Effect of spironolactone on cardiovascular and renal outcomes in patients with chronic kidney disease

Abstract Background Steroidal mineralocorticoid receptor antagonists (MRAs), including spironolactone, effectively treat resistant hypertension, reduce proteinuria, and lower mortality in heart failure with reduced ejection fraction. However, their long-term effects in chronic kidney disease (CKD) remain unclear. This study investigated spironolactone's impact on end-stage renal disease (ESRD), major adverse cardiovascular events (MACE), hyperkalemia, and mortality in CKD patients. Methods This retrospective hospital-based cohort study enrolled patients with CKD stage 3–5 between January 1, 2011, and June 30, 2023. The patients were classified as spironolactone users or nonusers, with each user matched to two nonusers by propensity scores. The outcomes of interest included ESRD, MACE, all-cause mortality, and severe hyperkalemia. MACE include nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death. Results After propensity score matching, 2711 spironolactone users and 5422 nonusers were included in this analysis. Spironolactone users exhibited higher risks of all-cause mortality (adjusted hazard ratio aHR, 1.23; 95% confidence interval CI, 1.11–1.37) and severe hyperkalemia (aHR, 1.44; 95% CI, 1.24–1.68) than nonusers. However, there was a lower risk of MACE (aHR, 0.90; 95% CI, 0.82–0.99), primarily due to a significant reduction in stroke risk (aHR, 0.79; 95% CI, 0.71–0.88). The risk of ESRD was similar between the two groups (aHR, 1.09; 95% CI, 0.85–1.38). Conclusions In patients with CKD, spironolactone use was associated with a decreased risk of stroke but increased risks of severe hyperkalemia and all-cause mortality, while the risk of ESRD remained unchanged. Individualized clinical decision-making and appropriate dose adjustment are important to balance the potential benefits and risks associated with spironolactone therapy.