Short-term superiority in proteinuria control with exploratory longitudinal trajectories: finerenone-dapagliflozin combination in non-diabetic kidney disease

Introduction Finerenone and dapagliflozin have demonstrated renal protective effects in diabetic kidney disease, but real-world evidence on their combination in non-diabetic kidney disease (NDKD) remains scarce. We assessed whether their combination improves short-term proteinuria control versus monotherapy, with long-term trajectories explored as hypothesis-generating outcomes. Methods This retrospective cohort study included 327 NDKD patients admitted to Nanjing Drum Tower Hospital (January 2022–March 2026). Patients were divided into three groups: finerenone monotherapy, dapagliflozin monotherapy, or combination therapy. Propensity score matching (PSM) was used to balance baseline characteristics. Short-term (3 months) efficacy, safety, and exploratory cost analysis were compared. Longitudinal data were analyzed using generalized estimating equations (GEE), with the primary inferential window at 3–6 months and a sensitivity analysis at 3–24 months. Multivariate logistic regression identified predictors of treatment failure in the full unmatched cohort. Exploratory subgroup analyses were performed in membranous nephropathy and hypertension. Results After PSM, at 3 months, combination therapy achieved a higher overall remission rate than dapagliflozin monotherapy (69.57% vs. 39.13%, OR = 3.56, 95% CI: 1.50–8.40, P = 0.003), but not versus finerenone monotherapy (68.29% vs. 51.22%, OR = 2.05, 95% CI: 0.84–5.05, P = 0.115). In the primary 3–6 months GEE analysis, time effects were significant for clinical remission rates and proteinuria; Sensitivity GEE analysis (3–24 months) was consistent. Descriptive analyses from 3 to 24 months showed numerical improvement trends across groups, but these are exploratory. Adverse event rates were low, but the analysis was underpowered to exclude increased hyperkalemia risk. In exploratory cost analysis, the ICER was 22.99 RMB per 1% increase in remission rate versus finerenone and 20.79 RMB versus dapagliflozin; probabilistic sensitivity analysis was broadly consistent with the base case, without judgment of economic superiority. Dapagliflozin monotherapy was independently associated with treatment failure (OR = 2.163, 95% CI: 1.073–4.362, P = 0.031) in the full unmatched cohort. Exploratory subgroup analyses suggested potential benefit in membranous nephropathy and hypertension. Conclusion Finerenone combined with dapagliflozin provides higher observed short-term (3 months) efficacy in NDKD, with low observed adverse event rates. Long-term outcomes require validation in larger prospective studies.