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Systematic review and meta-analysis of MRAs in dialysis patients shows reduced nonfatal CVD events but elevated hyperkalemia and gynecomastia risksNew analysis shows dialysis drugs cut heart attacks but raise dangerous potassium risks

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Key Takeaway
Consider MRA risks of hyperkalemia and gynecomastia despite reduced nonfatal CVD events in dialysis patients.

This systematic review and meta-analysis examined the use of mineralocorticoid receptor antagonists (MRAs) specifically in adults aged 18 years or older undergoing maintenance dialysis. The analysis included data from 4,525 patients and assessed outcomes over a follow-up period ranging from 3 to 40.8 months. The study compared MRA therapy against placebo or no intervention.

The authors synthesized findings regarding nonfatal cardiovascular events, cardiovascular mortality, all-cause mortality, severe hyperkalemia, and gynecomastia with breast pain. Results indicated a significant reduction in nonfatal cardiovascular events with a relative risk of 0.68 and a p-value of 0.04. Conversely, cardiovascular mortality showed no significant effect with a relative risk of 0.75 and a p-value of 0.14. All-cause mortality also showed no significant effect with a relative risk of 0.76 and a p-value of 0.05.

Safety outcomes revealed significantly elevated risks for severe hyperkalemia with a relative risk of 1.35 and a p-value of 0.009. Additionally, gynecomastia and breast pain occurred with a relative risk of 4.23 and a p-value less than 0.001. The review notes that while MRAs may reduce nonfatal cardiovascular events, clinicians must remain mindful of the risks of severe hyperkalemia and gynecomastia and breast pain in men when prescribing them.

People on dialysis often face serious heart risks. A new analysis looked at two common heart medicines called spironolactone and eplerenone. These drugs block a specific receptor in the body to help manage fluid and pressure. The study combined data from 4,525 adults who were already on maintenance dialysis.

The results showed a clear benefit for heart health. Patients taking these medicines had significantly fewer nonfatal cardiovascular events. This means fewer heart attacks or strokes that did not immediately lead to death. The reduction was strong enough to be considered real and important for patient care.

However, the study also found serious safety concerns. There was a significantly higher risk of severe hyperkalemia, which is a dangerous buildup of potassium in the blood. Men taking these drugs also faced a much higher risk of gynecomastia and breast pain. These side effects can be severe and may require stopping the medication.

Clinicians must balance the heart benefits against these specific risks. The evidence suggests these drugs can help prevent heart trouble, but doctors need to watch potassium levels closely. They must also discuss the potential for breast pain and swelling with male patients before starting treatment.

What this means for you:
These drugs reduce heart attacks in dialysis patients but raise risks of dangerous potassium levels and breast pain.

Study Details

Study typeMeta analysis
Sample sizen = 4,525
EvidenceLevel 1
PublishedDec 2026
View Original 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,  = 0.04) but had no significant effect on cardiovascular mortality (RR 0.75,  = 0.14) or all-cause mortality (RR 0.76,  = 0.05). They significantly elevated risks of severe hyperkalemia (RR 1.35,  = 0.009) and gynecomastia and breast pain (RR 4.23,  < 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.
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