Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, IN, USA.
Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.
Nephrol Dial Transplant. 2022 May 25;37(6):1014-1023. doi: 10.1093/ndt/gfaa294.
Despite the standard of care, patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) progress to dialysis, are hospitalized for heart failure and die prematurely. Overactivation of the mineralocorticoid receptor (MR) causes inflammation and fibrosis that damages the kidney and heart. Finerenone, a nonsteroidal, selective MR antagonist, confers kidney and heart protection in both animal models and Phase II clinical studies; the effects on serum potassium and kidney function are minimal. Comprising the largest CKD outcomes program to date, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) are Phase III trials investigating the efficacy and safety of finerenone on kidney failure and cardiovascular outcomes from early to advanced CKD in T2D. By including echocardiograms and biomarkers, they extend our understanding of pathophysiology; by including quality of life measurements, they provide patient-centered outcomes; and by including understudied yet high-risk cardiorenal subpopulations, they have the potential to widen the scope of therapy in T2D with CKD. Trial registration number: FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049).
尽管有标准的治疗方法，但患有慢性肾脏病 (CKD) 和 2 型糖尿病 (T2D) 的患者仍会进展为透析、因心力衰竭住院并过早死亡。矿物质皮质激素受体 (MR) 的过度激活会导致炎症和纤维化，从而损害肾脏和心脏。非甾体类、选择性 MR 拮抗剂非奈利酮在动物模型和 II 期临床研究中均能提供肾脏和心脏保护作用；对血清钾和肾功能的影响最小。FIDELIO-DKD（非奈利酮降低糖尿病肾病的肾脏衰竭和疾病进展）和 FIGARO-DKD（非奈利酮降低糖尿病肾病的心血管死亡率和发病率）是迄今为止最大的 CKD 结局项目，这两项 III 期试验研究了非奈利酮在 T2D 从早期到晚期 CKD 中对肾脏衰竭和心血管结局的疗效和安全性。通过纳入超声心动图和生物标志物，它们扩展了我们对病理生理学的理解；通过纳入生活质量测量，它们提供了以患者为中心的结果；通过纳入研究不足但风险较高的心肾亚群，它们有可能扩大 T2D 伴 CKD 的治疗范围。试验注册号：FIDELIO-DKD（NCT02540993）和 FIGARO-DKD（NCT02545049）。
