Albuminuria-Lowering Effect of Sodium-Glucose Cotransporter 2 Inhibitors, Finerenone, and Their Combination in Patients with CKD

Background: Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2is) and Finerenone reduce urine albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with Chronic Kidney Disease (CKD). Methods: We conducted a retrospective study in patients seen in a community nephrology practice with eGFR 25-90 ml/min per 1.73 m2 and UACR ≥30 mg/g Cr. Patients were stratified into 3 groups: 8 months treatment period with SGLT2is, 4 months treatment period with Finerenone, and 8 months with combination therapy (SGLT2i for 4 months followed by SGLT2i and Finerenone for additional 4 months). The outcome was the percent change in UACR from baseline. Results: Of 402 patients screened between 1/2022 and 9/2023, 85 were included with mean eGFR, 51.5 ml/min per 1.73 m2, and median UACR 594 mg/g. 47 patients received SGLT2i (dapagliflozin 10 mg/day or empagliflozin 10 mg/day), 19 received Finerenone (20 mg/d for eGFR > 60 or 10 mg/d for eGFR 25-60, and 19 were on combination therapy. The mean percentage change from baseline in UACR in the SGLT2is group and Finereone group was -46.35% (95% CI, -53.39 to -39.31) and -44.65% (95% CI, -68.67, -20.64), respectively. SGLT2i-Finerenone combination therapy decreased UACR by -65.5% (95% CI, -71.82, -59.17; P<0.001 vs SGLT2i; P=0.04 vs Finerenone) (Fig 1). Compared with the Finerenone group, the mean change in serum potassium level (mmol/L) was significantly lower in the combination group (+ 0.3 vs -0.02, P=0.01). (Fig 2) Conclusions: Combining dapagliflozin or empagliflozin with Finerenone resulted in a significantly additive UACR-lowering effect with a significant decrease in the risk of hyperkalemia.