Nonsteroidal mineralocorticoid receptor (MR) antagonists (MRAs) reduce the risk of renal and cardiovascular outcomes in patients with and without chronic kidney disease (CKD), findings from a new systematic review and meta-analysis suggest. Use of the drugs may also reduce albuminuria and blood pressure.

“Overactivation of [the] MR promotes inflammation, oxidative stress and fibrosis and is one of the key factors leading to the development and progression of kidney and cardiovascular damage,” Jingwei Zhou, MD, of Dongzhimen Hospital of Beijing University of Chinese Medicine in China and colleagues explained in Diabetes Research and Clinical Practice. “MR antagonists (MRAs) can directly target aldosterone to play an anti-inflammatory and antifibrotic role and can provide cardiorenal protection, including beneficial effects in hypertension, heart failure and chronic kidney disease (CKD),” they wrote.

The investigators pooled data from 11 randomized controlled trials and 1 meta-analysis including 17,517 patients. Of the cohort, 92.6% had stage 1-5 CKD, 91.0% had type 2 diabetes, and 92.1% had hypertension. Most patients (15,607) were treated with finerenone, whereas 1456 received esaxerenone (CS-3150), 292 apararenone (MT-3995), and 162 KBP-5074.

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The primary endpoint was a composite renal outcome of a sustained 40% or greater or 40% or greater decrease in estimated glomerular filtration rate (eGFR) from baseline, doubling of baseline serum creatinine, end-stage kidney disease (ESKD), or renal death.

Finerenone use was significantly associated with a 17% reduced risk of the renal composite endpoint compared with control, Dr Zhou and colleagues reported. By component, nonsteroidal MRA use was significantly associated with a 23% lower risk for ESKD  a 20% decreased risk of a decline in eGFR to less than 15 mL/min/1.73 m2, and a 17% decreased risk of a greater than 40% decline in eGFR.

In addition, the risk of cardiovascular composite endpoints significantly decreased by 14% and all-cause mortality by 13% with use of nonsteroidal MRAs, Dr Zhou’s team reported.

The investigators also found evidence that nonsteroidal MRAs reduce albuminuria. Compared with the control group, patients taking nonsteroidal MRAs experienced a urinary albumin to creatinine ratio (UACR) decline of 32%, a 2.9-fold greater likelihood of a 30% or more decrease in UACR, or an absolute UACR reduction of 105.13 mg/g. Systolic blood pressure decreased by an additional 2.58 mm Hg and diastolic blood pressure by an additional 1.82 mm Hg with use of the nonsteroidal MRAs compared with control.

With respect to safety, the investigators found no significantly greater risks of hyperkalemia, elevated serum potassium, hypotension, hypoglycemia, or urinary tract infection with nonsteroidal MRAs.

The investigators judged the quality of the evidence to be low to moderate and encouraged more well-controlled trials.


Chen Q, Liang Y, Yan J, et al. Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists for renal outcomes: A systematic review and meta-analysis. Diabetes Res Clin Pract. Published online December 9, 2022. doi:10.1016/j.diabres.2022.110210