Effects of Mineralocorticoid Receptor Antagonists for Chronic Kidney Disease: A Systemic Review and Meta-Analysis

Abstract

Introduction: The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD) are inconsistent. We aimed to summarize the significance of MRAs in treating CKD. Methods: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non–dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. Results: 53 trials with 6 different MRAs involving 22792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (WMD, -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-hour urinary protein excretion (WMD, -0.20 g, 95%CI, -0.28 to -0.12 g), eGFR (WMD, -1.99 ml/min/1.73 m2, 95% CI, -3.28 to -0.70 ml/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79 to 0.93) and cardiovascular events (RR, 0.84, 95% CI, 0.77 to 0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73 to 2.40) and hypotension (RR, 1.80, 95% CI, 1.41 to 2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56 to 0.75), but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79 to 1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57 to 0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02 to 1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26 to 25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22 to 1.22) increased the risk of breast disorders. Conclusions: In the CKD patients, MRAs, particularly in combination with ACEI/ARB, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increased the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs was superior in the reduction of more albuminuria with fewer peripheral edema events, and without the augment of breast disorders events.