A Systematic Review of Sodium Zirconium Cyclosilicate for Hyperkalemia Management in Heart Failure and Chronic Kidney Disease

SZC in HF and CKD

Abstract

Background: Hyperkalemia is common in chronic kidney disease (CKD) and heart failure (HF) and often limits the initiation, continuation, or up-titration of renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (SZC) is a non-absorbed, selective potassium binder used for both acute correction and maintenance therapy.

Methods: We systematically searched PubMed/MEDLINE) to identify randomized and real-world clinical studies evaluating SZC for hyperkalemia in adult CKD and/or HF populations; Embase and Cochrane Library were not searched, and no language restrictions were applied. Reporting was guided by the PRISMA 2020 statement, and study selection is summarized in a PRISMA flow diagram. Evidence was synthesized narratively due to heterogeneity in study designs and outcome reporting.

Results: Across randomized trials, SZC lowered serum potassium rapidly, with onset within 1 hour and clinically meaningful reductions within 24-48 hours. Maintenance-phase trials demonstrated sustained normokalemia during continued SZC dosing. In CKD with concomitant metabolic acidosis, SZC was associated with higher rates of normokalemia maintenance at 4 weeks and modest increases in serum bicarbonate. In HF with reduced ejection fraction during spironolactone optimization, SZC improved maintenance of normokalemia on guideline-directed mineralocorticoid receptor antagonist therapy. Based on observational real-world evidence, studies reported fewer urgent hyperkalemia interventions and improved RAASi persistence; edema related to sodium load and occasional hypokalemia were the most clinically relevant safety considerations.

Conclusion: SZC provides rapid and durable potassium control in CKD and HF and may facilitate continuation of guideline-directed RAASi therapy. Monitoring for sodium-related fluid retention and electrolyte overcorrection is warranted, and the lowest effective dose should be used in volume-sensitive patients. Reported clinical outcome benefits remain hypothesis-generating and require confirmation in prospective trials.