Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists for renal outcomes: A systematic review and meta-analysis

Novel nonsteroidal mineralocorticoid receptor antagonists (MRAs) are noted for their potential cardiorenal benefits for patients with type 2 diabetes mellitus and chronic kidney diseases; however, the effect of this regimen on renal outcomes remains uncertain. We performed a systematic review and meta-analysis of nonsteroidal MRAs focusing primarily on renal outcomes and safety in randomized, controlled trials. The MEDLINE, Embase, and Cochrane databases were systemically searched for trials published through April 2022. We included randomized, controlled trials assessing the effects of nonsteroidal MRAs on renal outcomes, as well as cardiovascular disease (CVD) effects in patients with chronic kidney disease (CKD). Summary estimates of risk ratios (RRs) reductions were calculated with a random-effects model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO under number CRD42022335464. In total, 11 trials and 1 pooled analysis including a total of 17,517 participants were enrolled. Nonsteroidal MRAs reduced renal composite endpoints by 17 % [HR = 0.83, 95 % (0.75, 0.91); low quality] with 16 % in kidney failure (high quality), 23 % in ESRD (high quality), 20 % in eGFR decreased to less than 15 mL/min/1.73 m2 (high quality), and 17 % with more than a 40 % decrease in eGFR (high quality); 14 % with cardiovascular composite endpoints [HR = 0.86, 95 % (0.78, 0.94); moderate quality]; and 13 % of all-cause mortality [HR = 0.87, 95 % (0.76, 0.98); moderate quality]. Nonsteroidal MRAs were also associated with additional benefits in lowering UACR levels (moderate quality) and lowering BP levels (moderate quality) compared with the control groups. However, nonsteroidal MRAs did not show a statistically significant effect on the risk of renal death (moderate quality), hospitalization for any cause (moderate quality) or change in GFR (low quality). Regarding safety, there was no significant difference in the risk of adverse events between the participants receiving nonsteroidal MRAs and the control group. Nonsteroidal MRAs had a statistically beneficial effect on reducing the risk of the composite kidney outcome, the composite of cardiovascular outcomes, and all-cause mortality. Nonsteroidal MRAs were also associated with benefits of proteinuria remission and blood pressure lowering. Although these findings provided positive evidence for the