Efficacy and Safety of Finerenone Combined with Dapagliflozin in the Treatment of Non-Diabetic Chronic Kidney Disease: A Single-Center Retrospective Study

Background: The combination of non-steroidal mineralocorticoid receptor antagonists (nsMRAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors has shown renoprotective benefits in diabetic kidney disease; however, their synergistic effects in non-diabetic chronic kidney disease (CKD) remain underexplored. This study evaluated the efficacy and safety of finerenone combined with dapagliflozin versus dapagliflozin monotherapy in patients with non-diabetic CKD. Methods: A single-center, retrospective cohort study was conducted on 121 patients with biopsy- or clinically confirmed non-diabetic CKD treated with either dapagliflozin alone (n = 77) or in combination with finerenone (n = 44) for ≥ 6 months. Propensity score matching (PSM) yielded 33 well-balanced pairs. The primary outcomes were changes in the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) over 6 months. Secondary outcomes included Blood Pressure, biochemical parameters, and treatment-related adverse events. Repeated-measures ANOVA and mediation analyses were used to assess longitudinal changes and mechanistic relationships. Results: Finerenone Combined with Dapagliflozin therapy significantly enhanced UACR reduction at 3 months (median 63.4% vs 47.8%, P = 0.007) and 6 months (66.9% vs 40.8%, P = 0.002), compared with dapagliflozin alone, with a higher proportion of patients achieving ≥ 50% reduction (84.9% vs 45.5%, P < 0.001). The eGFR was preserved or improved with combination therapy (+2.06% vs – 5.08%, P < 0.001), whereas dapagliflozin alone therapy was associated with a decline. Mediation analysis indicated that early UACR reduction explained only 1.45% of the treatment effect on eGFR changes, suggesting albuminuria-independent mechanisms. The incidence of adverse events, including hyperkalemia, did not differ significantly between the groups, and all events were mild and manageable. Conclusion: Finerenone combined with dapagliflozin yielded superior proteinuria reduction and better preservation of renal function compared with dapagliflozin alone in patients with non-diabetic CKD, without compromising safety. These findings provide real-world evidence for the potential additive renoprotective effects of dual therapy and underscore the need for prospective trials to validate its efficacy in non-diabetic populations. Keywords: finerenone, dapagliflozin, non-diabetic chronic kidney disease, albuminuria, estimated glomerular filtration rate