美国芝加哥大学George L. Bakris团队研究了Finerenone治疗2型糖尿病慢性肾脏病对患者预后的影响。2020年10月23日，该研究发表在《新英格兰医学杂志》上。

在涉及慢性肾脏病（CKD）和2型糖尿病患者的短期试验中，非甾体类选择性盐皮质激素受体拮抗剂Finerenone降低了白蛋白尿，但其对肾脏和心血管结局的长期影响尚不清楚。

在这项双盲试验中，研究组招募了5734名CKD和2型糖尿病患者，按1：1随机分配，分别接受Finerenone或安慰剂治疗。这些患者的尿白蛋白与肌酐之比（白蛋白以毫克为单位，肌酐以克为单位）小于或等于300，估计肾小球滤过率（eGFR）为25-60 ml/min/1.73m²（体表面积），伴糖尿病性视网膜病变，或尿白蛋白/肌酐比为300至5000，eGFR为25-75 ml/min/1.73m²。主要复合终点为肾功能衰竭、eGFR持续下降至少40％（基线）或肾脏原因死亡。关键次要复合终点为心血管原因死亡、非致命性心肌梗塞、非致命性中风或因心力衰竭住院。

在2.6年的中位随访期间，Finerenone组2833例患者中有504例（17.8％）发生主要复合终点，安慰剂组2841例患者中有600例（21.1％），组间差异显著。Finerenone组中有367例患者（13.0％）发生关键次要复合终点，显著低于安慰剂组（420例，14.8％）。总体而言，两组间不良事件发生率相似。Finerenone组中因高钾血症而停药的发生率为2.3%，显著高于安慰剂组（0.9%）。

总之，Finerenone治疗CKD和2型糖尿病患者，与安慰剂相比，可显著降低CKD进展和心血管事件的风险。

附：英文原文

Title: Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes | NEJM

Author: George L. Bakris, M.D.,, Rajiv Agarwal, M.D.,, Stefan D. Anker, M.D., Ph.D.,, Bertram Pitt, M.D.,, Luis M. Ruilope, M.D.,, Peter Rossing, M.D.,, Peter Kolkhof, Ph.D.,, Christina Nowack, M.D.,, Patrick Schloemer, Ph.D.,, Amer Joseph, M.B., B.S.,, and Gerasimos Filippatos, M.D.

Issue&Volume: 2020-10-23

Abstract:

Background

Finerenone, 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.

Methods

In 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 m2 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 m2. 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.

Results

During 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).

Conclusions

In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo.

DOI: 10.1056/NEJMoa2025845

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2025845