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Sodium zirconium cyclosilicate for renin-angiotensin-aldosterone system inhibitor therapy optimization: A systematic

Hamlet Ghukasyan1, David Abraham Batista da Hora2, Syeda Rubab Fatima3

  • 1Hospital Francesc de Borja, Gandía, Spain.

Nefrologia
|August 19, 2026
PubMed

Insights

Sodium zirconium cyclosilicate (SZC) helps maintain and optimize renin-angiotensin-aldosterone system inhibitors (RAASi) therapy in patients with hyperkalemia. This potassium binder reduces the need for RAASi dose reduction or discontinuation, improving treatment adherence.

Area of Science:

  • Nephrology
  • Cardiology
  • Pharmacology

Background:

  • Renin-angiotensin-aldosterone system inhibitors (RAASi) are crucial for managing chronic kidney disease (CKD) and heart failure (HF).
  • Hyperkalemia (HK) is a common side effect of RAASi therapy, often necessitating dose reduction or discontinuation.
  • Sodium zirconium cyclosilicate (SZC) is a novel potassium binder designed to manage HK and potentially support RAASi therapy.

Purpose of the Study:

  • To evaluate the association between Sodium zirconium cyclosilicate (SZC) therapy and the maintenance or optimization of Renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with hyperkalemia.
  • To assess the impact of SZC on RAASi up-titration, maintenance, and the risk of discontinuation or down-titration.

Main Methods:

  • A systematic meta-analysis of randomized controlled trials (RCTs), observational studies, and post-hoc analyses was conducted.
  • Searched databases included PubMed, Embase, Cochrane, and Web of Science up to August 2025.
  • Six studies (3 RCTs, 3 observational; n=79,956) with 3-12 months follow-up were included, focusing on RAASi maintenance, up-titration, and discontinuation/down-titration.

Main Results:

  • SZC was associated with a significantly higher likelihood of RAASi maintenance (RR 1.26) and up-titration (RR 1.47).
  • Patients receiving SZC had a lower risk of RAASi discontinuation or down-titration (RR 0.56).
  • Consistent benefits were observed in subgroup analyses, including patients with baseline potassium >5.0 mEq/L, and an association between potassium reduction magnitude and RAASi maintenance was found.

Conclusions:

  • Sodium zirconium cyclosilicate (SZC) supports the maintenance and optimization of Renin-angiotensin-aldosterone system inhibitors (RAASi) therapy in hyperkalemic patients.
  • SZC use is linked to a reduced risk of RAASi dose reduction or discontinuation.
  • Further randomized trials are required to ascertain the impact of SZC on cardiovascular and renal outcomes.
Abstract

Keywords:
Chronic kidney diseaseCiclosilicato de sodio y zirconioEnfermedad renal crónicaHeart failureHiperpotasemiaHyperkalemiaInhibidores del sistema renina-angiotensina-aldosteronaInsuficiencia cardíacaMeta-analysisMetaanálisisRAAS inhibitorsSodium zirconium cyclosilicate

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