Efficacy and Tolerability of Sodium Zirconium Cyclosilicate and Patiromer in Managing Hyperkalemia: A Systematic Review and Meta-Analysis of RCTs

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Efficacy and Tolerability of Sodium Zirconium Cyclosilicate and Patiromer in Managing Hyperkalemia: A Systematic Review and Meta-Analysis of RCTs

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Co-author 1

Wannasit Wathanavasin wannasit.medical@mfu.ac.th Charoenkrung Pracharak Hospital Nephrology unit, Department of Medicine Bangkok Thailand *

Co-author 2

Solos Jaturapisanukul solos@nmu.ac.th Vajira Hospital, Navamindradhiraj University Nephrology and Renal Replacement Therapy Division, Department of Internal Medicine Bangkok Thailand -

Co-author 3

Charat Thongprayoon charat.thongprayoon@gmail.com Mayo Clinic Division of Nephrology and Hypertension, Department of Medicine Rochester, Minnesota United States -

Co-author 4

Wisit Cheungpasitporn wcheungpasitporn@gmail.com Mayo Clinic Division of Nephrology and Hypertension, Department of Medicine Rochester, Minnesota United States -

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Introduction

Sodium zirconium cyclosilicate (SZC) and patiromer have recently been approved for the treatment of hyperkalemia. However, their potential to facilitate optimal Renin–Angiotensin–Aldosterone System (RAAS) inhibitor therapy and impact clinical outcomes remains to be fully defined. This study aims to assess their efficacy and tolerability in the management of hyperkalemia.

Methods

A comprehensive search of PubMed, Scopus, and CENTRAL was conducted up to June 6, 2025. Eligible studies included randomized controlled trials (RCTs) reporting the effects of SZC and patiromer on laboratory parameters, clinical outcomes, and safety profiles. Meta-analyses were synthesized using a random-effects model, with results presented as weighted mean differences (WMD) or relative risks (RR), along with 95% confidence intervals.

Results

Nineteen RCTs involving 3,627 patients (1,911 on SZC; 1,716 on patiromer) were analyzed. During the initial 48–72 hours, only SZC significantly reduced serum potassium (sK⁺) levels (WMD: –0.45; 95% CI, –0.61 to –0.29). At the end of treatment, both agents effectively lowered sK⁺ (SZC: WMD –0.50; 95% CI, –0.63 to –0.38; patiromer: WMD –0.36; 95% CI, –0.51 to –0.21). SZC significantly normalized sK⁺ and reduced hyperkalemia incidence, while patiromer enabled RAAS inhibitor optimization by supporting target dosing and reducing discontinuation due to hyperkalemia. However, SZC was associated with a higher incidence of edema (RR: 2.92; 95% CI, 1.08–7.90), and patiromer with increased rates of constipation (RR: 2.96; 95% CI, 1.21–7.22) and hypokalemia (RR: 1.46; 95% CI, 1.05–2.03).

Conclusion

Both SZC and patiromer effectively lower serum potassium, each offering distinct clinical advantages: SZC provides faster potassium normalization, while patiromer supports sustained RAAS inhibitor therapy. Selection should be individualized based on therapeutic intent, comorbidity profile, and adverse event risk.

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