Dose-Specific Network Meta-Analysis of Mineralocorticoid Receptor Antagonists in CKD

Mineralocorticoid receptor antagonists (MRAs) have reemerged as a key strategy for cardiorenal risk reduction after the success of finerenone in large trials. However, high costs have limited the global accessibility, raising a relevant question: whether widely available steroidal MRAs provide comparable efficacy and safety. In the absence of direct comparative trials, we performed a network meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses-2020 guidelines (CRD420251152929).

We searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus for randomized controlled trials (RCTs) evaluating MRAs in chronic kidney disease (CKD). A Bayesian network meta-analysis compared MRAs with standard care. The primary outcome was change in urine albumin-to-creatinine ratio (UACR). Secondary outcomes included change in estimated glomerular filtration rate (eGFR), hyperkalemia, and adverse events. Meta-regression explored effect modification by baseline eGFR and follow-up duration.

A total of 32 trials (N = 21,678) were analyzed. All evaluated MRA dose nodes, which significantly reduced UACR, with overlapping antiproteinuric effects. Spironolactone 25 mg and finerenone 20 mg were associated with similar reductions in albuminuria. Mild reductions in eGFR were observed across treatments, consistent with early hemodynamic adaptation largely informed by short-term studies. Hyperkalemia risk relatively increased, without consistent differences between subclasses. Meta-regression showed no association between UACR reduction and follow-up duration or baseline eGFR. Hyperkalemia and other adverse events were more frequent with longer follow-up and lower baseline eGFR.

Both steroidal and nonsteroidal MRAs were associated with reductions in albuminuria, with substantial overlap in antiproteinuric effects. Our findings underscore the continuing clinical relevance of steroidal MRAs as accessible therapeutic options and support further head-to-head outcome-driven trials in CKD.