Efficacy of finerenone in reducing proteinuria in diabetic kidney disease with maximum tolerable doses of dapagliflozin and telmisartan

非奈利酮在接受最大耐受剂量达格列净和替米沙坦治疗的糖尿病肾病患者中降低蛋白尿的疗效

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Abstract

BACKGROUND: Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease (ESRD), with persistent proteinuria contributing to renal and cardiovascular complications. Despite dual therapy with renin-angiotensin-aldosterone system (RAAS) blockers and sodium-glucose co-transporter-2 inhibitors (SGLT2is), residual proteinuria persists in a substantial subset of patients. Finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, has shown promise in reducing albuminuria and slowing chronic kidney disease progression. This study evaluated the additive effect of finerenone exclusively in patients receiving maximum tolerable doses of both dapagliflozin and telmisartan unlike previously available studies evaluating its effect on patients with maximum tolerated dose of angiotensin receptor blocker alone. AIM: To evaluate the efficacy and safety of finerenone in reducing proteinuria in patients with DKD who were receiving maximally tolerated doses of dapagliflozin and telmisartan. METHODS: A retrospective, single-center observational study evaluated 33 patients with DKD and residual proteinuria. All patients received finerenone 10 mg daily for 24 weeks. Key parameters assessed at baseline and follow-up included urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate, and serum potassium. Responders were defined as patients who exhibited a reduction in UACR at follow-up. RESULTS: The mean reduction in UACR was 9.5% (P = 0.256). Twenty-two patients (66.7%) responded to treatment with a reduction in UACR, while 11 patients (33.3%) showed no reduction. When stratified by baseline albuminuria, responders with initial UACR < 1000 mg/g, 1000-3000 mg/g, and > 3000 mg/g showed average reductions of -47.9%, -39.0%, and -32.8%, respectively, suggesting a gradient treatment effect. Finerenone was well tolerated with mild hyperkalemia (serum potassium > 5.0 mmol/L) noted in 15.2% of patients with mean increase in serum potassium by 6.4% (P = 0.016). No cases required treatment discontinuation due to hyperkalemia. Renal function remained stable during the study. CONCLUSION: Finerenone was associated with an overall reduction in albuminuria, with the magnitude of response varying according to baseline UACR. Greater proportional reductions were observed in patients with lower baseline albuminuria, while patients with moderate to severe albuminuria demonstrated a more heterogeneous response, including both responders and non-responders. Despite this variability, finerenone was generally safe and well tolerated. These findings support the use of finerenone as part of a multimodal strategy for proteinuria management in DKD, particularly as add-on therapy in patients receiving optimized RAAS blockade and SGLT2 inhibition, with the greatest benefit seen when introduced earlier in the course of albuminuric disease.

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