Timing of the CKD Complications: A Longitudinal Analysis

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Vincenzo Calabrese

DOI: 10.69097/41-06-2024-10

Calabrese V1, Gembillo G2, Longhitano E2, La Placa C2, Ferio C2, Cernaro V2, Santoro D2

1 Departmet of Medicine and Surgery, University of Enna “Kore”, 94100, Italy
2 Department of Clinical and Experimental Medicine, Unit of Nephrology and Dialysis, A.O.U. “G. Martino”, University of Messina, Messina, 98125, Italy

Corresponding author:
Vincenzo Calabrese
Tel: 328736905
E-mail: v.calabrese@outlook.it

 

Abstract

Background. Complications of chronic kidney disease include endocrine and metabolic abnormalities, anaemia and a wide range of disorders of homeostasis. Our study aims to better determine the role of CKD stage on the timing of the various complications associated with renal dysfunction.
Methods. We performed an observational study on 71 (F:M = 39:32) patients with 486 repeated measurements, recording anemia, BUN, hyperparathyroidism, hyperphosphatemia, hyperkalemia, metabolic acidosis. Data were summarized as mean and standard deviation, median and interquartile range, or absolute number. Differences among groups were tested through the Mann-Whitney test or Pearson’s Chi-Square. The associations between eGFR and each outcome was tested by Spearman’s correlation test. All variables related to the outcomes (with p-value <0.1) were included in the multivariate models. Longitudinal analysis was performed using generalized estimated equations (GEE) for binary outcome and by Linear Mixed Models for continuous variables. The ROC Curve with the Youden J index was evaluated for all binary outcomes. Results. Baseline analysis revealed hyperparathyroidism in 49 patients (69.1%), hyperphosphatemia in 11 patients (15.5%), hyperkalemia in 20 patients (28.6%), and mean serum urea was 78 mg/dl [IQR: 59-99]. CKD stage was related with all outcomes. Youden J index suggested an eGFR predictive value of 37 ml/min/m2 for anemia, 34 ml/min/m2 for hyperkalemia, 26 ml/min/m2 for hyperphosphatemia, and 46 ml/min/m2 for hyperparathyroidism.
Conclusion. Based on our findings, screening tests for endocrine and metabolic complications of CKD should be initiated at the beginning of the CKD stage III. We suggest screening for hyperphosphataemia at the CKD stage IV.

Keywords: Acidosis, Anemia, CKD, Parathormone, Phosphate, Potassium

Introduction

Chronic kidney disease (CKD) is characterized by an alteration of adequate metabolic homeostasis, increasing the risk of acidosis, hyperkalemia, hyperuricemia, hyperparathyroidism, hyperphosphatemia, and anemia.

This condition leads to a reduced excretory function, resulting in the accumulation of toxins in the body [1]. Among these catabolism products, urea is not completely excreted by the kidney when renal function is impaired.

As well for urea, renal filtration of hydrogen cations is altered when the residual nephron mass is impaired, increasing the risk of acidosis. Indeed, the severiry of acidosis is higher in patients with severe CKD [2]. Potassium removal is also reduced due to impaired renal function. Moreover, potassium is reabsorbed by proximal tubular cells through the exchange between H+ and K+ to correct acidosis [3].

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Hyperkalemia as a limiting factor in the use of drugs that block the Renin Angiotensin Aldosterone System (RAAS)

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Antonio Santoro1, Marcora Mandreoli2

1 Divisione di Nefrologia, Dialisi ed Ipertensione, Policlinico S.Orsola-Malpighi Azienda Ospedaliero-Universitaria di Bologna
2 UOC Nefrologia e Dialisi, Ospedale S. Maria della Scaletta, Imola

Autore corrispondente:
Antonio Santoro
Divisione di Nefrologia, Dialisi ed Ipertensione
Policlinico S.Orsola-Malpighi
Azienda Ospedaliero-Universitaria di Bologna
Via P. Palagi,9
40138 Bologna
E-mail: antonio.santoro@unibo.it

 

Abstract

Angiotensin-converting enzyme (ACE-I) inhibitors and ARBs have shown real efficacy in reducing blood pressure, proteinuria, in slowing the progression of chronic kidney disease (MRC) and in clinical improvement. in patients with heart failure, diabetes mellitus and ischemic heart disease. However, their use is limited by some side effects such as the increase in serum potassium (K), which can be particularly severe in patients with renal insufficiency. In the 23,000 patients followed by the PIRP project of the Emilia-Romagna Region, hyperkalaemia at the first visit (K> 5.5 mEq / L) was present in about 7% of all patients. The prevalence of K values> 5.5 mEq / L increased in relation to the CKD stage, reaching 11% in patients in stage 4 and 5. Among patients with values ​​of K> 5.5 at baseline, 44.8% were in therapy with ACE-I / ARB inhibitors, 3.8% with anti-mineralcortoid and a further 3.9% concurrently taking SRAA-blocking agents and K-sparing diuretics. Counter-measures to avoid the onset of hyperkalemia during treatment with drugs that block the RAAS range from the low-K diet, to diuretics and finally to drugs that promote fecal elimination of K. Among these, polystyrene sulfonates, which have more than 50 years of life, exchange K with sodium or calcium. These drugs, however, in chronic use, can lead to sodium or calcium overload and cause dangerous intestinal necrosis. Recently two new highly promising drugs have been introduced on the market for the treatment of hyperkalemia, the patiromer and sodium zirconium cyclosilicate. The patiromer, which is a potassium-calcium exchanger, acts at the level of the colon where there is a higher concentration of K and where the drug is most ionized. Sodium zirconium cyclosilicate (ZS-9) is a resin with micropores of well-defined dimensions, placed in the crystalline structure of the zirconium silicate. The trapped K is exchanged with other protons and sodium. However, even these drugs will have to demonstrate their long-term efficacy and safety to be considered true partners of RAAS blockers in some categories of patients.

Key words: potassium, hyperkalemia, ARB, ace-inhibitors, renal failure, patiromer, sodium zieconium cyclosylate, ZS-9, kayexalate

Sorry, this entry is only available in Italian.

Introduzione

Gli inibitori dell’enzima di conversione dell’angiotensina (ACE-I) ed i bloccanti dei recettori dell’angiotensina (ARB) hanno dimostrato una reale efficacia nel ridurre la pressione arteriosa,la proteinuria e nel rallentare la progressione della malattia renale cronica (1–3). Inoltre questi farmaci favoriscono il miglioramento clinico in pazienti con insufficienza cardiaca, diabete mellito e cardiopatia ischemica. Tuttavia, questa classe di farmaci è stata anche associata ad eventi avversi, a volte severi: comparsa di insufficienza renale acuta, iperkalemia severa (4, 5) importanti riduzioni della pressione arteriosa.

Il timore verso gli effetti avversi dei bloccanti del Sistema Renina Angiotensina Aldosterone (SRAA), spesso comporta una loro sottoutilizzazione o un sottodosaggio, in particolare nei sottogruppi di pazienti che sono maggiormente a rischio di sviluppare complicanze. Uno studio turco che si è occupato di valutare le barriere che limitano l’uso di ACE-I e ARB in pazienti con insufficienza renale cronica, ha riconosciuto nell’iperkalemia, l’elemento principale che porta alla sospensione dei bloccanti il SRAA (6). Anche lo studio di Shirazian ha evidenziato che l’iperkalemia rappresenta la causa principale di sottoutilizzo di ACE-I e ARB (7).

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