Comparative Kidney Outcomes of Spironolactone vs. Finerenone in Patients with CKD

Background: Spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA), reduces albuminuria in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Finerenone, a non-steroidal MRA, is now recommended for patients with T2DM and CKD with persistent albuminuria despite renin-angiotensin system and sodium-glucose cotransporter-2 inhibition. However, direct comparisons between spironolactone to finerenone on kidney outcomes are lacking. Methods: In this multicenter retrospective cohort study, we identified patients with Stage 3 CKD and T2DM who initiated spironolactone or finerenone between January 1, 2021, and December 31, 2024, using the TriNetX Research Network. Patients with heart failure with reduced ejection fraction and cirrhosis were excluded. The primary outcome was time to a composite of Stage 5 CKD (N18.5), ESKD (N18.6), or all-cause mortality, referred to as “MAKE”. Patients were followed for one year. Results: Among 22,826 eligible patients (spironolactone: 20,724; finerenone: 2,102), 1:1 propensity score matching yielded two balanced cohorts (n=1,843 each). MAKE occurred in 10.4% of the spironolactone group vs. 5.9% of the finerenone group (HR 1.74; 95% CI, 1.37–2.20; P<0.001) (Figure). All-cause mortality (HR 3.31; 95% CI, 2.12–5.17) and stage 5 CKD (HR 1.48; 95% CI, 1.00–2.20) were higher with spironolactone, while ESKD risk did not differ. Spironolactone users also had higher rates of AKI (RR 1.46) and hyperkalemia (RR 1.34). Conclusion: In this multicenter cohort study, patients with stage 3 CKD and T2DM initiated on spironolactone were more likely to experience adverse kidney outcomes compared with patients initiated on finerenone. Further studies are needed to confirm our findings.Figure 1. Kaplan-Meier survival curves comparing the composite outcome of Stage 5 CKD, ESKD, or all-cause mortality for patients with Stage 3 CKD initiated on spironolactone versus finerenone.