Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l'Université de Montréal, Montréal, Québec, Canada.
Université de Lorraine, INSERM Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.
Clin Sci (Lond). 2022 Jun 30;136(12):1005-1017. doi: 10.1042/CS20220212.
Despite strong preclinical data supporting the use of mineralocorticoid receptor antagonists (MRAs) to provide cardiorenal protection in rodent models of diabetes, the clinical evidence of their utility in treating chronic kidney disease (CKD) has been limited. Two major clinical trials (FIDELIO-DKD and FIGARO-DKD) including more than 13,000 patients with albuminuric CKD and Type 2 diabetes randomized to placebo or finerenone (MRA) have recently provided exciting results showing a significant risk reduction for kidney and cardiovascular outcomes. In this review, we will summarize the major findings of these trials, together with post-hoc and pooled analyses that have allowed evaluation of the efficacy and safety of finerenone across the spectrum of CKD, revealing significant protective effects of finerenone against kidney failure, new-onset atrial fibrillation or flutter, new-onset heart failure, cardiovascular death, and first and total heart-failure hospitalizations. Moreover, we will discuss the current evidence that supports the combined use of MRAs with sodium-glucose co-transporter-2 inhibitors, either by providing an additive cardiorenal benefit or by decreasing the risk of hyperkalemia. Although the mechanisms of protection by finerenone have only been partially explored in patients, rodent studies have shed light on its anti-inflammatory and anti-fibrotic effects in models of kidney disease, which is one of the main drivers for testing the efficacy of finerenone in non-diabetic CKD patients in the ongoing FIND-CKD trial.
尽管有强有力的临床前数据支持使用盐皮质激素受体拮抗剂 (MRA) 为糖尿病啮齿动物模型提供心脏肾脏保护,但它们在治疗慢性肾脏病 (CKD) 中的效用的临床证据一直有限。两项主要的临床试验(FIDELIO-DKD 和 FIGARO-DKD)包括了超过 13000 名患有白蛋白尿性 CKD 和 2 型糖尿病的患者,这些患者被随机分配至安慰剂或非奈利酮(MRA)组,最近提供了令人兴奋的结果,表明肾脏和心血管结局的风险显著降低。在这篇综述中,我们将总结这些试验的主要发现,以及事后和汇总分析,这些分析评估了非奈利酮在 CKD 全谱中的疗效和安全性,显示了非奈利酮对肾衰竭、新发心房颤动或扑动、新发心力衰竭、心血管死亡以及首次和总心力衰竭住院的显著保护作用。此外,我们将讨论目前支持 MRA 与钠-葡萄糖共转运蛋白-2 抑制剂联合使用的证据,这既可以提供额外的心脏肾脏益处,也可以降低高钾血症的风险。尽管非奈利酮在患者中的保护机制仅部分得到了探索,但啮齿动物研究揭示了其在肾脏病模型中的抗炎和抗纤维化作用,这是在正在进行的 FIND-CKD 试验中测试非奈利酮在非糖尿病性 CKD 患者中的疗效的主要驱动力之一。