Differences in Efficacy Among New and Old Potassium Binders in Dialysis Patients: A Systematic Review and Meta-Analysis.

Introduction. Hyperkalemia is a common and serious complication in dialysis patients, with increased incidence and severity over time. Newer potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), offer improved tolerability compared to older agents. This meta-analysis aims to evaluate the efficacy and safety of these newer binders in dialysis patients. Methods. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted, adhering to PRISMA guidelines. Searches were performed in MEDLINE, PubMed, CINAHL, and EMBASE up to November 1, 2024. RCTs comparing patiromer or SZC to placebo, sodium polystyrene sulfonate (SPS), or calcium polystyrene sulfonate (CPS) in dialysis patients were included. Primary outcomes were differences in serum potassium levels. Secondary outcomes included adverse events (AEs) and mortality. Data were analyzed using fixed and random-effects models, and heterogeneity was assessed. Results. Six RCTs, involving 3155 patients, were included. SZC and SPS significantly reduced pre-HD potassium levels compared to placebo (mean difference -0.68 mmol/L and -0.62 mmol/L, respectively; p<0.0001). Patiromer did not show a significant difference compared to placebo (mean difference -0.17 mmol/L; p=0.16). All treatments demonstrated a reduction in hyperkalemia events compared to placebo. Adverse event data were limited and not statistically analyzable, but no significant differences in total AEs were observed. Mortality data were sparse, with only one death reported in the placebo group. High heterogeneity was observed in the comparison between new and old binders/placebo. Conclusion. SZC and SPS effectively reduce pre-HD potassium levels in dialysis patients compared to placebo. Patiromer's effect was not statistically significant. All binders reduced hyperkalemia events. Safety profiles appeared comparable, but data were limited. The lack of sufficient RCTs, especially those directly comparing newer binders, highlights a significant knowledge gap. Further studies are needed to evaluate long-term outcomes, including quality of life and cardiovascular effects, and to directly compare the efficacy and safety of different potassium binders in this population.