Jianwei Ma,1,2, Qin Su,1, Hanlu Wang,1 Jiayan Xu,1,3 Chenyi Yuan,1 Guicai Fan,1,3 Jiapei Ying,1 Xueyan Bian1 1Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, People’s Republic of China; 2Department of Clinical Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Health Science Center, Ningbo University, Ningbo, 315211, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Xueyan Bian, Department of Nephrology, The First Affiliated Hospital of Ningbo University, 59 Liuting Street, Haishu District, Ningbo, 315010, People’s Republic of China, Email fyybianxueyan@nbu.edu.cnBackground: 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
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