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

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.

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

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.