Novel nonsteroidal mineralocorticoid receptor antagonists (MRAs) appear safe and effective in patients with chronic kidney disease (CKD) and type 2 diabetes, but may result in a modest increase in hyperkalemia risk, a new meta-analysis concludes.

In an indirect comparisons meta-analysis of 8 randomized controlled trials including 14,450 patients, urinary albumin to creatinine ratio (UACR) decreased by a significant weighted mean difference (WMD) of 0.40 with the novel MRAs compared with placebo, Xiaofeng Pu, MSc, of The Affiliated Hospital of Southwest Medical University in Luzhou, China, and colleagues reported in Frontiers in Pharmacology. Apararenone, esaxerenone, and finerenone decreased UACR by a WMD of 0.61, 0.54, and 0.30, respectively, compared with placebo. Systolic blood pressure also significantly decreased 4.84 mm Hg more with the novel MRAs than with placebo.

Estimated glomerular filtration rate (eGFR), however, significantly decreased 2.69 mL/min/1.73 m2 more with these medications. The investigators also found that the risk of hyperkalemia significantly doubled with use of novel MRAs. Whether the novel nonsteroidal MRAs provide aldosterone blockade with less risk for hyperkalemia compared with the traditional steroidal MRAs spironolactone and eplerenone warrants further study.

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There was no significant difference in the incidence of serious adverse events between groups.

“Despite the moderate increased risk of hyperkalemia, use of non-steroidal MRAs could reduce proteinuria and [systolic blood pressure] in patients with CKD and T2D,” the investigators concluded.

Further randomized controlled trials are needed to validate the findings and provide guidance for clinical treatment.


Jiang X, Zhang Z, Li C, et al. Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes: A systematic review incorporating an indirect comparisons meta-analysis. Front Pharmacol. Published online June 16, 2022. doi:10.3389/fphar.2022.896947