Endothelin receptor antagonists for diabetic kidney disease: back to the future?

IF 4.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert opinion on investigational drugs Pub Date : 2025-04-01 Epub Date: 2025-05-02 DOI:10.1080/13543784.2025.2500294

Panagiota Anyfanti, Marieta Theodorakopoulou, Fotini Iatridi, Pantelis Sarafidis

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引用次数: 0

Abstract

Introduction: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease worldwide. Endothelin-1 (ET-1) is a potent vasoconstrictor secreted by vascular endothelial cells, actively involved in the pathophysiology of numerous cardiovascular diseases. Based on the differential downstream effects of ET-1 binding to its two distinct types of receptors (ET_A/ET_B) within the kidney, selective ET_A receptor blockade has been long proposed as a promising treatment modality for DKD.

Areas covered: This review aims to examine the available evidence base for the use of ERAs in the treatment of DKD, by critically reappraising available landmark trials and discussing their possible position in the context of current treatment of this disease.

Expert opinion: Despite early enthusiasm and widespread expectations, endothelin receptor antagonists (ERAs) faded into obscurity following the release of the first randomized controlled trials (RCTs). More recent RCTs using different compounds have re-introduced ERAs as a promising treatment in the growing pharmaceutical armamentarium of DKD. While the future of DKD management will be based on a more personalized approach, new, robust evidence from appropriately designed RCTs is eagerly anticipated to clearly define the role of ERAs in DKD.

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内皮素受体拮抗剂治疗糖尿病肾病：回到未来？

糖尿病肾病（DKD）是世界范围内慢性肾脏疾病的主要原因。内皮素-1 （ET-1）是一种由血管内皮细胞分泌的强效血管收缩剂，积极参与多种心血管疾病的病理生理过程。基于ET-1与肾脏内两种不同类型受体（ETA/ETB）结合的不同下游效应，选择性ETA受体阻断一直被认为是DKD的一种有希望的治疗方式。涵盖领域：本综述旨在通过批判性地重新评估现有的里程碑式试验，并讨论它们在当前治疗这种疾病的背景下可能的地位，来检查在治疗DKD中使用ERAs的现有证据基础。专家意见：尽管早期的热情和广泛的期望，内皮素受体拮抗剂（ERAs）在第一批随机对照试验（rct）发布后逐渐淡出人们的视野。最近使用不同化合物的随机对照试验重新将ERAs作为一种有希望的治疗方法引入到不断增长的DKD药物装备中。虽然DKD管理的未来将基于更加个性化的方法，但人们热切期待来自适当设计的随机对照试验的新的、可靠的证据，以明确定义era在DKD中的作用。

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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来源期刊

Expert opinion on investigational drugs 医学-药学

CiteScore

10.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.