Abstract / Summary
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. Across 14 randomized trials in dialysis patients, mineralocorticoid receptor antagonists did not reduce cardiovascular or all-cause mortality. They lowered non-fatal cardiovascular events but increased severe hyperkalemia and gynecomastia. Routine use in unselected dialysis populations is not supported and requires careful monitoring.
Primary Source
Renal failure
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