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用斯巴森坦双重阻断内皮素 A 和血管紧张素 II 型 1 受体作为一种减轻 IgA 肾病的新型治疗策略。

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

机构信息

Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Division of Kidney Health and Aging, The Center for Integrated Kidney Research and Advance, Shimane University Faculty of Medicine, Shimane, Japan.

出版信息

Expert Opin Investig Drugs. 2024 Nov;33(11):1143-1152. doi: 10.1080/13543784.2024.2414902. Epub 2024 Oct 18.

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/ET 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.

摘要

简介

尽管免疫球蛋白 A 肾病 (IgAN) 已被发现超过 50 年,但仍有 30-40%的 IgAN 患者存在原发性肾小球疾病进展为终末期肾病。然而,近年来,IgAN 的各种治疗策略迅速扩展,包括内皮素 (ET) 受体拮抗剂。

涵盖领域

在这篇综述中,我们讨论了 ET-1/ET 受体轴在 IgAN 发展中的作用,特别关注沙库巴曲缬沙坦(一种双重 ET 和血管紧张素受体拮抗剂)作为 IgAN 新疗法的潜力。

专家意见

在 IgAN 时进行肾活检时评估 MEST-C 评分对于确定治疗策略很重要。如果病变主要处于急性阶段,如新月体肾炎,则应继续进行类固醇治疗。但是,如果病变主要处于慢性阶段,如肾小球硬化,则沙库巴曲缬沙坦而不是类固醇或血管紧张素 II 受体阻滞剂单独治疗可能会改善肾脏结局。虽然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,适当组合含有沙库巴曲缬沙坦的新药和常规药物治疗 IgAN,有望进一步抑制肾脏损害的进展。

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