Supplementary Material for: Finerenone in Chinese Patients with Chronic Kidney Disease and Type 2 Diabetes: A FIDELITY Subgroup Analysis

Background Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduced the risk of heart and kidney outcomes in patients with chronic kidney disease and type 2 diabetes in FIDELITY, a prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD trials. This subanalysis explored the efficacy and safety of finerenone vs. placebo in Chinese patients. Methods Patients with chronic kidney disease (urine albumin-to-creatinine ratio 30–5000 mg/g, estimated glomerular filtration rate [eGFR] ≥25 mL/min/1.73 m2) and type 2 diabetes, on optimized renin–angiotensin system inhibitors, were randomized 1:1 to finerenone or placebo. Key outcomes included a kidney composite (kidney failure, sustained ≥57% eGFR decrease from baseline over ≥4 weeks, or kidney-related death) and a cardiovascular (CV) composite (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure). An additional kidney composite outcome was kidney failure, sustained ≥40% eGFR decrease from baseline over ≥4 weeks, or kidney-related death. Treatment-emergent adverse events were also assessed. Results In this Chinese patient subanalysis (n = 697), finerenone reduced the risk of the ≥57% and ≥40% kidney composite outcomes (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.38–0.86; p = 0.0066 and HR 0.54; 95% CI 0.40−0.74; p < 0.0001, respectively) and CV composite outcome risk vs. placebo (HR 0.82; 95% CI 0.52–1.29; p = 0.3866). Safety outcomes were similar between treatment arms. Hyperkalemia leading to treatment discontinuation was low for finerenone (2.6%) and placebo (0.9%). Conclusion Finerenone demonstrated kidney benefits, favorable trends on CV outcome, and a manageable safety profile in the FIDELITY Chinese subpopulation.背景：非甾体类盐皮质激素受体拮抗剂（mineralocorticoid receptor antagonist）非奈利酮（finerenone），在FIDELITY研究——一项针对FIDELIO-DKD与FIGARO-DKD两项试验的预设合并分析——中，可降低慢性肾脏病合并2型糖尿病患者的心脏与肾脏不良事件发生风险。本亚组分析旨在探讨非奈利酮对比安慰剂在中国患者中的疗效与安全性。研究方法：纳入慢性肾脏病（尿白蛋白/肌酐比值30~5000 mg/g，估算肾小球滤过率[estimated glomerular filtration rate, eGFR]≥25 mL/min/1.73 m²）合并2型糖尿病，且已接受优化剂量肾素-血管紧张素系统抑制剂治疗的患者，按1:1比例随机分配至非奈利酮组或安慰剂组。主要终点包括肾脏复合终点（肾衰竭、估算肾小球滤过率较基线持续降低≥57%且持续≥4周，或肾脏相关死亡）及心血管（cardiovascular, CV）复合终点（心血管死亡、非致死性心肌梗死、非致死性卒中，或因心力衰竭住院）。额外预设肾脏复合终点为肾衰竭、估算肾小球滤过率较基线持续降低≥40%且持续≥4周，或肾脏相关死亡。同时评估治疗期间出现的不良事件。研究结果：本中国患者亚组分析共纳入697例受试者。与安慰剂组相比，非奈利酮可降低≥57%和≥40%两种肾脏复合终点的发生风险（风险比[hazard ratio, HR]分别为0.57；95%置信区间[confidence interval, CI] 0.38~0.86；P=0.0066，以及HR 0.54；95%CI 0.40~0.74；P<0.0001），同时呈现出降低心血管复合终点风险的趋势（HR 0.82；95%CI 0.52~1.29；P=0.3866）。两组安全性结局相似。导致治疗中断的高钾血症发生率较低，非奈利酮组为2.6%，安慰剂组为0.9%。研究结论：在FIDELITY研究的中国亚人群中，非奈利酮展现出明确的肾脏获益、良好的心血管结局趋势，且安全性耐受良好。