Abstract
End-stage kidney disease (ESKD) patients receiving dialysis bear a heavy burden of cardiovascular disease (CVD), the leading cause of mortality. Mineralocorticoid receptor antagonists (MRAs) have cardiovascular protective effects in non-dialysis patients, but their efficacy and safety in dialysis-dependent individuals remain controversial. This study aimed to clarify their clinical value via an updated systematic review and meta-analysis. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we systematically searched PubMed, EMBASE, and The Cochrane Library up to 25 August 2025. Eligible studies were parallel-design randomized controlled trials (RCTs) enrolling adults (≥18 years) on maintenance dialysis, comparing MRAs with placebo or no intervention. Two reviewers independently screened studies, extracted data, and assessed quality using the Cochrane Risk of Bias Tool 2.0. Meta-analysis was performed with Cochrane Review Manager 5.4. The results showed that a total of 14 RCTs involving 4,525 patients were included (13 used spironolactone, one used eplerenone; follow-up: 3-40.8 months). MRAs significantly reduced nonfatal CVD events (RR 0.68, p = 0.04) but had no significant effect on cardiovascular mortality (RR 0.75, p = 0.14) or all-cause mortality (RR 0.76, p = 0.05). They significantly elevated risks of severe hyperkalemia (RR 1.35, p = 0.009) and gynecomastia and breast pain (RR 4.23, p < 0.001). In conclusion, MRAs can reduce the incidence of nonfatal cardiovascular events in dialysis patients; however, clinicians also need to be mindful of the risks of severe hyperkalemia as well as gynecomastia and breast pain in men when prescribing them.