Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-Analysis

Clin J Am Soc Nephrol. 2021 Jun;16(6):916-925. doi: 10.2215/CJN.15841020. Epub 2021 Jun 11.

Abstract

Background and objectives: Patients with kidney failure have a high risk of cardiovascular disease due to cardiac remodeling, left ventricular fibrosis, and hyperaldosteronism, all of which can be potentially mitigated by mineralocorticoid receptor antagonists. However, because of the fear of hyperkalemia, the use of mineralocorticoid receptor antagonists in patients with kidney failure is limited in current clinical practice, and few studies have investigated the efficacy and safety. Thus, we aimed to determine the benefits and side effects of mineralocorticoid receptor antagonists in patients with kidney failure treated with dialysis.

Design, setting, participants, & measurements: This is a systematic review and meta-analysis of randomized controlled trials published from 2005 to 2020 that compared the effect of mineralocorticoid receptor antagonists with either placebo or no treatment in patients with kidney failure. Two reviewers independently searched the PubMed, EMBASE, and Cochrane databases for all published studies, extracted data, assessed the risk of bias, and rated the quality of evidence. A meta-analysis was conducted on 14 eligible randomized controlled trials, and a total of 1309 patients were included.

Results: High-quality evidence suggested that mineralocorticoid receptor antagonists are associated with lower cardiovascular mortality (relative risk, 0.41; 95% confidence interval, 0.24 to 0.70; P=0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; P<0.001), and the risk of hyperkalemia was comparable with that of control group (relative risk, 1.12; 95% confidence interval, 0.91 to 1.36; P=0.29). However, no significant decrease in nonfatal cardiovascular events and stroke was observed, and there was no significant improvement in BP or cardiac performance parameters, including left ventricular ejection fraction and left ventricular mass index.

Conclusions: Our meta-analysis suggests that mineralocorticoid receptor antagonists might improve clinical outcomes of patients with kidney failure without significant increase in the risk of hyperkalemia.

Keywords: cardiovascular disease; chronic dialysis; chronic renal failure; electrolytes; end-stage renal disease; heart disease; hemodialysis; mineralocorticoid receptor antagonists; peritoneal dialysis; renin angiotensin system.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Renal Dialysis*
  • Treatment Outcome

Substances

  • Mineralocorticoid Receptor Antagonists