prognoses. We also elaborate on diagnostic challenges, emphasizing the indispensable role of kidney biopsy, including advanced techniques like laser microdissection and mass spectrometry (LMD/MS) for deposit characterization, particularly in ambiguous or complex cases. Clinical management and treatment considerations, including the necessity for clone identification, are also discussed.

Keywords: Plasma Cell Dyscrasias, Monoclonal gammopathy, Monoclonal gammopathy of renal significance, Kidney biopsy

Immunoglobulin Light Chain Amyloidosis (AL) is a progressive disease which leads to organ dysfunction and death.  Tremendous progress has been made in staging, response, and treatment.  The key to better survival though is early diagnosis which can be difficult since the symptoms are often nonspecific and can be seen in more common conditions. Once the diagnosis is confirmed, staging systems are available to provide prognosis on overall and renal survival.  There are a number of treatments now available that are effective and well-tolerated. Response criteria have also been developed for hematologic and renal response in order to maximize response and minimize adverse effects.  Newer therapies are being developed in particular anti-fibril therapies that are in clinical trials.  For those patients who had a very good partial response or better, kidney transplantation may be an option if the kidney failure is not reversed.

Keywords: amyloidosis, light chain amyloidosis, light chain, kidney transplantation

Cancer transmission from solid organ donors to recipients is a known risk factor in transplantation. The Italian National Network for Transplantation (CNT) has adopted specific guidelines to evaluate the suitability of donors with history of malignancy. CNT also provides a Second Opinion service to assess oncological cases with a potential risk of neoplastic transmission to the recipient. CNT aims to minimize the risk of disease transmission from donors to recipients.

According to CNT guidelines, “standard” donors are defined as individuals with no signs of active malignancy and no history of cancer at the time of organ procurement. Unsuitable donors, defined as those with an “unacceptable risk”, are those patients with evidence of malignancy at the time of donation or in their medical history that carries an unacceptably high risk of disease transmission. Between these two categories, a broad spectrum of “non-standard” donors exists, where the risk of transmission is not entirely absent, but remains low enough to consider organ utilization. Malignancy should not be considered an absolute contraindication for organ donation.

CNT has also adopted a specific repository for adverse events (AE) after transplantation. Since 2012, with 10.493 donors and 34.193 performed transplants, 283 AE have been recorded, occurring in approximately 3% of donation processes and 1% of performed transplants. Oncological AE represented 13% of all reports. In the majority of cases, oncological AE resulted from missed diagnosis during organ procurement, benchwork, or transplantation surgery.

CNT guidelines, the oncological second opinion service, and the repository helped minimize the risk of cancer transmission with transplantation.

Keywords: cancer, organ donor, transplant

Onconephrology, an emerging field in modern medicine, is gaining importance due to its intricate challenges derived from the mixing field of tumorous and renal diseases. The growing incidence of tumors in transplant patients requires preventive strategies and accurate monitoring. Pre-transplant screening is crucial, focusing on subjects with oncological history. Post-transplant follow-up must be personalized, tailoring screenings for patients with cancer history. Immunosuppressive therapy, although essential to prevent organ rejection, represents a delicate balance between controlling the immune response and cancer risk management.
Immune checkpoint inhibitors emerge as a fascinating potential for cancer therapy, but their use in transplant patients requires caution and further research to carefully evaluate their safety and effectiveness, balancing potential benefits with actual risk of rejection. In summary, onconephrology is a growing field that requires an interdisciplinary approach and constant research, aimed at successfully addressing the complex challenges associated with oncological diseases in renal and transplant patients.

Keywords: Onconephrology, Kidney transplant, Immunosuppressive therapy, Immune check-point inhibitors

Individuals who suffer from end-stage renal disease are at a higher risk of developing certain types of tumors. This risk increases as kidney function deteriorates further. Dialysis patients often witness a surge in the incidence of such malignancies. Interestingly, after the initial period following a kidney transplant, there is a dip in the number of deaths related to neoplasms. However, a long-term view reveals a progressive increase in the risk of developing tumors. The evaluation process for transplant candidacy is thorough, taking into account several factors, including the individual’s history of neoplasms and the implications of immunosuppressive therapy. Immunosuppressive therapy is a double-edged tool in managing post-transplant complications, as it can foster environments conducive to neoplasm growth. It is essential to reevaluate, with the aid of an oncological opinion, the waiting time between cancer recovery and the listing for kidney transplantation, based on clinical data and follow-up. Independent of the type of tumor, the requirement to treat and achieve remission delays the listing process, consequently extending the time spent with end-stage renal disease and undergoing dialysis. These factors correlate with increased mortality, heightened risk of cardiovascular disease, and graft loss.

Keywords: Kidney transplant, cancer, immunosuppressant agents

The therapeutic landscape for renal cell carcinoma (RCC) has undergone significant changes in recent years. In this Literature review, we offer a synopsis of the latest scientific evidence in this field. The introduction of a standard of care in the adjuvant setting, based on immune checkpoint inhibitors (ICI), was a breakthrough. The efficacy of this treatment, calculated as the relapse risk reduction, can vary depending on multiple factors, whose knowledge is important for the clinician in the therapeutic choice. Another innovation concerns the first-line therapy for metastatic RCC. In this setting, the new standard is represented by an immune combination, a therapy based either on a doublet of ICIs or on a combination between an ICI and one VEGFR-TKI. Making the best choice between the available options requires careful evaluation, in order to tailor the most appropriate treatment for each patient. The critical analysis of the most recent clinical trials is a fundamental tool to tailor the correct clinical management of localized and advanced RCC. Finally, this review focuses on the role of the nephrologist in the management of RCC patients, across different disease settings.

Keywords: Renal cancer, immunotherapy, tyrosin kinase-inhibitors

Kidney cancer is one of the most common cancers globally, ranking 9th and 14th among men and women, respectively. Advances in diagnostic techniques have enabled earlier and potentially less invasive interventions, however, this progress poses a challenge in managing low-malignancy tumors that were previously undiagnosed. To navigate treatment pathways, a deep understanding of the bidirectional relationship between Chronic Kidney Disease (CKD) and Renal Cell Carcinoma (RCC) is essential, influenced by risk factors such as hypertension and obesity.
The debate between partial (PN) and radical nephrectomy (RN) continues to be fueled by a rich body of studies in the last two decades, aiming to determine the precise benefits of renal function preservation and overall survival. However, long-term monitoring remains inadequate. There is an urgent need for heightened clinical vigilance, urging meticulous periodic evaluations that include both eGFR and the urinary albumin-creatinine ratio, to identify potential deteriorations early.
Furthermore, non-neoplastic renal parenchyma requires equal attention, often overshadowed by the assessment of tumor mass. A nuanced analysis is necessary to identify a range of nephropathies that guide more effective therapeutic strategies. A collaborative strategy that brings nephrologists, urologists, nuclear radiologists, oncologists, and pathologists together on a unified platform, focusing on a personalized medicine approach grounded on a profound analysis of individual risk factors, is pivotal in shaping the future of management and prevention strategies.
This approach ensures a detailed therapeutic outlook and facilitates early interventions, marrying vigilance with interdisciplinary cooperation, thereby guarding against late diagnoses and offering patients a robust shield in their battle against kidney afflictions.

Keywords: renal cancer, acute kidney injury, acute kidney disease, chronic kidney disease, nephrectomy, partial nephrectomy, chemotherapy, targeted anticancer agents

Onconephrology is a rising and rapidly expanding field of medicine in which nephrology and oncology meet each other. Besides multidisciplinary meetings, oncologists and nephrologists often discuss on timing of the treatment, dosage, and side effects management. Cancer patients often encounter different electrolyte disorders. They are mostly secondary to the tumor itself or consequences of its treatment. In the last years, the great efforts to find new therapies like targeted, immune, and cell-based led us to many new side effects. Hyponatremia, hypokalemia, hyperkalemia, hypercalcemia, and hypomagnesemia are among the most common electrolyte disorders. Data have shown a worse prognosis in patients with electrolytic imbalances. Additionally, they cause a delay in chemotherapy or even an interruption. It is important to diagnose promptly these complications and treat them. In this review, we provide a special focus on hyponatremia and its treatment as the most common electrolytes disorder in cancer patients, but also on newly described cases of hypo- and hyperkalemia and metabolic acidosis.

Keywords: hyposodiemia, cancer patients, electrolyte disorders, hyperkalemia

The introduction of innovative therapies has changed the scenario of complications. The delay in the recognition of kidney adverse effects is partly due to the timing of the development of the kidney damage which occurs later than the observation period of registration studies, and partly to the exclusion of patients with known kidney impairment from registration trials.

Renal disease has a significant impact on the management of cancer patients and often leads to discontinuation of therapy. Histological evaluations of kidney disorders induced by targeted/immunotherapy are very limited. Renal biopsy is critical for the management of renal toxicities and should be especially encouraged for patients showing adverse renal effects to novel cancer agents.

We recently examined the histological features of patients treated with new cancer agents who underwent renal biopsy for new onset renal failure and/or urinary abnormalities. The cohort included 42 patients. The most frequently administered therapies were immunotherapy (54.8%) and anti-angiogenic treatments (45.2%). The most common adverse effect was tubular interstitial nephritis in the first group and thrombotic microangiopathy in the second one. Based on histological findings, definitive discontinuation of treatment could be restricted to a very limited number of patients. All of them had anti-VEGF-related TMA. Treatment discontinuation was unneeded in patients treated with ICIs. In patients treated with multidrug therapy, the histological findings made it possible to identify the weight of drug-related specific injury. Based on this data, renal biopsy should be considered in every cancer patient who develops urinary abnormalities or shows a worsening of renal function during treatment with immunotherapy or targeted therapy.

Keywords: Onconephrology, Immune checkpoint, Targeted Therapies, Renal biopsy in oncotherapy, Thrombotic Micro-angiopathy, Interstitial tubular nephritis

Tyrosine Kinase Inhibitors (TKIs) have significantly contributed to revolutionizing cancer treatment, as they are orally administered small molecules able to target key pathways involved in tumor growth and angiogenesis. However, the clinical utility of TKIs may be compromised by adverse effects, which can affect tissues and organs, including kidneys. This comprehensive review offers a general overview of studies reporting the incidence and clinical characteristics of TKI-related nephrotoxicity and it explores the mechanisms underlying the intricate relationship between TKIs and renal toxicity. The biological rationale for the kidney manifestations of toxicity associated with TKI agents is here discussed, underlying potential off-target effects and emphasizing the importance of accurate risk assessment and tailored patient management strategies.

Deep insight into the molecular mechanisms of TKI nephrotoxicity will help to improve the global understanding of the pathophysiology of this peculiar toxicity and to develop more effective and safer therapies.

Keywords: Tyrosine kinase inhibitors, kidney, renal toxicity, cancer

Acute renal failure (AKI) is a high-prevalence complication in patients with cancer. The risk of AKI after cancer diagnosis is 18% in the first year, 27% in the fifth year, and 40% of critically ill patients with cancer require renal replacement therapy.

The causes of AKI may be pre-renal due to hemodynamic problems, related to the cancer, metabolic complications, and drug or surgical treatment.

One must preventively protect renal function by hydration, use of non-nephrotoxic drugs, correction of anemia, prevention of contrast agent-induced AKI (CI-AKI), and adjustment of cancer therapy in patients with CKD. It is essential to check basal renal function, creatinine trend, electrolytes, urinalysis and proteinuria, perform imaging, renal biopsy if necessary.

The evaluation of patients should be multidisciplinary and timely including the initiation of renal replacement treatment (RRT). There are different modalities of replacement treatment depending on the clinical picture of the patient with AKI and cancer: intermittent hemodialysis (IHD), intermittent prolonged replacement therapy (PIRRT), and continuous replacement therapy (CRRT). The concept of dose administered, as opposed to prescribed dose, as well as the anticoagulation of extracorporeal circuits, which must be regional with citrate (RCA) as the first choice in the management of CRRT, turns out to be fundamental in order to achieve optimal circuit anticoagulation, with reduction of coagulation episodes and downtime, while maintaining the patient’s coagulation status.

The onco-nephrologic multidisciplinary approach is crucial to reduce the mortality rate, which is still high in this category of patients.

Keywords: AKI, cancer, RRT, citrate

Cancer and chronic kidney disease prevalence both increase with age. As a consequence, physicians are more frequently encountering older people with cancer who need dialysis, or patients on dialysis diagnosed with cancer. Decisions in this context are particularly complex and multifaceted. Informed decisions about dialysis require a personalised care plan that considers the prognosis and treatment options for each condition while also respecting patient preferences. The concept of prognosis should include quality-of-life considerations, functional status, and burden of care. Close collaboration between oncologists, nephrologists, geriatricians and palliativists is crucial to making optimal treatment decisions, and several tools are available for estimating cancer prognosis, prognosis of renal disease, and general age-related prognosis. Decision regarding the initiation or the termination of dialysis in patients with advanced cancer have also ethical implications. This last point is discussed in this article, and we delved into ethical issues with the aim of providing a pathway for the nephrologist to manage an elderly patient with ESRD and cancer.

Keywords: Chronic Kidney Disease, Cancer, Dialysis, Ethic, Onconephrology

The incidence of tumors is increased in patients with chronic renal failure and even more in patients on dialysis. Dialysis can affect both therapy and prognosis of oncological patients. It increases both cancer-related and non-cancer-related mortality rates and is the main cause of a suboptimal use of therapies. In patients with renal impairment, the dosage of many chemotherapies should be reduced but, due to the lack of real knowledge of the pharmacokinetic and pharmacodynamic properties of these drugs in dialysis, dosage adjustments are often done empirically and most often avoided.

Although many papers are available in the literature regarding chemotherapy in dialysis, there is a lack of consensus regarding drug dosages and administration schedules. Furthermore, guidelines are absent due to the lack of “evidence” for most of these patients, usually excluded from experimental treatments.

Specific onconephrologic trials are therefore mandatory to decide how much, how, and when to use chemotherapy in patients on dialysis and thereby ensure adequate treatment for these patients.

Keywords: onconephrology, dialysis, cancer, chemotherapy

Cancer is a leading cause of death in people with chronic kidney disease (CKD). The incidence of CKD in patients with cancer is higher than in the non-cancer population. Across various populations, CKD is associated with an elevated risk of cancer incidence and cancer death compared with people without CKD, although the risks are cancer site-specific. The potential mechanisms for the increased risk of cancer observed in CKD, include patient factors, disease, and treatment factors. CKD has also a major impact on the treatment of cancer patients. The kidney is the primary route of elimination of many anticancer drugs. Dosing of anticancer agents according to kidney function is essential to avoid undertreatment and toxicity. Because of the systemic exclusion of patients with severe kidney dysfunction from clinical cancer trials, data are lacking to guide dosing of anticancer drugs in patients with chronic kidney disease. As a consequence, many therapies are denied to CKD patients due to their possible toxicities. An orchestrated effort by all stakeholders is required to fill the knowledge gap and improve the outcome of cancer patients with kidney dysfunction.

Medical Oncology since the beginning of the new millennium has recognized a great positive evolution in the care of cancer.
In fact, for more than 60 years the two classical pillars of the antineoplastic therapy were hormone therapies mainly applied in breast, prostate and thyroid cancer, and chemotherapy seldom curative and heavily toxic.
Nowadays some new treatments are available thanks to the advances in genomics, proteomics and molecular biology of tumor cells either to the advances in immunology studies.
Specific pathways in cancer cells have been recognized and hit by targeted drugs.
Monoclonal antibodies, tyrosine kinase inhibitors, checkpoint inhibitors, cellular therapies and vaccines are the new tools for oncologists.
The last discovery is the antibody-drug conjugates (ADCs), which combine monoclonal antibodies with cytotoxic drugs.
Unfortunately, these impressive advances have caused the appearance of new scientific, social, and financial problems.
All these topics are discussed in the article.

Keywords: oncology, survival, therapy, innovation

A deadly embrace occurs between cancer and chronic kidney disease.   The estimation of kidney function in cancer patients is of utmost interest due to its direct impact on chemotherapy dosing, selection, and eligibility for chemotherapeutics. Overestimating kidney function (determined as estimated glomerular filtration rate -eGFR) can lead to overdosing and drug toxicity, while underestimating kidney function can prevent patients from receiving novel therapies. Notably, the current measures of eGFR are not validated in transplanted patients yet.

The field of onconephrology ranges from nephrotoxicity of existing and novel therapeutics, paraproteinemias, and cancer-associated electrolyte imbalance, fluid and acid-base disturbances, the effects of the destruction of cancer cells, and acute and/or chronic kidney injuries. Recently, the therapeutic armamentarium has been enriched with new agents that interfere with specific proteins involved in oncogenesis. These are the so-called target therapies, which although acquired as “targeted” therapies do not have absolute specificity and selectivity and tend to inhibit multiple targets, often involving the kidney. Renal biopsy may be critical in managing these adverse effects. Moreover, primary hematological and oncological disorders can have significant kidney implications in the form of glomerular or nonglomerular diseases presenting with proteinuria, hematuria, hypertension, and kidney function decline, specifically including cast nephropathy or systemic light chain amyloidosis, and paraneoplastic glomerulopathies that occur as a result of occult malignancy, such as Membranous Nephropathy and Minimal Change disease.

Keywords: Onconephrology, Target Therapies, Renal biopsy in onconephrology, Cancer and kidney

Onconephrology is a subspecialty of Nephrology with the aim of fully dealing with the complex and bidirectional relationship between the tumor and the kidneys.
In a world where Nephrologists still too often consider Oncological patients as “lost” and in which Oncologists are afraid to administer oncological therapies to patients with renal failure due to the absence of Literature data, Onconephrology was created with the aim of guaranteeing patients with renal disease the same treatment opportunities as the general population.
Over the years this subspecialty has developed and more nephrologists, experts in the field, daily support oncologists in clinical-therapeutic decisions by dealing with cases of renal toxicity from oncological therapy, managing treatments in patients with renal failure and dealing with all those conditions associated with both oncological and renal pathology in terms of prevention and treatment.
In this paper we will retrace the history of Onconephrology by analyzing what are the results achieved and what are the objectives for the future. 

Keywords: onconephrology, history of onconephrology, oncological therapies

Starting from the polysemy of capacity and its numerous expressive facets, the Author analyzes how and through which modalities the issue of the validity of consent and informed refusal is typically addressed in places of care. The discussion then moves on to examine the modifications brought about by the UN Convention on the Rights of Persons with Disabilities (CRPD) in this field, fully ratified by Italy, even though the law on informed consent and advance healthcare directives (Law No. 219 of 2017) did not take it into account. Finally, some practical suggestions are formulated to promote the virtuous practice of supported decision-making, which has not yet been developed in Italian care settings.

Keywords: legal capacity, decision-making capacity, Convention on the Rights of Persons with Disabilities, legal protectionism

Introduction. Acoustic Radiation Force Impulse (ARFI) is an ultrasound parameter which has shown promise in assessing liver stiffness, but there are limited data on the correlation of ARFI with chronicity markers in renal biopsies.
Objectives.

1. Determine ARFI values in ultrasound and correlate with chronicity markers in renal biopsy
2. Determine whether ARFI can be used as a non-invasive chronicity predictor compared to renal length, Resistive Index (RI), and cortical thickness.

Patients and Methods. Two hundred and fifty patients were enrolled in the study. The ultrasound variables ARFI, renal length, RI, and cortical thickness values were assessed by the radiologist prior to renal biopsy. The biopsy slides were graded as per the Mayo Clinic consensus report scoring system by an experienced pathologist.
Results. Among 250 study participants, 167 were males and 83 were females. IgA nephropathy was the most common pathology (n=47;19%), followed by diabetic nephropathy (n=42;17%), membranous nephropathy (n=35;14%), FSGS (n=27;11%), and MCD (n=19; 8%). The mean eGFR was 55.9 ± 42.12 ml/min/1.73 m². The average renal length was 10.086 ± 1.01 cm. The average cortical thickness was 0.707 ± 0.134 cm. Resistive index was 0.68 ± 0.09. Acoustic radiation force impulse had weak negative correlation (r=-0.286; p=0.0001) with total pathological score and weak positive correlation with eGFR (r=0.279; p=0.0001). RI was a better indicator for histologically evaluated chronicity with positive correlation coefficient (r=0.416; p=0.0005) compared to renal length, cortical thickness, and ARFI.
Conclusion. ARFI didn’t corelate with the pathological score in renal biopsies. RI had better predictive value for chronicity in native renal biopsies.

Keywords: ARFI, Resistive index, Cortical thickness, Renal length, Chronicity

Currently, the use of SGLT2 inhibitors is becoming more widespread, both for their role in controlling diabetes, and for their pleiotropic effects on glomerular hyperfiltration and heart failure. Along with their positive effects, these drugs can lead to various complications, the most severe being euglycemic ketoacidosis. The clinical case we have reported precisely describes this potentially serious complication which occurred in a 47-year-old patient who had been on SGLT2 inhibitor therapy for 5 years. In the resolution of this case we used, in addition to standard therapy, the continuous infusion of somatostatin, resulting in a rapid resolution of ketoacidosis and an improvement in the clinical condition.

Keywords: SGLT-2, somatostatin, euglycemic ketoacidosis

A proper management and tailored interventions represented two fundamental steps to ensure a long-term use of the arteriovenous fistula (AVF). AVF failure can be attributed to various factors, with stenosis being the most common cause. Different techniques are employed for treating complications, but percutaneous endovascular procedures are the most widely used. In addition to angioplasty (PTA), the possibility of utilizing stents, particularly stent grafts (SG), has further improved outcomes. However, the insertion of these devices involves commitment to a segment of the vessel, which may vary in length, making the indication necessitate a careful evaluation. The positioning of a stent graft indeed limits the space for needle insertion, and on the other hand, the cannulation of the device is considered off-label according to technical specification.

This work addresses the issue of puncturing these devices. Alongside a rapid overview, we describe a clinical case of continuous cannulation of a multiply stented AVF, for over 9 years, which opens up the discussion about the possibility of long-term cannulation through proper planning.

Keywords: stent, stentgraft, cannulation, arteriovenous fistula

We report a case of MPO-anti-neutrophil cytoplasmic antibody ANCA-associated vasculitis, with pulmonary-renal syndrome, after the mRNA booster third dose vaccine Pfizer BioNTech against COVID-19 in 71-year-old Caucasian man with no specific past medical history. A kidney biopsy diagnosed ANCA-associated pauci-immune crescentic glomerulonephritis. Renal function and constitutional symptoms have been partially improved with treatment with dialysis, intravenous rituximab and steroid pulse therapy. No disease following either infection or vaccination with fourth dose against COVID-19.

Keywords: ANCA vasculitis (AAV), booster dose, cytokine storm, mRNA vaccine, SARS-CoV-2

Tubulointerstitial nephritis is a common cause of acute renal failure, in two thirds of cases it is associated with drugs (mostly antimicrobials and NSAIDs), in 5-10% of cases it is associated with infections (bacterial/viral/parasitic), in 5-10% of cases it is idiopathic (this is the case of the TINU syndrome characterized by interstitial nephritis and bilateral uveitis, and the anti-glomerular basal membrane antibody syndrome), and finally in 10% of cases it is associated with systemic diseases (sarcoidosis, by Sjogren, LES). The pathogenesis is based on a cell-mediated immune response and in most cases removing the causative agent is the gold standard of therapy. However, a percentage of patients, in a variable range from 30% to 70% of cases, do not fully recover renal function, due to the rapid transformation of the interstitial cell infiltrate into vast areas of fibrosis.

Clozapine is a second generation atypical antipsycothic usually used for the treatment of schizophrenia resistant to other types of treatment; it can cause severe adverse effects among which the best known is a severe and potentially fatal neutropenia, furthermore a series of uncommon adverse events are recognized including hepatitis, pancreatitis, vasculitis. Cases of acute interstitial tubular nephritis associated with the use of clozapine have been described in the literature, although this complication is rare. Medical personnel using this drug need to be aware of this potential and serious side effect.

We describe the case of a 48-year-old man who developed acute renal failure after initiation of clozapine.

Keywords: Intestinal tubular nephritis, acute renal failure, clozapine

Introduction: Sleep disorders are very common in patients with chronic kidney disease, with a prevalence of poor sleep quality of around 40%.
Objectives: The purpose of the study is to compare the sleep quality of ESRD patients before hemodialysis (Pre-HD), three months (Post-HD 1) and six months after the start of treatment (Post-HD 2) through the use of the Pittsburgh Sleep Quality Index (PSQI).
Methods: Patients in ESRD were recruited from the U.O.C. of Nephrology and Dialysis of the Maggiore Hospital in Modica and biographical and anamnestic data were collected. The PSQI was administered in-person at the Pre-HD stage and by telephone re-test at the three- and six-month follow-up.
Results: A total of 71 patients (males=62%, age 68 ± 16) were included. At Pre-HD assessment 93% reported poor sleep quality, the percentage increased to 98% during Post-HD 1 and it partially improved during Post-HD 2 with a prevalence of 95%. Analysis of variance (ANOVA) by repeated measures showed a difference in sleep quality between the three time points.
Conclusions: Sleep quality undergoes important changes during the transition from conservative to hemodialysis patient, highlighting a critical period related to the first three months of treatment. More attention to this phase may improve the patient’s quality of life and reduce the associated risk of mortality.

Keywords: sleep, quality, hemodialysis, life, dialysis

This article describes the origin and development of the Nephrology School in Bari, which has noble roots in the Italian Medical School. The narrative begins with the description of my initial interest in Internal Medicine, and later in Nephrology, highlighting the important role that a teacher has on their students during their university education.

The second section describes the creation and development of the Nephrology School in Bari, which was influenced by the knowledge gained abroad and by the international scientific relationships that have been developed over the years.

The third section describes the historical origins of the Nephrology School in Bari, which has grown considerably over the course of 30 years. Finally, after a brief mention of my family, I could not hide my passion for sports, particularly running and soccer. Cinema and theatre are also excellent means of reflection.

In conclusion, my heartfelt hope is that my students will always remember to pursue goals of scientific excellence and, when choosing someone to train as a potential young researcher in the future, to always observe the two founding principles of the School: professional and scientific reliability, respectively based on excellent clinical expertise and scientific production.

Keywords: Nephrology School, Nephrology, Dialysis, Transplant, Clinical Research

Objectives. The results are reported here of the 8^th National Census (Cs-22) of Peritoneal Dialysis in Italy, carried out in 2022-23 by the Italian Society of Nephrology’s Peritoneal Dialysis Project Group and relating to 2022.
Methods. The Census was conducted in the 227 non pediatric centers which performed Peritoneal Dialysis (PD) in 2022. The results have been compared with the previous Censuses carried out since 2005.
Results. Incidence: in 2022, 1350 patients (CAPD=52.1%) started on PD (1^st treatment for ESRD). PD was started incrementally by 35.3% in 136 Centers. The catheter was placed exclusively by a Nephrologist in 17.0% of known cases. Prevalence: there were 4152 (CAPD=43.4%) patients on PD on 31/12/2022, with 21.1% of prevalent patients on assisted PD (family member caregiver: 86.3%). Out: in 2022 the PD drop-out rate (ep/100 pt-yrs) was: 11.7 to HD; 10.1 death, down; 7.5 Tx. The main cause of transfer to HD remains peritonitis (23.5%), although its reduction over the years is confirmed (Cs-05: 37.9%). Peritonitis/EPS: the incidence of peritonitis in 2022 was 0.176 ep/pt-yr (696 episodes). The incidence of new cases of EPS fell in 2021-22 (7 cases). Other results: the number of Centers using 3.86% for the peritoneal equilibration test (PET) (57.7%) increased. PD for heart failure continues to be used in 44 Centers (66 pts).
Conclusions. Cs-22 confirms PD’s good results in Italy.

Keywords: Peritoneal Dialysis, technique failure, incremental Peritoneal Dialysis, peritonitis, peritoneal equilibration test (PET)

Orellanic syndrome is caused by fungi of the Cortinarius orellanus and speciosissimus (Europe) species, Cortinarius fluorescens (South America), and Cortinarius rainierensis (North America). Orellanic syndrome is characterized by initially nonspecific symptoms such as muscle and abdominal pain, and a metallic taste sensation in the mouth. After a few days, more specific symptoms appear, such as intense thirst, headache, chills without fever, and anorexia, followed by a phase of polyuria and then of oligoanuria. Renal failure occurs in 70% of cases and is often irreversible. The clinical case involves a 52-year-old man who developed acute renal failure from Orellanic syndrome, necessitating hemodialysis.

Keywords: Orellanic syndrome, Cortinarius mushroom, dialysis

There is a strong correlation between SARS-CoV-2 and the onset of autoimmune neurological disease with atypical clinical presentation, characterized by limited response to medical therapy, likely caused by the underlying mechanism of the virus itself.

In situations like these, after the failure of pharmacological therapy, therapeutic apheresis, including immunoadsorption, can be pursued.

Treatments with IMMUSORBA TR-350 columns have proven to be particularly effective in managing refractory forms of post-Covid-19 nephropathies, leading to complete recovery of disability and elimination of neurological signs and symptoms.

We discuss the case of a patient with chronic inflammatory polyradiculopathy post-Covid-19, resistant to medical therapy, effectively treated with immunoadsorption.

Keywords: Polyradiculopathy, SARS-CoV-2, Apheresis, Immunoadsorption

Among the various problems associated with peritoneal dialysis, besides infectious causes, the risk of catheter malfunction plays a significant role in conditioning the continuation of the method, accounting for up to 15-18% of the total causes of dialysis drop-out. When non-invasive maneuvers, such as the use of laxatives to stimulate intestinal peristalsis or heparin and/or urokinase have no effect, videolaparoscopy is the only method that directly detects the precise causes of peritoneal catheter malfunction. Those found are, with decreasing frequency, the winding of the catheter between the intestinal loops and the omentum (wrapping), the dislocation of the catheter, the combination of wrapping and dislocation, the occlusion of the catheter by a fibrin plug, the adhesions between the intestine and abdominal wall, the occlusion of the catheter by epiploic appendages or adnexal tissue and, occasionally, the presence of a new formation of endoperitoneal tissue enveloping and obstructing the peritoneal catheter. We report the case of a young patient of African ethnicity who, only five days after catheter placement, experienced malfunction. A videolaparoscopy revealed wrapping with invagination of omental tissue inside the catheter. After omental debridement, a proper peritoneal cavity washout with heparin was resumed, and after a couple of weeks, APD was initiated. About a month later, a new malfunction without signs of coprostasis or problems with the abdominal radiogram was observed. However, a subsequent catheterography confirmed the blockage of drainage. This was followed by another catheterography and omentopexy, with definitive solution of the Tenckhoff malfunction.

Keywords: peritoneal dialysis, peritoneal catheter, omentopexy

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus.  Sepsis is a common complication in patients undergoing surgery and is a major risk factor for the development of acute kidney injury (SA-AKI). Prevention of AKI in surgery patients is largely based on identification of high baseline risk, monitoring, and reduction of nephrotoxic insults. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches.

Keywords: AKI, PO-AKI, sepsis, biomarkers, extracorporeal treatment

Obesity is recognized as a true chronic disease and an independent risk factor for kidney disease. In particular, a correlation was observed between obesity and the development of focal segmental glomerulosclerosis. The clinical consequences of obesity on the kidney can include albuminuria, nephrotic syndrome, nephrolithiasis, and increased risk of development and progression of renal failure. Conventional therapy, which includes low-calorie diet, exercise, lifestyle changes, and drug therapy, including GLP1-RA, phentermine, phentermine/topiramate, bupropion/naltrexone, orlistat, is not always able to achieve the desired results and above all does not guarantee stabilization of body weight over time. On the other hand, bariatric surgery is giving excellent results in terms of efficacy and duration. Bariatric surgery techniques that are generally divided into restrictive, malabsorptive, and mixed are not free from possible metabolic complications such as anemia, vitamin deficiency, and stones. However, they are able to ensure a good maintenance of weight loss obtained with disappearance or reduction of the incidence and severity of comorbidities related to obesity.

Keywords: obesity, renal failure, bariatric surgery, sleeve gastrectomy

Mushroom poisoning can represent an acute event which the clinical nephrologist must deal with and which often leads to the need for emergency dialysis treatment. Through the exposed clinical case, we describe the secondary clinical manifestations of an acute intoxication sustained by Amanita Echinocephalae, and we will provide an overview of the main fungal intoxications of renal interest, the clinical presentation, the diagnostic strategies, and the subsequent treatment.

Keywords: Mushroom poisoning, AKI, Amanita Echinocephala

Lactic acidosis is a potential adverse event related to metformin therapy. Although metformin-associated lactic acidosis (MALA) is a rare condition (about 10 cases / 100,000 patients / year), new cases continue to be reported, with a mortality of 40-50%. We describe two clinical cases characterized by severe metabolic acidosis, hyperlactacidemia, and acute renal injury. The first also with NSTEMI, successfully treated.

Keywords: lactic acidosis, metformin, acute renal failure

Hemodialysis patients have an increased risk of severe complications when infected with SARS-CoV-2. The introduction of the SARS-CoV-2 vaccine represented an important progress in limiting severe forms of the disease.

The focus of our study is the detection of the antibody titer in chronic hemodialysis patients vaccinated with the mRNA vaccine BNT162b2 (Comirnaty, Pfizer-BioNTech).

The antibody titers were measured in 57 hemodialysis patients, vaccinated with 3 doses according to ministerial criteria, by ElectroChemiLuminescence ImmunoAssay (ECLIA). The response was defined as an antibody titer above the dosable level > 0,8 UI/ml. A good antibody response was defined as titer > 250 UI/ml. Infections with SARS-CoV-2 and adverse effects to the vaccine were recorded.

Our study showed in 93% of the hemodialysis patients a dosable antibody response after the second dose of the vaccine. After the third dose of the vaccine, 100% of the hemodialysis patients reached a dosable antibody titer. The vaccine proved to be safe, no serious adverse events were observed. After the third dose, SARS-CoV-2 infections were still observed, but with reduced severity. A vaccination course against SARS-CoV-2 infection with three doses of BNT162b2 in the dialysis patient is associated with a good immune response and protects against severe infections.

Keywords: Hemodialysis patients, SARS-CoV-2, mRNA vaccine BNT162b2, ElectroChemiLuminescence ImmunoAssay (ECLIA)

Dialysis (hemodialysis and peritoneal dialysis) is one of the main therapeutic alternatives for patients with end-stage renal disease. It can be provided in different settings, including the home setting. Published literature shows that home dialysis improves both survival and quality of life, while producing economic advantages. However, there are also significant barriers. Home dialysis patients often report “abandonment issues” by healthcare personnel.

This work aimed at assessing the efficiency of the Doctor Plus® Nephro telemedicine system (adopted in the Nephrology Center of the P.O. G.B. Grassi di Roma-ASL Roma 3) in monitoring patient health status and improving the quality of care. From 2017 to 2022, N=26 patients were included in the analysis (mean duration of observation: 2.3 years). The analysis showed that the program was able to promptly identify possible anomalies of the vital parameters and activate a series of interventions aimed at normalizing the altered profile. During the study period, the system issued N=41,563 alerts (N=1.87 alerts per patient/day), of which N=16,325 (39.3%) were clinical and N=25,238 (60.7%) were missed measurements. These warnings ensured stabilization of the parameters, with clear benefits on patients’ quality of life. A trend of improvement was reported by patients, regarding their perception of the health state (EQ-5D questionnaire; +11.1 points on the VAS scale), the number of hospital admissions (-0.43 accesses/patient in 4 months), and of working days lost (-3.6 days lost in 4 months). Therefore, Doctor Plus® Nephro represents a useful and efficient tool for home dialysis patients’ management.

Keywords: chronic renal insufficiency, dialysis, hemodialysis, Doctor Plus® Nephro, remote monitoring

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune. We describe a case of a variant in which there is anti-MBG positivity in serum but negative immunofluorescence and offer a review of the literature and potential treatments.

Keywords: anti-GBM, crescents, immunofluorescence

The nutritional aspect has a critical relevance in the educational and care path of nephropathic patients. The Nephrology-Dietology synergy in the Hospital is conditioned by various factors, such as the difficulty for Dietology to provide capillary and personalized follow-up to nephropathic patients.

Hence the experience of a transversal II level nephrological clinic, dedicated to nutritional aspects throughout the path of nephropathic patients, from the earliest stages of kidney disease to replacement treatment. The access flowchart provides a nephrological indication: from chronic kidney disease (CKD), kidney stones, immunopathology, hemodialysis, peritoneal dialysis, and transplantation clinics, from the nephrological department, patients are selected for evaluation.

The clinic is conducted by an expert nephrologist and trained dietitians, and is divided into different settings: educational meetings in small groups (patients and caregivers); simultaneous dietary and nephrological visits to advanced CKD; nutritional-nephrological visits on specific problems: from metabolic screening of kidney stones to action on the intestinal microbiota in immunological pathologies, to the application of the ketogenic diet in obesity, metabolic syndrome, diabetes, and early kidney damage, to onconephrology. Submission to further dietological assessment is limited to critical and selected cases.

The synergistic model between nephrology and dietetics offers clinical and organizational advantages: guarantees a capillary follow-up, reduces the number of hospital accesses, thus enhancing compliance and clinical outcomes, optimizes available resources, and overcomes the critical issues of a complex hospital with the advantage of the always profitable multidisciplinarity.

Keywords: dietetic-nutritional therapy, nephrology, chronic kidney disease

Cancer is a major cause of morbidity and mortality in solid organ transplantation. Nonmelanoma skin cancer (NMSC) such as basocellular (BCC) and spinocellular (SCC) carcinoma, are common in renal transplant recipients. We report a case of an SCC affecting a lacrimal gland in a subject with kidney transplantation.

A man aged 75 years who had suffered from glomerulopathy since 1967 and subsequently started haemodialysis, in 1989 was transplanted from a living donor. In 2019, he suffered paresthesia and pain in his right eyebrow arch and he was diagnosed to have neuralgia of the fifth cranial nerve. The failure of medical treatment and the development of a mass in his eyelid plus exophthalmos induced healthcare professionals to perform a magnetic resonance. The latter showed a retrobulbar mass measuring 39×22×16 mm³. Biopsy revealed an SCC and the patient underwent eye exenteration.

Although NMSC of the eye is an extremely rare condition, risk factors such as male sex, history of glomerulopathy, and duration of immunosuppression should be taken into consideration at the time of the onset of eye symptoms.

Keywords: Renal transplantation, immunosuppression, non-melanocitic skin cancer, eye cancer

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO₂ removal (ECCO₂R) procedures have been developed. ECCO₂R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT).
Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO₂R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient’s pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity.
Conclusions. This case supports using ECCO₂R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.

Keywords: pregnancy, COVID-19, lung-protective ventilation, hypercapnia, CO₂ removal, acute kidney injury, continuous renal replacement therapy

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF).

The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena.

Keywords: Acute Kidney Injury (AKI), burn, sepsis, Continuous Renal Replacement Therapy (CRRT)

In this article we describe a case of acute kidney injury caused by ethylene glycol intoxication which partially reversed after temporary hemodialysis treatment. The diagnosis was obtained after the patient’s clinical history and the finding of ethylene glycol in the blood, numerous intratubular crystals at renal biopsy, and the presence of large amounts of atypical – spindle-like and needle-like – calcium oxalate crystals in the urinary sediment.

Keywords: Ethylene glycol, acute kidney injury, urinary sediment, calcium oxalate crystals

Guidelines on the use of dialysis treatment in patients with chronic kidney disease (CKD) and TPM (Topiramate) intoxication are controversial. A 51-year-old man with epilepsy and CKD was carried to our emergency department for dysuria and sickness. He chronically assumed TPM 100 mg 3/day. Creatinine level was 2.1 mg/dL, blood urea nitrogen 70 mg/dL, and inflammation indexes were increased.

We started empirical antibiotic therapy and rehydration. The day two he had diarrhea and an acute insurgence of dizziness, confusion, and bicarbonate levels reduction. Brain CT resulted negative for acute events. During the night his mental status worsened, and urinary output results were about 200 mL in 12h. EEG showed desynchronized brain bioelectric activity. Thereafter, there was an episode of seizure and then anuria, hemodynamic instability, and loss of consciousness. Creatinine value was 5.39 mg/dL with a serious metabolic acidosis non-anion gap. We decided to start 6-hours Sustained Low Efficiency Hemo-Dia-Filtration (SLE-HDF). We assisted in the recovery of consciousness and later in the improvement of kidney function after 4 hours of treatment. TPM levels before SLE-HDF resulted in 123.1 µg/mL. At the end of treatment resulted in 30 µg/mL. To our knowledge, this is the first report of TPM involuntary intoxication in a patient affected by CKD who survived such a high TPM concentration treated with renal replacement therapy. SLE-HDF resulted in moderate elimination of TPM and acidemia resolution, continuous monitoring patient’s vital parameters in relation to his hemodynamic instability, since blood flow and dialysate flow are lower than conventional hemodialysis.

Keywords: Intoxication, Sustained Low-efficiency dialysis, hemodialysis, metabolic acidosis, continuous venovenous haemofiltration

Introduzione: L’ipotensione intradialitica è una delle complicanze più frequenti del trattamento emodialitico e si associa ad aumento della mortalità. Ad oggi non esistono fattori predittivi validati per stimare a priori la tolleranza emodinamica alla sottrazione idrica in corso di trattamento dialitico.
Scopo dello studio è stato valutare se i parametri ecografici inerenti alla vena cava inferiore (VCI) a inizio dialisi possano essere predittivi di tolleranza all’ultrafiltrazione in pazienti emodializzati cronici, clinicamente stabili, previa valutazione dello stato di idratazione con un’ecografia polmonare bed-side.
Materiali e metodi: Abbiamo condotto uno studio spontaneo, prospettico, osservazionale, monocentrico, esplorativo su 17 pazienti in emodialisi cronica. Prima dell’inizio della seduta dialitica, sono state eseguite l’ecografia della VCI e l’ecografia polmonare. Abbiamo confrontato i dati ecografici rilevati dal gruppo di pazienti che ha presentato almeno un episodio di ipotensione intradialitica con quelli dei pazienti che non ne hanno presentati.
Risultati: Dei 17 pazienti arruolati, 4 hanno presentato ipotensione. L’indice di collassabilità della VCI (IC-VCI) dei pazienti che presentavano ipotensione intradialitica è risultato significativamente aumentato rispetto ai pazienti che non andavano incontro a ipotensione. Il diametro minimo della VCI (VCI min) è risultato significativamente minore nei soggetti con ipotensioni intradialitiche. Il risultato si confermava anche nelle analisi multivariate in cui tali parametri si mantenevano significativi anche al netto del B-lines-score.
Conclusioni: I risultati del nostro studio permettono di ipotizzare che IC-VCI e VCI min possano essere considerati predittori di rischio di ipotensione intradialitica inpazienti in emodialisi cronica. Studi ulteriori saranno necessari per confermare i dati osservati.

Parole chiave: emodialisi, ipotensione intradialitica, ecografia vena cava inferiore, ecografia polmonare

Introduction: Secondary hyperparathyroidism (SHPT) is a common and major complication of chronic kidney disease (CKD) among patients on dialysis and in patients with CKD stage G3 to G5. SHPT in CKD is caused by disturbances in metabolic parameters. Paricalcitol (PCT), other active vitamin D analogous (doxercalciferol and alfacalcidol), and active vitamin D (calcitriol) have been commonly used to treat SHPT in non-dialysis CKD (ND-CKD) for several years. However, recent studies indicate that these therapies adversely increase serum calcium, phosphate, and fibroblast growth factor 23 (FGF-23) levels. Extended release calcifediol (ERC) has been developed as an alternative treatment for SHPT in ND-CKD. The present meta-analysis compares the effect of ERC against PCT in the control of PTH and calcium levels.
Methods: A systematic literature review was conducted, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to identify studies for inclusion in the Network Meta-Analysis (NMA).
Results: 18 publications were eligible for inclusion in the network meta-analysis and 9 articles were included in the final NMA. The estimated PTH reduction from PCT (-59.5 pg/ml) was larger than the PTH reduction from ERC (-45.3 pg/ml), but the difference in treatment effects did not show statistical significance. Treatment with PCT caused statistically significant increases in calcium vs. placebo (increase: 0.31 mg/dl), while the marginal increase in calcium from treatment with ERC (increase: 0.10 mg/dl) did not reach statistical significance.
Conclusions: The evidence suggests that both PCT and ERC are effective in reducing levels of PTH, whereas calcium levels tended to increase from treatment with PCT. Therefore, ERC may be an equally effective, but more tolerable treatment alternative to PCT.

Keywords: secondary hyperparathyroidism, PTH, calcium, vitamin D

Introduction: The quality of life of patients with chronic kidney disease stage V is strongly affected by the recommended therapies. Such a situation alters the state of anxiety, which expresses a perception connected to a specific context and it overlaps with trait anxiety, which evaluates relatively stable aspects of being prone to anxiety.
The study aims to analyze the anxiety level of uremic patients and to demonstrate the benefit of psychological support either in person or online in order to mostly reduce the state of anxiety.
Materials and methods: 23 patients treated at the Nephrology Unit of the San Bortolo Hospital in Vicenza have undergone at least 8 psychological sessions. The first and the eighth sessions have been held in person, while the others were either in person or online based on the patients’ preference.
The State-Trait Anxiety Inventory (STAI), which means to evaluate the current state of anxiety and aspects of being prone to anxiety, was submitted during the first and the eighth sessions.
Results: Patients, before being submitted to psychological treatment, showed high rates of both State and Trait anxiety levels. After eight sessions the trait anxiety features and even better the state anxiety ones have significantly reduced both thanks to in-person or online treatments.
Conclusions: A treatment of minimum eight sessions shows a significant improvement of the nephropathic patient’s trait and, even better, state anxiety level and it also fosters the achievement of advanced adjustment levels compared to the new clinical status together with an improvement of the quality of life.

Keywords: psychological support, chronic kidney disease, state anxiety, trait anxiety

Chronic kidney disease is a complex phenotype that results from the association of underlying kidney disease and environmental and genetic factors. In addition to the traditional risk factors, genetic factors are involved in the etiology of renal disease, including single nucleotide polymorphisms which could account for the increased mortality from cardiovascular disease of our hemodialysis patients. The genes that influence the development and rate of progression of kidney disease deserve to be better defined. We have evaluated the alterations of thrombophilia genes in hemodialysis patients and in blood donors and we have compared the results obtained. The objective of the present study is to identify biomarkers of morbidity and mortality, which allow us to identify patients with chronic kidney disease at high risk, thanks to which it is possible to implement accurate therapeutic strategies and preventive strategies that have the objective of intensifying controls in these patients.

Keywords: single nucleotide polymorphisms, thrombophilia panel, biomarkers of mortality, omic sciences, chronic kidney disease, hemodialysis

IgG4 related renal disease represents a frequent manifestation of the wider IgG4 related disease, a fibroinflammatory disorder with a not fully understood etiology that affects several organs. Through the clinical case presented, we will focus attention on this pathology and on the diagnostic difficulties that may arise, and on the investigations necessary for the diagnosis. Finally, the main therapeutic options will be discussed.

Keywords: IgG4 related disease, IgG4 related kidney disease, fibroinflammatory disorders

Granulomatosis with polyangiitis (GPA) is an ANCA-positive systemic vasculitis that mainly involves lungs and kidneys. This condition rarely overlaps with other glomerulonephritides. A 42-year-old man with constitutional symptoms and haemophtoe was admitted to the Infectious Diseases department, where he was subjected to fibrobronchoscopy with BAL (broncho-alveolar lavage) and lung transbronchial biopsy that showed histological signs of vasculitis. The association with severe acute kidney injury with urine sediment alterations (microscopic haematuria and proteinuria) led the consultant nephrologist to a diagnosis of GPA. Thus the patient was transferred to the Nephrology department. During the hospitalization, the worsening of the clinical course and the development of alveolitis, respiratory failure, purpura, and rapidly progressive kidney failure (nephritic syndrome – serum creatinine 3 mg/dl) required the start of steroid therapy, according to EUVAS. The presence of florid crescents in 3 out of 6 glomeruli in the renal biopsy and the IgA positive immunofluorescence allowed to make a diagnosis of overlap of GPA and IgA nephropathy. Rituximab (RTX 375 mg/m² per week for 4 weeks) and plasma exchange (7 sessions) were added to steroid therapy. During follow-up, partial functional recovery was achieved after 4 months, whereas total regression, i.e. the absence of protein and red blood cells in urine sediment, was reached during the 4-years follow-up. The main therapy during the first 2 years of follow-up was RTX, followed by mycophenolate mofetil for the remaining 2 years.

Keywords: granulomatosis with polyangiitis, ANCA-associated vasculitis, IgA nephropathy and granulomatosis with polyangiitis-overlap, rituximab

Background. This real-world study aimed to provide insights on the characteristics, drug utilization, and economic burden of chronic kidney disease non-dialysis-dependent (NDD-CKD) patients with anemia prescribed Erythropoiesis Stimulating Agents (ESA) in Italian clinical practice settings.
Methods. A retrospective analysis was performed based on administrative and laboratory databases covering around 1.5 million subjects across Italy. Adult patients with a record for NDD-CKD stage 3a-5 and anemia during 2014-2016 were identified. Eligibility to ESA was defined as the presence of ≥ 2 records of Hb < 11 g/dL over 6 months, and patients eligible and currently treated with ESA were included.
Results. Overall, 101,143 NDD-CKD patients were screened for inclusion, of which 40,020 were anemic. A total of 25,360 anemic patients were eligible to ESA treatment and 3,238 (12.8%) were prescribed ESA and included. The mean age was 76.9 years and 51.1% was male. More frequently observed comorbidities were hypertension (over 90% in each stage), followed by diabetes (37.8-43.2%) and cardiovascular condition (20.5-28.9%). Adherence to ESA was observed in 47.9% of patients, with a downward trend while progressing across stages (from 65.8% stage 3a to 35% stage 5). A consistent proportion of patients did not have nephrology visits during the 2 years of follow-up. Costs were mainly due to all drugs (€4,391) followed by all-cause hospitalization (€3,591) and laboratory tests (€1,460).
Conclusions. Findings from the study highlight an under-use of ESA in the management of anemia in NDD-CKD as well as a sub-optimal adherence to ESA and showed a great economic burden for anemic NDD-CKD patients.

Keywords: anemia, administrative databases, Erythropoiesis Stimulating Agents (ESA), chronic kidney disease (CKD), nephrology, real life

Purpose: Tolvaptan (TVP), a vasopressin receptor antagonist, represents a therapeutic option in the syndrome of inappropriate anti-diuresis (SIAD). The aim of this study was to evaluate the effect of TVP to treat and solve hyponatremia in oncologic patients.
Methods: 15 oncologic patients who developed SIAD have been enrolled. Patients receiving TVP belonged to group A, whereas group B was characterized by hyponatremic patients treated with hypertonic saline solutions and fluid restriction.
Results: In group A, the correction of serum sodium was achieved after 3.7±2.8 days. In group B, the target levels were obtained more slowly, after 5.2±3.1 days (p: 0.01) than in group A. The hospital stay and incidence of re-hospitalization were higher in group B than in group A. In this latter, 37% of patients had hyponatremic relapses, notwithstanding the progressive increase of doses from 7.5 to 60 mg per day of TVP, revealing a complete lack of response to TVP. In these patients, a growth of tumor mass or new metastatic lesions has been revealed.
Conclusion: TVP improved hyponatremia more efficiently and stably than hypertonic solutions and fluid restrictions. Positive consequences have been obtained about the rate of chemotherapeutical cycles concluded, hospital stay, rate of relapse of hyponatremia, and re-hospitalization.
Our study also suggested potential prognostic information that could be deduced from TVP patients, in whom sudden and progressive hyponatremia occurred, despite TVP dosage increase. A re-staging of these patients to rule out tumor mass growth or new metastatic lesions is suggested.

Keywords: hyponatremia, paraneoplastic syndrome, syndrome of inappropriate anti-diuresis, tolvaptan, vasopressin

High-output cardiac failure is a well-known phenomenon of high-flow fistula in hemodialysis patients. The definition of “high flow” is varied and almost always connected to proximal arteriovenous fistulas (AVF).
High flow access is a condition in which hemodynamics is affected by a greater rate of blood flow required for hemodialysis and this can compromise circulatory dynamics, particularly in the elderly in the context of pre-existing heart disease.
High access flow is associated with complications like high output heart failure, pulmonary hypertension, massively dilated fistula, central vein stenosis, dialysis associated steal syndrome or distal hypoperfusion ischemic syndrome.
Although there is no single agreement about the values of AVF flow volume, nor about the definition of high‐flow AVF, there is no doubt that AVF flow should be considered too high if signs of cardiac failure develop.
The exact threshold for defining high flow access has not been validated or universally accepted by the guidelines, although a vascular access flow rate of 1 to 1.5 l/min has been suggested.
Moreover, even lower values may be indicative of relatively excessive blood flow, depending on the patient’s condition.
The pathophysiology contributing to this disease process is the shunting of blood from the high-resistance arterial system into the lower resistance venous system, increasing the venous return up to cardiac failure.
Accurate and well-timed diagnosis of high flow arteriovenous hemodynamics by monitoring of blood flow of fistula and cardiac function is required in order to stop this process prior to cardiac failure.
We present two cases of patients with high flow arteriovenous fistula with a review of the literature.

Keywords: Blood flow, cardiac failure, vascular access, hemodialysis

Dialysis adequacy and a state of “eunutrition” are two essential elements to consider in the evaluation of patient undergoing dialysis treatment.

Dialysis inadequacy is often associated with malnutrition, and the combination of these two factors significantly worsens the prognosis.

In the following monocentric and prospective study, the correlation between nutritional markers and dialytic adequacy was tested in a cohort of patients permanently followed by the peritoneal dialysis clinic, followed consistently for two years.

It was therefore evaluated if modification of dialysis therapy, aimed to reach adequacy parameters, could simultaneously improve metabolic parameters.

Although there were no frankly malnourished patients, the group of “inadequate” patients had a significantly lower nPCR value.

In this same group, after about 6 months, therapeutic measures adopted allowed an overall improvement in Kt/V and nPCR, with other nutritional parameters (such as body weight, albumin, pre-albumin, total cholesterolemia) remaining stable.

At the end of the follow-up period the Kt/V of the “inadequate” (<1.7) was higher ​​than the baseline, reaching statistical significance at the 12th and 24th months. Early identification of a dialysis inadequacy, therefore, allowed the execution of therapeutic changes necessary to achieve a lasting improvement in “adequate” replacement therapy, and a temporary improvement in the patient's nutritional status. Suddenly, despite the persistent improvement of the Kt/V there was a new reduction of the nPCR. Keywords: Peritoneal Dialysis, Malnutrition, Dialytic Adequacy

We report the case of a 75-year-old man who developed acute myocardial infarction 12 hours after the first dose of ChAdOx1 nCov-19 vaccine. The event was associated with a transient decrease of platelet count and the detection of anti-PF4 antibodies approximately 45 days after the event.
Vaccine-induced thrombotic thrombocytopenia (VITT) is characterized by the onset of venous or arterial thrombosis in temporal relationship to the administration of anti-Sars-Cov-2 viral vector vaccines (ChAdOx1 nCov-19 and Ad26.COV2.S), thrombocytopenia and the production of anti-PF4 antibodies. It occurs mainly at a young age, even if the median age is 54 years; it is often associated with thrombosis in atypical sites, such as the cerebral sinus.
Our reported case does not present all the diagnostic criteria of VITT. However, the close temporal relationship between ChAdOx1 nCov-19 vaccine administration, thrombosis, and concomitant anti-PF4 antibodies positivity makes the case suggestive of a possible slight form of VITT.

Keywords: Sars-CoV-2, chronic kidney disease, vaccine, ChAdOx1 nCov-19, vaccine-induced immune thrombotic thrombocytopenia, VITT

Anti-angiogenic drugs are widely used in cancer therapy. Their main targets of action are the vascular endothelial growth factor (VEGF) and its receptors (VEGF-R). Anti-angiogenic drugs are used to reduce the growth of the tumor and its metastases by acting on the phenomenon of tumor neo-angiogenesis. However, they are known for their side effects such as hypertension, acute kidney injury (AKI), and congestive heart failure.
Methods: retrospective study conducted on 57 consecutive patients known for ovarian cancer. Patients treated with Bevacizumab, as first-line, relapse, or maintenance treatment (2015-2022).
Results: according to FIGO staging, 98.2% (56 out of 57) of the patients in the study had third degree disease (G3). 49% of patients developed hypertension after starting Bevacizumab therapy (82% grade 2 according to CTCAE v.5). 89% of hypertensive patients started treatment and its management was multidisciplinary with nephrological consultation in 68% of cases. Only 3 out of 57 women discontinued treatment due to hypertension, and in only one of them it was not possible to restart it.
Conclusions: the evaluation of the patient by a multidisciplinary team (gynecologist and nephrologist) is essential to minimize the morbidity and mortality of patients, and to avoid the interruption of antineoplastic treatment.

Keywords: anti-angiogenic drugs, kidney injury, proteinuria, hypertension, ovarian cancer, multidisciplinary team

In patients on hemodialysis, the reduced alkali urinary loss makes metabolic acidosis less severe. Unexpected is the large occurrence of respiratory alkalosis and acidosis.
During the therapy, the convective/diffusive inward fluxes of CO₂ and bicarbonate and the loss of organic anions affect acid-base homeostasis.
In bicarbonate-dialysis, the neutralization of acids by bicarbonate and gain of gaseous CO from the dialysate cause an increase of CO₂ content in the body water, which requires an increase in lung ventilation (>10%) to prevent hypercapnia. In on-line hemodiafiltration, the infusate drags additional CO₂ into bloodstream, while in acetate – free biofiltration the dialysate is CO₂ – free and this prevents any addition of CO₂.
Bicarbonate and acetate diffuse into extracellular fluid according to their bath-to-blood concentration gradients. The initially large bicarbonate flux decreases rapidly because of the rapid increase in blood concentration. The smallest acetate flux is instead constant with time providing a constant source of alkali.
Rapid alkalinization elicits H⁺ mobilization that consumes most of the bicarbonate added. Some H⁺ are originated by back-titration of body buffers, but others are originated by new organic acid production, a maladaptive event that wastes metabolic energy. In addition, organic anions diffuse into dialysate causing a substantial increase in net acid production.
A novel dialysis protocol prescribes a low initial bath bicarbonate concentration and a stepwise increase during the therapy. Such a staircase protocol ensures a smoother increase of blood bicarbonate concentration avoiding the initial rapid growth and reducing the rate of organic acid production, thus making the treatment more effective.

Keywords: Acid-base, Bicarbonate, Carbon Dioxide, Dialysate, Hemodialysis

Despite the advances in immunosuppressive therapies and improvements in short-term allograft survival, acute rejection still represents one of the major causes of graft loss. We present a case of early acute T-cell-mediated rejection treated efficaciously with pulse steroids and we review the current literature on the pathogenesis, diagnosis, and treatment of acute T-cell-mediated rejection. Pathogenetic mechanisms involve recruitment, activation, and proliferation of donor-specific T-cells, capable of inducing graft injury through direct and indirect mechanisms. Histologically, Banff classification provides standardized and reproducible definitions and scoring for rejection categories, including T-cell mediated rejection (TCMR) and borderline for TCMR. Although allograft biopsy still represents the gold standard for acute rejection diagnosis, new non-invasive biomarkers are emerging to improve diagnostic timeliness and assist therapeutic choices.

Therapy of TCMR largely depends on histologic severity and may range from the adjustment of maintenance immunosuppressive therapy to the use of thymoglobulin and other aggressive immunosuppressive approaches. Finally, the response to the anti-rejection treatment is normally detected through serum creatinine and surveillance biopsies. However, new biomarkers are emerging to non-invasively monitor this response.

Keywords: Kidney transplantation, Graft rejection, Graft rejection diagnosis, Graft rejection treatment, Graft rejection prognosis

Background: The purpose of the study is to identify, through a survey, the parameters that need to be monitored during a hemodialysis session and to merge them into a surveillance flow sheet that allows the optimal conduction of the treatment.
Methods: The study was conducted using the questionnaire methodology and involved 78 nurses working in the nephrological area in Italy. The majority of participants have an age of service greater than 10 years and belong to a hemodialysis context.
Results: The data show how the surveillance flow sheet is a diversified tool according to the treatments carried out. However, the majority of dialysis flow sheets have a section dedicated to the medical-nursing diary, a space for recording the access characteristics and there is also a good level of digitalization of the instrument.
The frequency of detection of vital and monitor-related parameters varies on the basis of the treatment carried out, the registration of the identification number and the filter label are not a uniform practice. Finally, the majority points out the need for an improvement of the surveillance card in use.
Conclusions: The research highlights the lack of uniformity of the dialysis surveillance process.
The study proposes as a solution to the problem a universal medical-nursing flow sheet, called CUSTODE, which can guide the professional in the management of hemodialytic treatment, through the registration of a minimum data set.

Keywords: hemodialysis surveillance flow sheet, minimum data set, hemodialysis, safety

Background: Kidney transplant patients bear a higher risk of bone disease. The monoclonal antibody Denosumab (Den), by binding RANKL, reduces osteoclastic activity and increases mineral density (BMD), thus limiting the risk of bone fractures. We evaluated the efficacy and safety of Den in kidney transplant patients who developed bone fractures.
Methods: Thirteen kidney transplant recipients (aged from 50 to 79 years 7M and 6F, with an average 9,9 years follow up after transplantation, and nearly normal renal function (GFR 62±15 ml/min/1.73m²), who developed low-energy vertebral fractures (21 dorsal and 1 lumbar) after transplantation, had been evaluated for 2 years with Dual-energy X-ray absorptiometry (DEXA) and morphometric absorptiometry (MXA) while receiving Den (four 60-mg doses). Data for vertebral heights and posterior-anterior height ratios (P/A), and BMD values for vertebral, femoral, and radius were obtained. The immunosuppressive regimen consisted of CNI and MMF, and 8 out of 13 were taking prednisone. A fixed dose of 450.000 UI-year of cholecalciferol was prescribed to all patients. Whole-PTH, 25-OHD3, and alkaline phosphatase (ALP) were also evaluated.
Results: After 2 years of Den treatment, we observed a significative increase in vertebral T-score (from -2.12±0.35 to -1.67±0.35; p< 0.02), while T score of femoral neck and radius did not show significative variation (-1.86±0.21 versus -1.84±0.23 and -3.04±0.42 versus -3.19±0.45, respectively). We found a lower incidence of fracture/patient-year pre and post Den 0.17 [95 CI 0.11-0.24] vs 0.07 [95% CI 0.02-0.3] respectively. No significative variations were observed in whole-PTH (89.31±19.9 pg/ml versus 68.38±9.8 pg/ml), 25OHD3 (24.02±2.75ug/L versus 26.67±2.29 ug/L) and alkaline phosphatase (78.46±12.73UI/L versus 56.77±7.14UI/L). No adverse events were registered. Conclusions: Treatment with Den improve BMD in vertebral bone and possibly reduces the risk of low-energy vertebral fractures in kidney transplant patients.

Keywords: Denosumab, low-energy fracture, transplant osteopathy

The global coronavirus 2019 (COVID-19) pandemic required vaccination even in children to reduce infection.
We report on the development of acute kidney injury (AKI) and minimal change disease (MCD) nephrotic syndrome (NS), shortly after the first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech).
A 12-year-old previously healthy boy was referred to our hospital with complaints of peripheral edema and nephrotic range proteinuria.
Nine days earlier he had received his first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech).
Seven days after injection, he developed leg edema, which rapidly progressed to anasarca with significant weight gain. On admission, serum creatinine was 1.3 mg/dL and 24-hour urinary protein excretion was 4 grams with fluid overload.
As kidney function continued to decline over the next days, empirical steroid treatment and renal replacement therapy with ultrafiltration were started and kidney biopsy was performed.
Seven days after steroid therapy, kidney function began to improve, gradually returning to normal.
The association of MCD, nephrotic syndrome and AKI hasn’t been previously described following the Pfizer-BioNTech COVID-19 vaccine in pediatric population, but this triad has been reported in adults.
We need further similar case reports to establish the real incidence of this possible vaccine side effect.

Keywords: nephrotic syndrome, Acute Kidney Injury (AKI), SARS-CoV-2 vaccines, pediatric population

The interest in determining the number of nephrons in the kidney dates back to the 1960s, when an influential laboratory method for determining ex vivo the number of nephrons in the kidneys was described by Bricker. Over the years, various methods have been developed to estimate the number of nephrons in living beings as accurately as possible. These modern methods combine data such as the glomerular density, the percentage of glomeruli in sclerosis calculated from biopsy samples, and the kidney volume, which can be precisely estimated from magnetic resonance, CT scan, or specific ultrasound methods. As the reduction in the number of functioning nephrons is closely connected with an increased risk of progression of renal disease (especially in patients with nephrotic syndrome) and hypertension, its introduction into clinical practice could allow a precise stratification of progression risk in patients with kidney disease and a better understanding of the mechanisms that contribute to the loss of functioning nephrons.

Keywords: nephrons number, kidney biopsy, CKD

Background: Nutcracker syndrome (NCS) is caused by extrinsic compression of the left renal vein (LRV), usually between the abdominal aorta (AA) and superior mesenteric artery (SMA). This rare disease includes symptoms such as hematuria, left flank pain or abdominal pain, varicocele in males, proteinuria, anemia, gynecological symptoms (dyspareunia, dysmenorrhea).
Case report: We report the case of a 48-year-old female patient, who experienced left abdominal colic after intensive physical exercise, finally resulting in a diagnosis of NCS. This abdominal pain was disabling for daily activities, it was controlled by analgesic drugs and led to hospital admissions. In-depth examinations were recommended to the patient to investigate the etiology of these attacks. A bad rotated and ectopic left kidney, which was located superior to the spleen, at the level of the left hemithorax base, was found due to the presence of a diaphragmatic relaxation in the posterior area, which caused an upward displacement of the kidney, part of the colon and omental fat. Because of the presence of a compression of the LRV by the SMA and the AA, the nephrologist diagnosed a NCS, presenting with abdominal pain following physical exercise, proteinuria and dysmenorrhea. Conservative treatment was chosen for the patient.
Conclusions: The patient was recommended to engage in a moderate and regular physical activity, avoiding acute and intense exercise: hypopressive abdominal gymnastics was suggested. The role of physical exercise in triggering painful attacks and its role in rehabilitation to prevent the same attacks was crucial for the patient.

Keywords: physical exercise, nutcracker syndrome, abdominal pain, diaphragmatic relaxation

Historically, findings on light and electron microscopy have been used to subclassify membranoproliferative glomerulonephritis (MPGN). Recent advances in understanding of the underlying pathobiology have led to a classification scheme based on immunofluorescence findings. MPGN can result from subendothelial and mesangial deposition of complement owing to dysregulation of the alternative pathway of complement. Complement-mediated MPGN includes dense deposit disease and proliferative glomerulonephritis with C3 deposits. Dysregulation of complement cascade can result from genetic mutations or development of autoantibodies to complement regulating proteins. MPGN is also a pattern of injury that results from subendothelial and mesangial deposition of immune complexes (IC). The common causes of IC-mediated MPGN include chronic infections, autoimmune diseases, and monoclonal gammopathy/dysproteinemias. This category also includes mixed cryoglobulinaemia-glomerulonephritis. Most of these cases are associated with the presence of a hepatitis C virus (HCV) infection. A number of patients with high clinical suspicion for cryoglobulinaemic vasculitis show negative results for the detection of cryoglobulins using standard methods, but are found to have detectable levels of cyoprecipitable immunoglobulins (hypocryoglobulins) using more sensitive techniques. A subset of patients with low level of circulating hypocryoglobulins can present with glomerulonephritis, often isolated, with membranoproliferative pattern MPGN. They can be negative for HCV infection detection and can have normal rheumatoid activity and complement levels. Hypocryoglobulinemic nephritis might represent a distinct entity.

Keywords: Membranoproliferative Glomerulonephritis, C3 Glomerulonephritis, Hypocryoglobulinemic Nephritis

La nefropatia cronica del trapianto è una condizione patologica multifattoriale presente in una larga percentuale di reni trapiantati la cui comprensione è stata accelerala dall’estesa applicazione della biologia molecolare e dall’impiego della biopsia protocollare in molti centri nefro-trapiantologici. Grazie a queste innovazioni, si è compreso che questo processo può comparire molto precocemente nel post-trapianto e che la microinfiammazione parenchimale gioca un ruolo chiave. Molte condizioni patologiche, anche precoci (come il danno da ischemia/riperfusione, la presenza di rigetti cellulari e umorali, e le infezioni virali e batteriche) possono contribuire alla genesi della fibrosi renale. Da un punto di vista prettamente biologico, il danno cronico inflammatorio-mediato del graft è orchestrato da cellule immunitarie (principalmente macrofagi, cellule dendritiche, linfociti) e cellule effettrici che mediano la deposizione di matrice extracellulare (ECM) e la fibrosi. Molti degli elementi chiave di questi pathway biologici potrebbero rappresentare in futuro ottimi bersagli terapeutici. Al momento, però, non esiste una terapia specifica per arginare questa condizione, ma appare evidente che l’impiego di una immunosoppressione sostenibile (utilizzo combinato di più farmaci alle più basse dosi possibili) e l’attenzione alle comorbidità (dedicando sufficiente tempo al follow-up clinico e incrementando il network multi-specialistico) sia la via da perseguire per ottenere un accettabile rallentamento della progressione delle lesioni croniche del graft e una sua maggiore sopravvivenza.

Parole chiave: Nefrologia, Trapianto renale, Microinfiammazione, Fibrosi, Immunosoppressione

In recent years, the complement system, which plays a crucial role in the innate immunity, fostered renewed scientific interest. This process has brought a rare kidney disorder, named C3 glomerulopathy, in the center of a real revolution, highlighting the complex interactions between genotype, triggers and kidney microenvironment, which together contribute to the final phenotype of the disease. At the same time, experimental studies and clinical trials testing new complement inhibitors have multiplied enormously. It’s a very promising time for patients affected by C3 glomerulopathy, which didn’t have so far effective therapies in preventing the progression to the end-stage kidney disease.

Keywords: Membranoproliferative glomerulonephritis, C3 glomerulopathy, complement system, alternative pathway, kidney biopsy

The genetic system that most influences the outcome of organ transplants is the Major Histocompatibility Complex (MHC), which in humans is also known as the HLA (Human Leucocyte Antigens) system. These genes are highly polymorphic, meaning that each individual in the population has inherited a set of genes that combine in an almost unique way. They encode cell surface glycoproteins which therefore vary from one individual to another and are recognized as a target in the case of transplantation by the recipient’s immune system.

It is considered that the right match for HLA characteristics between donor and recipient can explain less than half of the immunological causes of transplant failure. It is well known that differences in other genetic characteristics may be responsible for a not small share of transplant failure due to immunological causes. These characteristics are defined as minor histocompatibility genes (and antigen their products).

The new approaches to study the genome allow to examine all the variability of a recipient, and compare it with that of the donor: in this way it is possible to evaluate whether particular genetic collisions (i.e. incompatibility for some of them) can influence the outcome of the transplant. These studies made it possible to define new genes whose compatibility between donor and recipient may be relevant for the success of the transplant.

Keywords: transplants, genomics, histocompatibility

A historical research was made on papers published by Italian scientists on cardiorenal diseases. The investigated period is between the beginning of the 20th century and the entry of Italy into the Second World War, 1940. 34 papers dealing with the relationship between the kidney and the cardiovascular system were retrieved. All but two articles were published in Italian medical periodicals. The topics covered are varied and range from cardiotoxicity of substances in uremia to the role of renal disease in vascular damage. Some articles are forerunners of later pathophysiological concepts and research technologies. These concern early atherosclerotic vascular damage and the presence of dialyzable cardiotoxic substances in renal insufficiency. Unfortunately, these highly innovative researches have had little diffusion and have fallen into oblivion in Italy and abroad. In conclusion, our research shows that in the first half of the 20th century in Italy there was a lively interest in cardio-renal diseases and that some researchers had produced precursor results of what was confirmed many years later.

Keywords: cardionephrology, cardiorenal studies, Italian scholars, history of nephrology

The author analyzes the possible paths for the formalization of the anticipated will regarding the care provided for by law no. 219/2017, identifying them in the advance treatment provisions (DAT) and in the shared care planning (advance care planning) of which he examines the merits and related defects. He proposes to invest better and more in shared care planning, indicating the advantages and opportunities that derive from its gradual formation within the care relationship, while signaling the need to proceed promptly with the appointment of the trustee, provided in an optional form by the law. He then addresses the role exercised by this representative figure which is to assist the care team throughout the disease trajectory and not only when it is necessary to honor the wishes and preferences expressed by the person when he was in a position to do so, and he does it criticizing the choice made by the legislator who indicated it in full possession of the ability to understand and want.

Keywords: anticipated will, advance treatment provisions, advance care planning, trustee, ability to understand and want, decision making

The major haemodialysis arteriovenous fistula (AVF) complication is stenotic disease. It is represented by a reduction of the arterial or venous caliper forming the AVF. Most frequently it is located in the juxta- anastomotic region of the venous segment.
There are a lot of mechanisms responsible for the stenosis formation; some are correlated by the shear stress in the wall of venous tract with a lot of biochemical mechanisms, others are associated with the repetition of venipuncture during haemodialisys treatment
It is recommended that each dialysis center activate an AVF monitoring program capable of identifying and treating stenosis.
We describe a clinical case of a young woman with a multiple stenosis disease of a brachio-basilical transposed AVF.

Keywords: AVF, haemodialysis, stenosis, PTA, ecoguided PTA

Malaria is one of the most common infectious diseases in the world with a high prevalence in developing countries. Renal impairment occurs in 40% of Plasmodium falciparum infections; glomeruli, tubules or interstitium can be involved with different pathophysiological mechanisms. We describe a case of severe acute renal failure caused by P. falciparum malaria in a young woman from the Ivory Coast. Renal biopsy revealed severe and widespread acute tubular necrosis and the presence of blackish pigment granules in the glomerular and peritubular capillaries, negative for iron histochemical staining; in electron microscopy we found rounded-oval-shaped structures containing cytoplasmic organelles, electrondensic granules and cellular debris, likely of infectious origin, within monocyte-macrophages located in the tubular lumen. Specific Antigen for P. falciparum and malarial parasite in blood were positive, with very rare trophozoites and gametocytes compatible with Plasmodium falciparum. Steroid therapy and specific antiparasitic therapy were set up with progressive functional improvement until complete recovery. This case highlights the importance of paying maximum attention to low incidence pathologies in our country, considering the continuous migratory movements of these years that can cause an increase in these diseases; anamnestic data are essential for a timely diagnosis which can contribute to a rapid remission avoiding severe complications.

Keywords: malaria, acute kidney failure, tubular necrosis, Plasmodium falciparum

Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematous (SLE). Clinically, LN may occur with extremely variable clinical presentations, ranging from urinary anomalies to rapidly progressive glomerulonephritis. Renal biopsy remains the gold standard for the diagnosis of LN, as the clinical-laboratory presentation doesn’t always correlate with histological data. Treatment of LN includes supportive therapies and targeted immunosuppressive therapies with an induction phase, now called initial treatment and a maintenance phase, now called subsequent treatment. In addition to steroids, mycophenolate mofetil and cyclophosphamide, new drugs such as calcineurin inhibitors (voclosporin) and monoclonal antibodies such as belimumab and rituximab have been introduced in recent decades. Although patient and renal survival have significantly improved from 1970, LN still remains an important negative prognostic factor. Early diagnosis, targeted therapeutic protocols, prevention, and management of complications are the most important factors for the prognosis of these patients.

Keywords: lupus nephritis, immunosuppression, end-stage kidney disease, remission

Anti-glomerular basement membrane disease is a rare small-vessel immune-complex vasculitis (incidence <1/1.000000/year), characterized by the presence of serum antibodies directed against glomerular and pulmonary basement membrane antigens. It is characterized by rapidly progressive crescentic glomerulonephritis, active urinary sediment, subnephrotic proteinuria and oligo-anuria, often coupled to alveolar haemorrage. The main renal lesion on histology specimen is the presence of crescents, often associated to fibrinoid necrosis and linear pattern anti-glomerular basement membrane antibodies positivity on direct immunofluorescence. Lung involvement can be determined clinically, radiologically or by bronchoscopy, by isolation of macrophagic hemosiderin deposits. In order to rapidly remove the pathogenetic autoantibody, plasmapheresis is the mainstay of treatment, associated with cyclophosphamide and steroids, both to control the inflammation and reduce antibody production. A deep knowledge of the pathogenetic mechanisms involved in the anti-GBM disease is mandatory to reach a more and more appropriate diagnostic-therapeutic approach: on one hand, new triggers of the disease (SARS-COV2 infection) and new pathogenetic autoantigens (laminin-521, peroxidasin) have been identified; on the other hand, new therapeutic approaches to lower antibody clearance emerged. The monoclonal anti-CD20 antibody Rituximab can be reasonably used in refractory disease with persistence of antibody anti-GBM, or where standard therapy is not suitable. IdeS (Immunoglobulin G degrading enzyme of Streptococcus pyogenes), which cleaves pathogenetic IgG in a specific site, could be used in place of apheresis, if associated with immunosuppressive therapy. New studies are necessary to better understand pathogenesis, etiology, and treatment options. Key words: Anti-GBM, vasculitis, laminin-521, COVID-19, RItuximab, IdeS

The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a fatal and immune-mediated idiosyncratic drug reaction, with symptoms of fever, skin eruptions (that involves more than half of the body surface), facial oedema and hematological disorders, all presenting within the latent period following drug intake. Effects can also be seen on multiple organs, most notably hepatitis in liver and acute interstitial nephritis in kidney, generally post-administration of allopurinol. The European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) classifies the DRESS Syndrome cases as “definite”, “probable” or “possible”, based on clinical and laboratory features. Different pathogenetic mechanisms have been involved in this disease, including immunological reactions and HHV-6 reactivation. In our experience, a 72-year-old male, affected by myeloma in peritoneal dialysis, developed a rare case of DRESS syndrome after lenalidomide administration (less than ten cases are known) with HHV-6 reactivation. According to literature, we withdrew the drug and gave methylprednisolone 0,8 mg/kg orally and IVIG 1 gr/kg for two days. Despite this therapy, DRESS syndrome relapsed during steroid taper with rash, thrombocytopenia, hepatitis and high troponin level. A single cycle of intravenous immunoglobulin 0,5 g/kg for four days was enough for syndrome remission. Only few cases are reported in literature, but because of the increasing use of lenalidomide and the autoimmune sequelae of DRESS syndrome, a broad workup and a multidisciplinar careful approach could help in diagnosis, treatment and follow-up.

Keywords: eosinophilia, systemic drug reaction, DRESS Syndrome, interstitial nephritis, multiple myeloma, Lenalidomide

La glomerulonefrite acuta post-infettiva è una nefropatia ben definita, immunomediata, che si verifica a causa e successivamente ad un evento infettivo prevalentemente di origine batterica. Nel passato, la forma più frequente di glomerulonefrite acuta post-infettiva era la post-streptococcica, più diffusa nei bambini e a prognosi benigna. Negli ultimi decenni si è osservata una variazione dello scenario epidemiologico e clinico con prevalenza maggiore negli adulti fragili, sostenuta da infezioni non streptococciche, a prognosi sfavorevole con evoluzione verso la malattia renale cronica.

Parola chiave: glomerulonefrite acuta post-infettiva

About 5% of patients with heart failure (HF) reach the end-stage of disease, becoming refractory to therapy. The clinical course of end-stage HF is characterized by repeated hospitalizations, severe symptoms, and poor quality of life. Peritoneal ultrafiltration (PUF), removing water and sodium (Na+), can benefit patients with end-stage HF. However, effects on fluid and electrolyte removal have not been fully characterized.

In this pilot study in patients with chronic HF and moderate chronic renal failure, we evaluated the effects of water and sodium removal through PUF on ventricular remodeling, re-hospitalization, and quality of life.

Patients with end-stage HF (NYHA class IV, ≥3 HF hospitalization/year despite optimal therapy), not eligible for heart transplantation underwent peritoneal catheter positioning and began a single-day exchange with icodextrin at night (n=6), or 1-2 daily exchanges with hypertonic solution (3.86%) for 2 hours with 1.5-2 L fill volume (n=3).

At baseline, average ultrafiltration was 500±200 ml with icodextrin, and 700±100 ml with hypertonic solution. Peritoneal excretion of Na+ was greater with icodextrin (68±4 mEq/exchange) compared to hypertonic solution (45±19 mEq/exchange).

After a median 12-month follow-up, rehospitalizations decreased, while NYHA class and quality of life (by Minnesota Living with HF questionnaire), improved.

In end-stage HF patients, PUF reduced re-hospitalization and improved quality of life. It can be an additional treatment to control volume and sodium balance.

Keywords: Peritoneal ultrafiltration, heart failure, sodium balance, renal failure

Most dialysis patients with end-stage kidney disease (ESKD) lack access to palliative care services. According to the data of the Dialysis Outcomes and Practice Study (DOPPS), Italy when compared to other countries included in the study, had the lowest rates of dialysis discontinuation. Indeed, there is a growing interest in the implementation of international and national programs for the co-management between nephrology and palliative care in end-of-life decision-making for patients with ESKD. On behalf of this, since 2017, we started in the nephrology outpatient clinic and hemodialysis facilities of the Provincia Autonoma of Trento a shared program between Nephrology and Palliative Care Units to improve the end-of-life quality of care in ESKD patients in conservative and dialytic therapy.
Methods: A retrospective analysis, from the 1st of January 2019 to 31st December 2021, of dialysis withdrawal in a cohort of patients undergoing hemodialysis and peritoneal dialysis.
Results: Dialysis withdrawal and subsequent death, according to the integrated protocol with the Palliative Care resources, were 24 in 2019, 20 in 2020, and 28 in 2021. The mean age was 75 years in 2019, 78 years in 2020, and in 2021. Most of the patients were male. Dialysis discontinuation was higher in chronic dialysis patients (80% in 2019 and 2020, and 79% in 2021), and considering the annual rates of death of all the dialysis patients, those who died because of dialysis withdrawal were 38% in 2019, 31% in 2020 and 40% in 2021. Survival after dialysis withdrawal was in most of the cases less than 7 days; only few patients lived more than 30 days. Furthermore, the data, in the 3 years considered, showed a reduction of hospitalization and an increase of the rate of death at home.
Conclusions: As described in the present study, strategies to expand palliative care by a shared protocol among nephrology and palliative care staff improved the quality of care in the end of life and reduced the hospitalization rates of admission of patients after dialysis withdrawal.

Keywords: Dialysis withdrawal, shared end-of-life management, palliative care

Membranous Nephropathy (MN) is characterized by the presence of subepithelial deposits. MN has been traditionally classified as primary if it is not associated with other pathologies, or secondary if it is associated with autoimmune diseases, infections or malignancies. The identification of target podocyte antigen was a critical point in the understanding of the disease: firstly in 2009 with M-type phospholipase A2 receptor (PLA2R) and then in 2014 with Thrombospondin Type 1 Domain Containing 7A (THSD7A). In the last years using an innovative approach based on laser microdissection and tandem mass spectrometry (MS/MS) has allowed the identification of new target antigen/protein as EXT1/2, NELL-1, NCAM1, SEMA3B, PCHD7, HTRA1, TGFBR3. Some of these proteins have been found in both primary and secondary MN, blurring the line between the two forms. Further studies are necessary to define and understand the clinical features of different antigen associated diseases. The aim of this review is to take a closer look at the new antigens and to evaluate how their discovery can change MN classification.

Keywords: Membranous Nephropathy, Renal Pathology, podocyte antigens, mass spectrometry

Atypical hemolytic uremic syndrome is an ultra-rare disease characterized by acute kidney injury, thrombocytopenia, and microangiopathic hemolytic anemia (thrombotic microangiopathy) that occurs with a reported incidence of approximately 0.5 per million per year.

At least 50% of patients with aHUS have an underlying inherited and/or acquired complement abnormality, which leads to dysregulated activity of the alternative pathway at the endothelial cell surface.

Until recently, the prognosis for aHUS was poor, with the majority of patients developing end-stage renal disease within 2 years of presentation. However, with the introduction of eculizumab, a humanized monoclonal antibody against C5, effective to inhibit complement-mediated thrombotic microangiopathy, it is now possible to control the renal disease and prevent development of end-stage renal disease.

Dosing schedule and treatment duration remain controversial and should be rigorously studied.

On this regard, C5b-9 endothelial deposition assay may represent an advance to monitor complement activity in aHUS and to individualize therapy, but currently it can be performed in only specialized laboratories.

Keywords: Atypical hemolytic uremic syndrome, complement, anti-C5 monoclonal antibody, C5b-9 assay

Xenotransplantation, or transplantation between individuals from different species, has long been investigated with the objective to solve the shortage of human organs, tissues and cells for clinical transplantation. Decades of research have convinced scientists that the pig is the most appropriate donor species. Indeed, in addition to numerous anatomical and physiological similarities between pig and man, pig husbandry lends itself to providing the large number of animals necessary to meet the clinical demand.

In the last few years, research in the field of solid organ xenotransplantation has made sensational progress. In particular, in vitro studies and pre-clinical research using pig-to-nonhuman primate transplantation models have clarified the key immunological and physiological barriers to xenotransplantation and provided a better comprehension of the mechanisms underlying the lesions observed in rejected xenografts. This has ultimately resulted in the genetic engineering of specifically-designed, more compatible donor pigs.

The present review article describes the major hurdles that need to be overcome to enable successful solid organ xenotransplantation in humans. These include immunological, physiological and biosafety issues. Discussion on the ideal organ source and on the selection of the most appropriate candidates for first-in-human studies is provided. Particular attention has been dedicated to kidney xenotransplantation. Indeed, at this stage it would appear that the critical immunological and physiological obstacles to clinical xenotransplantation have never been perceived as surmountable as they appear today.

Keywords: Kidney, Patient selection, Genetically-engineered pigs, Xenotransplantation, Physiology

Il rene e il sistema immunitario sono caratterizzati da una stretta e complessa relazione multidirezionale. Il sistema immunitario è causa di nefropatie immunomediate oltre ad essere un fondamentale mediatore del danno parenchimale renale in corso di nefropatie acute e croniche. Occorre inoltre sottolineare come la disfunzione renale, soprattutto se cronica, ha un impatto determinante sulla funzionalità del sistema immunitario causando un’immunosenescenza accelerata ed “inflammaging”.

Questo articolato cross-talk fornisce potenzialmente numerose possibilità di intervento; da notare infatti come l’armamentario terapeutico per la gestione delle nefropatie immunomediate sia in significativo aumento con numerosi farmaci immunomodulanti già entrati nella pratica clinica o in prossimità di entrarvi. D’altro canto, strumenti in grado di modificare significativamente l’impatto del sistema immunitario sulla progressione del danno renale in corso di nefropatia, così come strumenti in grado di modulare l’effetto della nefropatia cronica sulla disfunzione ad essa secondaria del sistema immunitario, non sono ancora disponibili nella pratica clinica.

Scopo di questa review è quello di discutere la complessa interazione esistente tra rene e sistema immunitario con un focus particolare sulle potenziali traslazioni cliniche attuali e future.

Parole chiave: glomerulopatia, autoimmunità, complemento, anti-CD20, Blyss

Chronic kidney disease (CKD) is a clinical condition associated with a high risk of cardiovascular (CV) events, mortality and progression to most severe stage of the disease, also known as kidney failure (KF). CKD is characterized by a wide variability of progression, which depends, in part, on the variability of individual response to nephroprotective treatments. Thus, a consistent proportion of patients have an elevated residual risk both CV and renal events, confirmed by the evidence that about 70% of CKD patients followed by the nephrologist have residual proteinuria. Among the new therapeutic strategies, which have been developed precisely with the aim of minimizing this residual risk, a class of particular interest is represented by the new non-steroidal mineralocorticoid receptor antagonists (non-steroidal MRA). These drugs exert an important anti-fibrotic and anti-proteinuric effect and, unlike steroid MRAs, are associated with a much lower incidence of adverse effects. The non-steroidal MRA molecule for which the most data is available, which is finerenone, is potent and extremely selective, and this partly explains the differences in efficacy and safety compared to steroid MRAs. In clinical trials, finerenone has been shown to significantly reduce the risk of progression to KF. Furthermore, there is also evidence that the combination of non-steroidal MRAs together with SGLT2 inhibitors may represent a valid alternative to reduce the residual risk in CKD patients. Given this evidence, non-steroidal MRAs are gaining momentum in the care, and particularly in individualized care, of CKD patients.

Keywords: CKD, epidemiology, aldosterone, iperkalaemia, kidney failure, cardiovascular risk

Campylobacteriosis is caused by Gram bacteria. Most common species are C. jejuni and C. coli. Campylobacteriosis is a rare cause of sepsis, and in some European countries it is more common than salmonellosis, becoming a public health problem.
We have treated a 66-year-old patient, hypertensive, ischemic cardiopathic, scheduled for coronary angiography, hospitalized with AKI, in a state of shock after some days of acute diarrhea.
Because of the pathogen’s seasonal nature and the patient’s clinical features, in addition to common coproculture also Campylobacter has been sought, and found. Treated with volume repletion and antibiotics, within one week normal kidney functions were fully restored. He had a coronary angiography a week after being discharged from the hospital.

Keywords: Campylobacteriosis, AKI, diarrhea

Introduction: Chronic kidney disease (CKD) and the number of transgender people is on the rise. Hormone replacement therapy may be associated with the development of adverse effects, including kidney disease.
Objective: To report the case of a transgender patient using hormone therapy who developed CKD.
Case Report: Male transgender patient, 28 years old, using testosterone cypionate every 15 days, without any comorbidity. Evolved with hypertensive peaks of 160-150/110 mmHg and loss of kidney function (Ur 102 mg/dl, Cr 3.5 mg/dl, estimated Glomerular Filtration Rate (eGFR) of 22 ml/min/1.73m² considering male gender and 16.6 ml/min/1.73m² considering female gender). Abdominal ultrasound showed chronic parenchymal nephropathy. Due to the significant reduction in eGFR, the patient was referred for kidney transplantation, but he was not included in the list because he had a creatinine clearance of 23 ml/min/1.73m² for males and 21.5 ml/min/1.73m² for females in the most recent tests.
Conclusion: Hormone replacement may have contributed to the increase in the patient’s blood pressure and, consequently, to the development of CKD. There is still no well-established consensus on the best way to estimate the GFR in transgender people, and it seems to be more appropriate to consider the gender to which the person self-identifies or to perform the calculation for both genders, obtaining an estimate of the range in which the patient’s GFR lies.

Keywords: Transgender persons, chronic renal insufficiency, hypertension, hormone replacement therapy.

A 44 years old man was admitted for nephrotic syndrome and rapidly progressive renal failure. Two firm, tumour-like masses were localized around the left shoulder and the right hip joint. Since the age of 8 years old, the patient had a history of metastatic calcification of the soft tissues suggesting hyperphosphatemic pseudotumoral calcinosis. Despite treatment for a long time with phosphate binders the metastatic calcinosis had to be removed with several surgeries. The patient had also a history of recurrent fever associated with pain localized toward the two masses and underwent multiple antibiotic courses. Laboratory findings at admission confirmed nephrotic syndrome. S-creatinine was 2.8 mg/dl. Calcium was 8.4 mg/dl, Phosphorus 8.2 mg/dl, PTH 80 pg/ml, 25 (OH)VitD 8 ng/ml. Serum amyloid A was slightly increased. We performed renal biopsy and we found AA amyloid deposits involving the mesangium and the tubules. The bone marrow biopsy revealed the presence of AA amyloid in the vascular walls. During the next two months renal failure rapidly progressed and the patient started hemodialysis treatment. We performed genetic analysis that confirmed homozygous mutation of the FGF23 gene. After 14 months on hemodialysis, the patient’s lesions are remarkably and significantly reduced in dimension. The current phosphate binder therapy is based on sevelamer and lanthanum carbonate. Serum amyloid A is persistently slightly increased as well as C reactive protein. Proteinuria is in the nephrotic range without nephrotic syndrome.

Keywords: pseudotumoral calcinosis, tumoral calcinosis, FGF23, AA amyloid, renal failure, dialysis

Conceived and developed since 2001 at the Alba Center, Videodialysis (VD) was used initially to prevent dropout in  prevalent PD patients by guiding them in performing dialysis (VD-Caregiver).

Subsequently, its use was extended to the clinical follow-up of critical patients (VD-Clinical), problems relating to transport to the Center (VD-Transport), and since 2016 for training/retraining all patients (VD-Training).

Since 2017 other Centers have employed VD using modalities analyzed in this paper.

Methods: the paper reports the findings of an Audit (February 2021) of the Centers using VD on 31-12-2020.

The Centers provided the following information:

• the characteristics of the patients using VD;
• the main and secondary reasons for using VD, considering nursing home (VD-NH) patients separately;
• VD outcomes: duration, drop-out, peritonitis, patient/caregiver satisfaction (minimum: 1 – maximum: 10).

Results: VD, which began between 09-2017 and 12-2019, has been used in 6 Centers for 54 patients at 31-12-2020 (age:71.8±12.6 years – M:53.7% – CAPD:61.1% – Assisted PD:70.3%).

The most frequent reason has been VD-Training (70.4%), followed by VD-Caregiver (16.7%), VD-NH (7.4%), VD-Clinical (3.7%), and VD-Transport (1.9%), with differences between Centers.

VD-Training is used most with self-care patients (93.8% – p<0.05), while with patients on Assisted PD it is associated with secondary reasons (95.7% – p<0.02). VD-Training (duration: 1-4 weeks) has always been completed successfully.

No peritonitis was reported; satisfaction was 8.4±1.4.

Conclusion: videodialysis is a flexible, effective, safe, and valued tool that can be employed using various modalities depending on the choice of the Center and the complexity of the patient.

Keywords: Peritoneal Dialysis, Assisted Peritoneal Dialysis, Telemedicine, Videodialysis, Training

Vascular access is the lifeline for hemodialysis patients. Autologous artero-venous fistula (AVF) is still the most popular vascular access for hemodialysis even if declining during the last decades. Compared to central venous catheters and vascular grafts, AVF is characterized by a lower risk of infection and lower number of hospitalizations, and by a better quality of life, higher dialysis efficiency, and more prolonged life expectancy for patients. Since the year 1966 when the two surgeons Cimino and Brescia had the idea of connecting the forearm vein and artery for chronic dialysis, several data have accumulated on surgical procedures, positioning of AVF (distal vs proximal), time for the first use, monitoring and surveilling.

All guidelines suggest that special care should be given by monitoring and surveilling AVF to avoid its failure or fatal closing. Attention should be paid to the patient’s vasculature before surgery, through the “maturation” phase and chronic use. Indeed, AVF requires constant and careful care. The crucial role is played by the patient itself in cooperation with devoted clinical staff participated by skilled nurses, nephrologists, surgeons, radiologists, and sonographers.

Literature on AVF is evaluated and guidelines suggestions reported as well as the data attained by the Accesso Vascolare per Emodialisi (AVE) project. This project aimed to evaluate the benefits of monitoring and surveilling, operated by a multidisciplinary team on dialysis adequacy, AVF longevity, and patient’s mortality.

Keywords: artero-venous fistula, dialysis, mortality, monitoring, surveilling

Chronic kidney disease is characterized by increasingly amplified fibrotic processes regardless of etiology. The severity of renal fibrosis seems to correlate with an increased risk of end-stage renal disease; therefore, monitoring of renal fibrosis over time may play an important role in the follow-up of both focal and diffuse renal diseases and in evaluating the response to treatments. Renal biopsy is the only method capable of providing objective and comparable information on the extent of fibrosis, but it is not suitable for outpatient monitoring of chronic kidney disease due to its invasiveness. Elastosonography is an innovative and non-invasive ultrasound method that allows the measurement of tissue elasticity through the transmission of mechanical waves and the measurement of their propagation speed. Although some authors have demonstrated the usefulness of elastosonographic techniques for the quantification of liver fibrosis, few studies have investigated the applications of elastosonography in renal pathology. Furthermore, the depth of native kidneys, the high anisotropy of the renal tissue, and the possibility of examining only a small region of interest currently limit its spread in clinical practice. The aim of this review is to examine the physical principles of elastosonography and to review the latest evidence about the possible applications of the ARFI (acoustic radiation force impulse) technique in the study of kidney diseases.

Keywords: ultrasound, fibrosis, renal elastosonography, ARFI, quantitative imaging

Itching is an annoying symptom, which afflicts patients with chronic renal failure. To assess the diffusion of itching in the dialysis population in Italy, we carried out a questionnaire, which was distributed to patients of various Italian dialysis centers. The purpose of this investigation was to bring out all those aspects, which make itching a state of chronic suffering, which daily undermines the quality of life of patients. The questionnaire had 16 questions on the intensity of itching, the timing of appearance, the report to doctors and nurses, and any suggested remedies, in addition to some other concerning age, sex, and dialysis age. The questionnaires were distributed to 153 Dialysis Centers and received 1905 responses. In 46.7% of the answered questionnaires, the patients declared the absence of itching. Instead, 53.3% of the patients interviewed reported having itching with varying degrees of intensity. We used for quantifying the intensity of itching the numerical rating scale (NRS). Among the interviewees, those (20.4%) who reported a greater intensity and severity of the symptom described it as often present always, even at night, so as to heavily condition sleep. Only 32.5% of patients solved the problem by contacting their nephrologist or dialysis nurse, and a lower percentage by contacting the dermatologist or general practitioner.

Keywords: itching in dialysis, survey, VAS scale, remedies for itching

An Italian nephrologist, during her long experience in the Middle East, is a guest at the SIUT (Sindh Institute of Urology & Transplantation) in Karachi, the largest centre of nephrology-urology and transplantation in South Asia. She discovers the “SIUT model” which guarantees a constant quality of health care, fighting organ trafficking despite the poor economic conditions of the country, Pakistan.

From mid-March 2020, the pandemic caused by COVID 19 has placed health facilities in front of the need to implement a rapid and profound reorganization. However, many hospitals have not had time to organize a rapid and effective response, both for the speed of spread of the virus, and for the lack of previous experience with a pandemic of this magnitude. With the aim of assessing the knowledge and adoption of the procedures and recommendations disseminated by hospitals during the COVID-19 pandemic, in the dialysis and hemodialysis services of Italian centers, a cross-sectional survey was designed by the Society of Nurses in Nephrology (SIAN). The online survey was conducted among nurses who work in the Italian services of dialysis and hemodialysis during the first and second waves.

The online survey was completed by 150 nurses. Although hospitals have set up protocols and procedures for patient management during the COVID-19 pandemic, among participants not all were aware of it. With regard to the training of personnel in the use of personal protective equipment, 18.6% declared that they have not received it. The majority implemented specific precautions for patient management, awareness and information.

Keywords: hemodialysis, peritoneal dialysis, nursing skills procedures, COVID-19

Introduction: The evaluation of renal function is computed using the estimated glomerular filtration rate methods or the measured glomerular filtration rate. Cystatin C has been well studied as marker of renal function compared to serum creatinine, but only few studies compare Glomerular Filtration Rates estimated including both creatinine and cystatin (eGFRcyst-crea) to creatinine clearance (CrCl). This cross-sectional study compares CrCl and eGFRcyst-crea with eGFRcrea and searches for correlation with comorbidities.
Methods: This cross-sectional study consists of 78 patients hospitalized for acute and/or chronic renal disease. We performed the concordance correlation coefficient analysis between the eGFRcrea and the CrCl and eGFRcyst-crea in the whole sample and in the various subgroups.
Results: Steiger’s comparison of correlations from dependent samples showed a correlation coefficient between C-reactive protein and eGFRcyst-crea stronger than between C-reactive protein and CrCl (Z: 2.51, p=0.012). Similar results were showed with the association with procalcitonin (Z: 5.24, p<0.001), serum potassium (Z: -3.13, p=0.002), and severe CKD (Z: -2.54, p=0.011). The concordance correlation coefficient test showed major differences between diagnostic methods compared to eGFR-crea in diabetic subgroup, severe CKD, and in procalcitonin higher than 0.5ng/ml. Discussion: The demonstration of a strong concordance between the eGFRcrea and the eGFRcyst-crea allows us to diagnose and to stage CKD better than creatinine clearance in patients with high inflammatory status. Furthermore, this information opens new research scenarios, and further, larger studies are needed to confirm these hypotheses.
Keywords: Phosphorus, Hemoglobin, Anemia, Chronic Kidney Disease, FGF23, Generalized estimating equation

Background: Nephrology, dialysis and kidney transplant facilities welcome patients with such different characteristics that they push the nurse into the sphere of care complexity, often generating criticality for the client and the professional. The purpose of the study is to understand the perception nephrological area nurses have about safety and the main difficulties encountered during the training course.

Methods: The research was carried out through the questionnaries methodology and involved 104 nurses who work or have worked in the nephrological area in Italy. 58% of participants have an age of service over 16 years.

Results: The data show how much the study path is judged to be lacking in the ability to provide adequate basic knowledge to deal with insertion in a context of Nephrology and dialysis. The study shows that those who have worked for less than 5 years consider the training methods unsatisfactory, generating insecurity at the end of the course. The main technical-professional difficulties encountered are the conduct of the hemodialysis and the management of the arteriovenous fistula.

Conclusions: The research demonstrates how the construction of core competencies in the new hire is an issue widely experienced by the professional but not always shared nationwide.

Keywords: safety, training, skill building, nephrology and dialysis.

The huge spreading of sonography in the field of nephrology led to the use of more performant equipment with construction of better quality images, but with an unfavorable signal/noise ratio, that bring to the generation of artifacts: false signals which creates images not corresponding to reality.

Interaction between ultrasounds and biological structures generates a lot of physical phenomena: reflection, dispersion, absorption and diffraction; these elements create not only the images but also the artifacts.

The artifacts, which don’t correspond to anatomic reality, could be related to the extreme difference of acoustic impedance between the biological structures, or to an error in the settings of B-Mode and color-doppler functions.

Sometimes they can be dangerous and make a diagnosis hard, but most of the time they are useful and pathognomonic of a lesion or physiologic structure.

It’s fundamental for the sonographer being able to discern between real to artifact; the rule is that everything that is repeated in all scans with different insonation angles is true, while what is not repeated in all scans can be an artifact.

Keywords: B-mode artifacts, Colordoppler artifacts, nephrological sonography

This interview describes the numerous and important contributions that Vito Cagli, who was born in Ancona in 1926, has given to the Italian Nephrology and to other fields of Medicine. These contributions, that are very poorly known today, were produced especially in the years in which Cagli worked as deputy director of the Centre for the Investigation and Treatment of Hypertension and Renal Diseases at Policlinico Hospital Umberto I in Rome. This interview also describes the early phase of Italian Nephrology before the introduction in our country of renal biopsy and of hemodialysis.

Keywords: History of Nephrology, History of Italian Nephrology, History of arterial hypertension

Background: Pandemic condition due to Coronavirus disease (COVID-19) caused a fastest augmentation of hospitalization, impairing the healthcare organization. As a consequence, diagnostic and therapeutic delays have been showed. COVID-19-associated coagulopathy is an endothelial disease related to SARS-CoV-2 infection. Our study evaluated the thrombosis of arteriovenous fistula (AVF) as risk marker of mortality.
Methods: the analysis included 24 dialysis-dependent patients admitted in a period between March 2020 and June 2021. Patients were divided based on AVF thrombosis: the A group without AVF thrombosis (13 patients), and the B group with AVF thrombosis events (11 patients). Pearson or Spearman’ correlation tests were performed to detect possible confounding variable to include in multivariate models. Kaplan Meier and Cox regression analysis were performed to compute mortality analysis.
Results: Delta D-dimer (Rho: 0.613, p=0.007), over-infections (Rho 0.456; p= 0,026), C-reactive Protein (CRP) (Rho=0.417, p=0.043), death (Rho=0.492, p=0.027), positive pulmonary imaging (Rho 0.388, p=0.074), and high OLT (0.408, p=0.047) were related to AVF thrombosis, using Pearson or Spearman correlation tests. Kaplan Meier test showed a death average of 19 days in group B compared to a global average of 38 days (p=0.029), and Cox analysis showed an HR of 5.01, 95% CI 1.01-24.99, p=0.049. Furthermore, AVF thrombosis explained about the 68% of the mortality, evaluated through the Harrel’s C test.
Conclusion: We can speculate that AVF thrombosis in hemodialysis patients with COVID-19 could be an early marker of both pro-coagulative process and severe clinical disease and it could be used to stratify patients and identify the ones that can be considered “frail”.

Keywords: COVID-19, Thrombosis, Hemodialysis, Survival analysis

Objectives: Analysis of the results of the 7th National Census (Cs-19) of Peritoneal Dialysis in Italy, conducted in 2020-21 by the Peritoneal Dialysis Project Group of the Italian Society of Nephrology, for the year 2019.
Materials and methods: The data was initially collected using specially designed software, which after entering the data of individual patients allows the aggregate extraction of the necessary information. The difficulties due to the COVID pandemic made it necessary to also use the traditional on-line questionnaire used previously. Of the 237 Centers envisaged, 198 responded, of which 177 with complete data for HD also in 2016.
Results: Overall incidence and prevalence (31/12/2019) were respectively 1,363 (CAPD/APD = 741/622) and 3,922 (CAPD/APD = 1,857 / 2,065) patients. The percentage incidence and prevalence (177 Centers) decreased compared to 2016, respectively, from 23.8% to 22.1% and from 17.3% to 16.6%. 31.4% started PD incrementally in 60.3% of the Centers. The catheter is placed by the Nephrologist alone in 19.7%. Assisted PD is used by 24.5% of the prevalent patients, mostly (83.8%) by a family member. In 2019, the exit from PD (ep/100 years-pts: 11.6 in HD; 8.9 death; 6.0 Tx) is decreasing for all causes. The main cause of transfer to HD remains peritonitis (26.8%). The incidence of peritonitis in 2019 dropped further to 0.190 ep/year-pts as well as the incidence of new cases of EPS (0.103 ep/100 years-pts).
Conclusions: The Cs-19 confirms the good results of the DP in Italy.

Keywords: Peritoneal Dialysis, technique failure, incremental Peritoneal Dialysis, peritonitis, home visits, peritoneal equilibration test (PET)

Intoxications are a common problem all over the world and cause acid-base balance disturbances, dysionias or acute renal failure; they can develop rapidly leading to severe cellular dysfunction and death.

Intoxications and drug overdoses often require the intervention of Nephrologists, for the correction of acidosis, the administration of selective inhibitory enzymes and also hemodialysis treatment. Extracorporeal therapies have been used to remove toxins for over fifty years and have acquired an increasing role, thanks to the use of new treatment modalities in intoxicated patients. In our clinical practice in the Covid period we have found an increase in clinical cases of intoxication with psychiatric drugs, including benzodiazepines, clozapine, lithium, quetiapine and cocaine.

KEYWORDS: intoxication, neuroleptic abuse, rhabdomyolysis, extracorporeal therapy, Covid 19.

Rupture of a renal cyst can be spontaneous, iatrogenic or consequent to a trauma even of minor entity, especially in predisposing conditions such as cysts, tumors or hydronephrosis.

Kidneys are, in fact, involved in about 25% of abdominal traumas. The grading system of the American Association for the Surgery of Trauma (AAST) classifies renal injuries into five categories based on renal involvement and abnormalities detected on contrast-enhanced CT, modality of choice in the evaluation of abdominal trauma with suspicion of intraperitoneal hemorrhage.

Hematuria and/or flank pain are the most frequent presenting symptoms, although some patients may be also asymptomatic.

Treatment is usually conservative, but sometimes nephrectomy may be necessary.

In our manuscript we describe the case of a patient who comes to our observation with left side pain reporting a minor accidental fall occurred the day before.

Ultrasound examination and CT with contrast medium revealed hemoretroperitoneum resulting from rupture of a hemorrhagic renal cyst. We will describe the imaging characteristics and therapeutic choices below.

Keywords: renal cyst, renal hemorrhage, blunt renal trauma, hemoperitoneum

Introduction: persistent hypercalcemic secondary hyperparathyroidism (PSHPT) in kidney transplantation (KTx) can expose renal transplant recipients (RTRs) to a series of complications. Cinacalcet has been shown to be effective in controlling hypercalcemic PSHPT. Therefore, we evaluated the efficacy and tolerability of cinacalcet, over a period of 3 years, in the treatment of hypercalcemic PSHPT in a group of RTRs.

Patients and Methods: eight patients with a kidney transplant age > 12 months, parathyroid hormone (PTH) levels > 120 pg/ml and total serum calcium (TCa) levels > 10.5 mg/dl, were treated with cinacalcet at an initial dose of 30 mg/day. Hypercalcemic PSHPT picture must have been present for at least 6 months before the start of treatment with cinacalcet. Every 6-8 weeks were determined: estimated glomerular filtration rate (eGFR), PTH, TCa, serum phosphorus, fractional excretion of calcium (FECa), tubular maximum reabsorption rate of phosphate (TmP/GFR), serum tacrolimus. Annually all patients underwent to ultrasound control of the transplanted kidney. The main endpoints of the study were the reduction of PTH levels > 30% from baseline and the normalization of TCa levels (<10.2 mg/dl).

Results: the results are shown as median ± interquartile range (IQR). At follow-up PTH levels decreased from 223 (202-440) to 135 pg/ml (82-156) (P < 0.01), with a percentage decrease of -54 (-68;-44), TCa levels decreased from 11.0 (10.7-11.7) to 9.3 mg/dl (8.8-9.5) (P < 0.001). Serum phosphorus levels increased from 2.7 (2.0-3.0) to 3.2 mg/dl (2.9-3.5) (P < 0.05). Fractional excretion of calcium did not change, while TmPO₄/GFR increased even not significantly. Renal function and serum levels of tacrolimus did not change throughout the observation period. At end of the study the average cinacalcet dosages were 30 mg/day (30-30). Ultrasound scans of the transplanted kidney showed no development of nephrocalcinosis and/or nephrolithiasis. Conclusions: cinacalcet has proved effective and well tolerated in the treatment of hypercalcemic PSHPT in RTRs.

Keywords: cinacalcet, hypercalcemia, persistent hypercalcemic secondary hyperparathyroidism, renal transplant.

Autosomal dominant polycystic kidney disease (ADPKD) is responsible of the 10% of the dialysis patients. Tolvaptan is a consolidate option for treatment of ADPKD patients; it slows renal deterioration rate and cysts’ growth, although its acquaretic effects often impact on quality of life (QoL) and treatment adherence. Few studies have documented the tolvaptan long term efficacy and safeness profiles and, mostly, the impact of treatment with tolvaptan on patients’ QoL. Our study aimed to investigate in 13 ADPKD patients of our cohort the differences in terms of QoL before and after the start of treatment via a questionnaire based on SF-36 and PSQI tests, integrated with other original questions. In addition we have also examined the tolvaptan long term efficacy and safeness profiles.

The results of our study show that tolvaptan does not significantly reduce patients QoL notwithstanding its expected acquaretic effects, the only reported side effects. Finally, the average annual renal deterioration rate was lower in patients treated with tolvaptan than in the others.

Relevant limits of our study are the small number of selected patients and the relative short study duration. However, on one hand, the results of our study provide further information to the few data available in literature; on the other hand, they may serve as a useful working hypothesis for further studies with a larger number of patients enrolled and an extended study duration. They would demonstrate the absence of significant impact of tolvaptan on patients’ QoL.

Keywords: ADPKD, tolvaptan, QoL

Background. Chronic renal failure is an epidemic in elderly patients. Older population have an increased prevalence of frailty and sarcopenia, associated with a wide range of adverse health outcomes such as falls, hospitalization, disability.
Aim. Describe the sociodemographic and clinical variables of an elderly Lombard population and identify predictors of renal insufficiency.
Materials and methods. Cross-sectional observational study conducted in hospitals, in recreational centers for the elderly, in the Universities of the Third Age of the provinces of Milan and Monza-Brianza conducted through a convenience sampling of 1250 subjects over the age of 65.
Results. The study identified living alone, annual individual income < € 10,000, polypharmacy, sarcopenia and frailty as predictors of chronic kidney failure. The sample has a mean eGFR of 71.74 mL/min/1.73m² (SD ± 16.56). Older people living alone are more likely to develop CRI (P = 0.031, confidence interval, CI [1.031-1.905]) as well as having an income < € 10,000 (P = 0.002, CI [0.392-0.923]). Taking more than 11 drugs a day increases the probability of having chronic renal failure by 16 times (P = 0.012, CI [1.155-3.16]). Sarcopenia and frailty increase the likelihood of having chronic renal failure (CRI) (P = 0.001, CI [1.198-2.095]).
Conclusions. Identifying predictors of chronic kidney failure is a key step in introducing preventive measures and providing better care to the elderly population.

Keywords: Chronic Kidney Failure, elderly, fraility, sarcopenia

The prevalence of chronic kidney disease is 7.05% in Italy [1]. The replacement dialysis treatments determine greenhouse gas emissions [2] thus contributing to climate change, an important source of risk to global health [3]. Furthermore, the percentage of the Italian Gross Domestic Product destined to public health expenditure has progressively contracted [4]. The province of Belluno has an area of 3610 km², with a population density of 56 people/km², an old age index of 248.5 [5], and offers 4 dialysis centers; however, several patients take up to 8 hours/week to commute to the dialysis center, with a consequent significant environmental and economic impact.

We have investigated the Home Hemodialysis (H-HD) models, both as Assisted Home Hemodialysis (AH-HD), and as Not-assisted Home Hemodialysis (NH-HD), to evaluate their environmental and economic sustainability, and the actual impact due to their adoption by 5 patients.

Thanks to AH-HD it is possible a reduction up to 3767 kg of CO₂ per year, and an economic saving of € 32 456 per year. Utilizing a NH-HD treatment, it is possible a reduction of 5330 kg of CO₂ per year, and a reduction in annual healthcare costs up to € 30 156 per year. Furthermore, the adoption of H-HD treatment for 5 patients allowed an effective reduction of 14 537 kg of CO₂ emitted and a net economic saving of 57 975 €.

Therefore, we consider H-HD methods a valid option for patients living in areas with low population density, where transports have a significant impact, allowing a net reduction of CO₂ equivalent emissions and a considerable saving of the health resources.

Keywords:  In-center Hemodialysis, Home Hemodialysis, economic sustainability, healthcare expense, environment sustainability, CO₂ emission.

Staphylococcus-associated glomerulonephritis (SAGN) represents a possible version of parainfectious glomerulonephritis and is a pathological entity that’s now constantly increasing in developed countries. It is known how bacterial infections can be a possible trigger for various type of glomerulonephritis with clinical onset and evolution comparable to the ones observed in parainfectious glomerulonephritis. Furthermore, in clinical practice the identification and isolation of the pathogenic microorganism responsible for the development of parainfectious glomerulonephritis is not always possible. Therefore, in those cases in which SAGN is suspected, it is often necessary to recur to kidney biopsy in order to come to as much as possible correct diagnosis. Historically, according to scientific literature, the most distinctive anatomopathological feature of SAGN is represented by predominant or codominant mesangial IgA deposits, sometimes associated with C3 deposits. These findings make the differential diagnosis between SAGN and IgA nephropathy often necessary. However, many reports describe how SAGN can also be characterized by a varying spectrum of immunological deposits. In some cases, for example, IgA deposits can be absent and in some other cases it is described a net dominance of C3 deposits. In this case, it becomes extremely important to exclude a possible occurrence of C3 glomerulopathy (C3GN), considering how different are the therapeutic approach and the prognostic implications associated to it. However, the differential diagnosis between SAGN and C3GN can be very hard.

Here’s a case report about a patient who has been hospitalized into our Unit after developing a form of Staphylococcus Aureus associated glomerulonephritis which presented atypical anatomopathological features.

Keywords: staphylococcus-associated glomerulonephritis, C3GN, differential diagnosis, histopathology features.

Introduction: The term incremental haemodialysis (HD) means that both dialysis dose and frequency can be low at dialysis inception but should be progressively increased, to compensate for any subsequent reduction in residual kidney function. Policy of the Matera Dialysis Center is to attempt an incremental start of HD without a strict low-protein diet in all patients choosing HD and with urine output (UO) >500 ml/day. The present study aimed at analyzing the results of this policy over the last 20 years.
Subjects and methods: The dataset of all patients starting HD between January 1^st, 2000 and December 31^st, 2019 was retrieved from the local electronic database. Exclusion criteria were: urine output <500 ml/day or follow-up <3 months after the start of the dialysis treatment.
Results: A total of 266 patients were retrieved; 64 of them were excluded from the study. The remaining 202 patients were enrolled into the study and subdivided into 3 groups (G1, G2 and G3) according to the frequency of treatment at the start of dialysis: 117 patients (57.9%) started with once-a-week (1HD/wk) (G1); 46 (22.8%) with twice-a-week (2HD/wk) (G2); 39 (19.3%) with thrice-a-week (3HD/wk) dialysis regimen (G3). Patients of G1 remained on 1HD/wk for 11.9 ±14.8 months and then transferred to 2HD/wk for further 13.0 ±20.3 months. Patients of G2 remained on 2HD/wk for 16.7 ±23.2 months. Altogether, 25943 sessions were administered during the less frequent treatment periods instead of 47988, that would have been delivered if the patients had been on 3HD/wk, thus saving 22045 sessions (45.9%). Gross mortality of the entire group was 12.6%, comparable to the mean mortality of the Italian dialysis population (16.2%). Survival at 1 and 5 years was not significantly different among the 3 groups: 94% and 61% (G1); 83% and 39% (G2); 84% and 46% (G3). Conclusions: Our long-term observational study suggests that incremental HD is a valuable option for incident patients. For most of them (80.7%) it is viable for about 1-2 years, with obvious socio-economic benefits and survival rates comparable to that of the Italian dialysis population. However, randomized controlled trials are lacking and therefore urgently needed. If they will confirm observational data, incremental HD will be a new standard of care.

Keywords: haemodialysis, incremental haemodialysis, kidney urea clearance, urea kinetic modeling, urine output

Calcific uremic arteriolopathy (CUA), often referred to as calciphylaxis, is a rare condition potentially life-threatening seen in 1-4% of patients with kidney failure on chronic dialysis. Pathogenesis is not clear, but several risk factors have been identified, one of the most known among them is coumarin anticoagulants therapy (tAC). When CUA occurs, tAC is contraindicated: the left atrial appendage occlusion, in dialysed patients affected by non-valvular atrial fibrillation, could be contemplated in replacement of tAC, that should be considered by nephrologist and discussed by a multidisciplinary team including cardiologists.

Keywords : Calciphylaxis, Warfarin, anticoagulant therapy, left atrial appendage occlusion, chronic kidney disease

Renal cell carcinoma (RCC) is the most common type of urogenital cancer. It has a mortality rate of 30-40% and is more commonly seen in men than women. In addition to gender, other risk factors of RCC include obesity, hypertension, smoking, and chronic kidney disease. Following the improvements in diagnostic tests, such as CT and MRI imaging, the incidence of patients diagnosed with RCC has rapidly increased over the past decades. The most common type of RCC, based on histological and molecular subtypes, is clear cell carcinoma which occurs frequently due to mutations in the VHL gene. Nephron-sparing surgery is a selective technique to maintain kidneys in patients while radical nephrectomy and partial nephrectomy are used to remove small tumors. In addition to surgical approaches, adjuvant therapy and targeted therapy are applied in patients with metastatic RCC. In this review, we give an overview of the most recent research on RCC which would help physicians to better manage patients with RCC.

Keywords: renal cell carcinoma, kidney cancer, genetics

The COVID-19 pandemic has caused millions of infections and deaths so far. After recovery, the possibility of reinfection has been reported.

Patients on hemodialysis are at high risk of contracting SARS-CoV-2 and developing serious complications. Furthermore, they are a relatively hypo-anergic population, in which the development and duration of the immune and antibody response is still partially unknown. This may play a role in the possible susceptibility to reinfection. To date, only 3 cases of SARS-CoV-2 reinfection from strains prior to the Omicron variant in patients on chronic hemodialysis have been reported in literature. In all of them, the first infection was detected by screening in the absence of symptoms, potentially indicating a poor immune response, and there are no data about the antibody titre developed.

We report a case of recurrence of COVID-19 in 2020 − first infection likely from Wuhan strain; reinfection likely from English variant (Alpha) after 7 months − in a hemodialysis patient with clinical symptoms and pulmonary ultrasound abnormalities. Swabs were negative in the interval between episodes (therefore excluding any persistence of positivity) and the lack of antibody protection after the first infection was documented by the serological test.

The role of the potential lack − or rapid loss − of immune protection following exposure to SARS-CoV-2 in hemodialysis patients needs to be better defined, also in consideration of the anti-COVID vaccination campaign and the arrival of the Omicron variant, which appears to elude the immunity induced by vaccines and by previous variants. For this purpose, prospective multicenter studies are in progress in several European countries.

This case also highlights the need for a careful screening with nasopharyngeal swabs in dialysis rooms, even after patients overcome infection and/or are vaccinated.

Keywords: SARS-CoV-2, COVID, hemodialysis, COVID-19 recurrence

Diagnosis of monoclonal gammopathy of renal significance (MGRS) with histopathologic features of proliferative GN with monoclonal immunoglobulin deposits (PGNMID) is a challenge for clinicians because of the absence of laboratory findings suggestive of glomerular involvement in paraproteinemia. Renal biopsy remains the gold standard for diagnosis of PGNMID because it is a monoclonal gammopathy with kidney damage often “without a detectable serum/urine clone”. Through this case report, we want to focus on the complexity both in the diagnostic process and in monitoring the renal-hematological response to therapy.

Keywords: monoclonal gammopathies, nephrotoxic paraproteins, kidney damage

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis. Rapidly progressive glomerulonephritis (RPGN) is a rare complication of EGPA. We report a case of a 60-year-old man, who is also a skilled cyclist, who was hospitalized to investigate a symptomatology that had arisen over the previous months and worsened in the last few weeks, to the point of limiting normal everyday activities. The physical examination revealed the presence of livedo reticularis of the four limbs, purpura of the lower limbs, arthritis of the ankles, and low-grade fever; the patient showed intense asthenia, loss of appetite, retrosternal heartburn, and a scarcely pharmacologically controlled asthma. He also reported weight loss (about 5 kg in the last 6 months). Rapidly progressing renal failure was observed with hyper-eosinophilia (4.7 thousand/μL eosinophils, 44% of total leukocytes), pulmonary opacities on chest computed tomography (CT), and sinusitis on CT of the facial massif. The search for antibodies directed against neutrophil cytoplasm (ANCA) revealed a high level of pANCA (pANCA ++, ELISA anti-MPO 666 UI/ml), associated with an increment of inflammation indicators. The induction therapy was high-dosage intravenous glucorticoids and cyclophosphamide, to improve the short and long-term prognosis. After 7 months of treatment, the patient reported a considerable improvement of the symptoms, which at that point did not necessitate pharmacological interventions. The eosinophils value was 0 cells/mm³, the inflammation indexes were back to the norm, and the renal function appeared significantly improved.

Keywords: eosinophilic granulomatosis with polyangiitis, Churg-Strauss Syndrome, rapidly progressive glomerulonephritis, ANCA-associated vasculitis

Background: This retrospective observational study aimed at describing patients on hemodialysis with/without uremic pruritus (UP), their healthcare resource consumption and costs from the perspective of the Italian National Health Service (INHS).

Methods: Through the cross-linkage of the healthcare administrative data collected in the ReS (Ricerca e Salute) database from 2015 to 2017, patients undergoing in-hospital/outpatient hemodialysis (index date) for ≥2 years were selected. After the exclusion of subjects with other causes of pruritus, UP/non-UP cohorts were created based on the presence/absence of UP-related treatment supplies and characterized. Treatments, hospitalizations and costs were analyzed.

Results: Of 1239 patients on hemodialysis for ≥2 years (20.2% of all hemodialysis subjects), 218 (17.6%) were affected by UP. Both cohorts were mostly males and elderly. One year before and after the index date, 58.1% and 65.1% of UP patients received UP-related treatments, of which >50% were treated with antihistamines (mostly cetirizine), 10% gabapentin and 1.4% ultraviolet light therapy. The mean annual overall cost per patient with/without UP was €37,065/€35,988. Outpatient specialist services accounted for 80% (>77% hemodialysis), hospitalizations for 10% (>60% hemodialysis).

Conclusions: Though the prevalence of UP and related healthcare costs charged to the INHS were underestimated, the burden of UP was not negligible. High-efficiency dialytic therapies performed to UP patients seemed to largely weigh on the overall mean annual cost. The availability of specific and effective treatments for UP might offer cost and healthcare offsets.

Keywords: chronic kidney disease, pruritus, public health practice, database

La malattia renale policistica autosomica dominante (ADPKD) è la malattia renale monogenica più frequente e causa ipertensione arteriosa e malattia renale progressiva, entrambe legate allo stress ossidativo (OxSt). Il tolvaptan è una opzione di trattamento nota in ADPKD ma i meccanismi molecolari coinvolti non sono stati completamente chiariti. Questo studio valuta lo OxSt In 9 soggetti per gruppo attraverso: l’espressione proteica di p22^phox, lo stato della fosforilazione di MYPT-1 (Western blot) e l’eme ossigenasi-1 (HO-1) (ELISA).

L’espressione proteica di p22^phox era ridotta nei pazienti ADPKD trattati con tolvaptan e nei soggetti di controllo rispetto ai pazienti ADPKD non trattati: 0.86 ±0.15 d.u. p=0.015; 0.53 ±0.11, p<0.001; 1.42 ±0.11. Lo stesso si riscontrava per la fosforilazione di MYPT-1: 0.68 ±0.09, p=0.013, 0.47 ±0.13, p<0.001, 0.96 ±0.28 mentre HO-1 dei pazienti non trattati era ridotta sia rispetto ai controlli che ai pazienti trattati: 1.97 ±1.22, ng/mL, 2.08 ±0.79, p=0.012, 5.33 ±3.34, p=0.012. I pazienti ADPKD trattati con tolvaptan presentano una riduzione dello OxSt che potrebbe contribuire a rallentare la perdita di funzione renale. Parole chiave: tolvaptan, ADPKD, stress ossidativo, Rho chinasi

Creating an arteriovenous fistula (AVF) is complicated by the gradual increase in the average age of patients initiating chronic haemodialysis treatment and by the greater prevalence of pathologies that impact the cardiovascular system.

In the past, the choice of which vessels to use for the creation of the AVF was essentially based on the physical examination of the upper limbs. Current international guidelines suggest that a colour doppler ultrasound (DUS) should be performed to complete the physical examination. Similarly, vascular ultrasound is fundamental in the post-operative phase for appropriately monitoring the access.

We have conducted a retrospective analysis on the use of DUS in clinical practice in our centre, in order to determine the repercussions on vascular access survival. To this end, we identified three phases, according to the methods that were used for pre-operative vascular evaluation and monitoring of the AVF, that saw the progressive integration of clinical and ultrasound parameters.

The analysis of the data highlighted a statistically significant higher rate of survival for all vascular accesses, evaluated as a whole, and for distal AVFs, in the third phase, despite a greater percentage of patients over 75 (48% vs 28%).

In conclusion, we believe that an approach integrating clinical and ultrasound evaluation is indispensable to identify the most suitable AVF site and guarantee its efficiency over time.

Keywords: haemodialysis, arteriovenous fistula, colour doppler ultrasound, monitoring, vascular access

Introduction: Some hemodialysis patients are reluctant to undergo COVID-19 vaccination for the fear of developing adverse events (AEs). The aim of this study was to verify the safety of the mRNA-1273 vaccine in hemodialysis patients.

Methods: We conducted a retrospective analysis of in-center hemodialysis patients who underwent mRNA-1273 vaccine from March 1^st to April 30^th, 2021. All AEs occurring after the first and the second doses were collected and classified as local or systemic.

Results: Overall, 126 patients on chronic maintenance dialysis without a prior COVID-19 diagnosis were vaccinated with two doses of mRNA-1273 vaccine. Mean age was 68 (IQR, 54,7-76) years and 53.6% of patients were aged ≥65 years. During the observational period of 68 (IQR, 66-70) days, AEs occurred in 57.9% and 61.9% of patients after the first dose and second dose, respectively. The most common AEs were: injection-site pain (61.9%), erythema (4.8%), itching (4.8%), swelling (16.7%), axillary swelling/tenderness (2.4%), fever (17.5%) headache (7.9%), fatigue (23.8%), myalgia (17.5%), arthralgia (12.7%), dyspnoea (2.4%), nausea/vomiting (7.1%), diarrhoea (5.6%), shivers (4%) and vertigo (1.6%). The rates of local AEs were similar after the first and second doses (P=0.8), whereas systemic AEs occurred more frequently after the second dose (P=0.001). Fever (P=0.03), fatigue (P=0.02) and nausea/vomiting (P=0.03) were significantly more frequent after the second dose of the vaccine. There were no age-related differences in the rate of AEs. Overall, vaccine-related AEs in hemodialysis patients seem to be lower than in the general population.

Conclusion: The RNA-1273 vaccine was associated with the development of transient AEs after the first and second doses in patients on chronic maintenance hemodialysis. They were mostly local, whereas systemic AEs were more prevalent after the second dose. Overall, all AEs lasted for a few days, without any apparent sequelae. 

Keywords: COVID-19, mRNA-1273, safety, vaccine, hemodialysis, HD, side effects, SARS-COV-2

In order to fight the SARS-CoV-2 pandemic, mass-vaccination programs have been launched globally starting December 2020. The pace of COVID-19 vaccines development was impressive and although data from clinical trials and post-authorization studies showed acceptable safety profile, additional studies and long-term population-level surveillance are needed. A possible link between all type of vaccination and immunological diseases is perhaps one of the hottest topics in literature; correspondingly, there is growing concern over the small but growing number of case reports linking COVID-19 vaccines with the development of glomerular disease. Our group conducted a systematic review of such cases. Results showed that IgA nephropathy (IgAN) and Minimal Change Disease (MCD) are the most frequently associated glomerulopathies. Interestingly, IgAN cases are mostly flares occurring few hours after the second dose of RNA vaccines and have a good clinical outcome, while both de novo and recurring MCD can occur up to 28 days after the first or second dose of vaccines. RNA vaccines are the most common vaccine type to be associated with glomerulopathy. Of course, this may simply reflect the more widespread use of these vaccines. However, compared to traditional vaccines, they do seem produce a higher antibody response and a stronger CD8+ T- and CD4+ T-cell response, including higher production of chemokines and cytokines.

Keywords: anti-SARS-CoV-2 vaccination, glomerulopathy, immuno-mediated nephropathy

Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related and share several risk factors (i.e. hypertension, diabetes mellitus, congestive heart failure). As consequence, AF is very common among CKD patients, especially in those with end stage renal disease (ESRD). Moreover, patients with AF and advanced kidney disease have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. The adequate long-term oral anticoagulation in this subgroup of patients represents a major challenging issue faced by physicians in clinical practice. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD while vitamin K antagonists (VKAs) are characterized by a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients.

Keywords: atrial fibrillation, chronic kidney disease, warfarin, direct oral anticoagulants, end stage renal disease, left atrial appendage occlusion

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, responsible for 10% of patients on renal replacement therapy. The disease is well known to be associated with many extrarenal manifestations. Leukopenia may also be present, even if it is not commonly identified as a typical extrarenal manifestation.

Herein we describe two case reports of ADPKD patients with leukopenia. The first case is about a 47-year-old patient affected by ADPKD, regularly treated with peritoneal dialysis, who showed a progressive reduction of white blood cell count, mostly of lymphocytes. Lymphocytic leukopenia was so severe that, when he was called for transplantation from a deceased donor, he was considered temporarily not eligible. We then describe a second ADPKD patient regularly treated with peritoneal dialysis, who had stable lymphopenia for years. Six years after starting PD, it was necessary to perform bone marrow aspirate to investigate the simultaneous presence of hypogammaglobulinemia together with M-protein and to exclude monoclonal gammopathy.

All the exams performed did not show any significant results, the patients were re-included in the waiting list and one of them was transplanted. Given our experience and what is reported in the literature, there seems to be enough evidence to consider leukopenia as an extrarenal manifestation of ADPKD.

However, the clinical significance of leukopenia in ADPKD patients is not known. It could be interesting to investigate the leucocytes’ function and if ADPKD patients with leukopenia are more susceptible to infection, or not. Moreover, it would be very useful to analyze the relationship between such manifestation and genotype/phenotype.

Keywords: ADPKD, lymphopenia, leukopenia, kidney transplant, chronic kidney disease

In questi mesi contraddistinti dalla pandemia da Covid-19, il lockdown a domicilio è stato considerato una strategia fondamentale per rallentare il diffondersi del virus. Anche la domiciliazione terapeutica ha rappresentato una parte importante del confinamento. La dialisi peritoneale, pur essendo praticata autonomamente dal paziente a casa propria con un’efficacia depurativa sovrapponibile all’emodialisi, è ancora oggi utilizzata solo da circa l’11% della popolazione in dialisi. Nei pazienti in dialisi peritoneale si è osservato globalmente una ridotta incidenza di infezione da SARS-Cov-2 rispetto ai pazienti in emodialisi. Questi ultimi devono recarsi più volte la settimana in ospedale esponendosi al rischio di contagio. La domiciliazione della metodica si è dimostrata il principale fattore protettivo che ha permesso ai pazienti in dialisi peritoneale di esser meno coinvolti dalla pandemia. Gli strumenti logistici ed economici messi in campo in aiuto alla sanità italiana dovrebbero stimolare anche una maggiore utilizzazione della dialisi peritoneale con l’assistenza infermieristica domiciliare e con incentivi economici per i caregiver. Serve altresì una maggiore collaborazione tra le Unità di nefrologia per permettere a tutti i pazienti di accedere alla dialisi peritoneale anche se non disponibile nella sede di residenza.

Parole chiave: dialisi peritoneale, pandemia da COVID-19, teledialisi

Monoclonal gammopathy of renal significance (MGRS) designates disorders induced by a monoclonal protein secreted by plasma cells or B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form MGRS.

Until now, no guidelines to decide the best therapeutic approach to manage PGNMID exist, and most patients progress to End Stage Renal Disease (ESRD) without therapy. Recently, daratumumab has showed an acceptable improvement in proteinuria and renal function in patients with PGNMID.

We report the clinical outcome and the histological renal evolution and treatment complication of our patient, who was initially treated with a combination regimen including bortezomib, dexamethasone, and cyclophosphamide and then with anti-CD38 monoclonal antibody-based regimen.

Keywords: monoclonal gammopathy of renal significance, proliferative glomerulonephritis with monoclonal immunoglobulin deposits, histological evaluation, pharmacological therapies, case report

Ascites is a pathological accumulation of fluid in the peritoneal cavity due to various etiologies, often associated with renal failure. Paracentesis is a simple method of removing ascitic fluid by inserting a needle into the peritoneal cavity, often performed at the patient’s bedside. It can be both diagnostic and therapeutic. Ultrasound imaging allows the diagnosis of ascites, the identification of the puncture site on the abdominal wall during the pre-procedural phase, the real time evaluation of the needle and the continuous course of the maneuver. This eco-guide technique has higher effectiveness and lower risk of complications than the “blind” venipuncture technique. Ultrasound-guided paracentesis, when performed by nephrologists, reduces the waiting time both for the execution of paracentesis and for the diagnosis, treatment and follow-up of ascites.

Keywords: ascites, paracentesis, ultrasonography, bedside, cirrhosis, peritoneal cavity

A recent study called FRASNET enrolled on a voluntary basis a cohort on 1240 elderly people. They were either patients of the Nephrology and Dialysis unit at San Raffaele hospital in Milan, guests of care homes, or members of cultural, social and recreational centers for the elderly in the wider Milan area. Demographic, anthropometric and biochemical data were collected, together with information on comorbidities and pharmacological therapies, psychophysical test results and biological samples.

After the first wave of the SARS-Cov-2 pandemic, we have interviewed the members of this same cohort to gather information on possible coronavirus infections and evaluate the impact of the pandemic on frail patients. It emerged that the prevalence of SARS-Cov-2 infections was 0.7% within this cohort. This encouraging result seems to confirm the effectiveness of the measures taken at the start of the pandemic, especially social distancing and personal protective equipment.

Keywords: FRASNET study, frail patients, elderly, SARS-Cov-2

Gout is a common, complex, systemic and well-studied form of chronic inflammatory arthritis in adults. It is due to the deposition of sodium monourate crystals in peripheral joints and periarticular tissues driven by hyperuricemia. Gout is the oldest recorded inflammatory arthritis to affect humankind, with roots stretching back to 2460 BC. It is known as “the rich man’s disease”, “the patrician malady”, “a disease of plenty”, “disease of kings”, “disease of Western Society”, and also “a life-style disease”. Few studies have addressed the problem of gout among popes, affluent people who usually live longer than their contemporaries and are among the most scrutinized persons. Pius X (1835-1914) was the last pope with gout.

Gout seems to have affected 26 out of 265 popes (9.81%) from Saint Peter to Benedict XVI (34-2013 AD). The first was Gregory I Magnus, who was pope in the years 590-604, the last was Pius X, who reigned from 1903 to 1914 at age 79. Their age at death was 71.7 ±9.2 years (Mean ± SD). All popes were elderly men, some had voracious appetites and/or were wine drinkers. Several were sedentary and obese, while others were sober eaters, who took long walks or went riding. Chiragra (arthritic pain in the hands), podagra (arthritic pain in the big toe) and renal stone disease were among the most frequent disturbances.

The causes of death, due to CKD, strokes and infections are discussed along with the fact that gout disappeared from the Vatican Palace on August 22, 1914. However, in accordance with the Theory of Epidemiological Transition, gout seems likely to become a problem for the general population, increasingly adopting unhealthy lifestyle choices, in the absence of a correct education.

Keywords: gout, popes, Pius X, renal death, death due to infection, death due to stroke

Exit site infections (ESI) and peritoneal catheter tunnel infections are strongly associated with peritonitis. Alternative exit-site dressings can include the use of water and soap and the absence of sterile gauze. This article reports our experience with “naked” exit-sites, meaning without any kind of gauze to cover them. From January 2017 to October 2020, we enrolled 38 patients of the Nephrology and Dialysis Unit of the “San Martino” Hospital in Belluno. Nine of these patients had a “naked” exit-site. At the end of the study, no significant differences were found in the percentage of ESI-free patients, in the incidence rate of ESI, in the relative risk of developing ESI and in the incidence rate of peritonitis.

Keywords: peritoneal dialysis, exit-site dressing, exit-site infections

Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplantation (HSCT) associated with kidney injury and significant mortality. Recent studies indicate that dysregulation of the alternate complement pathway may be at the basis of the development of TA-TMA. Currently, there are no pre-transplant screening tools to identify patients at risk. To explore the mechanism of TA-TMA, we performed a genetic study that allowed us to identify the deletion of the CFHR3-CFHR1 region in homozygosity.

We report the clinical case of a 47-year-old woman who underwent haploidentical HSCT complicated by TA-TMA confirmed by renal biopsy. The patient discontinued treatment with calcineurin inhibitors (potential inducers of TA-TMA) with a brief introduction of prednisone until complete resolution of renal damage and microangiopathy.

Identifying genetic variants that affect the mechanism of the alternate complement pathway could help in the stratification of the risk of TA-TMA and in implementing a personalized therapeutic approach.

Keywords: transplant-associated thrombotic microangiopathy, genetic susceptibility, hematopoietic cell transplantation, complement alternative pathway

Urinary tract infections (UTIs) are an emerging health problem. Kidney patients with UTI are at increased risk of antimicrobials resistance (AMR) and bad prognosis. In the nephrological setting, optimizing the management of UTIs is certainly a challenge, but it is indispensable for a favorable clinical outcome and in fighting AMR.

When UTIs caused by multidrug-resistant germs are suspected, it is necessary to initiate empirical antibiotic therapy timely, pending microbiological study and bacterial sensitivity. The empirical choice of antibiotic must be based on: guidelines, resistance rates recorded in the region, and knowledge of pharmacokinetic and pharmacodynamic characteristics of the drug, in order to maximize efficacy, reduce adverse effects and minimize AMR development.

Recently, the clinical use of old drugs such as colistin has increased, due to the limited circulation of resistant bacterial strains. On the other hand, ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, imipenem/cilastatin/relebactam and meropenem-vaborbactam are very promising new antibiotics. Ongoing clinical studies will be able to determine the place for these interesting molecules in the treatment of infections and in fighting AMR.

Keywords: urinary tract infections, antibiotics, antibiotic resistance

This article describes the birth and development of the Renal Immunopathology Group of the Italian Society of Nephrology. It collects the stories of nephrologists and pathologists who, since the early Seventies up to the first decade of this century, devoted their professional lives to the study of renal pathology with a strong personal involvement, characterized by enthusiasm, commitment, ability, strong spirit of cooperation, and friendship. All this enabled the Group to: propose the criteria for a standardized histological and immuno-histological examination of renal biopsies and reporting; produce several multicenter studies, whose results were also published in important international journals; to set up a national registry of renal biopsies; to organize a number of courses, some of which were associated with the publication of monographs, on various renal diseases.

This article also traces the history of renal pathology in Italy from the second half of the Sixties – when young Italian nephrologists and pathologists from different institutions moved to French laboratories to learn new techniques to apply to renal biopsies – up to the present days. It also shows us how Italian renal pathology has been an essential tool for the development of the nephrological clinical practice and the advancement of scientific research.

Keywords: history of Renal Immunopathology Group, history of Italian Society of Nephrology, history of Italian Nephrology, history of Italian Nephropathology

Alport syndrome is a hereditary clinical condition characterized by multisystemic changes (sensorineural and ocular deafness) associated with hematuria and proteinuria. Due to its genetic variability and multiple symptoms, it is often diagnosed by chance and too late.

The present work focuses on this pathology through a clinical case report. It also mentions the new therapeutic possibilities relating to this disease.

Keywords: Alport syndrome, kidney damage, clinical case, novel therapies

Background: SARS‑CoV‑2-induced severe acute respiratory syndrome is associated with high mortality in the general population; however, the data on chronic haemodialysis (HD) patients are currently scarce.
Methods: We performed a retrospective analysis to evaluate the onset of acute respiratory distress syndrome (ARDS) in patients with SARS‑CoV‑2-induced interstitial pneumonia diagnosed by PCR test and detected by high resolution computed tomography (HRCT). For each patient, we calculated a CT score between 0 and 24, based on the severity of pneumonia. The primary outcome was the onset of ARDS, detected by P/F ratio >200. We included 57/90 HD patients (age: 66.5 ±13.4 years, 61.4 % males, 42.1% diabetics, 52.6% CV disease) treated at the Cardarelli Hospital in Naples (Italy) from 1^st September 2020 to 31^st March 2021. All patients were treated with intermittent HD.
Results: Patients who experienced ARDS had a more severe pneumonia (CT score: 15 [C.I.95%:10-21] in ARDS patients vs 7 [C.I.95%: 1-16] in no ARDS; P=0.015). Logistic regression showed that the CT score was the main factor associated with the onset of ARDS (1.12; 95% c.i.: 1.00-1.25), independently from age, gender, diabetes, chronic obstructive pulmonary disease, and prior CV disease. Thirty-day mortality was much greater in ARDS patients (83,3%) than in no-ARDS (19.3%).
Conclusions: This retrospective analysis highlights that HD patients affected by SARS-CoV-2 pneumonia show an increased risk of developing ARDS, dependent on the severity of CT at presentation. This underlines once again the need for prevention strategies, in primis the vaccination campaign, for these frail patients.

Keywords: SARS‑CoV‑2, acute respiratory distress syndrome, chronic haemodialysis, retrospective analysis, prevalence, associated factors

Acute Kidney Injury (AKI) is described as a rapid decline in Glomerular Filtration Rate (GFR), reflected by an increase in serum creatinine (SCr) and/or contraction of diuresis. The traditional paradigm considers pre-renal, renal and post-renal causes of AKI. However, there are some settings in which an elevated SCr does not reflect a real decline in GFR. Here we describe the case of a pseudo-AKI, consequence of a massive intraperitoneal urinary leakage due to a traumatic bladder rupture. Besides the pathophysiological considerations, we want to raise awareness about this condition, especially in relation to patients presenting with oliguria, hematuria, apparent AKI, abdominal pain and ascites, particularly after trauma; we do this not only to prevent late diagnosis complications, but also to avoid costly and risky overtreatment.

Keywords: pseudo-AKI, creatinine, urinary ascites, bladder rupture, trauma

Chronic kidney disease (CKD) is growing worldwide, with increasing numbers of patients facing end-stage renal disease, high cardiovascular risk, disability and mortality. Early recognition of CKD and improvements in lifestyle are crucial for maintaining or recovering both physical function and quality of life.

It is well known that reducing sedentariness, increasing physical activity and initiating exercise programs counteract cardiovascular risk and frailty, limit deconditioning and sarcopenia, and improve mobility, without side-effects. However, these interventions, often requested by CKD patients themselves, are scarcely available. Indeed, it is necessary to identify and train specialists on exercise in CKD and to sensitize doctors and health personnel, so that they can direct patients towards an active lifestyle. On the other hand, effective and sustainable interventions, capable of overcoming patients’ barriers to exercise, remain unexplored.

Scientific societies, international research teams and administrators need to work together to avoid that exercise in nephrology remains an empty narrative, a niche interest without any translations into clinical practice, with no benefit to the physical and mental health of CKD patients.

Keywords: chronic kidney disease; physical activity; exercise; quality of life; sarcopenia; disability; physical function; barriers.

The psychologist’s work at the Nephrology and Dialysis Unit of SS. Annunziata Hospital in Chieti begins at the early stages of chronic kidney disease and continues in pre-dialysis and after renal replacement therapy begins. Psychological intervention aims to provide support to patients and caregivers facing a chronic organ disease, as well as to the health personnel constantly exposed to chronic patients.

The perceptual and emotional experience of dialysis changes according to the different modalities of renal replacement therapy: hospital or home hemodialysis, peritoneal dialysis. These different emotional and perceptive experiences seem to emerge while the patient prepares for dialysis and influence the process of accepting and adapting to the disease and its therapy.

Keywords: psychology, nephrology, dialysis, psychological intervention, pre-dialysis

Background: Kidney transplant (KT) recipients with COVID-19 are at high risk of poor outcomes due to the high burden of comorbidities and immunosuppression. The effects of immunosuppressive therapy (IST) reduction are unclear in patients with COVID-19.
Methods: A retrospective study on 45 KT recipients followed at the University Hospital of Modena (Italy) who tested positive for COVID-19 by RT-PCR analysis.
Results: The median age was 56.1 years (interquartile range,[IQR] 47.3-61.1), with a predominance of males (64.4%). Kidney transplantation vintage was 10.1 (2.7-16) years, and 55.6 % of patients were on triple IST before COVID-19. Early immunosuppression minimization occurred in 27 (60%) patients (reduced-dose IST group) and included antimetabolite (88.8%) and calcineurin inhibitor withdrawal (22.2%). After SARS-CoV-2 infection, 88.9% of patients became symptomatic and 42.2% required hospitalization. One patient experienced irreversible graft failure. There were no differences in serum creatinine level and proteinuria in non-hospitalized patients before and post-COVID-19, whereas hospitalized patients experienced better kidney function after hospital discharge (P=0.019). Overall mortality was 17.8%. without differences between full- and reduced-dose IST. Risk factors for death were age (odds ratio [OR]: 1.19; 95%CI: 1.01-1.39), and duration of kidney transplant (OR: 1.17; 95%CI: 1.01-1.35). One KT recipient developed IgA glomerulonephritis and two ones experienced symptomatic COVID-19 after primary infection and SARS-CoV-2 mRNA vaccine, respectively.
Conclusions: Despite the reduction of immunosuppression, COVID-19 affected the survival of KT recipients. Age of patients and time elapsed from kidney transplantation were independent predictors of death . Early kidney function was favorable in most survivors after COVID-19.

Keywords: COVID-19, kidney transplant, immunosuppressive therapy, graft function, proteinuria, mortality, transplant, SARS-COV-2, reinfection

Optimal glycemic control in diabetic patients remains a difficult goal to achieve. Hypoglycemia, nausea and weight gain can compromise the patients’ adherence to antidiabetic therapy over time. GLP-1 receptor agonists have been shown to improve glycemic control and reduce the incidence of side effects both when used in monotherapy and in combination with other hypoglycemic drugs. The growing interest of nephrologists in GLP-1 receptor agonists derives from numerous studies showing that not only they positively affect traditional cardiovascular risk factors, but also exert a protective effect on renal function regardless of their hypoglycemic effects, thus delaying the development and progression of diabetic nephropathy. The aim of this paper is to review the latest evidence on pharmacokinetics and pharmacodynamics and the direct and indirect mechanisms through which GLP-1 receptor agonists confer nephroprotection, improving the renal outcomes of diabetic patients.

Keywords: diabetes mellitus type 2, incretins, GLP-1, kidney protection

The First World War was a turning point for medicine worldwide and the following 20 years brought many important innovations. Kidney studies in Italy were part of this general trend. In this contribution, all the papers relating to kidney physiology, pathology and therapeutics produced by Italian scientists in the years between the two World Wars are retrieved and examined. The authors who produced strictly nephrological articles are also singled out and their activity described. This research retrieved 638 articles dealing with kidneys and published by Italian scientists over the period described. The topics covered were up-to-date, and the level was consistent with that of foreign contemporaries. Among the authors, a group of young scientists particularly dedicated to the study of the kidney emerges. Most of them would subsequently be among the founders of the Italian Society of Nephrology and leaders of Italian nephrology.

Keywords: history, nephrology, Italy, scientists, World Wars

Kidney transplantation is the gold-standard treatment of end-stage renal disease. Receiving a pre-emptive transplant ensures the best survival for both the recipient and the allograft. However, due to an overwhelming discrepancy between available donors and patients on the transplant waiting list, the vast majority of transplant candidates require prolonged periods of dialytic therapy before transplant.

Peritoneal dialysis and hemodialysis have been traditionally considered as competitive renal replacement therapies. This dualistic vision has been recently questioned by emerging evidence suggesting that an individualized and flexible approach may be more appropriate. Tailored and cleverly planned shifts between different modalities, according to the patient’s needs, represents the best option.

Remarkably, recent data seem to support the use of peritoneal dialysis over hemodialysis in patients waiting for a kidney transplant. In this specific setting, the perceived advantages of PD are better overall recipient survival and quality of life, longer preservation of residual renal function, lower incidence of delayed graft function and reduced cost.

Keywords: peritoneal dialysis, kidney transplant, hemodialysis, renal replacement therapy, waiting-list, residual renal function, quality of life, delayed graft function

The increase in patients’ average age, the enhancement of anticoagulation therapy and the growth of vascular interventions represent the perfect conditions for the onset of atheroembolic renal disease. AERD is observed in patients with diffuse atherosclerosis, generally after a triggering event such as surgery on the aorta, invasive procedures (angiography, catheterization of the left ventricle, coronary angioplasty) and anticoagulant or fibrinolytic therapy. The clinical signs are heterogeneous, a consequence of the occlusion of downstream small arterial vessels by cholesterol emboli coming from atheromatous plaques of the aorta, or one of its main branches. The proximity of the kidneys to the abdominal aorta, and the high flow of blood they receive, make them a major target organ. For this reason, AERD represents a pathological condition that always needs to be taken into account in the nephropathic patient, although its systemic nature makes the diagnosis difficult.

This manuscript presents a review of the existing literature on this pathology, to provide an updated summary of the state of the art: risk factors, diagnostics, histology and therapeutic approaches.

Keywords: atherosclerosis, cholesterol crystal embolism, contrast media, acute kidney injury, chronic kidney disease

Home dialysis is a primary objective of Italian Ministry of Health. As stated in the National Chronicity Plan and the Address Document for Chronic Renal Disease, it is mostly home hemodialysis and peritoneal dialysis to be carried out in the patient’s home. Home hemodialysis has already been used in the past and today has found new technologies and new applications. The patient’s autonomy and the need for a caregiver during the sessions are still the main limiting factors.

In this multicenter observational study, 7 patients were enrolled for 24 months. They underwent six weekly hemodialysis sessions of 180′ each; periodic medical examinations and blood tests were performed (3, 6, 12, 18 and 24 months). After 3-6 months of home hemodialysis there was already an improvement in the control of calcium-phosphorus metabolism (improvement in phosphorus values, (p <0.01), a reduction in parathyroid hormone (p <0.01)); in the number of phosphorus binders used (p <0.02); in blood pressure control (with a reduction in the number of hypotensive drugs p <0.02). Home hemodialysis, although applicable to a small percentage of patients (10-15%), has improved blood pressure control, calcium-phosphorus metabolism and anemia, reducing the need for rhEPO.

Keywords: chronic kidney disease, home dialysis, home hemodialysis

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and accounts for∼10% of patients on renal replacement therapy. In the last decade, no specific treatment was available and only preventive measures could be put in place to delay the onset of ESRD. Following the results of the TEMPO 3:4 study, tolvaptan was approved in many countries, for the purpose of slowing the progression of renal insufficiency.

In Italy tolvaptan is available since 2016 for patients with chronic kidney disease (CKD) stage 1-3, and since 2020 for patients with CKD stage 4, who fulfil the criteria of “rapid disease progression”, according to the European recommendations.

After this approval, Italian nephrology units have had to change their organization to be able to identify the patients eligible for the drug and to guarantee frequent patient monitoring.

In this paper, we present our three-year experiences with tolvaptan, focusing on its safety profile and tolerability, but also on the high burden of care that such therapy represents not only for doctors, but also for patients. Strategies to implement remote monitoring may be useful to reduce the burden of assistance on one side, and the medicalization of ADPKD patients in the early stage of the disease, on the other.

Keywords: ADPKD, tolvaptan, remote monitoring, burden of care

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary nephropathy and is the fourth most common cause for end-stage renal disease in Europe. ADPKD is a systemic disease; besides the typical renal involvement, characterized by progressive cyst expansion leading to massive enlargement and distortion of the kidney architecture and, ultimately, to end-stage renal disease, multiple extrarenal manifestations can be observed included cysts in other organs, diverticulosis, cardiac valvulopathies, abdominal and inguinal hernias, vascular anomalies. The rupture of an intracranial aneurysm is one of the most serious complications in ADPKD patients. Aim of this review is to provide useful indications for the clinician to define the risk of intracranial aneurysms in ADPKD population, to identify screening criteria (which patients to screen, how often and with which diagnostic methods), to estimate the risk of rupture of intracranial aneurysms, which may require intervention.

Keywords: ADPKD, intracranial aneurysms, screening, risk of rupture, treatment

Kidney cancer accounts for about 3.5% of all malignant neoplasms; in 85% of cases the tumor arises from cells of the renal parenchyma, with an incidence of 70% of the clear cells subtype.

Surgery, at present, is the treatment of choice for most renal cancers; medical therapy, on the other hand, has only palliative purposes and is used only in the relapsed or metastatic patients.

The therapeutic toolbox available in the fight against renal cancer is continuously renewed due to the approval of new drugs. In particular, in the 2000s, antiangiogenic drugs were introduced and showed good efficacy in terms of increased survival in patients with advanced renal carcinoma.

Immunotherapy was a treatment strategy for renal cancer in the 1980s, when cytokines such as Interleukin-2 and Interferon were administered. The advent of antiangiogenic drugs had bound immunotherapy to a secondary role until the discovery of immune check-point inhibitors (ICIs), which have been approved in the various lines of treatment, in monotherapy or in combination with other drugs, as they have shown to increase the oncological outcome.

In this review we analyze the evolution of immunotherapy for the treatment of kidney tumor from the viewpoint of nephrologists, with a special focus on renal adverse events, pembrolizumab and its recent approval as first line therapy in association with axitinib.

Keywords: immunotherapy, kidney cancer, interstitial nephritis, acute kidney injury, molecularly targeted agents.

We describe the case of a 26-year-old male patient with a previous diagnosis of Alström Syndrome who presented drowsiness, dyspnea, tremors, and a dull abdominal pain, without signs of peritoneal irritation. The patient also presented sensorineural hearing loss, decreased vision, due to chorioretinal dystrophy, difficulty walking with back-lumbar double curve scoliosis, impaired glycemic homeostasis, and a significant deterioration of renal function.

Alström syndrome is a multisystem disease characterized by rod-cone dystrophy, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy, and progressive renal and hepatic dysfunction. Around 450 cases have been identified worldwide. Clinical signs, age of onset and severity can vary significantly between different families and within the same family.

Careful nephrological follow-up is necessary in patients with syndromic ciliopathies, since long-term kidney problems can have an impact on other diseases, eg. cardiovascular disease.

Keywords: rare diseases, ciliopathies, chronic kidney failure

The COronaVIrus Disease 2019 (Covid-19) pandemic has rapidly changed hospital structures in our country, radically modifying clinical activity. Nephrology, and kidney transplant in particular, has been heavily influenced by it, with a reduced number of organ donations and, consequently, transplantations.

Here we report the data on kidney transplants in our region, Sicily, for the period 2019-July 2021, and we analyze the effects of the pandemic.

Keywords: Covid-19, pandemic, kidney transplantation, Sicilian experience

Peritoneal dialysis is an efficient renal replacement therapy for uremic patients but is currently under-prescribed. This is partly due to the unfavorable effects on peritoneal morphology and function (bioincompatibility) of current glucose-based solutions. Use of standard solutions can cause several peritoneal alterations including inflammation, mesothelial to mesenchymal transition, and neo-angiogenesis. The final step is fibrosis, which reduces the peritoneal filtration capacity and can lead to ultrafiltration failure and transfer of the patient to hemodialysis. Bioincompatibility can be local (peritoneum) but also systemic, due to the excessive absorption of glucose from the dialysate. Several strategies have been adopted to improve the biocompatibility of peritoneal dialysis solutions, based on the alleged causal factors. Some new solutions available on the market contain low glucose degradation products and neutral pH, others contain icodextrin or aminoacids. Clinical benefits have been associated with the use of these solutions, which however have some limitations and a debated biocompatibility profile. More recent strategies include the use of cytoprotective agents or osmo-metabolic agents in the dialysate. In this article, we review the different approaches currently under development to improve the biocompatibility of peritoneal dialysis solution and hence the clinical outcome and the viability of the technique.

Keywords: peritoneal dialysis, biocompatibility, peritoneum, dialysate, peritoneal dialysis solution

Introduction: Dialysis is a form of renal replacement therapy that requires several changes in the relational, emotional, work, and family sphere. It can be a cause of stress due to various factors.

Objective: The purpose of our study has been to evaluate the perception of the nursing care received by dialyzed patients.

Method: In 2021, a cross sectional study was conducted in Perugia hospital by administering to dialyzed patients a questionnaire built on the Newcastle satisfaction with nursing scale.

Results: 30 patients participated in the study: the mean age was 68.9 ±15.1, 66.7% were male, 50% had a high school diploma, 86.7% were retired, and 50% were dialyzed for less than 5 years. Negative perceptions of the assistance received were mainly reported by women, younger patients, and patients who had been in therapy for only a few years.

Discussion: Our study highlights several aspects that are fundamental to improving the quality of nursing care. There also needs to be a greater attention to certain types of patients, to improve their experience and consequently their quality of life.

Keywords: nursing, quality, dialysis, questionnaire, Newcastle satisfaction with nursing scale

Dysfunctional AVF represents one of the leading causes of morbidity in the hemodialysis population, with venous stenosis-related dysfunction being the most common underlying problem.

Cephalic arch is a well-known site for the development of stenosis, especially in patients with brachiocephalic fistulas. The pathophysiology of cephalic arch stenosis (CAS) is still being investigated and various contributing factors have been suggested.

The treatment options for CAS are many and include angioplasty, endovascular stent insertion, access flow reduction and surgical interventions, but none of the current modalities are ideal. Therefore, the treatment of CAS is difficult, as the stenosis in this area tends to recur leading to the need for repeat angioplasty, stents or surgical revision.

A 57-year-old woman undergoing hemodialysis (HD) through a right brachiocephalic arteriovenous fistula was found to have high venous pressure during HD and prolonged bleeding after HD. Clinical examination revealed a hyperpulsatile fistula suggestive of outflow obstruction. Doppler ultrasound examination showed cephalic vein thrombosis, severe outflow stenosis and juxta-anastomotic area. A 10 x 40 mm stent (Cordis Smart stent) was positioned appropriately in the cephalic arch and deployed, the stenotic lesion in juxta-anastomotic area was dilated with angioplasty balloon with improvement in flow.

After 14 months, the fistula is still working perfectly with adequate flow.

Keywords: cephalic arch, stenosis, brachiocephalic fistula, hemodialysis

Over a half of patients with Systemic Lupus Erythematosus will develop lupus nephritis (LN). The diagnosis of LN, suspected based on clinical data (proteinuria, active urinary sediment, renal dysfunction), is confirmed with renal biopsy. The immunosuppressive treatment of proliferative classes of LN is based on an induction phase, where high-dose steroids are used in conjunction with mycophenolate mofetil (MMF) or cyclophosphamide, and a subsequent maintenance phase, that combines low-dose steroids with MMF or azathioprine. Different classes of drugs (calcineurin inhibitors, anti-CD20) can be used as an alternative, or in resistant forms of LN, although their role is less well-established. Recently published (or nearing completion) studies have opened up the possibility of using new drugs in LN. In particular, depletion (Obinutuzumab, anti-CD20 monoclonal antibody) or neutralization (Belimumab, anti-“B-cell activating factor” monoclonal antibody) of B lymphocytes, and the use of a calcineurin inhibitor with a low profile of renal and systemic toxicity (Voclosporin) demonstrated an improvement in renal response in addition to standard therapy.

Keywords: lupus nephritis, immunosuppressive treatment, systemic lupus erythematosus

Background. Physical exercise is a health intervention in the treatment of numerous chronic diseases. In patients on hemodialysis, physical exercise has been introduced during hemodialysis for different outcomes. Several meta-analyses show uncertainty about the effects.
Objective. Our systematic review and meta-analysis aim at summarizing and evaluating the evidence of the effects of physical exercise on cardiovascular endurance and functional capacity of hemodialysis patients.
Results. Five studies were included in the review (462 patients). Physical exercise brought an improvement in cardiovascular endurance and functional capacity (MD, 95%CI:62.24 [18.71, 105.77], p=0.005), compared to the control group. Most trials were at high risk of bias due to lack of blinding between the patients and the personnel, and between the patients and the outcome assessor.
Conclusions. Physical exercise may have beneficial effect on cardiovascular endurance and functional capacity in hemodialysis patients. The quality of evidence is low and the strength of recommendations is weak for cardiovascular endurance. Future studies should consider a power analysis for an adequate sample size and minimize the risk of sample bias. Further research should provide the additional results required for an acceptable estimate of the effects of physical exercises in hemodialysis patients.

Keywords: physical exercise, hemodialysis, cardiovascular endurance, functional capacity, systematic review, meta-analysis

Patients with chronic kidney disease or end-stage renal disease experience tremendous cardiovascular risk. Cardiovascular events are the leading causes of death in these patient populations, thus the interest in non-traditional risk factors such as hyperhomocysteinemia, folic acid and vitamin B12 metabolism is growing.  Hyperhomocysteinemia is commonly found in CKD patients because of impaired renal metabolism and reduced renal excretion. Folic acid, the synthetic form of vitamin B9, is critical in the conversion of homocysteine to methionine like vitamin B12. Folic acid has also been shown to improve endothelial function without lowering homocysteine, suggesting an alternative explanation for the effect of folic acid on endothelial function. Whether hyperhomocysteinemia represents a reliable marker of cardiovascular risk and cardiovascular mortality or a therapeutic target in this population remains unclear. However, it is reasonable to consider folic acid with or without methylcobalamin supplementation as appropriate adjunctive therapy in patients with CKD. The purpose of this review is to summarize the characteristics of homocysteine, folic acid, and vitamin B12 metabolism, the mechanism of vascular damage, and the outcome of vitamin supplementation on hyperhomocysteinemia in patients with CKD, ESRD, dialysis treatment, and in kidney transplant recipients.

Keywords: hyperhomocysteinemia, folic acid, vitamin B12, chronic kidney disease, end-stage renal disease, cardiovascular disease

About 60% of the world population has access to the Internet in 2021, making it the main tool in fostering communication between people. Lately, digital information and communication have especially taken place on platforms known as Social Media (SoMe) or Social Networks. In the last decade the usefulness of these tools in carrying information aimed at updating professionals in Medicine and Nephrology has become evident. There are several examples of SoMe utilization in Nephrology, as demonstrated by the existing accounts or Pages operated by the main international nephrological Scientific Societies, or the most renowned specialized medical journals. Twitter, Facebook and YouTube are the most versatile SoMe for these objectives; however, other platforms such as Tik Tok, Linkedin, Instagram, and WhatsApp may serve the same purpose. This digital revolution in disseminating information has proved very useful during the recent COVID-19 pandemic, even though some inappropriate uses have emerged, such as the diffusion of fake news, which has favored the emergence of “adverse effects” or a surge of antiscientific positions.

In this review, we examine how physicians and nephrologists can take advantage of digital information for their continuing education. We quote the main resources in the international scenario and illustrate some specific national examples, such as the Journal Club of the Nephrology post-graduate program of the University of Milan and the Facebook group “Medical and Nephrology Community”.

Keywords: social media, social network, internet, continuing education, digital dissemination of scientific information

COVID-19 has a wide spectrum of clinical presentation, ranging from asymptomatic or mild symptoms to severe multiorgan failure. In Portugal, the first cases affecting patients on a chronic hemodialysis program arose in the city of Oporto.

The authors report here two cases of COVID-19 infection in patients incident in renal replacement therapy in the Alentejo region and hypothesise that the high serum concentration of urea may decapitate the appearance of typical symptoms of the SARS-CoV-2 infection. The fact that the hemodialysis population can present active infection without fever may lead to a delayed diagnosis and consequently an increased risk of mortality.

Keywords: COVID-19, hemodialysis, urea, case reports, Alentejo region

Purpose: According to the Surviving Sepsis Campaign, aminoglycosides (AG) can be administered together with a β-lactam in patients with septic shock. Some authors propose administering a single dose of an AG combined with a β-lactam antibiotic in septic patients to extend the spectrum of antibiotic therapy. The aim of this study has been to investigate whether a single shot of AG when septic patients present at the Emergency Department (ED) is associated with acute kidney injury (AKI).

Methods: We retrospectively enrolled patients based on a 3-year internal registry of septic patients visited in the Emergency Department (ED) of Pordenone Hospital. We compared the patients treated with a single dose of gentamicin (in addition to the β-lactam) and those who had not been treated to verify AKI incidence.

Results: 355 patients were enrolled. The median age was 71 years (IQR 60-78). Less than 1% of the patients had a chronic renal disease. The most frequent infection source was the urinary tract (31%), followed by intra-abdominal and lower respiratory tract infections (15% for both). 131 patients received gentamicin. Unmatched data showed a significant difference between the two groups in AKI (79/131, 60.3% versus 102/224, 45.5%; p=0.010) and in infectious disease specialist’s consultation (77/131, 59% versus 93/224, 41.5%; p=0.002). However, after propensity score matching, no significant difference was found.

Conclusion: Our experience shows that a single-shot administration of gentamicin upon admission to the ED does not determine an increased incidence of AKI in septic patients.

Keywords: aminoglycosides, acute kidney injury, gentamicin, safety, sepsis

Proteinuria is a well-known marker of renal damage and, at the same time, an important factor in the progression of chronic kidney disease itself. The scientific community has always sought to investigate and provide answers on how nutritional therapy can influence and modify proteinuria and therefore limit its impact on progression to end-stage renal disease. However, despite the importance of the topic, the studies rarely take the form of randomized and controlled trials; in any case, they are often limited to protein intake only, conducted on very heterogeneous populations and, finally, they rarely indicate the precise values of proteinuria. The aim of this work is to explore the different nutritional approaches and their implications in the pathological conditions associated with proteinuria.

Keywords: proteinuria, end stage renal disease, diet, low protein, chronic renal failure

In this interview Attilio Losito tells us about his first nephrological experiences gained in the late sixties of the past century in the Institute of Patologia Medica in Perugia directed by Giovanni Gigli, and his subsequent experiences, which also included a period at Guy’s Hospital in London. The interview also describes the important contributions that the school of Perugia produced in the field of nephrology and its main protagonists. This nephrological life story highlights: the role that internal medicine, with its multidisciplinary approach, had in the development of nephrology in its beginnings; the importance of cooperation with foreign institutions; the contributions that specialised research laboratories attached to renal units have given to the improvement of the diagnosis and to the understanding of the pathogenesis of nephropathies.

Keywords: history of nephrology, history of Italian nephrology, history of Italian internal medicine

In the last year, the Italian National Health Service as a whole and the Nephrology community have been severely challenged by the pandemic. It has been a dramatic stress test for the entire healthcare system, not only in Italy but worldwide. The general organization of our Nephrology units and our models of care were put under extreme pressure, and we had to quickly adopt unprecedented clinical practice recommendations and organizational models to overcome the impasse caused by the pandemic. The time has come to evaluate these new experiences, ask how we could have been better prepared and look for change. In this editorial, we outline a few proposals and suggestions for the future, weighing the information gathered in the 2018 Nephrology Census against the new organizational requirements imposed by the COVID-19 pandemic.

Keywords: Nephrology Census, National Health Service, new organizational requirements, COVID-19 pandemic

L’infezione da SARS-CoV-2 è responsabile della malattia sistemica da coronavirus 2019 (COVID-19). Nel complesso quadro della COVID-19 è possibile riscontrare anche un danno renale dalla patogenesi non univoca e multifattoriale che clinicamente si può presentare con alterazioni urinarie come proteinuria ed ematuria, accompagnate o meno ad una riduzione della funzionalità renale. Il danno renale acuto (AKI) non è infrequente, soprattutto nei pazienti critici ospedalizzati in terapia intensiva. L’AKI è un fattore prognostico negativo ed è gravato da una elevata mortalità intraospedaliera. La diagnosi tempestiva di danno renale acuto e la valutazione dei fattori di rischio eventualmente presenti, permetterà al nefrologo di attuare strategie terapeutiche adeguate del tipo farmacologico o di supporto extracorporeo. La mortalità nei pazienti con AKI in corso della COVID-19 rimane ancora elevata. La COVID-19 AKI è una area di studio tuttora in evoluzione.

Parole chiave: COVID-19, AKI, Cotugno, CRRT, terapie di purificazione extracorporee

Background: Frailty is a known predictor of mortality and poor outcomes during hospital admission. In this large renal retrospective cohort study, we investigated whether frailer COVID-19 positive renal patients had worse outcomes.

Design: All SARS-Cov-2 positive renal patients aged ≥18 years who presented to the emergency department at the Royal Free Hospital or at the satellite dialysis centres from 10^th of March until the 10^th of May 2020, with recent data on frailty, were included. The follow up was until 26^th of May 2020. Age, gender, ethnicity, body mass index, chronic kidney disease stage, modality of renal replacement therapy, co-morbidities, Rockwood clinical frailty score (CFS), C reactive protein and the neutrophil-to-lymphocyte count were collected at presentation. The primary outcome was the overall mortality rate following COVID-19 diagnosis. Secondary outcomes included the need for hospital admission.

Results: A total of 200 renal patients were SARS-Cov-2 positive. In the 174 patients who had a CFS recorded, the age was 65.4 years ± 15.8 (mean ± SD) and 57,5% were male. At the end of follow up, 26% had died. Frail patients (CFS 5-7) were more than three times more likely to die compared to less frail patients (CFS of 1-4) (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.0-10.6). 118 patients (68%) required admission, but there was no difference in hospital admission rates for frail vs non-frail patients (OR 0.6, CI 0.3-1.7).

Conclusions: Frailty is a better predictor of mortality than age and co-morbidities in COVID-19 positive renal patients.

Keywords: frailty, renal patients, SARS-Cov-2

Hemoglobinuria, clinically revealing as gross hematuria associated with anemia, increased hemolysis indices, acute kidney injury (AKI), can all be caused by mechanical intravascular hemolysis following mitral valve surgery. It can result from factors related to the surgical procedure or acquired later, such as paravalvular leak (PL), whose definite diagnosis is based on transesophageal echocardiography. 

We report the case of a patient who experienced macrohematuria and AKI, initially attributed to acute glomerulonephritis, two months after mitral valve surgery. Careful microscopic examination of the urinary sediment was a diriment diagnostic tool to differentiate acute renal failure caused by hemoglobinuria from hematuria in the course of acute glomerulonephritis, directing clinicians to investigate post-operative valvular dysfunction. From the literature review we can deduce that, notwithstanding new technologies in cardiac surgery, this rare form of AKI from intravascular hemolysis requires immediate nephrological attention and that the use of microscopic urinary sediment is decisive.

Keywords: hemoglobinuria, urinary sediment, gross hematuria, acute kidney injury (AKI), mitral valve surgery, hemolytic anemia

Hemodialysis is the most common treatment in patients with end-stage chronic kidney disease and the wide accessibility of this therapy has prolonged the patients’ lifespan. However, it involves alterations in their emotional sphere and, often, a reduction in therapeutic compliance as the chronicity of kidney disease requires lifestyle changes difficult to maintain in the long term. The management of a chronic medical condition is in fact a complex process that necessarily requires multidisciplinary action.

The concepts of “Self-efficacy” and “Self-management” fall within the Self-Determination Theory and are relevant in this context because they refer to the beliefs that everyone has about their abilities to control behavior and determine the success in adhering to prescribed therapies.

Furthermore, the promotion of self-efficacy and self-management through an educational approach that makes use of so-called “eHealth” tools can help develop greater self-awareness in dialysis patient, a better control over their care choices and an increased adherence to therapeutic-dietary indications.

This article aims at highlighting the importance of implementing an approach based on eHealth in the management of hemodialysis patients. It also wants to raise awareness of the related multidisciplinary theories to be applied in this clinical context to promote greater therapeutic adherence, and therefore a better quality of life and care.

Keywords: self-efficacy, self-management, hemodialysis, kidney disease, eHealth

Diverse terapie farmacologiche, pur correttamente condotte, possono favorire sia la comparsa di precipitati cristallini a livello dei tubuli e dell’interstizio renale, con aspetti morfologici di nefrocalcinosi e quadri clinici di insufficienza renale acuta, sia la formazione di veri e propri calcoli, con possibili fenomeni di uropatia ostruttiva.

I cristalli e i calcoli possono essere costituiti dal farmaco somministrato, oppure dai componenti litogeni urinari di più comune riscontro (sali di calcio o acido urico), precipitati in conseguenza di alterazioni metaboliche indotte dalla terapia farmacologica. In quest’ultimo caso, la corretta diagnosi causale può talora sfuggire, giacché la composizione chimica dei calcoli è identica a quella osservabile in caso di litiasi idiopatica.

In questo articolo sono illustrate le caratteristiche cliniche e metaboliche essenziali delle tipologie più significative di nefrolitiasi farmaco-correlata, con alcuni riferimenti anche ai rari casi riportati di nefrolitiasi riconducibile a sostanze tossiche.

I calcoli contenenti i farmaci sono per lo più radiotrasparenti e rilevabili mediante ecografia oppure TC con mezzo di contrasto. La metodica più idonea a definirne la composizione chimica è la spettrofotometria a raggi infrarossi, applicabile sia sui calcoli espulsi, sia su depositi cristallini eventualmente riscontrabili in campioni bioptici renali.

Dal punto di vista terapeutico, la sospensione del farmaco e/o la sua sostituzione con altra molecola più solubile in ambiente urinario sono generalmente risolutive. Le misure di profilassi generale della calcolosi urinaria (idratazione e manipolazione del pH urine ove possibile), oltre a prevenire l’insorgenza della malattia nei casi a rischio, quando sia sospesa la terapia farmacologica possono contribuire alla progressiva dissoluzione dei cristalli presenti nel rene.

In alcuni casi, i precipitati cristallini possono indurre reazioni infiammatorie con reliquati fibrotici permanenti a livello del parenchima renale.

Parole chiave: nefrolitiasi, urolitiasi, nefrocalcinosi, farmaci.

In un’ottica di preservazione del danno acuto e cronico del graft, negli ultimi anni sta emergendo una nuova filosofia terapeutica per i pazienti affetti da trapianto renale che contempli l’utilizzo combinato di tutti i farmaci immunosoppressivi disponibili in commercio e la minimizzazione/sospensione degli inibitori della calcineurina. Lo scopo di questa nuova visione (immunosoppressione sostenibile) è quello di contrastare lo sviluppo di comorbidità ed evitare un drammatico impatto negativo sulla sopravvivenza dei pazienti nefro-trapiantati. L’utilizzo degli inibitori di mTOR e di nuovi agenti biologici (come Belatacept e il nuovissimo Iscalimab) potrebbe aiutarci a raggiungere questo obiettivo e superare il classico approccio alle cure “organo-centrico” verso quello “paziente-centrico”.

Gli inibitori della calcineurina (CNI) hanno rivoluzionato i risultati del trapianto d’organo e sono tuttora i farmaci immunosoppressori più usati nel trapianto. I CNI inibiscono un sistema di fosfatasi necessario per consentire la translocazione  nel nucleo di un fattore di trascrizione da cui dipende la sintesi di interleuchina-2. Questo passaggio è fondamentale per la successiva proliferazione e differenziazione delle cellule T. In questo articolo vengono brevemente riassunte le caratteristiche farmacocinetiche e farmacodinamiche di CNI, i loro  potenziali effetti collaterali renali ed extra-renali ed i risultati ottenuti con CNI nel trapianto renale. Per prevenire eventi avversi  le dosi di CNI  dovrebbero essere ridotte  in presenza di insufficienza renale o ipertensione severa, l’uso di farmaci nefrotossici dovrebbe essere evitato quando possibile, molta attenzione dovrebbe essere posta nell’usare   farmaci che interferiscono con l’attività del citocromo P450 o della glicoproteina P. Inoltre, non va fatto troppo affidamento ai livelli ematici di CNI, che non riflettono la concentrazione intracellulare, che è molto superiore e molto più importante  di quella plasmatica.

I due inibitori della calcineurina (CNI) attualmente in commercio sono ciclosporina (CsA) e tacrolimus (TAC). CsA è un polipeptide ciclico composto da circa 11 aminoacidi derivato dal fungo Tolypocladium inflatum gums. TAC è un antibiotico macrolide derivato dal fungo Streptomyces tsukubaensis. I due CNI hanno una struttura molecolare diversa, ma entrambi hanno simili caratteristiche farmacologiche ed un simile meccanismo d’azione consistente nell’inibizione della calcineurina intra-cellulare.

I due CNI originali sono stati sostituiti rispettivamente da una nuova microemulsione per la CsA  (Neoral) e da una formulazione che consente una mono-somministrazione giornaliera per il TAC (Adavagraf). Sono anche disponibili formulazioni generiche.

Steroid minimization has always been one of the most desired goals regarding immunosuppressive therapy after renal transplantation. Following the introduction of cyclosporine different steroid-free protocols became available, but their implementation was limited due to the high risk of acute rejection. In the last few years, the use of a very low dose of prednisone (5 mg/day) has been deemed to guarantee a good balance between steroid toxicity and efficacy. However, high interpatient variability in prednisolone exposure prevented the standard low dose to be as safe as expected in all patients. Therefore, steroid side effects can still be observed in a variable percentage of patients. In this setting, the personalization of steroid dosage might prevent an over exposure to the drug, but this strategy is not available yet. Thus, steroid withdrawal remains the only available strategy to limit side effects. In the last 40 years, we learned that steroid free protocols are associated with a higher risk of acute rejection, but they do not reduce graft survival. Hence, patients at higher risk for acute rejection or recurrence of their primary renal disease are usually excluded from these protocols. Early steroid withdrawal (within 7 days after transplantation) has been widely used and also suggested by American guidelines. However, steroid withdrawal 3-4 months after transplantation has been preferred by many Authors and deemed equally efficient. In addition, early but not late steroid withdrawal should always be associated to induction therapy. Lastly, Tacrolimus plus Mycophenolic Acid has become the most used association in steroid minimization protocols.

Le aree specifiche di trattamento farmacologico in dialisi peritoneale (DP) sono riassumibili in trattamento delle peritoniti e delle infezioni dell’exit-site e tunnel del catetere, la prevenzione del degrado sclerotico del peritoneo e la cura della peritonite sclerosante incapsulante.

La peritonite batterica è una comune complicanza della DP e il tasso di episodi viene considerato un indicatore di qualità. Tutti i programmi di DP hanno un protocollo terapeutico empirico che prevede gli antibiotici direttamente nel liquido peritoneale e l’utilizzo di almeno due antibiotici in associazione ad ampio spettro in attesa dei risultati delle colture. Vengono indicati: vancomicina o cefalosporine di prima generazione per i germi Gram positivi associate a cefalosporine di terza generazione o aminoglicosidi per i germi Gram negativi. Successivamente all’isolamento si procede con terapia mirata.

Le infezioni legate all’exit-site e al tunnel sottocutaneo del catetere peritoneale costituiscono un fattore di rischio di peritonite. La ricerca microbiologica tramite tampone e coltura deve essere mirata agli episodi di infezione con evidenza di secrezione. La terapia antibiotica empirica utilizza cefalosporine di prima generazione o penicilline protette per via orale. Il trattamento successivo è mirato. L’isolamento di stafilococco aureo e di pseudomonas aeruginosa richiede due antibiotici mirati in associazione e un trattamento di almeno tre settimane.

La sclerosi peritoneale semplice è un processo di fibrosi diffusa della membrana legato alla DP nel tempo. La prevenzione prevede l’utilizzo di soluzioni per DP biocompatibili, la riduzione dell’esposizione a elevate concentrazioni di glucosio e l’eliminazione dei betabloccanti, infine è opportuno valutare attentamente i pazienti con peritoniti ripetute e quelli con un tempo in DP lungo. Risulta dimostrato che inibire il SRAA contrasta la sclerosi per cui ACEI e ARB sono i farmaci antipertensivi di prima scelta nei pazienti in DP.

La peritonite sclerosante incapsulante (EPS) è una complicanza della DP molto rara ma temibile. Gli aspetti infiammatori e immunologici delle biopsie peritoneali supportano l’approccio immunosoppressivo con steroidi, ciclofosfamide e/o micofenolato. Importanti evidenze mostrano che il trattamento tamoxifene riserva una maggiore sopravvivenza indipendentemente da altri farmaci associati. Per l’EPS post-trapianto nei pazienti in DP vi sono evidenze che gli inibitori della calcineurina (ciclosporina e tacrolimus), svolgano un ruolo pro-fibrotico, per cui potrebbe essere indicato un protocollo immunosoppressivo personalizzato per il trapianto nei pazienti in DP basato su mTOR-I, steroidi e micofenolato.

Parole chiave: Dialisi peritoneale, trattamenti farmacologici, peritonite, infezione dell’exit-site, antibioticoterapia, sclerosi peritoneale semplice, peritonite sclerosante incapsulante.

La polifarmacologia dei pazienti in emodialisi è nota: da una indagine di prevalenza in ottobre 2019 nel nostro centro dialisi di Trieste si è osservato che su una popolazione di 154 emodializzati il numero dei farmaci assunti per os a domicilio era in media di 8,3 e che quelle infusi per via endovenosa in fine dialisi era di 2,2. Tra i farmaci più frequentemente utilizzati nei pazienti emodializzati erano gli antipertensivi (90%) gli inibitori di pompa (73%), gli antianginosi-antiaritmici (68%). Il 50% dei pazienti assumeva almeno tre farmaci per il controllo CKD – MBD. Solo il 7% della popolazione assumeva farmaci antalgici oppiacei per il controllo del dolore. Nel caso clinico 1 si descrive un paziente emodializzato affetto da cheratoacantoma recidivante trattato con metotrexate intralesionale con un evidente guarigione della lesione, ma che ha sviluppato una aplasia midollare. Nel caso clinico 2 si descrive un paziente emodializzato affetto da calcifilassi coinvolgente l’80% della superficie corporea che oltra alla terapia di supporto è stato trattato con Sodio Tiosolfato. L’effetto collaterale più grave del STS è l’ipotensione.

Investigators in the 1960s found that patients with poor kidney function were predisposed to various adverse drug reactions. Research demonstrated that impaired kidney function affects not only clearance but also absorption, distribution, metabolism and non-renal-clearance of drugs: these aspects represents the pharmacokinetic (PK) of drugs and the basic rules was written by Calvin Kunin and Luzius Dettli. To determinate the right dose of drugs doesn’t depend only by PK, but also by the pharmacodynamics (PD) that represents the effect that drug achieve; the therapeutically effective range of a drug depends on its Hill coefficient. To provide precision in pharmacotherapy, near PK and PD, there is pharmacogenomics that tests for genetic variation in genes that are responsible for drug metabolism, transport and target of drug action and can be used to select the best medication or aid in dosing. To better study the drug toxicity, the PK and physiology of kidney, there are novel technology in the field of engineering which provides new options like kidney-on-a-chip that mimic organ level functions and disease to replace some traditional animal and human studies.

L’onconefrologia è una recente disciplina sorta in campo nefrologico e oncologico, volta ad esplorare le numerose connessioni tra patologie neoplastiche e renali. Tra i numerosi campi di applicazione dell’onconefrologia, un ruolo significativo è ricoperto dalla gestione degli eventi avversi in corso di terapia antineoplastica attraverso una analisi individualizzata dei fattori di rischio del paziente, delle caratteristiche dei farmaci oncologici prescritti e l’instaurazione di un preciso follow-up che spesso prosegue anche al termine del trattamento oncologico. Lo scopo di questa revisione è, oltre che descrivere i fattori di rischio per la nefrotossicità da farmaci antitumorali, analizzare le principali criticità onco-nefrologiche legate alle specifiche classi di farmaci. I chemioterapici classici presentano un profilo variabile di tossicità renale, per la maggior parte dei casi ben definito, che consente di mettere in campo delle collaudate strategie terapeutiche per la gestione degli eventi avversi renali. Le terapie a bersaglio molecolare e i farmaci immunoterapici nonostante abbiano dimostrato di migliorare significativamente la prognosi a breve e lungo termine in numerose neoplasie presentano un ampio profilo di tossicità renale ancora in fase di definizione. La costante analisi dei report relativi alle specifiche molecole, associata ad un a condotta proattiva per la definizione istologica delle lesioni renali in questo contesto clinico, è la chiave per completare rapidamente la definizione del profilo di sicurezza ampliando contestualmente la platea dei pazienti che potranno beneficiare  dei nuovi farmaci antineoplastici.

Parole chiave: Danno renale acuto, AKI, cisplatino, gemcitabina, anti-VEGF, immunoterapia, bevacizumab

Antibiotics are a relatively common cause of acute kidney injury that occurs mainly in patients with underlying risk factors. Adverse reactions from antibiotics can be classified as type A when they are foreseeable, we know the cause and are often dose dependent and type B when they occur in an unpredictable way, are independent of the dose and due to hypersensitivity and / or immunoallergic phenomena. All compartments of the kidney are prone to antibiotic damage which, clinically, results in tubular dysfunction, acute renal failure, nephritic syndrome and chronic renal failure. The drugs most responsible are vancomycin, aminoglycosides and beta lactamines. The occurrence of acute renal failure correlates with the length of hospitalization and the risk of death. It therefore becomes of fundamental clinical importance to know the antibiotics with potential nephrotoxic effect in order to establish the dosage on the basis of renal function and correct all the factors that can enhance their toxicity.

Keywords: nephrotoxicity, direct antibiotics-related renal toxicity , antibiotics, adverse drug reactions

I farmaci antiinfiammatori non steroidei (FANS) rappresentano una delle classi di farmaci maggiormente prescritta ed utilizzata a livello globale, con milioni di somministrazioni quotidiane, e con un mercato mondiale in ulteriore espansione.

La situazione italiana, invece, appare in controtendenza, come dimostrato dai report annuali dell’Agenzia del Farmaco (AIFA), con un lento progressivo decremento sia della prescrizione che dell’utilizzo complessivo includendo quello da automedicazione (over-the-counter). Sebbene la prescrizione ed il consumo di FANS in Italia riconosca differenze evidenti tra le regioni settentrionali e quelle meridionali, si conferma comunque la progressiva contrazione annuale del mercato.

Nonostante siano ben conosciuti gli effetti collaterali e tossici di questa classe di farmaci a carico di diversi organi ed apparati, le segnalazioni di eventi avversi (AEs) renali risultano minimali nei registri AIFA se rapportate agli effetti collaterali su altri organi ed apparati. La sottostima degli eventi avversi renali risulta ancora più evidente se si considera che nella popolazione geriatrica italiana, generalmente sottoposta a multiterapia farmacologica (in media 6.7 sostanze pro-capite), i FANS rappresentano il 32% delle prescrizioni risultando la quarta classe di farmaci più prescritta dopo antiulcera, antitrombotici e ipolipemizzanti.

Nella review sono elencate in sintesi le principali complicanze (alterazioni funzionali o comparsa di danno istologicamente definito) renali da FANS, le condizioni favorenti indispensabili per il determinismo del danno e cenni sui possibili meccanismi patogenetici.

Resta però evidente, pur a fronte di una sicura e non meglio quantificabile sottostima degli eventi avversi , che la loro frequenza sia abbastanza contenuta nella popolazione generale aumentando discretamente in quella a rischio.

La conoscenza dei meccanismi farmacologici e delle condizioni cliniche coinvolte nella genesi degli eventi avversi renali associati ai FANS, nonché l’epidemiologia e la frequenza delle complicanze, possono certamente contribuire alla acquisizione di una appropriatezza prescrittiva in equilibrio tra demonizzazioni semplicistiche e sottovalutazioni colpevoli. La accuratezza della diagnosi sulla causa del dolore risulta quindi prioritaria per la scelta terapeutica ragionata sul bilancio rischio-beneficio.

Al nefrologo esperto compete quindi  la responsabile (in)formazione sull’approccio non semplicistico e fai-da-te della terapia antalgica nei soggetti anziani ad alto rischio renale.

Here we present a case of acute renal failure needing dialysis in a heroin addict patient chronically treated with Metadone.  This give us the opportunity to review the renal effects of the main drugs of abuse, highlighting the shift occured from the four “old sisters” (Marijuana, Cocaine, Heroin and Amphetamine) to the news synthetic drugs (chiefly  Synthetic  Cathinones and Cannabinoids), that poses problems due to  large diffusion, easy  procurement, legal  non-regulation and difficult analytical identification,  raising medical and forensic questions. From a Nephrological point of view is essential to take great care over the need to diagnose this kind of pathology and to widen the search trying anyway to recognize the substances potentially involved.

Key Words: Acute Kidney Injury; Acute renal failure; Illicit drugs; Rhabdomyolysis.

Traditional medicine is a widespread treatment method in the world. Despite the WHO’s confirmation of the progressive spread of national policies responsible for controlling the production and distribution of phytotherapy, the risk of toxic side effects is high even if the real incidence is not known. These risks largely result from the self-prescription supported by the assumption that what is natural is not dangerous to health. The phytotherapic industry turnover is progressively increasing, favored by the ease with which products can be purchased without prescription in pharmacies in some countries or online.

In particular, Chinese herbs can be nephrotoxic and clinicians should consider the possibility of their role in some cases of AKI or CKD with unknown etiology. Furthermore, in the collection of the pharmacological history of patients with CKD or kidney transplantation it is necessary to exclude the use of some phytotherapics of common use that may be contraindicated for possible interactions with drugs of conventional medicine.

Keywords: Traditional Medicine, Phytotherapy, Chinese herbs, Aristolochic acid, nephrotoxicity.

In biochimica i Metalli Pesanti  (MP) vengono definiti come composti cationici in grado di formare dei complessi citoplasmatici intracellulari: in tal classificazione rientrano sia gli elementi in traccia come Arsenico, cobalto, ferro e iodio ma anche i MP propriamente detti che sono tossici anche a basse concentrazioni come cadmio, mercurio, cromo e piombo.

Sono oltre 30 i composti metallici in grado di causare danno renale; i MP più comunemente coinvolti nelle patologie renali sono arsenico, bario, cadmio, cobalto, rame, piombo, litio, mercurio platino, tallio; la loro tossicità dipende da fattori fisici (stato fisico, temperatura), da fattori chimici (solubilità e cinetica) ma anche da fattori biochimici come il tropismo per le catene mitocondriali umane.

Il rene è un organo bersaglio per i MP, a causa della sua abilità nello riassorbire e concentrare i metalli divalenti; gran parte degli effetti si esplicano a livello del segmento convoluto del tubulo prossimale. La forma ionizzata del MP è responsabile di tossicità cellulare diretta verso la membrana apicale del tubulo prossimale; la forma non ionizzata o inerte del MP viene coniugata con metallotioneine e glutatione, rilasciata nel sangue dal fegato e infine riassorbita  per endocitosi nel semento S1 del tubulo prossimale.
L’entità e la modalità del danno renale dipende dal tipo di metallo, dalla dose e dal tempo di esposizione.

L’approccio terapeutico in presenza di una intossicazione acuta da metalli pesanti prevede misure di supporto (fluidi e.v, supporto inotropo, ventilatorio, emotrasfusioni), la decontaminazione (lavanda gastrica, emetici, carbone attivo), le metodiche depurative extracorporee (quando indicate) e ovviamente la terapia chelante.

Si stima che siano circa 70.000 le persone alle quali, ogni anno in Italia, viene diagnosticata una nefropatia direttamente o indirettamente causata dall’inquinamento ambientale di aria, acqua e suolo. In aggiunta a descrivere alcuni aspetti epidemiologici delle nefropatie in Italia, vengono qui  prese in esame le evidenze prodotte in tema di  inquinamento e malattie renali dovute alla presenza di sostanze nefrotossiche disperse negli ambienti di vita quotidiana.

Arterious-venous fistula (AVF) represents the first-choice vascular access for haemodialysis. Pre-surgery evaluation is mandatory to identify the appropriate vessels and to predict the success of AVF creation. Echo-color Doppler provides a wealth of morphological and functional values useful to create an optimal vascular access for haemodialysis. The purpose of this study has been to identify pre-surgery echo-color Doppler parameters useful to predict AVF maturation. 44 patients were enrolled, and 44 AVF created. During pre-surgery evaluation we collected the following data: cephalic vein and radial artery calibers; radial artery flow and caliber; flow and resistive index (RI) of the brachial artery. We also performed a reactive hyperemia test. During the post-surgery evaluation after 30 days, we collected: AVF flow; resistive index of the brachial artery; post-anastomosis cephalic vein caliber. The results showed a direct correlation between AVF flow and some parameters: cephalic vein, radial artery and brachial artery caliber, reduction of RI after reactive hyperemia test and, in the post-surgery evaluation, between AVF flow and post-anastomosis cephalic vein caliber. We divided patients into two groups: “A”, representative of AVF adequate maturation, and “B”, representative of AVF early failure (EF) and AVF failure to mature (FTM). We observed some statistically significant differences in the two groups. With the creation of Receiver Operating Characteristic (ROC) curves we identified two parameters able to predict the AVF outcome (Δ IR = 0.15; Δ flow = 150 ml/m). This study identifies pre-surgery echo-color Doppler parameters that could be useful, together with others, to predict the outcome of the AVF creation.

Keywords: echo-color Doppler, arterious-venous fistula, resistive index, fistula flow, reactive hyperemia

C3 Glomerulonephritis (C3GN) is a rare disease with an estimated incidence of 1-2 cases per million, caused by an alteration in the alternative complement pathway, although its complete physiopathology remains uncertain. Treatment evidence is poor. Immunosuppressive therapy can be initiated in more severe cases. Progression rates to end stage kidney disease are of up to 50% within a decade, and the posttransplant recurrence rates of 45-60%. We describe the case of a young man without any past medical history, with lower extremities edema, dyspnea, and kidney function deterioration. The patient was ultimately diagnosed with C3GN.

Key words: C3 glomerulopathy, glomerulonephritis, alternative complement pathway

Lithium is the milestone of psychiatric patients’ therapy, in particular in bipolar disorder. Despite its high therapeutic efficacy, there are several side effects (renal, thyroid, parathyroid, dermatological) and management problems linked to its narrow therapeutic range, which exposes patients to a high risk of toxicity.

We describe the case of a male patient with bipolar disorder in therapy with lithium sulfate who developed a severe acute-on-chronic intoxication. He came to our attention in a somnolent state with lithemia >3 mEq/L and therefore underwent hemodialysis.

In view of the high toxicity of lithium, a timely and correct therapeutic choice is important to improve the patient’s outcome. In this context, considering lithemia, but also kidney function and the patient’s clinical status, it is necessary to consider extracorporeal treatments, of which hemodialysis is the most preferable.

Keywords: lithium, poisoning, dialysis, bipolar disorder

Acute flaccid paralysis is a medical emergency that may be caused by primary neuro-muscular disorders, metabolic alterations, and iatrogenic effects. Severe hyperkalemia is also a potential cause, especially in elderly patients with impaired renal function. Early diagnosis is essential for appropriate management.

Here, we report the case of a 78-year-old woman with hypertension and diabetes presenting to the emergency department because of pronounced asthenia, rapidly evolving in quadriparesis. Laboratory examinations showed severe hyperkalemia of 9.9 mmol/L, metabolic acidosis, kidney failure (creatinine 1.6 mg/dl), and hyperglycemia (501 mg/dl). The electrocardiography showed absent P-wave, widening QRS, and tall T-waves. The patient was immediately treated with medical therapy and a hemodialysis session, presenting a rapid resolution of electrocardiographic and neurological abnormalities. This case offers the opportunity to discuss the pathogenesis, the clinical presentation, and the management of hyperkalemia-induced acute flaccid paralysis.

Keywords: hyperkalemia, acute flaccid paralysis, hemodialysis, diabetes

Multiple myeloma represents one of the main universal oncological diseases. Due to its clinical characteristics, it is often diagnosed only too late, when it has already determined systemic effects; this results in greater therapeutic difficulty and worse prognostic results. Through the clinical case discussed in this article, we want to focus on the often aspecific manifestations of this pathology and on the need for a correct clinical and diagnostic framework. The main renal manifestations secondary to the deposition of immunoglobulins in both the glomerular and tubular areas will also be examined.

Keywords: AKI, multiple myeloma, plasma cell dyscrasias, kidney injury

Iron deficiency afflicts about 60% of dialysis patients and about 30% of non-dialysis-dependent CKD patients (ND-CKD). The role of iron deficiency in determining anemia in CKD patients is so relevant that guidelines from the Kidney Disease Improving Global Outcomes (KDIGO) initiative recommend treating it before starting with erythropoiesis-stimulating agents. KDIGO guidelines suggest oral iron therapy because it is commonly available and inexpensive, although it is often characterized by low bioavailability and low compliance due to adverse effects.

A new-generation oral iron therapy is now available and seems to be promising. We therefore conducted a study to determine whether an association of iron sucrose, folic acid and vitamins C, B6, B12, can improve anemia in ND-CKD patients, stage 3-5. Our study shows that iron sucrose is a safe and effective oral iron therapy and that it is capable of correcting anemia in ND-CKD patients, although it does not seem to replete low iron stores.

Keywords: iron deficiency, chronic kidney disease, CKD, anemia, oral iron

Despite the many potential benefits of peritoneal dialysis (PD), the percentage of dialysis patients treated with PD is around 10% worldwide. Up to 70% of the subjects who progress to end-stage renal disease (ESRD) start dialysis without a well-defined therapy plan. Most of these patients are unaware of having chronic kidney disease, while others with stable CKD incur in unpredictable and acute worsening of kidney function.

As a matter of fact, 80% of incident HD patients start dialysis with a central venous catheter (CVC) even though starting HD with a CVC is independently associated with increased mortality, high rates of bacteremia, and increased hospitalization rates. Thus, PD is an excellent but underused mode of dialysis. Offering it to patients who present late to dialysis therapy, due to uremic state or hypervolemia, may help increase its application in the future.

This approach has been recently denominated “urgent-start peritoneal dialysis” (UPD). Based on the break-in period, it is possible to differentiate UPD from “early-start peritoneal dialysis” (EPD). The outcome of UPD depends on the right selection of patients, the appropriate placement of the catheter and the adequate education of the nursing and medical staff. Moreover, using modified catheter insertion technique aimed at creating a tight seal between the inner cuff and the abdominal tissues, as well as employing protocols that use low-volume exchanges in a supine posture, could minimize the occurrence of early mechanical complications.

Although the probability of mechanical complications is higher in early-start PD patients, UPD/EPD show a mortality rate, a PD survival and an infectious complication rate comparable with conventional PD. In comparison to urgent-start hemodialysis via a CVC, UPD can be a safe and cost-effective alternative that decreases the incidences of catheter-related bloodstream infections and hemodialysis-related complications. Furthermore, UPD can promote the diffusion of PD.

Keywords: peritoneal dialysis, urgent-start, early-start, leakage, displacement, low-volume

Primary hyperoxaluria type 1 is a rare genetic disease; the onset of symptoms ranges from childhood to the sixth decade of life and the disease may go unrecognized for several years. There is an urgent need for drugs able to inhibit the liver production of oxalate and to prevent the disease progression; lumasiran, an innovative molecule based on RNAi interference, is one of the most promising drugs. A group of leading Italian experts on this disease met to respond to some unmet medical needs (early diagnosis, availability of genetic tests and dosage of plasma oxalate, timing of liver transplantation, need for etiologic treatment), based on the analysis of the main scientific evidence and their personal experience. Children showing the characteristic symptoms of the disease usually undergo a metabolic screening and obtain an early diagnosis, while the experience is very limited in adults and the diagnosis difficult. It is therefore essential to increase the knowledge around this disease and the importance of metabolic and genetic screening to define a checklist of shared clinical and laboratory criteria and to establish a multidisciplinary management of potential patients. Oxalate is the cause of the disease: it is crucial to reduce both oxaluria and oxalemia through appropriate therapeutic strategies, able to prevent and/or reduce renal and systemic complications of primary type 1 hyperoxaluria. Lumasiran allows to significantly reduce the levels of oxalate both in blood and in urine, halting the course of the disease and preventing serious renal and systemic complications, if the therapy is started at an early stage of the disease.

Keywords: primary hyperoxaluria type 1, hyperoxalemia, hyperoxaluria, lumasiran

The public emergency caused by Covid-19 has forced health services to reorganize in order to separate positive patients from negative ones. In nephrology, this reorganization involves several levels of assistance concerning hospitalizations, ambulatory care and haemodialysis.

Within the Complex Unit of Nephrology in Ragusa, the distribution of nephro-dialytic resources has involved four different hospitals, hence ensuring haemodialysis services for asymptomatic and pauci-symptomatic Covid-19 patients as well as for patients in Covid-Unit, Sub-Intensive Therapy and Intensive Care Unit. In this complex context, we had to create a common protocol involving all the professionals who provide assistance in our Unit, across the different structures.

We also report some encouraging data that seem to indicate the effectiveness of the protocols put in place.

Keywords: Covid-19, Nephrology, devices for individual protection, management of the renal patient, dedicated paths

The new coronavirus disease (Covid-19) pandemic in Italy formally started on 21^st February 2020, when a 38-years old man was established as the first Italian citizen with Covid-19 in Codogno, Lombardy region. In a few days, the deadly coronavirus swept beyond expectations across the city of Bergamo and its province, claiming thousands of lives and putting the hospital in Treviglio under considerable strain.

Since designated Covid-dialysis hospitals to centrally manage infected hemodialysis patients were not set up in the epidemic areas, we arranged to treat all our patients. We describe the multiple strategies we had to implement fast to prevent/control Covid-19 infection and spread resources in our Dialysis Unit during the first surge of the pandemic in one of the worst-hit areas in Italy. The recommendations provided by existing guidelines and colleagues with significant experience in dealing with Covid-19 were combined with the practical judgement of our dialysis clinicians, nurses and nurse’s aides.

KEYWORDS: COVID-19, hemodialysis, end-stage kidney disease, coronavirus, pandemic.

The SARS-CoV-2 (Covid-19) has infected about 124 million people worldwide and the total amount of casualties now sits at a staggering 2.7 million. One enigmatic aspect of this disease is the protean nature of the clinical manifestations, ranging from total absence of symptoms to extremely severe cases with multiorgan failure and death.

Chronic Kidney Disease (CKD) has emerged as the primary risk factor in the most severe patients, apart from age. Kidney disease and acute kidney injury have been correlated with a higher risk of death. Notably the Italian Society of Nephrology have reported a 10-fold increase in mortality in patients undergoing dialysis compared to the rest of the population, especially during the second phase of the pandemic (26% vs 2.4). These dramatic numbers require an immediate response.

At the moment of writing, three Covid-19 vaccines are being administered already , two of which, Pfizer-BioNTech and Moderna,  share the same mrna mechanism and Vaxzevria (AstraZeneca) based on a more traditional approach.  All of them are completely safe and reliable. The AIFA scientific commission has suggested that the mRNA vaccines should be administered to older and more fragile patients, while the Vaxzevria (AstraZeneca) vaccine should be reserved for younger subjects above the age of 18. The near future looks bright: there are tens of other vaccines undergoing clinical and preclinical validation, whose preliminary results look promising.

The high mortality of CKD and dialysis patients contracting Covid-19 should mandate top priority for their vaccination.

Keywords: SARS-CoV-2 (Covid-19), chronic kidney disease, vaccine

Hyperphosphoremia is common in patients with chronic kidney disease and is an important risk factor in this patient population. Phosphate binding drugs are a key therapeutic strategy to reduce phosphoremia levels, although they have significant side effects especially in the gastrointestinal tract, such as gastritis, diarrhoea and constipation. We report the case of a haemodialysis-dependent patient suffering from chronic kidney disease stage V KDIGO secondary to polycystic autosomal dominant disease; treated with phosphate binders, the case was complicated by the appearance of diverticulosis, evolved into acute diverticulitis.

Keywords: hyperphosphoremia, phosphate binding drugs, chronic kidney disease, polycystic autosomal dominant disease, diverticulosis, acute diverticulitis

This article retraces the nephrological life of Giovanni Barbiano di Belgiojoso, which started in the late 1960s. Since the beginning renal pathology was his main interest and he was among the pioneers who introduced in Italy the use of immunofluorescence technique in the examination of renal biopsies. Over the years Barbiano di Belgiojoso has carried out, often in cooperation with other nephrological groups, many clinico-pathological studies on a wide spectrum of glomerular diseases. He also played a key role in the foundation and in the activities of the “Group of Renal Immunopathology” of the Italian Society of Nephrology.

Keywords: history of nephrology, history of Italian nephrology, history of renal pathology

Waldenström’s disease is a rare haematological neoplasm involving B lymphocytes, characterized by medullary infiltrated lymphoplasmacytic lymphoma and by the presence of a monoclonal M paraprotein. Although rarely, this condition may lead to heterogeneous renal involvement and cause severe renal failure.

We report the clinical case of a patient with overt nephrotic syndrome in Waldenström’s disease treated with a combination chemotherapy (rituximab, cyclophosphamide, dexamethasone) until complete renal and haematological remission.

Keywords: Waldenström’s disease, nephrotic syndrome, rituximab, cyclophosphamide, dexamethasone

Background: Living donor kidney transplantation (LDKT) is the treatment of choice for end stage renal disease. LDKT involves complex psychosocial issues, which remain partially unexplored.
Methods: The study involved all potential living donors and recipient pairs consecutively referred for psychosocial evaluation from the nephrologist. Clinical and sociodemographic variables including prior psychiatric history, previous and current use of psychopharmacological therapy, motivation and information about the transplant procedure were collected. Study participants completed the Symptom Checklist-90-R (SCL-90-R) to assess psychopathological distress.
Results: Fifty-three donor/recipient pairs underwent psychiatric and psychological evaluation. Seven subjects (13%) in the recipient group and 13 subjects (25%) in the donor group reported a history of psychological distress and/or psychiatric conditions. A psychiatric diagnosis was confirmed in 4 recipients (7.5% of the study sample, including autism spectrum disorder, histrionic personality disorder, and anxiety-depressive disorders) and 5 donors (9%, including narcissistic personality disorder in one case and anxiety-depressive disorders). SCL-90-R GSI mean scores were 0.3 ±0.3 and 0.2 ±0.2 for the recipient and donor groups, respectively. Overall, 8 couples (15%) suspended the living donation pathway before transplantation. Four couples were excluded for a new onset medical condition. The psychological and psychiatric evaluation excluded one candidate. One couple dropped out before completing the scheduled exams. One recipient refused to undergo crossover renal transplantation, while 1 donor candidate withdrew her consent for transplantation at the end of the evaluation process.
Conclusions: Limited but significant psychopathological distress in donors and recipients supports the usefulness of psychiatric and psychological competencies within the transplant team.

Keywords: living donor kidney transplantation, psychiatric disorders, psychological distress

Despite being recommended by most guidelines, the metabolic evaluation of patients with nephrolithiasis has limited diffusion due to difficulties relating both to the access to laboratory investigations and to urine collection modalities. Consequently, in addition to the classical 24-h collection, alternative and simplified collection modes have been proposed. We report here on the comparison between metabolic evaluation carried out on 24-h double collection (Lithotest) and overnight spot urines (RF test). Fifty-four patients with stone disease were enrolled, excluding patients with infection or cystine stones. For Lithotest, we measured all analytes necessary to calculate state of saturation (ß) with calcium oxalate, brushite and uric acid, by means of Lithorisk.com. For RF, we measured calcium, magnesium, oxalate, citrate, sulphate, phosphate, pH and creatinine. The comparison was made with creatinine ratios. An estimate of ßCaOx, ßbrushite and ßAU was obtained also on RF urines by using simplified algorithms. We found highly significant correlations between all parameters, despite quite different means. There was a nice correspondence between the two sets of measurements, assessed by the Bland-Altmann test, for calcium, oxalate, citrate, sulphate, urate and pH. Overnight urine had higher saturations compared to 24-h one owing to higher concentration of the former. In conclusion, RF test on overnight urine cannot completely replace Lithotest on 24-hr urine. However, it can represent a simplified tool for either preliminary evaluation or follow-up of patients with stone disease.

Keywords: metabolic evaluation, state of saturation, 24-h urine, spot urine, calcium nephrolithiasis, uric acid nephrolithiasis

Introduction and aims: Stages 4 and 5 of chronic kidney disease (CKD) have always been considered hard to modify in their speed and evolution. We retrospectively evaluated our CKD stage 5 patients (from 01/1/2016 to 12/31/2018), with a view to analyzing their kidney function evolution.

Material and Methods: We included only patients with longer than 6 months follow-up and at least 4 clinical-laboratory controls that included measured Creatinine Clearance (ClCr) and estimated GFR with CKD-EPI (eGFR). We evaluated: the agreement between ClCr and eGFR through Bland-Altman analysis; progression rate, classified as fast (eGFR loss >5ml/min/year), slow (eGFR loss 1-5 ml/min/year) and non-progressive (eGFR loss <1 ml/min/year or eGFR increase). We also evaluated which clinical-laboratory parameters (diabetes, blood pressure control, use of ACEi/ARBs, ischemic myocardiopathy, peripheral obliterant arteriopathy (POA), proteinuria, hemoglobin, uric acid, PTH, phosphorus) were associated to the different eGFR progression classes by means of bivariate regression and multinomial multiple regression model. Results: Measured CrCl and eGFR where often in agreement, especially for GFR values <12ml/min. The average slope of eGFR was -3.05 ±3.68 ml/min/1.73 m²/year. The progression of kidney function was fast in 17% of the patients, slow in 57.6%, non-progressive in 25.4%. At the bivariate analysis, a fast progression was associated with poor blood pressure control (p=0.038) and ACEi/ARBs use (p=0.043). In the multivariable model, only peripheral obliterative arteriopathy proved associated to an increased risk of fast progression of eGFR (relative risk ratio=5.97).

Discussion: Less than one fifth of our patients presented a fast GFR loss (>5 ml/min/year). The vast majority showed a slow progression, stabilisation or even an improvement. Despite the limits due to the small sample size, the data has encouraged us not to consider CKD stage 5 as an inexorable and short journey towards artificial replacement therapy.

Keywords: chronic kidney disease, CKD, disease progression, glomerular filtrate, chronic renal failure

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are rare autoimmune diseases characterised by medium and small vessels inflammation. Renal vasculitic involvement is one of the most severe manifestations, with high mortality in case of a delayed diagnosis and a significant impact on patients’ long-term prognosis. Histological classifications and scores for the definition of renal involvement in AAV exist and correlate with the renal outcome. Current induction regimen consists of a high dose of glucocorticoids and immunosuppressive drugs: cyclophosphamide (CYC), rituximab (RTX) or a combination of both. RTX use is expanding thanks to randomised control trials suggesting its non-inferiority compared to the standard CYC therapy in general AAV and a better safety profile; its cost has also reduced thanks to the availability of biosimilars. However, the equivalence of RTX and CYC in patients with severe renal involvement is still debated.

The quest for the ideal induction regimen in AAV is moving towards a more personalized approach: on the one hand, efforts are made to use already existing therapies in the most appropriate way; on the other, new insights into AAV pathogenesis has allowed the discovery of new targets, such as the complement factor C5a.

Thanks to this new AAV management, renal outcome and overall survival has visibly improved. New studies are needed to reach a more personalized approach in the induction regimen of ANCA-associated glomerulonephritis and AAV in general.

Keywords: ANCA, vasculitis, glomerulonephritis, rituximab, cyclophosphamide, renal biopsy

Infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy with peritoneal dialysis (PD). Despite great efforts in the prevention and treatment of infective complications over the two past decades, catheter-related infections represent the most relevant cause of technical failure. Recent studies support the idea that exit-site/tunnel infections (ESI/TI) have a direct role in causing peritonitis. Since the episodes of peritonitis secondary to TI lead to catheter loss in up to 86% of cases, it is advised to remove the catheter when the ESI/TI does not respond to medical therapy. This approach necessarily entails the interruption of PD and, after the placement of a central venous catheter, the shift to haemodialysis (HD). In order to avoid the change of dialytic method, the simultaneous removal and replacement (SCR) of the PD catheter has also been proposed. Although SCR avoids temporary HD, it requires the removal/reinsertion of the catheter and the immediate initiation of PD, with the risk of mechanical complications such as leakage and malfunction. Several mini-invasive surgical techniques have been employed as rescue procedures: curettage, cuff-shaving, the partial reimplantation of the catheter and the removal of the superficial cuff with the creation of a new exit-site. These procedures allow to save the catheter and have a success rate of 70-100%. Therefore, in case of ESI/TI refractory to antibiotic therapy, a mini-invasive surgical revision must always be considered before removing the catheter.

Keywords: peritoneal dialysis, exit-site infection, tunnel infection, peritonitis, cuff-shaving, ultrasounds.

Currently, CEUS (Contrast-Enhanced UltraSound) is used in the evaluation of different organs and systems. It offers valuable information about vascular disease, both on a macro- and a micro-vascular level, and has a series of well-established applications in the monitoring of adult patients; official guidelines and recommendations are also available. Its use in a nephrological setting is constantly growing thanks to the lack of nephrotoxicity of the contrast agent, the absence of ionizing radiation and the possibility of characterizing focal pathologies, for diagnosis and in clinical practice. We describe here 3 clinical cases relating to renal diseases and we review the relevant literature with a specific focus on the use of CEUS in a nephro-urological setting.

Keywords: Contrast-enhanced ultrasound, CEUS, contrast agents, imaging, microbubbles

The author singled out the first decade of the 20th century as the time in which the renewal of academic medicine in post-unification Italy was concluded, while the changes that would be induced by the following war had not yet started. A bibliographic research relating to this period was undertaken with the aim of investigating the number and the quality of the studies on kidneys published by Italian scientists. A total of 176 publications of Italian scientists dealing with kidney diseases or physiology was retrieved, 10.8% of which was published on foreign journals. The analysis of the topics treated shows that they were up to date and comparable with the contemporary studies across Europe. Moreover, the issues raised remained of interest throughout the following decades up to our day. Top Italian researchers were fairly cited, especially if they published on international journals. While at the time the state of other organs was mainly assessed by examining physical signs and symptoms, kidney studies required laboratory facilities. This limitation meant that kidney scholars usually belonged to well established medical faculties. From these schools, a few figures stood out among the others for the importance of their studies, both physiological and clinical in nature. The same figures also gave birth to the major Italian schools of internal medicine from which, half a century later, originated the Italian Society of Nephrology. The findings of this research support the conclusion that the basis of modern nephrology can be traced back to that decade.

Keywords: nephrology, history, Italy, clinical schools.

This article collects the personal stories of the young doctors who in the early sixties contributed to the birth and development of the Croff pavilion at the Policlinico Hospital in Milan. Inaugurated on October 19, 1964, this has been the first institute in Italy entirely devoted to patients with kidney diseases. Since its inception, it has significantly contributed to the progress of nephrology thanks to important and pioneering investigations in the main fields of our specialty, which still continue nowadays. The different stories reported here follow the chronological order in which the young doctors arrived at Croff, each story representing a personal narrative that interweaves and integrates that of others. This gives rise to a vivid many-voiced account, from which emerge not only the figures of these young doctors, but also those of patients, nurses, and laboratory technicians.

Keywords: history of nephrology, history of Italian nephrology, history of dialysis, history of kidney transplant, history of renal histopathology

Background: Distal arterio-venous fistula (AVF) is considered the gold standard for vascular access in hemodialysis. The aim of this retrospective study is to report our experience on two innovative techniques, Intraoperative Transluminal Angioplasty (ITA) and Vessel Pre-Dilatation (VPD).
Methods: We collected data from all the consecutive patients directly admitted to our Department from January 2014 to October 2018 in order to create or repair an AVF. Early Failure (EF), Failure to Mature (FTM), Late Failure (LF), Primary and Secondary patency rate were evaluated.
Results: All patients underwent VPD; of the total 647 AFVs, 128 received an ITA for the presence of suboptimal vessels. 98.3% of AVFs were located on the forearm. EF occurred in 83 cases; in 67 of these a new AVF was successfully created upstream from the previous one. LF occurred in 100 cases; of these, the access was abandoned in 32 cases and we performed a new AVF upstream from the previous one in 68 cases. FTM occurred in 57 cases, 31 of which were treated with Percutaneous Transluminal Angioplasty (PTA) whilst 26 were resolved performing a new anastomosis upstream. Primary and secondary patency at 1, 2, 3 and 4 years were, respectively, 80%, 74%, 68%, 64% and 94%, 91%, 89%, 88%. By dividing patients into an ITA group and a control group, we did not find any difference in primary and secondary patency.
Conclusions: VPD and ITA could be useful to increase the incidence and the prevalence of distal AVF.

Keywords: intraoperative transluminal angioplasty, vessel pre-dilatation, distal arterio-venous fistula, early failure, failure to mature, late failure, patency

In the last decades there have been important changes in the epidemiology and natural history of bacterial infection-related glomerulonephritides. Once defined as an infancy-onset acute nephritic syndrome following a streptococcal infection, and characterized by a relative benign course, infection-related glomerulonephritis nowadays also affects the adult population, particularly the elderly and the chronically ill. The infectious agents and infection sites have become more diversified, and the prognosis is burdened by a higher rate of mortality, chronic kidney disease, end-stage renal disease and acute overload complications.

In this review we highlight the main clinical features of infection-related glomerulonephritis, offering an insight into its pathogenesis and the elements that allow an appropriate differential diagnosis. We also address the uncertainties around the role of immunosuppression in its therapeutic management.

Keywords: glomerulonephritis, infection, nephrotic syndrome, Staphylococcus.

Chronic kidney disease is associated with an increased cardiovascular risk. Several uremic toxins are also vascular toxins and may contribute to the increase of the cardiovascular risk through the development of aortic stiffening. In this process, oxidative stress and endothelial dysfunction play an important role. Considering that aortic stiffness is a known cardiovascular risk factor and a vascular biomarker involved in the development of chronic cardiac dysfunction, and that the reduction of aortic stiffness is associated with an improved survival of patients with end-stage kidney disease, we aim at reviewing the therapeutic options to reduce aortic stiffness and potentially the cardiovascular risk.

Keywords: arterial stiffness, cardiorenal syndrome, chronic kidney disease, inflammation, intima-media thickness, uremic toxins

The recent application of proteomics and metabolomics to clinical medicine has demonstrated their potential role in complementing genomics for a better understanding of diseases’ patho-physiology. These technologies offer the clear opportunity to identify risk factors, disease-specific or stage-specific biomarkers and to predict therapeutic response. This article is an overview of the recent insights obtained by metabolomic and proteomic studies in inherited kidney disorders. Proteomics studies have allowed the definition of a detailed picture of protein composition, post-translational modifications and interactions in kidney-derived samples, improving our understanding of renal physiology, especially of tubular transport and primary cilium-related functions. Studies on patients’ urine samples and experimental models of inherited kidney diseases have provided clues suggesting novel potential pathological mechanisms and biomarkers of disease, for example in polycystic kidney disease. Metabolomic-based studies have been recently applied to assess biological system disturbances caused by specific genetic mutations resulting in inherited kidney disorders. These studies have been mainly carried out on mouse and rat models of cystic and metabolic disorders (such as Fabry disease), and on patients’ urine samples. They have provided a significant contribution in understanding disease pathophysiology, promoting the discovery of aberrant biochemical pathways and contributing to the development of targeted therapies.

Keywords: proteomics, metabolomics, inherited kidney disorders, ciliopathies, tubulopathies, Fabry disease

Our Nephrology and Dialysis Unit includes three Haemodialysis Centres based in Savona, Albenga and Cairo Montenotte. These provide assistance to 150 patients. We have a Peritoneal Dialysis Clinic with 35 patients, two Post-Transplant Clinics with about 120 patients in follow-up in Savona and Albenga, and three Pre-Dialysis Clinics across the three locations. Finally, there is an autonomous hospital ward with 15 beds that has continued its activity, even if at reduced regimes.

With this report we intend to share the strategy we used to prevent the spread of the SARS CoV-2 virus among the patients and the staff at our Unit, following the National, Regional and Corporate guidelines published during “Phase 1”.

We decided that the Haemodialysis Centres needed to remain a safe place. To insure this, medical and nursing staff and patients had to behave conscientiously and collaboratively, and according to the official Hospital guidance. Our main concern was to protect patients who, despite suffering complications and being at high risk because of their age, immunodepression and multiple comorbidities, were forced to leave their house three times a week to be treated with dialysis.

The results of this strategy have ensured that, of the 150 patients undergoing haemodialysis, only 3 have been tested positive: no patients in Albenga, 2 in Savona and 1 in Cairo Montenotte, all of them lived and were infected in their nursing homes. Also, there was no positivity among any of the staff members across the three locations.

Our results are extremely positive and confirm the validity that prevention and protection procedures had in the earlier stages of the pandemic.

Keywords: COVID-19, safety, prevention, dialysis

Patients on chronic dialysis have an increased risk for SARS CoV-2 virus disease and its complications because of multiple comorbidities and alterations in the immune response caused by renal disease. In this retrospective observational study we describe the clinical features and the evolution of SARS CoV-2-related disease in 19 patients of our Pesaro and Fano facilities, where incidence and mortality of the epidemic were among the highest in Italy. A total of 176 patients were undergoing chronic treatment, 153 hemodialysis and 23 peritoneal dialysis. The incidence of infection was 10,8%, with 84% needing hospitalization and mortality amounting to 53%. The most frequent onset symptom was fever (84,2%) and the most used therapy was an association of low molecular weight heparin and hydroxychloroquine (57,9%).

Comparing the deceased and survivor populations we noticed significant differences in age and presence of cardiopathy for what concerns anamnestic data and in fatigue and dyspnea in terms of clinical presentation. LDH and CPK resulted highest among deceased patients, while the use of enoxaparin was more frequent in survivors. By observing contagions over time, we also noticed that most of the cases, and the ones with worse clinical condition and outcome, all occurred in the early stage of the epidemic and in particular within the first 20 days from the implementation and codification of the measures to prevent its spread, the only modifiable factor that had an unmistakable effect on the evolution of events.

Keywords: SARS Cov-2, COVID-19, dialysis, nephrology

The SARS-CoV-2 pandemic has forced a reshaping of economic, productive, commercial and healthcare systems. The last one had the dual mandate to limit intra-hospital infections and strengthen its ability to deal with the ongoing emergency. In this paper we report the experience gained by the staff of the Nephrology and Dialysis Unit of the AULSS7 Pedemontana (Vicenza – Veneto region) and the organizational model pursued during the first wave of the pandemic.

Keywords: hemodialysis, SARS-Cov2, COVID center, CRRT

Nursing requires a complex set of skills encompassing professional clinical judgment, values and attitudes. In order to outline the future career path of the specialist nurse, the European Federation of Nurses Association compared the EU Directive 2013/55/EU with the Competency Framework, an important document on guidelines written by a group of experts and focusing on the recognition of nurses’ educational requirements.

The aim of our research is to identify the special skill set required from nurses on haemodialysis wards through the development of an exploratory survey and the comparison of its results with the EFN guidelines and the Directive 2013/55/EU. The survey was conducted across eighteen dialysis centers in Tuscany. Through focus groups, debates and reflections, 28 skills were identified as pertaining exclusively to nurses working with haemodialysis patients.

This preliminary study aims at demonstrating the need to define and recognize these specialist skills in order to ensure an effective and integrated nursing leadership in disease management.

Keywords: haemodialysis, skills, specialization, nurse

Hemodialysis (HD) patients are at high risk for infectious complications such as spondylodiscitis. The aim of this retrospective study was to evaluate the cases of infective spondylodiscitis occurred between May 2005 and October 2019 among HD patients at our center.

In 14 years, there were 9 cases (mean age 69±12 years). The main comorbidities found were diabetes mellitus (55.6% of patients), hypertension (55.6%), bone diseases (22.2%), cancer (11.1%) and rheumatoid arthritis treated with steroids (11.1%). The clinical onset included back pain (100% of cases), fever (55.6%), neurological deficits (33.4%), leukocytosis (55.6%) and elevated CRP level (88.9%).

Most cases were diagnosed by magnetic resonance imaging (66.7%) with more frequent involvement of lumbar region (77.8%). Blood cultures were positive in five patients (mostly for S. aureus); three of them used catheters as vascular access and, in two cases, their removal was necessary. The mean time interval between the onset of symptoms and the diagnosis was 34±42 days.

All patients received antibiotic treatment for a mean duration of 6 weeks; most cases were initially treated with vancomycin or teicoplanin plus ciprofloxacin. Most patients (77.8%) recovered after a mean of 3.5 months; one patient had a relapse after 2 years and one patient had long-term neurologic sequelae.

Infective spondylodiscitis in HD must be suspected in the presence of back pain, even in the absence of fever or traditional risk factors. An early diagnosis could improve the outcome. Close monitoring of vascular access, disinfection procedures and aseptic techniques are important to avoid this complication.

Keywords: spondylodiscitis, hemodialysis, back pain, vascular access, infectious complications, bacteremia

The surveillance of a vascular access (VA) is of primary importance for its outcome and for the patients’ survival. However, there is still confusion about its usefulness, who should make it (physician or nurse) and when, and what is the best functional test to use. This retrospective analysis reports our experience of VA monitoring; it is based on the collaboration between concept doctors and nurses and on parameters integration, realized with the help of a software for vascular access monitoring (SMAV) designed by us. The analysis confronts the data gathered on a group of 100 patients, 13 months before the adoption of the SMAV, and another 100 patients, 19 months after. Of these patients, 13 belonged to both groups and were “controls of themselves”. The number of thrombosis and angioplasties (PTA) plummeted in the 19 months in which the SMAV was used, from 10 (10%; 0.008 thrombosis/patient month) to 1 (1%; 0.0005 thrombosis/patient month) (p <0.01) and from 49 (49%; 0.037 PTA/patient month) to 27 (27%; 0.014PTA/patient month) (p <0.05) respectively. In the 13 control patients, a reduction of 70% in the number of PTA (from 26 to 8) was observed. SMAV allowed us to integrate the many functional parameters, making it easy to share information, encouraging teamwork, strengthening professional skills, and favouring the best management of AVs. The result was a reduction in thrombotic events and, surprisingly, a reduction of the need for PTA, most likely thanks to the higher level of attention in the evaluation and puncture of AV.

Keywords: arterio-venous fistula, surveillance, SMAV

Introduction: Etelcalcetide has proven effective and well tolerated in the treatment of secondary hyperparathyroidism (IPS) in patients on hemodialysis (HD). Since long-term studies are scarce, we assessed the efficacy and safety of etelcalcetide in the treatment of severe IPS in a group of HD patients over a 12-month period. Patients and Methods: We selected 24 HD patients with PTH levels > 500 pg/mL (range 502-2148 pg/mL), despite following a therapy with cinacalcet and/or vitamin D analogues. The initial dosage of etelcalcetide was 7.5 mg/week, then it was adjusted based on the trend of the levels of the total albumin-corrected serum calcium (CaALb_c) and PTH. Treatment was temporarily suspended if CaALb_c levels were <7.5 mg/dL or if hypocalcemia was symptomatic. CaALb_c, phosphorus, PTH and total alkaline phosphatase (t-ALP) were measured monthly. The main endpoint was the decrease in PTH levels >30% compared to baseline values. Results: At F-U, the reduction in PTH levels was > 30% in 83% of our patients. PTH levels decreased from 1169 ± 438 to 452±241 pg/mL at F-U (P <0.001). The percentage of reduction in PTH levels at F-U was -56 ± 25%. CaALb_c and phosphate levels decreased from 9.8 ± 0.4 mg/dL to 9.0 ± 0.6 mg/dL (P <0.001), and from 6.1 ± 1.3 mg/dL to 4.9 ± 1.3 mg/dL (P <0.01), respectively. The main side effect was hypocalcaemia, but never so severe as to require the interruption of treatment. Hypocalcemia was more pronounced in patients with higher basal levels of PTH and t-ALP. During the study, the percentage of patients treated with calcium carbonate increased from 33% to 54% and that of patients treated with paricalcitol from 33% to 79%. At F-U the average weekly dosage of etelcalcetide was 21.0 ± 9.5 mg (range 7.5-37.5 mg/week). Conclusions: The treatment of severe IPS with etelcalcetide has been proved effective and safe in the long term. Hypocalcaemia, the most frequent side effect, was more evident in patients with the most severe forms of IPS and was probably due to a reduction in bone turnover rather than to the direct effect of etelcalcetide.

Key words: etelcalcetide, hemodialysis, secondary hyperparathyroidism, paricalcitol, cinacalcet.

We report the case of a 93-year-old woman on haemodialysis treatment for more than 30 months and with multiple comorbidities who recovered from a Covid-19 infection without any significant clinical problems. The patient has shown a delay in viral clearance with swab test negativization (confirmed) after 33 days; after testing positive again, she has resulted persistently negative, (confirmed after 49 days).

After the first negative swab, IgG and IgM antibodies have been found; these have remained persistently positive after a month. As well as highlighting an unexpected resilience in an extremely fragile context, the analysis of this case draws attention to patients’ management and, potentially, to the need to arrange dialysis treatments in isolation for some time after their “laboratory recovery”.

Keywords: Covid-19, dialysis, resilience, nasal swab, antibodies

We report the case of a 68-year-old patient who arrived at the hospital with a fever and a cough for 7 days, a history of high blood pressure and chronic kidney failure stage 2 according to CKD-EPI (GFR: 62 ml/minute with creatinine: 1.2 mg/dl). Home therapy included lercanidipine and clonidine. A chest radiograph performed in the emergency department immediately showed images suggestive of pneumonia from COVID-19, confirmed in the following days by a positive swab for coronavirus. Kidney function parameters progressively deteriorated towards a severe acute kidney failure on the 15^th day, with creatinine values of 6.6 mg/dl and urea of 210 mg/dl. The situation was managed first in the intensive care unit with CRRT cycles (continuous renal replacement therapy) and then in a “yellow area” devoted to COVID patients, where the patient was dialyzed by us nephrologists through short cycles of CRRT. In our short experience we have used continuous techniques (CRRT) in positive patients hemodynamically unstable and intermittent dialysis (IRRT) in our stable chronic patients with asymptomatic COVID -19. We found CRRT to be superior in hemodynamically unstable patients hospitalized in resuscitation and in the “yellow area”. Dialysis continued with high cut-off filters until the normalization of kidney function; the supportive medical therapy has also improved the course of the pathology and contributed to the favorable outcome for our patient. During the COVID-19 pandemic, our Nephrology Group at Savona’s San Paul Hospital has reorganized the department to better manage both chronic dialyzed patients and acute patients affected by the new coronavirus.

Keywords: COVID-19, “yellow area”, AKI, ACE2, viral particles, nephrology, CRRT

Coronavirus disease 2019 is an infectious respiratory syndrome caused by the virus called SARS-CoV-2, belonging to the family of coronaviruses. The first ever cases were detected during the 2019-2020 pandemic. Coronaviruses can cause a common cold or more serious diseases such as Middle Eastern Respiratory Syndromes (MERS) and Severe Acute Respiratory Syndrome (SARS). They can cause respiratory, lung and gastrointestinal infections with a mild to severe course, sometimes causing the death of the infected person. This new strain has no previous identifiers and its epidemic potential is strongly associated with the absence of immune response/reactivity and immunological memory in the world population, which has never been in contact with this strain before. Most at risk are the elderly, people with pre-existing diseases and/or immunodepressed, dialyzed and transplanted patients, pregnant women, people with debilitating chronic diseases. They are advised to avoid contacts with other people, unless strictly necessary, and to stay away from crowded places, also observing scrupulously the recommendations of the Istituto Superiore di Sanità.

In this article we detail the recommendations that must be followed by the nursing care staff when dealing with chronic kidney disease patients in dialysis or with kidney transplant patients. We delve into the procedures that are absolutely essential in this context: social distancing of at least one meter, use of PPI, proper dressing and undressing procedures, frequent hand washing and use of gloves, and finally the increase of dedicated and appropriately trained health personnel on ward.

Keywords: COVID-19, hemodialysis, transmission, prevention

The epidemic wave that hit Italy from February 21st, 2020, when the Italian National Institute of Health confirmed the first case of SARS‑CoV‑2 infection, led to a rapid and efficient reorganization of Dialysis Centers’ activities, in order to contain large-scale spread of disease in this clinical setting.

We herein report the experience of the Hemodialysis Unit of Parma University Hospital (Azienda Ospedaliero-Universitaria, Parma, Italy) and the Dialysis Centers of Parma territory, in the period from March 1st, 2020 to June 15, 2020.

Among patients undergoing chronic haemodialysis, 37/283 (13%) had positive swabs for SARS‑CoV‑2, 9/37 (24%) died because of COVID-19. Twenty-three patients required hospitalization, while the remaining were managed at home.

The primary measures applied to contain the infection were: the strengthening of personal protective equipment use by doctors and nurses, early identification of infected subjects by performing oro-pharyngeal swabs in every patient and in the healthcare personnel, the institution of a triage protocol when entering Dialysis Room, and finally the institution of two separate sections, managed by different doctors and dialysis nurses, to physically separate affected from unaffected patients and to manage “grey” patients.

Our experience highlights the importance and effectiveness of afore-mentioned measures in order to contain the spread of the virus; moreover, we observed a higher lethality rate of COVID-19 in dialysis patients as compared to the general population.

Keywords: COVID-19, haemodialysis, Parma, Emilia-Romagna

Lombardy was violently hit by Covid-19 between the end of February and the beginning of March 2020. On 09.05.2020 there were 81225 total registered Covid-19+ cases (8051 / million inhabitants) with 14924 deaths (1479 deaths / million inhabitants). The province of Cremona presented a higher number of Covid-19+ cases and a worse relative mortality than the already high regional average.

Patients on regular hemodialysis treatment present a high risk of infection due to the co-pathologies present, while healthcare workers may represent a risk for themselves and for the patients, due to the treatment environment and the close contact with them.

All patients and healthcare workers of the Dialysis Center in Crema were evaluated (oro-pharyngeal swab for viral RNA research, qualitative anti-Covid-19 antibodies, quantitative IgG antibodies, co-pathologies), regardless of the symptomatology, over a 60-day period.

Hemodialysis patients have a risk of infection that is 12.7 times that of the local population, while healthcare workers outperform the patients for Covid-positivity (30.3% vs 21.6%). Lethality in infected patients is high (31% of Covid-19+ subjects), while it is zero among healthcare professionals. The antibody response (qualitative and quantitative) in Covid-19+ patients is adequate, when compared to that of Covid-19+ healthcare staff.

In our Center, the most critical phase lasted about 45 days but, thanks to the measures taken, it was possible to make the dialysis area Covid-free, as it remains after 128 days.

Keywords: Covid-19, Haemodialysis, LIAISON SARS-CoV2 S1/S2, JusCheck 2019-nCoVIgG/IgM

We report the brief experience of the Nephrology Center located in a “no-COVID” Hospital in Massa Marittima.

We describe the actions taken to prevent the transmission of the virus SARS-CoV-2 among hemodialysis patients and healthcare workers and the methods for diagnosing COVID-19, with particular attention to serological tests and nasopharyngeal swabs in asymptomatic subjects.

The detection of IgM and IgG antibodies through the serological test performed on 34 patients, all negative for nasopharyngeal swabs, showed positivity in 41,18% of cases. These have been classified as false positives following repeated negative nasopharyngeal swabs, the evaluation of clinical and epidemiological history and of clinical manifestations and, finally, a second serological test performed after 18 days, which resulted negative for all patients.

Interpreting serological tests is not easy; the strategies for diagnosis should include clinical and epidemiological history and clinical manifestations, as well as the results of confirmation tests and the evaluation over a precise observation period. Otherwise, there is a risk of considering as protected by antibodies subjects that are in fact false positives.

Keywords: COVID-19, SARS CoV-2, serological tests, asymptomatic subjects, false positives

Introduction: Vitamin D deficiency (25(OH)D <30 ng/mL) in renal transplant recipients (RTRs) is a frequent finding and represents an important component in the pathogenesis of secondary hyperparathyroidism (SHPT). Therefore, its more systematic supplementation is recommended. We herein report our experience on the impact of cholecalciferol supplementation on PTH and 25(OH)D levels in a group of RTRs with 25(OH)D <30 ng/mL and SHPT. Patients and Methods: For this purpose, 52 RTRs with SHPT were treated with cholecalciferol at the fixed dose of 25,000 IU p.o. weekly for 12 months. For the control group we selected 23 RTRs with SHPT and 25(OH)D levels <30 ng/mL. Every 6 weeks eGFR, sCa and sPO4 levels were evaluated; PTH, 25(OH)D, FECa e TmPO₄ were evaluated every 6 months. Results: At baseline, the two groups had similar clinical characteristics and biohumoral parameters. Parathormone was negatively correlated with 25(OH)D levels (r=-0.250; P <0.001) and TmPO4 values (r=-0.425; P<0.0001). At F-U there was a significant reduction in PTH levels in the supplemented group, from 131 ± 46 to 103 ± 42 pg/mL (P<0.001), while vitamin D levels, TmPO4 values, PO4 and sCa levels increased significantly, from 14.9 ± 6.5 to 37.9 ± 13.1 ng/mL (P<0.001), from 1.9 ± 0.7 to 2.6 ± 0.7 mg/dL (P<0.001), from 3.1 ± 0.5 to 3.5 ± 0.5 mg/dL (P<0.001), and from 9.3 ± 0.5 to 9.6 ± 0.4 (P<0.01), respectively. During the study there were no episodes of hypercalcaemia and/or hypercalciuria, while 25(OH)D levels always remained <100 ng/mL. In the control group, at F-U, PTH levels increased from 132 ± 49 to 169 ± 66 pg/ml (P <0.05), while 25(OH)D levels remained stable at <30 ng/mL. Conclusions: Vitamin D deficiency in RTRs is very frequent. Cholecalciferol supplementation is associated with a better control of SHPT and a correction of vitamin D deficiency in most patients, representing an effective, safe and inexpensive therapeutic approach to IPS.

Keywords: vitamin D, cholecalciferol, renal transplant, secondary hyperparathyroidism

As much as 16-17% European and American patients on renal replacement therapy do not have a conclusive diagnosis of the cause of their renal failure. This may have important implications on the types of morbidity they can develop in case of systemic diseases with extrarenal involvement, or recurrent renal diseases in transplanted patients. A better knowledge of the underlying disease can have important prognostic and therapeutic repercussions.

In this study we evaluated the rate of uremic patients who can benefit from a genomic diagnostic approach. Patients liable to a future genomic diagnostic study were selected based on two criteria: (i) age of dialysis entry less or equal to 55 years, and (ii) presence of a non-conclusive diagnosis. Based on the data extracted from the REGDIAL registry, we analyzed 534 patients undergoing renal replacement therapy. We identified 300 patients with age of entry into replacement therapy <55 years (56.2% of the overall study population). Among these, we identified 107 patients with missing or inconclusive diagnosis, which was equal to 20% of the overall population. Of these patients, 32.8% reported a positive family history of kidney disease. This study confirms that a significant proportion of patients on renal replacement therapy do not have an etiological diagnosis and may be subject to a genomic evaluation. With the increasing availability of genomic sequencing technology and the falling of related costs, nephrologists will be increasingly inclined to incorporate clinical genetic testing into their diagnostic armamentarium. There is therefore a need for in-depth, multicenter studies aimed at developing evidence-based guidelines, clear indications and at confirming the usefulness of genetic testing in nephrology. Keywords: end stage renal disease, epidemiology, nephrosclerosis

Background and objectives: Chronic dialysis in frail nephropathic patients can worsen the symptom load and their functional autonomy, increasing the risk of early mortality. It is key to evaluate if dialysis treatment represents a real advantage for these patients; Maximum Conservative Therapy (MCT) associated with palliative care, could improve their residual quality of life, avoiding dialysis. The aim of this work is to describe the application and the relative terms of MCT in a complete series of cases followed in our Nephrological Clinic.

Study design and setting: This is a retrospective observational study on a cohort of 48 frail nephropathic patients in MCT and 58 on dialysis, in the period between January 2013 and December 2019. The place of death, Incidence Rate (IR) and Incidence Rate Ratio (IRR) related to survival and hospitalization rates were studied.

Results: The average duration of MCT was 9.7 months vs 13.5 months of dialysis treatment. One-year probability of survival of dialysis patient was 0.52 [CI 0.38-0.64] vs 0.48 [CI 0.33-0.62] in MCT patients; however, dialysis patients had higher rates of hospitalization (IR 2.780 vs 1.269 in MCT patients), IRR 2.19 [CI 1.66-2.89], according to literature [13]. 67% of dialysis patients died in hospital versus 35% of MCT patients. 34% of MCT patients are still alive at the time of data analysis (January 31, 2020); no dialysis patients are still alive on the same date.

Conclusions: The use of dialysis has shown a marginal, even though significant, effect on the average survival of frail nephropathic patients; however, they present a higher hospitalization rate, with consequent impact on the quality of life. The choice of the treatment (MCT vs dialysis) should not be merely based on the presence of comorbidities, but rather on the type of comorbidity found, which represents each time an element in favor of MCT or dialysis.

Keywords: conservative therapy, dialysis, survival, fragility

Gitelman’s syndrome (GS) is a rare autosomal recessive disorder characterized by hypokalemia, hypomagnesaemia, metabolic alkalosis, hypocalciuria and secondary hyperaldosteronism. The impact of GS on pregnant patients is still not clear, despite the many clinical cases described in literature. In particular, there is no data on the development of gestational diabetes. Altered glucose metabolism and insulin sensitivity have recently been described in patients with GS.

We describe here the clinical case of a young woman suffering from GS who started pregnancy and developed gestational diabetes. Our experience, while confirming the need of assiduous ionic monitoring especially in the first trimester of pregnancy, seems to help scaling down the maternal-fetal risk in patients suffering from GS. We also suggest the introduction of a low-glucose diet to prevent the onset of gestational diabetes, a condition burdened with severe complications. Finally, a reminder that drugs active on ionic balance must be of proven maternal and fetal safety.

Keywords: Gitelman’s Sydrome, Gestational diabetes, Hypokalemia, Hyperaldosteronism, rare deseases

Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogenous disease caused by a disregulation of the alternative pathway of the complement cascade. Specifically, microvascular damage is produced that can lead to acute kidney disease, hemolytic anemia and thrombocytopenia. It accounts for 10% of all hemolytic uremic syndromes and can result in death or in end stage renal disease since the first episode [1,2]. We can differentiate two forms of aHUS: a sporadic form (80%), affecting adult people, and a familial form (20%) that usually became manifest during infancy [1, 4]. In the acute phase of the disease, frequent and severe anemia requires multiple blood transfusions, exposing patients to the risk of catching an infective disease. HCV hepatitis is the most prevalent chronic hepatitis worldwide, with approximately 170 million chronically infected individuals – many of which are unaware of their condition. The evolution of the HCV infection is variable: almost 20% of patients spontaneously clear the infection over time (Anti HCV positive, HCV RNA negative patients); 80% of patients cannot control the virus and develop chronic infection (Anti HCV positive; HCV RNA positive patients) that can evolve into liver cirrhosis and hepatocellular carcinoma [12, 15]. The aim of this paper is to describe a clinical case of acute HCV hepatitis in a patient with aHUS treated with Eculizumab.

Keywords: atypical hemolytic uremic syndrome, aHUS, hepatitis C virus, HCV, Eculizumab, acute hepatitis

Amyloidosis represents a heterogeneous group of pathologies characterized by the deposit, in the form of fibrils, in the various organs and tissues of the body, of abnormal proteins; the deposits made up of these fibrils are called amyloid or amyloid substance. AL amyloidosis, also called “light chains”, is a primary form characterized by deposits of light chains of monoclonal immunoglobulins, proteins that are produced by the bone marrow with the aim of protecting the body from pathological processes; for unknown reasons, these immunoglobulins, once fulfilled their function, do not dissolve but, on the contrary, they transform into amyloid fibrils and accumulate progressively, transported by the bloodstream, in the various organs and tissues. Below we report the case of a 77-year-old Caucasian male patient hospitalized at our Operative Unit for nephrotic syndrome and creatinine increase in the last couple of months, compared to previous normal tests. The patient underwent a renal biopsy and a bone marrow smear with evidence of AL amyloidosis (or primary amyloidosis) and of the presence, at serum immunofixation, of small IgG multiple myeloma k. Treated with bortezomib (1 mg/m²) and soldesam (10 mg) first and with lenalidomid after, the patient had a clinical course burdened by symptomatic hypotension, due to severe dysautonomia. He had to start replacement treatment with haemodiafiltration for terminal kidney disease two months after the onset of illness. He died 4 months after the first hospitalization for nephrotic syndrome.

Keywords: AL amyloidosis, multiple myeloma, renal failure, haemodiafiltration

Pleuro-peritoneal leakage is an uncommon complication of peritoneal dialysis (PD). In this study, we report the case of a male patient (age 83), treated with PD (daytime single-exchange). In October 2019, hospitalization was necessary due to dyspnoea and a reduction of peritoneal ultrafiltration. A right pleural leakage resulted at chest x-ray. A regression of the pleural leakage was immediately observed after interrupting PD.

It was then performed a pleuro-peritoneal CT scan at baseline, followed by a second scan performed 4 hours after the injection of 2 L of isotonic solution with 100ml of contrast medium, which evidenced a pleuro-peritoneal communication. It was then decided to perform a video-assisted thoracoscopic surgery (VATS), that showed no evidence of diaphragm communication. It was then executed a pleurodesis using sterile talcum. The patient was released on the 3^rd day, with a conservative therapy and a low-protein diet. After 2 weeks a new pleuro-peritoneal CT scan with contrast medium was executed. This time the scan evidenced the absence of contrast medium in the thoracic cavity. The patient then resumed PD therapy, with 3 daily exchanges with isotonic solution (volume 1.5 L), showing no complications.

Concerning the treatment of pleuro-peritoneal leakage, VATS allows both the patch-repairing of diaphragmatic flaws and the instillation of chemical agents. In our case, VATS allowed the chemical pleurodesis which in turn enabled, in just 2 weeks of conservative treatment, the resuming of PD. In conclusion, this methodology is a valid option in the treatment of pleuro-peritoneal leakage in PD patients.

Keywords: pleuro-peritoneal leakage, video-assisted thoracoscopic surgery, peritoneal dialysis, end stage renal disease

Erythropoiesis Stimulating Agents (ESAs) are well-tolerated and effective drugs for the treatment of anaemia in patients with chronic kidney disease.

In the past, scientific research and clinical practice around ESAs have mainly focused on the haemoglobin target to reach, and to moving towards the normality range; more cautious approach has been taken more recently. However, little attention has been paid to possible differences among ESA molecules. Although they present a common mechanism of action on the erythropoietin receptor, their peculiar pharmacodynamic characteristics could give different signals of activation of the receptor, with possible clinical differences.

Some studies and metanalyses did not show significant differences among ESAs. More recently, an observational study of the Japanese Registry of dialysis showed a 20% higher risk of mortality from any cause in the patients treated with long-acting ESAs in comparison to those treated with short-acting ESAs; the difference increased in those treated with higher doses. These results were not confirmed by a recent, post-registration, randomised, clinical trial, which did not show any significant difference in the risk of death from any cause or cardiovascular events between short-acting ESAs and darbepoetin alfa or methoxy polyethylene glycol-epoetin beta. Finally, data from an Italian observational study, which was carried out in non-dialysis CKD patients, showed an association between the use of high doses of ESA and an increased risk of terminal CKD, limited only to the use of short-acting ESAs.

In conclusion, one randomised clinical trial supports a similar safety profile for long- versus short-acting ESAs. Observational studies should always be considered with some caution: they are hypothesis generating, but they may suffer from bias by indication.

Keywords: anaemia, erythropoiesis stimulating agents, ESAs, mortality, chronic kidney disease, long acting, short acting

Chronic kidney disease (CKD) is a progressively chronic disease that carries a high burden of morbidity and mortality and is associated with significant healthcare utilization and costs. Recent trends shown that the prevalence of CKD is stable in Europe and USA, whereas tends to decline in some countries with a high standard of care.

According to international guidelines, chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (eGFR) less than 60 ml/min. This staging method has a main drawback, its imprecise assessment of renal function at the extremes of the age bracket: the use of a fixed threshold value (glomerular filtration rate [GFR <60 ml /min]) to define chronic renal failure appears an imprecise measure in the young and in the elderly. In these two groups, in fact, the measurement of GFR is difficult to categorize in a "rigid" system of classification. The reduction of the GFR with aging is due to a complex process that leads to a steady reduction of the functioning nephrons over 40 years of age. Taken together, these findings should spur us to adopt a new definition of CKD. An age-adapted definition of CKD could be a good solution to avoid a diagnosis of CKD in elderly patients (GFR >45 ml/min) when there are no prognostic implications on survival. The adoption of this new definition would also reduce the high prevalence of the disease in the general population, with a beneficial reduction of the costs associated with monitoring a mildly decreased eGFR.

Focal segmental glomerulosclerosis (FSGS) is a pathological spectrum subtended by heterogeneous etiologies. A good knowledge of FSGS and its causes should be included in the nephrologists’ clinical background, as it deeply influences the subsequent management of the affected patients. In fact, while immunosuppressive treatment should be considered in idiopathic FSGS, the treatment of secondary forms should primarily aim at curing or containing the underpinning etiologic factors. Furthermore, in contrast to secondary FSGS, idiopathic FSGS tends to relapse after kidney transplantation.

Although FSGS has a wide spectrum of etiologies, several pathogenetic “moments” are shared. Furthermore, recent studies have identified a pool of glomerular cells potentially capable of regenerating lost podocytes; these cells might represent a promising therapeutic target.

The primary aim of this review is to describe the etiologic factors associated with FSGS, with a focus on the main pathogenetic mechanisms involved in its development.

Keywords: focal segmental glomerulosclerosis, nephrotic syndrome, podocytopathy

Epidemiological data show an increasing diffusion of diabetes mellitus worldwide. In the diabetic subject, the risk of onset of chronic kidney disease (CKD) and its progression to the terminal stage remain high, despite current prevention and treatment measures. Although SGLT2 inhibitors have been approved as blood glucose lowering drugs, they have shown unexpected and surprising cardioprotective and nephroprotective efficacy. The multiple underlying mechanisms of action are independent and go beyond glycemic lowering. Hence, it has been speculated to extend the use of these drugs also to subjects with advanced stages of CKD, who were initially excluded because of the expected limited glucose-lowering effect. Non-diabetic patients could also benefit from the favorable effects of SGLT2 inhibitors: subjects with renal diseases with different etiologies, heart failure, high risk or full-blown cardiovascular disease. In addition, these drugs have a good safety profile, but several post-marketing adverse event have been reported. The ongoing clinical trials will provide clearer information on efficacy, strength and safety of these molecules. The purpose of this review is to analyze the available evidence and future prospects of SGLT2 inhibitors, which could be widely used in nephrology clinical practice.

Keywords: diabetes, oral hypoglycemic agents, SGLT2 inhibitors, chronic kidney disease

Background: Given the public health challenge represented by chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyze structural and human resources, organizational aspects, activities and workload, referring to the year 2018. Methods: An on-line questionnaire including 60 questions, exploring structural and human resources, organizational aspects, activities and epidemiological data referred to 2018, was sent to the heads of all identified Italian renal or dialysis unit. Results: 567 renal units were identified, 3.3 public and full renal unit pmp. The nephrology beds are about 37.6 pmp. The nurses were 8,130 in HD wards, 1,827 in the nephrology wards, only 432 for outpatient clinics. Conclusions: Data from this census may be used for benchmarking and comparison between centers, regions and groups of regions. These data offer a snapshot of the clinical management of renal disease in Italy.

Keywords: census, nephrology unit, organization, workforce, workload

Background: Given the public health challenge represented by chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyze structural and human resources, organizational aspects, activities and workload, referring to the year 2018. Methods: An on-line questionnaire including 60 questions, exploring structural and human resources, organizational aspects, activities and epidemiological data referred to 2018, was sent to the heads of all identified Italian renal or dialysis unit. Results: Renal and dialysis activity was performed by over 2,718 physicians (41 pmp). The management of the acute renal failure was one of the most relevant activities in the public renal units (3,000 pmp patients in ICU and 183.000 dialysis sessions). Italian Nephrologists performed about 6000 AV fistulas out of a total of 9300. In the survey there are a lot of data regarding organization, workforce and workload of the renal unit in Italy. Conclusions: Data from this census may be used for benchmarking and comparison between centers, regions and groups of regions. These data offer a snapshot of the clinical management of renal disease in Italy.

Keywords: census, nephrology unit, organization, workforce, workload

Home dialysis, and mainly peritoneal dialysis, is indicated as the optimal choice as far as the comfort and lifestyle of uremic patients is concerned. Despite this, home treatments show a lack of growth. The reasons are mainly linked to the patients’ cognitive, psychosocial, familiar and physical barriers due to aging and morbidity. To overcome these barriers, we analyzed all the available institutional aids: civil disability, not-self-sufficiency funds, home, social and nursing assistance, expenses refunds. 

The assessment of the patients’ needs is performed through validated instruments such as multidimensional evaluation (VMD) and equivalent economic index (ISEE). Overall, economic relief is limited to low income patients, and those in serious distress. Some Italian regions have issued specific measures dedicated to home dialysis. Our review shows a great heterogeneity of measures, centered in some cases on economic aids and on home assistance in others. Moreover, some Italian dialysis centers directly provide caregivers for home dialysis. 

The international literature describes many experiences relating to home dialysis assistance. Their common message is that, in developed countries, economic help is generally sustainable despite the heterogeneity of health care systems. Home support and economic aids for dialysis, in fact, are made possible by the overall savings enabled by home treatments and by the careful redistributions of the funds.

Keywords: home dialysis, peritoneal dialysis, economic aids, assisted peritoneal dialysis sustainable assistance models

The correct management of patients with kidney stones is a crucial issue for nephrologists. In recent years, the incidence and prevalence rates of nephrolithiasis have maintained a growing trend worldwide, showing a strong correlation with other systemic disease such as diabetes mellitus, hypertension, obesity, metabolic syndrome and chronic kidney disease. International guidelines indicate computed tomography as the first choice for all adult patients with suspected acute symptoms for obstructive nephrolithiasis. Intravenous pyelogram is more useful in the follow-up of patients with relapsing nephrolithiasis and known stone composition, while the high costs and the long image acquisition times limit the routine use of magnetic resonance. Recent innovative tools have improved the accuracy of kidney stone localization and measuring with B-Mode and color Doppler imaging, thereby reducing the gap between ultrasonography and computer tomography. The aim of this review is to report the latest evidence on risk factors and on the pathophysiology of nephrolithiasis, and to compare the utility of the available imaging techniques in the management of patients with kidney stones, focusing on the role of ultrasonography and the present and future strategies to improve its accuracy.

Keywords: nephrolithiasis, diagnostic imaging, ultrasonography, B-Mode imaging, color Doppler imaging, twinkling artifact

Peritoneal dialysis (PD) related infections continue to be a major cause of morbidity and mortality in patients undertaking renal replacement therapy with PD. Nevertheless, despite the great effort invested in the prevention of PD infective episodes, almost one third of technical failures are still caused by peritonitis. Recent studies support the idea that there is a direct role of exit-site (ESIs) and tunnel infections (TIs) in causing peritonitis. Hence, both the prompt ESI/TI diagnosis and correct prognostic hypothesis would allow the timely start of an appropriate antibiotic therapy decreasing the associated complications and preserving the PD technique.

The ultrasound exam (US) is a simple, rapid, non-invasive and widely available procedure for the tunnel evaluation in PD catheter-related infections.

In case of ESI, the US possesses a greater sensibility in diagnosing a simultaneous TI compared to the clinical criterions. This peculiarity allows to distinguish the ESI episodes which will be healed with antibiotic therapy from those refractories to medical therapy. In case of TI, the US permits to localize the catheter portion involved in the infectious process obtaining significant prognostic information; while the US repetition after two weeks of antibiotic allows to monitor the patient responsiveness to the therapy.

There is no evidence of the US usefulness as screening tool aimed to the precocious diagnosis of TI in asymptomatic PD patients.

Keywords: peritoneal dialysis, exit-site infection, tunnel infection, peritonitis, ultrasounds, Tenckhoff catheter.

Intravenous iron supplementation is essential in hemodialysis (HD) patients to recover blood loss and to meet the requirements for erythropoiesis and, in patients receiving erythropoietin, to avert the development of iron deficiency. In a recent real-world study, Hofman et al. showed that a therapeutic shift from iron sucrose (IS) to ferric carboxymaltose (FCM) in HD patients improves iron parameters while reducing use of iron and erythropoietin. The objective of this economic analysis is to compare the weekly cost of treatment of FCM vs IS in hemodialysis patients in Italy. The consumption of drugs (iron and erythropoietin) was derived from Hofman’s data, while the value was calculated at Italian ex-factory prices. The analysis was carried on the total patient sample and in two subgroups: patients with iron deficiency and patients anemic at baseline. In addition, specific sensitivity analyses considered prices currently applied at the regional level, simulating the use of IS vs iron gluconate (FG) and epoetin beta vs epoetin alfa. In the base-case analysis, the switch to FCM generates savings of -€12.47 per patient/week (-21%) in all patients, and even greater savings in the subgroups with iron deficiency -€17.28 (-27%) and in anemic patients -€23.08 (-32%). Sensitivity analyses were always favorable to FCM and confirmed the robustness of the analysis. FCM may represent a cost-saving option for the NHS, and Italian real-world studies are needed to quantify the real consumption of resources in dialysis patients.

Keywords: ferric carboxymaltose, intravenous iron supplementation, chronic kidney disease, hemodialysis, drugs consumption, economic impact

Iodinated contrast-induced nephropathy is one of the most feared complications of percutaneous coronary interventions and is associated with increased cardio-vascular mortality and a faster progression towards end stage renal disease. The effects of the iodinated contrast medium on intra-renal hemodynamics and its direct cytotoxic action on proximal tubular cells contribute synergistically to the pathophysiology of renal damage. Since the therapeutic options are extremely limited, the rapid identification of risk factors and the timely implementation of preventive strategies are mandatory to reduce the incidence of iodinated contrast-induced nephropathy. To date, the criteria for defining and staging contrast medium nephropathy are still based on the increase of serum creatinine and/or contraction of diuresis, which are lacking in specificity and therefore do not allow early diagnosis. The aim of this review is to report the latest evidence on the pathophysiological mechanisms that contribute to renal damage by iodinated contrast medium, on the risk stratification tools and on the new early biomarkers of contrast-induced nephropathy, while also focusing on the most validated prevention strategies.

Keywords: contrast medium, nephropathy, risk factors, early diagnosis, prevention

The natural history of urinary kidney stone disease includes the risk of relapses and can be associated with the risk of chronic kidney disease, bone and cardiovascular disease. For this reason, a wide clinical-metabolic assessment of the kidney stone patient is of great importance since the first presentation of the stone, to set an appropriate preventive treatment. The proposed diagnostic-therapeutic pathway includes a careful medical history, in order to highlight a secondary kidney stone disease and the main risk factors for kidney stones, chronic renal disease, or cardiovascular and bone disease; a metabolic evaluation on multiple levels, according to the severity of the disease, and the presence or absence of risk factors, and appropriate instrumental investigations.

Thus, the information collected makes it possible to set a preventive treatment consisting of general rules and, if necessary, specific pharmacological or nutritional interventions.

This paper has been prepared by the Italian Multidisciplinary Study Group for Kidney Stone Disease, and it is addressed to the several professional figures involved in the management of patients suffering from nephrolithiasis, from the emergency doctor to the general practitioner, urologist, nephrologist, radiologist, and dietician.

A diagnostic-therapeutic pathway for patients with kidney stone disease was first published on this Journal in 2010. The present contribution aims at amending and updating the article published exactly ten years ago, to serve as an easy-to-use reference and to guide good clinical practice in this field.

Keywords: kidney stones, urolithiasis, nutrition, diagnosis, prevention

The aim of this editorial is to illustrate the new public funding framework of the Italian National Health System following the Covid-19 pandemic. The document reviews the measures put in place by the Italian Government and European Institutions such as the European Commission (EC), the European Central Bank (ECB) and the European Stability Mechanism (ESM) to deal with this health crisis and subsequent severe economic recession, with particular reference to sources and uses of resources.

The use of new budgetary financial spaces in deficit entails greater attention to the assessment of interventions and makes it necessary to keep expenditure under strict control. At the same time, the remodeling of expenditure within its aggregates, public investment in innovation, and the removal of administrative obstacles can strengthen the capacity of the healthcare system to meet the extraordinary needs deriving from the spread of Covid-19 and its resilience to future health shocks.

Keywords: Covid-19, public governance, health spending review, national health system, ESM, digital healthcare

This contribution delves into the EU Regulation 2016/679 that defines the accountability of data controllers, with regard to the processing of personal data, and imposes the adoption of technological and organizational measures demonstrating a full commitment to European data protection laws. A risk-based analysis and an impact-based approach are recommended for all personal data, and especially those concerning health, in order to safeguard the rights and freedoms of the data subjects.

The article also describes the processes that should be put in place to avoid errors and violations in the handling of personal data, which can result in physical, material or non-material damage to natural persons. The controller, in fact, needs to evaluate the situation carefully and follow a series of compulsory steps to assess any potential weaknesses in the system.

A balancing act between public health concerns and privacy protection is necessary; this can be obtained through a detailed analysis of the norms and their careful implementation.

Keywords: data concerning health, privacy, risk-based analysis, impact-based approach, data protection

The use of a preoperative echocolordoppler improves the clinical evaluation because provides anatomical and hemodynamic information that make it an important tool in planning vascular access strategy.

The preoperative ultrasound study of the vessels can significantly reduce the failure rate and the incidence of complications of vascular access.

We describe the experience of our center, lasting 10-year, where the ultrasound assessment was performed in all patients before the creation of vascular access.

Indeed, ultrasound reduces the rate of fistula failure and increases the utilization of fistula, allowing proper selection of vessels.

In addition, the presence of the vascular access team has allowed us to achieve quite satisfactory results.

Keywords: vascular access, imaging, ecocolordoppler, presurgical evaluation, hemodyalisis

Introduction: Vitamin D deficiency is common among hemodialysis (HD) patients and is an important component in the pathogenesis of secondary hyperparathyroidism (SHPT). We herein report our experience on the impact of cholecalciferol supplementation on PTH levels in a group of HD patients.

Patients and methods: We selected 122 HD patients. The main selection criteria were 25-hydroxyvitamin D (25(OH)D) levels ≤30 ng/mL and SHPT defined as PTH levels >300 pg/mL or PTH levels between 150-300 pg/mL during therapy with cinacalcet or paricalcitol. 82 patients agreed to receive cholecalciferol at the fixed dose of 25,000 IU per week orally for 12 months, while the remaining 40 represented the control group. The main endopoints of the study were the reduction in PTH levels ≥30% compared to baseline values and the increase of 25(OH)D levels to values >30 ng/mL.

Results: At follow-up PTH levels decreased in the supplemented group from 476 ±293 to 296 ± 207 pg/mL (p<0.001), 25(OH)D levels increased from 10.3 ± 5.7 to 33.5 ± 11.2 ng/mL (p<0.001), serum calcium increased from 8.6 ± 0.5 to 8.8 ± 0.6 mg/dL (p<0.05) while serum phosphorus did not change. In this group the mean doses of paricalcitol were significantly reduced, from 8.7 ± 4.0 to 6.1 ± 3.9 µg/week (p<0.001). Moreover, in this group there were a significant increase of hemoglobin levels, from 11.6 ± 1.3 to 12.2 ± 1.1 g/dL (p <0.01) and a significant reduction of erythropoietin doses (p<0.05). In the control group the 25(OH)D and PTH levels did not change, while cinacalcet doses increased from 21 ±14 to 43 ± 17 mg/d (p<0.01).

Conclusions: Vitamin deficiency is very common in HD patients. Cholecalciferol treatment significantly increased serum 25(OH)D levels, significantly decreased PTH levels and paricalcitol doses, concurrently entailing a better control of anemia. 

Keywords: vitamin D, cholecalciferol, hemodialysis, secondary hyperparathyroidism, paricalcitol

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic kidney disease, alone responsible for over 10% of patients with end-stage renal disease, and with an important impact on public health. Tolvaptan (TOLV) has recently been approved in many European countries for its ability to slow disease progression in patients that are eligible for treatment. Nevertheless, the doctor’s choice to prescribe the drug and the patient’s compliance are strongly influenced by the aquaretic effect complications. In a cohort of patients pertaining to the Nephrology clinic of the AOU Federico II of Naples and  treated with TOLV, we assessed  not only the adherence to the treatment and the safety of the drug, but also the real feasibility of this therapy through specific questionnaires on sleep quality, abdominal-renal pain, quality of life and patients’ general satisfaction. Within the limits of preliminary data and on the basis of the responses of our population, followed for a period  of at least one year and administered the maximum titration dosage, it can be asserted that the doubts regarding the real compliance of the patients can be overcome.

Keywords: ADPKD, Tolvaptan, “real life” experience, quality of life

The follow-up automated peritoneal dialysis (APD) patients has been recently improved as data can be transmitted remotely to an internet cloud. The introduction of remote patient monitoring (RPM) technologies also allows a better clinical control and tailoring of dialysis treatment through a web-based software (Claria-Sharesource Baxter). The aim of the present study is to determine the impact of RPM in a single center, both in clinical and organizational terms, compared to traditional technologies. We studied 26 prevalent APD patients aged 69±13 years, observing them for a period of six months while using the traditional technology and then further six months using the new technology. The patients had been on dialysis for 9 months before the start of the study and a relevant portion of them lived in mountainous or hilly areas. Our study shows an increase in the number of proactive calls from the center to the patients, a reduction of anxiety in patients and caregivers, an earlier detection of clinical problems, a reduction of unscheduled (urgent) visits and finally a reduction of hospitalizations after the adoption of RPM software. In our experience, the RPM system showed a good performance and a simple interface, allowing for the precise assessment of daily APD. Furthermore, RPM system improved the interaction between patients and healthcare providers, with a significant benefit in terms of safety and of care quality.

Keywords: automated peritoneal dialysis, dialysis prescription, remote patient monitoring, telemedicine, hospitalization

Thrombotic microangiopathy (TMA) is a frequent and severe complication in systemic lupus erythematosus (SLE). It is reported in almost 20-25% of renal biopsies of patients with lupus nephritis (LN) and is associated with a poor renal prognosis. We report the case of a patient suffering from an aggressive form of proliferative LN in association with thrombotic microangiopathy (TMA-LN), who was resistant to standard combined immunosuppressive treatment with corticosteroids and cyclophosphamide, as well as to plasma exchange (PEX). Eculizumab was given as a rescue therapy with an optimal clinical response. We performed a systematic review of the literature and identified 11 papers, published between 2011 and 2018, with a total of 20 patients, in which eculizumab was used, always as rescue therapy, to treat TMA-LN. All reported cases showed a positive clinical response to eculizumab with a high rate of remission. Even if sparse, available clinical cases and case series support the use of eculizumab in highly selected cases as rescue treatment for LN-TMA resistant to conventional combined immunosuppressive treatment.

Keywords: lupus nephritis, systemic lupus erythematosus, Thrombotic microangiopathy, eculizumab

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies – hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) – seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Keywords: lithium, drug toxicity, dialysis, sustained low efficiency dialysis (SLED)

The term “inflammation” is certainly one of the oldest medical terms still in use. However, its meaning has changed over the centuries. This work gives a historical and critical review of the concept of inflammation, with special reference to kidney diseases. Over time the definition of inflammation has shifted from a pure collection of symptoms to a histopathological definition, characterized by the tissue “inflammatory infiltrates” and different subcategories according to the cell type involved. The advantages of this classification are the generally good response to corticosteroids (with only a few exceptions) and the availability of specific drugs for each inflammatory infiltrate. Finally, a “molecular” definition of inflammation has arisen, where the inflammatory infiltrates make room to a plethora of plasma mediators. The authors show that the use of plasma biomarkers as a tool to define inflammatory state leads to net inflation of the number of “inflammatory” diseases – an effect that shows clearly in the field of nephrology.

Keywords: inflammation, acute phase proteins, nephritis, immune suppressors

Valle d’Aosta, Italy’s smallest region, faced a Covid-19 epidemic trend of absolute relevance. In line with data concerning the local general population, the predominance of the illness among uremic patients has been high. The authors report here preliminary data on the spread of this disease within the region and on the clinical trend of the infected patients who needed to be hospitalised.

Keywords: Covid-19, outbreak, dialysis

Hemodialysis cannulation is often done with a notoriously harmful device that also exposes operators to a high risk of accidental puncture. It is very interesting to look at the Japanese experience, that has introduced, with an excellent success rate, a new device for the cannulation of FAV: a plastic cannula.

The aim of this review is to verify if the literature describes any advantages in the use of the plastic cannula in hemodialysis compared to the traditional metal needle, in relation to mechanical and hemodynamic vascular trauma, treatment adequacy, patient comfort and operator safety. The study has been conducted by researching, reviewing and selecting scientific articles through search engines and specialized journals.

The peculiarities of the device’s design allow to expand the current possibilities in the practice of cannulation, producing positive outcomes for the patient and the operator. There is a need, however, for further studies and an update of device’s features.

Keywords: hemodialysis plastic cannula, vascular access cannulation, arteriovenous fistula