Risk of nephrolithiasis with finerenone versus other chronic kidney disease medications: a comparative real-world evidence study

Finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA), has shown renoprotective benefits for chronic kidney disease (CKD) in people with type 2 diabetes (T2DM); however, its impact on nephrolithiasis remains unexplored. This study compared the risk of incident nephrolithiasis between patients treated with finerenone, spironolactone, or other standard CKD pharmacological therapies. We conducted a new-user, active-comparator retrospective cohort study using the TriNetX US Collaborative Network from June 1, 2021 to June 1, 2024. Adult finerenone initiators were compared with 1:1 propensity-score matched (PSM) cohorts initiating spironolactone, SGLT2 inhibitors (SGLT2i), or Angiotensin-Converting enzyme inhibitors/Angiotensin II receptor blockers (ACEi/ARB). The primary outcome was nephrolithiasis diagnosis (ICD 10: N20-N23) occurring between 4 and 16 months after medication initiation, evaluated using Cox models and time-varying analyses. After PSM, finerenone was associated with a significantly higher risk of incident nephrolithiasis compared to spironolactone (hazard ratio [HR]: 1.328, 95% CI: 1.065–1.657), SGLT2i (HR: 1.483, 95% CI: 1.118–1.967), and ACEi/ARB (HR: 1.495, 95% CI: 1.145–1.953), representing a 32.8%, 48.3%, 49.5% higher relative risk respectively. This increased risk remained consistent across subgroups, including CKD, T2DM, and hypertension. Among patients with T2DM already receiving SGLT2i, the addition of finerenone was significantly associated with an increased stone risk compared to SGLT2i monotherapy. Conclusively, finerenone is associated with a higher incidence of new-onset nephrolithiasis, and it may influence the potential stone-protective effects of SGLT2i.