Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes
Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes
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DOI：
10.1056/nejmoa2025845
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发表时间：
2020-12-03
影响因子：
158.5
通讯作者：
Filippatos, Gerasimos
中科院分区：
文献类型：
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作者：
Bakris, George L.;Agarwal, Rajiv;Filippatos, Gerasimos
非甾体类、选择性盐皮质激素受体拮抗剂非利酮在慢性肾脏病（CKD）和2型糖尿病患者的短期试验中可减少蛋白尿。然而，其对肾脏和心血管outcomes.MethodsIn这个双盲试验的长期影响是未知的，我们随机分配5734例CKD和2型糖尿病患者在1：1的比例接受非那利酮或安慰剂。合格患者的尿白蛋白/肌酐比值（白蛋白以毫克测量，肌酐以克测量）30至小于300，估计肾小球滤过率（eGFR）为25至小于60 ml/min/1.73 m2体表面积，以及糖尿病视网膜病变，或者他们的尿白蛋白/肌酐比值为300至5000，eGFR为25至小于75 ml/min/1.73 m2。所有患者均接受了肾素-血管紧张素系统阻滞剂治疗，在随机分组前已调整至制造商标签上的最大剂量，不会引起不可接受的副作用。在至事件发生时间分析中评估的主要复合结局为肾衰竭、eGFR较基线持续降低至少40%或肾脏原因死亡。关键的次要复合结局，也在时间-事件分析中进行评估，是心血管原因导致的死亡、非致命性心肌梗死、非致命性卒中或因心力衰竭住院治疗。2833例患者中有504例发生主要结局事件非那利酮组2841例患者中有600例（17.8%）和安慰剂组2841例患者中有600例（21.1%）（风险比，0.82; 95%置信区间[CI]，0.73至0.93; P=0.001）。两组分别有367例患者（13.0%）和420例患者（14.8%）发生了关键次要结局事件（风险比，0.86; 95% CI，0.75 - 0.99; P=0.03）。总体而言，两组不良事件的频率相似。高钾血症相关的中断的试验方案的发生率与非那利酮高于安慰剂（2.3%和0.9%，分别）。结论在CKD和2型糖尿病患者中，非那利酮治疗导致CKD进展和心血管事件的风险低于安慰剂。（由拜耳资助; VIDELIO-DKD ClinicalTrials.gov编号，NCT 02540993。）在这项双盲试验中，慢性肾脏疾病和2型糖尿病患者被随机分配接受非甾体类，选择性盐皮质激素受体拮抗剂非那利酮或安慰剂。与安慰剂相比，非那利酮治疗导致慢性肾脏疾病结局和心血管结局的风险降低。
BackgroundFinerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown.MethodsIn this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m(2) of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m(2). All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.ResultsDuring a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P=0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P=0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively).ConclusionsIn patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.)In this double-blind trial, patients with chronic kidney disease and type 2 diabetes were randomly assigned to receive the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone or placebo. Treatment with finerenone resulted in lower risks of chronic kidney disease outcomes and cardiovascular outcomes than placebo.