Hyperkalemia treatment in chronic kidney disease patients: overview on new K binders and possible therapeutic approaches

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Toni De Stefano

Toni De Stefano, Silvio Borrelli, Carlo Garofalo, Michele Provenzano, Luca De Nicola, Roberto Minutolo, Giuseppe Conte

Affiliazione: Cattedra di Nefrologia-Università degli studi della Campania “Luigi Vanvitelli”; P.O. S.M.d.P. Incurabili, Napoli

Autore Corrispondente:
Dott. De Stefano Toni
Cattedra di Nefrologia, Università degli studi della Campania “Luigi Vanvitelli”
Dip. Scienze Mediche, Chirurgiche, Metaboliche e dell’invecchiamento
Piazza Miraglia, 80138 Napoli
Tel/Fax: 0812549409
E-mail: toni-ds@live.it

 

Abstract

Hyperkalaemia is a common complication in patients with nondialysis Chronic Kidney Disease (CKD). It is associated with weakness, paralysis, arrhythmias and increased mortality. Higher serum potassium levels refractory to treatment is one of the most frequent reasons to initiate immediately renal replacement treatment in advanced stages of CKD. Hyperkalaemia is also indirectly associated with the progression of CKD; in fact higher serum potassium levels may lead to withdrawal of renin-angiotensin-system inhibiting drugs that currently represent the most effective tools to postpone ESRD. It is therefore essential to identify patients at higher risk of increase of serum K and to implement therapeutic interventions aimed at preventing and treating hyperkalaemia, such as diet modifications and greater use of diuretics and potassium binders. Sodium and calcium-polystyrenesulfonate (SPS) are the resins currently available in Italy. However, few studies showed that SPS is efficacious to reduce serum K and is associated with increased risk of severe adverse effects. Patiromer and ZS-9 represent a significant pharmacological progress in the treatment of hyperkalemia. Indeed, recent studies showed that these novel binders are efficient to reduce serum levels of K with minor occurrence of side effects than polystyrensulfonates. Furthermore, Patiromer, sodium free agent, might have a further advantage in CKD patients, reducing the salt intake in these patients. In addition, ZS-9, being fast-acting drug, might be used also in the treatment of acute hyperkalaemia.

Keywords: Hyperkalaemia, L binder, SPS, CPS, Patiromer, ZS-9

Sorry, this entry is only available in Italian.

L’iperkaliemia (o iperpotassiemia) è uno dei più comuni disturbi elettrolitici osservabili in pazienti con malattia renale cronica (CKD) o scompenso cardiaco congestizio. In accordo con la letteratura corrente, non c’è una definizione univoca: si può parlare di iperkaliemia sia quando il livello di potassio (K) nel sangue supera il cut-off di 5,0 mEq/L (1–3) sia quando supera il cut-off di 5,5 mEq/L (4, 5).

L’iperkaliemia è piuttosto rara nella popolazione generale poiché una funzione renale conservata consente una regolazione fine ed efficace l’omeostasi del potassio (6).

 

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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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