Dual blockade of endothelin A and angiotensin II type 1 receptors with sparsentan as a novel treatment strategy to alleviate IgA nephropathy.

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert opinion on investigational drugs Pub Date : 2024-10-18 DOI:10.1080/13543784.2024.2414902
Hajime Nagasawa, Hitoshi Suzuki, Seiji Ueda, Yusuke Suzuki
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Abstract

Introduction: Although immunoglobulin A nephropathy (IgAN) had been discovered more than 50 years ago, 30-40% of IgAN patients still have primary glomerular disease that progresses to end-stage renal disease. However, various treatment strategies for IgAN have rapidly expanded in recent years to include endothelin (ET) receptor antagonists.

Areas covered: In this review, we discuss the role of the ET-1/ETA receptor axis in the development of IgAN, especially focusing on the potential of sparsentan, a dual ET and angiotensin receptor antagonist as a novel therapy for IgAN.

Expert opinion: Evaluation of the MEST-C score at the time of renal biopsy in IgAN is important in determining treatment strategies. If lesions are mainly in the acute phase, such as crescents, steroid therapy should be continued. However, if lesions are mainly in the chronic phase, such as glomerulosclerosis, sparsentan rather than steroid or angiotensin II receptor blocker alone may improve renal outcomes. Although further clinical studies are needed to back up these assumptions, appropriate combination of new drugs containing sparsentan and conventional drugs for IgAN treatment at the appropriate disease stage is expected to further inhibit the progression of renal damage.

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用司帕生坦双重阻断内皮素 A 和血管紧张素 II 1 型受体,作为缓解 IgA 肾病的新型治疗策略。
简介尽管免疫球蛋白A肾病(IgAN)早在50多年前就已被发现,但仍有30%-40%的IgAN患者患有原发性肾小球疾病,并发展为终末期肾病。然而,近年来IgAN的各种治疗策略已迅速扩展,包括内皮素(ET)受体拮抗剂:在这篇综述中,我们讨论了 ET-1/ETA 受体轴在 IgAN 发病过程中的作用,尤其关注了 sparsentan(一种 ET 和血管紧张素受体双重拮抗剂)作为 IgAN 新型疗法的潜力:专家意见:在 IgAN 肾活检时评估 MEST-C 评分对于确定治疗策略非常重要。如果病变主要发生在急性期,如新月体,则应继续使用类固醇治疗。但是,如果病变主要处于慢性期,如肾小球硬化,则单用司帕生坦而非类固醇或血管紧张素 II 受体阻滞剂可能会改善肾脏预后。尽管还需要进一步的临床研究来支持这些假设,但在适当的疾病阶段,将含有 sparsentan 的新药与用于 IgAN 治疗的传统药物适当结合,有望进一步抑制肾损害的进展。
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来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
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.
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