The non-steroidal mineralocorticoid receptor antagonist finerenone is a novel therapeutic option for patients with Type 2 diabetes and chronic kidney disease.

Jonatan Barrera-Chimal, Casimiro Gerarduzzi, Patrick Rossignol, Frédéric Jaisser
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引用次数: 3

Abstract

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.

非甾体矿物皮质激素受体拮抗剂芬尼酮是2型糖尿病和慢性肾病患者的一种新的治疗选择。
尽管强有力的临床前数据支持矿皮质激素受体拮抗剂(MRAs)在糖尿病啮齿动物模型中提供心肾保护,但其治疗慢性肾脏疾病(CKD)的临床证据有限。两项主要的临床试验(FIDELIO-DKD和FIGARO-DKD)包括13000多名白蛋白尿CKD和2型糖尿病患者,随机分配给安慰剂或芬尼酮(MRA),最近提供了令人兴奋的结果,显示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,这些分析已经允许评估芬纳酮在CKD范围内的有效性和安全性,揭示芬纳酮对肾衰竭、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全部心力衰竭住院的显著保护作用。此外,我们将讨论目前支持MRAs与钠-葡萄糖共转运蛋白2抑制剂联合使用的证据,无论是通过提供附加的心肾益处还是通过降低高钾血症的风险。虽然芬尼酮的保护机制在患者中只被部分探索,但啮齿动物研究已经揭示了其在肾脏疾病模型中的抗炎和抗纤维化作用,这是在正在进行的FIND-CKD试验中测试芬尼酮对非糖尿病性CKD患者疗效的主要驱动因素之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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