Efficacy and Safety of Low-dose Spironolactone for Chronic Kidney Disease in Type 2 Diabetes

Abstract

Abstract Context Although adding spironolactone to renin-angiotensin system blockers reduces albuminuria in adults with chronic kidney disease and type 2 diabetes, it increases the risk of hyperkalemia. Objective To assess whether a lower dose of spironolactone (12.5 mg/d) reduces the risk of hyperkalemia while maintaining its effect on reducing albuminemia. Design Multicenter, open-label, randomized controlled trial. Setting This study was conducted from July 2016 to November 2020 in ambulatory care at 3 diabetes medical institutions in Japan. Patients We enrolled 130 Japanese adults with type 2 diabetes and albuminuria (≥30 mg/gCre), estimated glomerular filtration rate ≥30 mL/min/1.73 m2, and serum potassium level <5.0 mEq/L. Interventions The participants were randomly assigned to the spironolactone-administered and control groups. Main outcome measures Changes in urine albumin-to-creatinine ratio (UACR) from baseline over the 24-week interventional period. Results The spironolactone group showed a significant reduction in UACR from baseline (mean decrease, 103.47 ± 340.80 mg/gCre) compared with the control group, which showed an increased UACR (mean increase, 63.93 ± 310.14 mg/gCre; P = .0007, Wilcoxon rank-sum test and t test). Although the spironolactone group had a statistically significant increase in serum potassium levels, none of the participants had a potassium level ≥5.5 mEq/L at 24 weeks. Further, participants with a higher initial serum potassium level tended to have a smaller increase (estimate, −0.37, analysis of covariance). Conclusions Low-dose spironolactone administration reduced albuminuria without causing hyperkalemia. Spironolactone administration, the oldest known and most cost-effective mineralocorticoid receptor antagonist, at lower doses should be reconsidered.