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非奈利酮,一种新型非甾体盐皮质激素受体拮抗剂,对心血管疾病、慢性肾脏病和血压的影响。

Effects of Finerenone, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, on Cardiovascular Disease, Chronic Kidney Disease, and Blood Pressure.

机构信息

Internal Medicine Residency Program, Cleveland Clinic Foundation, Cleveland, OH, USA.

Section of Preventive Cardiology and Rehabilitation, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Mail Code JB1, Cleveland, OH, 44195, USA.

出版信息

Curr Cardiol Rep. 2022 Oct;24(10):1251-1259. doi: 10.1007/s11886-022-01750-0. Epub 2022 Aug 4.

Abstract

PURPOSE OF REVIEW

Finerenone, an FDA-approved nonsteroidal mineralocorticoid receptor (MR) antagonist, has been evaluated in context of chronic kidney disease (CKD) and associated cardiovascular disease (CVD). In this review, we summarize pre-clinical and clinical studies focused on the impact of finerenone on these disease processes.

RECENT FINDINGS

Activation of the MR upregulates genes encoding for facilitators of tissue damage. Finerenone binding to a helix domain in this receptor inhibits receptor function. Studies in murine models of kidney disease, heart failure, hypertension, and vascular injury demonstrate significant protective effects of finerenone against further disease progression, as well as association with reduced oxidative stress, inflammation, and fibrosis. Phase 1-3 clinical trials with finerenone show safety and efficacy in improving renal and cardiovascular outcomes in patients with CKD. Research thus far encourages the addition of finerenone to the standard of care for certain CKD patients, especially those especially at risk for or with pre-existing cardiovascular disease. Continued study of the effect of finerenone in diverse patient populations and different disease states is needed.

摘要

目的综述

非奈利酮是一种获得 FDA 批准的非甾体类盐皮质激素受体(MR)拮抗剂,已在慢性肾脏病(CKD)和相关心血管疾病(CVD)的背景下进行了评估。在这篇综述中,我们总结了非奈利酮对这些疾病过程影响的临床前和临床研究。

最新发现

MR 的激活上调了编码组织损伤促进因子的基因。非奈利酮与该受体中螺旋结构域的结合抑制了受体功能。在肾脏病、心力衰竭、高血压和血管损伤的小鼠模型中进行的研究表明,非奈利酮对疾病的进一步进展具有显著的保护作用,并与降低氧化应激、炎症和纤维化有关。非奈利酮的 1-3 期临床试验显示,其在改善 CKD 患者的肾脏和心血管结局方面的安全性和有效性。迄今为止的研究结果鼓励将非奈利酮添加到某些 CKD 患者的标准治疗中,尤其是那些有发生心血管疾病风险或已有心血管疾病的患者。需要进一步研究非奈利酮在不同患者群体和不同疾病状态下的效果。

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