Protected: ADPKD and IPMN: Mere Coincidence or Double Trouble?

Abstract

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

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COVID-19 and Lupus Nephritis Flares in Unvaccinated Patients: A Case Report and Literature Review

Abstract

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

Sorry, this entry is only available in Italian.

Introduzione

La nefrite lupica rappresenta una delle manifestazioni più severe del Lupus Eritematoso Sistemico (LES) e colpisce circa il 35-60% dei pazienti a seconda del sesso, dell’etnia e dell’età di insorgenza della malattia [1]. Sulla base della classificazione ISN/RPS [2, 3], la nefrite lupica viene classificata in sei classi istologiche, in cui il rischio di morte per causa renale diventa particolarmente significativo per le classi di tipo proliferativo (classe III, IV e V). Le classi III e IV, infatti, sono associate a prognosi peggiore, con un maggior rischio di progressione verso l’End-Stage Kidney Disease (ESKD) che si manifesta nel 10% dei pazienti.

In questo contesto i flare renali costituiscono una delle principali cause di perdita dei nefroni e pertanto della progressione della funzione renale verso l’ESKD [1, 4]. Per “flare” o recidiva di malattia si intende un incremento di attività della stessa che richiede rimodulazioni terapeutiche. I flare possono essere classificati in nefritici e proteinurici, lievi, moderati o severi. In particolare, si definiscono nefritiche le recidive in cui vi è un aumento riproducibile della creatinina sierica ≥30% (o, una diminuzione del GFR di >10%) e un sedimento urinario attivo con aumento dell’ematuria glomerulare di ≥10 globuli rossi per campo, indipendentemente dalla presenza o meno di proteinuria. I flare nefrosici, invece, sono definiti dal raddoppio riproducibile del rapporto proteine urinarie/creatininuria (UPCR) a >100 mg/mmol dopo una risposta completa o il raddoppio riproducibile dell’UPCR a >200 mg/mmol dopo una risposta parziale [4, 5]. 

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When a Headache Is Not Just Hypertension: A Case of Atypical Hemolytic Uremic Syndrome in a Young Patient

Abstract

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

Sorry, this entry is only available in Italian.

Introduzione

Le microangiopatie trombotiche (TMA) comprendono un gruppo di patologie che, pur presentando una differente eziopatogenesi, sono accumunate da alcune caratteristiche come: danno endoteliale, formazione di microtrombi, trombocitopenia da consumo, anemia emolitica microangiopatica e presenza di danni ischemici secondari polidistrettuali. Le principali entità patologiche incluse nelle TMA sono rappresentate dalla porpora trombotica trombocitopenica (TTP) e dalla sindrome emolitico uremica (HUS) [1]. La TPP è una patologia secondaria alla carenza di una metalloproteasi (ADAMTS13 A Disintegrin And Metalloproteinase with TromboSpondin type 1 motif number 13) normalmente deputata al clivaggio dei multimeri di grandi dimensioni del fattore di von Willebrand (VWF) presenti sull’endotelio vascolare o liberi in circolo [2]. Nella HUS, invece, non si osserva un deficit di ADAMTS13, ma per molteplici cause si innesca un danno endoteliale con successivo quadro di microangiopatia trombotica che, a differenza di quanto osservato nella TTP, presenta un prevalente coinvolgimento renale [3]. La TTP ha un’incidenza di circa 1.5-4 casi su un milione di adulti all’anno, sulla base dei dati del registro TTP-HUS dell’Oklahoma [4]. L’età media per la diagnosi di TTP immunitaria è di 40 anni, con un ampio intervallo (da 9 a 78 anni). 

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Two Cases of Pseudo-Bartter Syndrome in Childhood: When to Suspect a Rare Onset Pattern of Cystic Fibrosis

Abstract

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

Sorry, this entry is only available in Italian.

Introduzione

La fibrosi cistica (FC) è una malattia genetica a trasmissione autosomica recessiva, caratterizzata dalla mutazione del gene che codifica per una proteina (CFTR: cystic fibrosis transmemebrane regulator) coinvolta nel trasporto transmembrana del cloro. Il gene responsabile si trova a livello del braccio lungo del cromosoma 7. Il CFTR è espresso sulle cellule epiteliali delle vie aeree, del tratto digerente, del pancreas, delle vie biliari, nelle ghiandole sudoripare e nell’apparato genitourinario. Le conseguenze del malfunzionamento sono l’incapacità di eliminare secrezioni mucose per lo scarso contenuto di acqua, un elevato contenuto di sali nel sudore e nelle altre secrezioni sierose e infezioni respiratorie croniche. La mutazione più comune del gene è una delezione che determina l’assenza di fenilalanina nella posizione 508 (ΔF508), tuttavia sono state descritte più di 2.000 mutazioni e le conseguenze molecolari di tali mutazioni possono essere raggruppate in 7 classi sulla base del tipo di alterazione (sintesi, maturazione, trasporto, funzionalità) [1]. 

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Anti-Proteinuric Effect of GLP1-RA as Add-On to SGLT2-i and ACE-i in a Diabetic Patient with IgA Nephropathy

Abstract

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

Introduction

IgA nephropathy is the most frequent glomerular disease worldwide. Its clinical course is variable, but in most cases there is a decline in renal function and, despite advances in our understanding of its pathogenesis, treatment strategies haven’t changed much over the last 2 or 3 decades. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h and reduced glomerular filtration rate at diagnosis [1].

There are no disease-specific therapies for IgA nephropathy and the established treatment approach for most patients is to apply supportive measures that include the use of renin-angiotensin-aldosterone system blockade (RAAS) [1, 2] and more recently SGLT2i (as evidenced by the DAPA-CKD study [3] and by the subanalysis of EMPAKIDNEY study, in which 25% of patients were affected by glomerular diseases) [4].

At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents or anticoagulants. The role of immunosuppressive therapy remains controversial and is usually reserved for patients who don’t respond to supportive measures [2]. 

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Contrast-Enhanced Ultrasound as a Diagnostic Procedure in Renal Diseases: A Case Report

Abstract

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

Ultrasound (US) is a non-invasive technique commonly used for first level investigation in renal diseases. It is known to be an easy-to-use and relatively inexpensive approach. Computed tomography (CT) and magnetic resonance (RM) are also used for these indications, but they certainly have a higher cost and risks such as exposure to ionizing radiation in the case of CT. Standard US finds wide use as a screening procedure, but it is not always able to characterize lesions. In fact, lesions may present as isoechoic to the renal parenchyma on grey-scale imaging, and the micro-circulation can be detected with difficulty using Doppler. In addition, the standard US fails to make differential diagnosis between benign and malignant lesions [1].

In contrast, the clinical use of contrast-enhanced ultrasonography (CEUS) in the kidney has been very well defined by the guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2017. Based on these indications, CEUS is appropriate in identifying suspected vascular disorders such as infarction and cortical necrosis; in differentiating between solid and cystic lesions as well as between tumors and pseudotumors. CEUS is useful in the characterization and follow-up of complex cystic masses and in the identification of renal abscesses, as also in radiofrequency ablation of non-surgical masses [2]. 

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Cuff Shaving in Recurrent Exit-Site Infections in a Patient on Peritoneal Dialysis

Abstract

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

Sorry, this entry is only available in Italian.

Introduzione

La via d’accesso al peritoneo continua a costituire un problema nodale nella gestione e nella sopravvivenza della dialisi peritoneale, come lo è l’approccio vascolare in emodialisi. La presenza di un corpo estraneo, il catetere peritoneale, che collega l’ambiente esterno al peritoneo, attraverso cute, sottocute, muscoli e fasce, può favorire le infezioni locali e costituire una via d’accesso per i batteri fino alla cavità peritoneale.

La presenza della cuffia costituisce una barriera protettiva contro l’ingresso dei batteri nel peritoneo, ma a sua volta può essere un fattore irritativo o addirittura un buon nido per i batteri che l’abbiano raggiunta.

La gestione dell’emergenza cutanea del catetere (exit-site) in un paziente in dialisi peritoneale è fondamentale per prevenire ed eventualmente trattare una potenziale infezione della stessa che può rappresentare la porta d’ingresso per i germi e l’evoluzione verso una complicanza più complessa, quale può essere la peritonite che rappresenta poi il rischio fondamentale di fallimento della terapia sostitutiva peritoneale e passaggio all’emodialisi. 

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Steroid-Dependent Nephrotic Syndrome Due to Minimal Change Glomerulonephritis Treated with Rituximab

Abstract

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

Sorry, this entry is only available in Italian.

Introduzione

La glomerulonefrite a lesioni minime (Minimal Change Disease ‒ MCD) rappresenta circa il 15% delle sindromi nefrosiche dell’adulto. Sebbene l’esatta eziologia della MCD rimanga sconosciuta, nella patogenesi sembra giocare un ruolo importante l’attivazione del sistema immunitario. La MCD è generalmente considerata autolimitante con decorso benigno e con un rischio estremamente basso di progressione verso un end-stage renal disease. Tuttavia negli adulti le manifestazioni cliniche sono più severe. Nuovi approcci sono stati adottati nel tentativo di limitare la sindrome nefrosica negli adulti con MCD. La terapia deve essere in grado di indurre una rapida remissione, evitare recidive e limitare gli effetti avversi [1].

Ci sono pochi trial clinici volti a valutare la terapia in questa condizione negli adulti. Il gold standard per il trattamento rimane tutt’oggi la terapia corticosteroidea [2]. Tuttavia solo il 30% degli adulti va incontro a remissione in 8 settimane, che rappresenta il tempo medio di remissione nei casi pediatrici. Negli adulti che hanno risposta alla terapia il 25% va incontro a relapse e il 30% diventa steroide-dipendente [3].  Inoltre il prolungato uso di steroide provoca numerosi effetti collaterali.

L’approccio terapeutico nella MCD non responsiva alla terapia steroidea si avvale di altri farmaci immunosoppressivi quali inibitori delle calcineurine, ciclofosfamide, micofenolato. 

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Examination of Urinary Sediment in a Patient with Lupus-Like HIV-Associated Immune Complex Kidney Disease (HIVICK) – Case Report and Review of the Literature

Abstract

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

Sorry, this entry is only available in Italian.

Introduzione

Nei pazienti affetti da infezione da HIV è molto frequente un coinvolgimento renale. Il fenotipo della malattia renale in corso di HIV varia dalla più frequentemente variante “collapsing” (HIVAN), alla glomerulosclerosi focale e segmentale (GSFS), dalla “lupus-like HIV-immune complex kidney disease” (HIVICK) passando per la malattia a lesioni minime (MCD) e la microangiopatia trombotica. La forma lupus-like è caratterizzata da un quadro istologico che richiama la nefropatia lupica, che può mostrare in maniera variabile ipercellularità endocapillare e/o mesangiale, focale e/o diffusa, oppure un pattern membranoso; caratteristici aggregati tubulo-reticolari nelle cellule endoteliali ben visibili alla microscopia elettronica e un pattern ‘Full House’ con positività anche per C1q all’immunofluorescenza [1]. Non è ben chiaro in che modo l’infezione da HIV possa provocare un coinvolgimento renale. Tra le varie teorie, si pensa che il virus possa direttamente danneggiare i glomeruli e ciò sarebbe supportato da evidenze che dimostrano una regressione del quadro di patologia renale in relazione con la sola terapia antiretrovirale [2] e una maggiore prevalenza di tale condizione in quei pazienti con HIVRNA > 400 copie/ml [3]. Un’altra teoria è a favore di un meccanismo indiretto mediato da anticorpi diretti contro gli antigeni p24 (capside) e gp120 (envelope) dell’HIV, che formerebbero immunocomplessi in circolo che poi precipiterebbero a livello glomerulare, dando i quadri istologici più disparati [1]. Esistono inoltre evidenze secondo le quali il polimorfismo del gene APOL1 sia associato a un maggior rischio, nei pazienti sieropositivi, di sviluppare malattia renale cronica [4] ma non ad una più alta frequenza di HIVICK [1].

I quadri istopatologici sono molto eterogenei e sono riassunti in Tabella 1 [1]. Mancano in letteratura dati di sedimenti urinari in queste condizioni che, come nel seguente caso clinico, potrebbero risultare necessari per vicariare la diagnosi, corroborando tale informazione con quelle fornite dall’agobiopsia renale. 

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Use of CFTR Modulators for Cystic Fibrosis in a Patient with Liver Transplant and ESRD on Hemodialysis

Abstract

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

Introduction

Cystic fibrosis (CF) is an inherited disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, expressed on the epithelial cells of many organs, including respiratory tract, pancreas, liver, intestine, reproductive tract.

The main clinical manifestations include chronic productive cough, difficulty in breathing, intolerance to exercise, pancreatic insufficiency, intestinal malabsorption, meconium ileus at birth.

The main burden to quality of life and the major cause of mortality in CF is progressive lung disease secondary to chronic airway obstruction that predisposes to recurrent pulmonary infection.

Classical treatment of CF is focused on the consequences of CFTR dysfunction and it includes respiratory physiotherapy, muco-active agents, aggressive antibiotic therapy, pancreatic enzyme replacement, high-calorie and high-fat diet.

The newest therapy approach to CF aims to correct structural and functional abnormalities of CFTR protein using CFTR modulators.

To date, there is no experience of CFTR modulators use in patients with end-stage renal disease (ESRD) and in patients undergone organ transplantation. 

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