Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis

Zhang et al., 2021 | Cardiovasc Drugs Ther | Meta Analysis

Citation

Zhang Yaru, Xu Ruiling, ... Lin Shan. Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis. Cardiovasc Drugs Ther. 2021-Oct;35(5):1057-1066. doi:10.1007/s10557-020-07134-2

Abstract

BACKGROUND: Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK+) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. METHOD: We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included. RESULTS: Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (-0.42 mmol/L; 95% CI: -0.63 to -0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK+ tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups. CONCLUSIONS: SZC effectively decreased the sK+ level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.

Key Findings

Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (-0.42 mmol/L; 95% CI: -0.63 to -0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phas

Outcomes Measured

• Requires manual extraction

Population

MeSH Terms

• Diabetes Mellitus
• Dose-Response Relationship, Drug
• Humans
• Hyperkalemia
• Ion Exchange Resins
• Potassium
• Randomized Controlled Trials as Topic
• Renal Insufficiency, Chronic
• Renin-Angiotensin System
• Silicates

Evidence Classification

• Level: Meta Analysis
• Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review
• Vertical: potassium

Provenance

• PMID: 33459923
• DOI: 10.1007/s10557-020-07134-2
• PMCID: PMC8452568
• Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09