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IgA肾病靶向治疗的最新进展:自身免疫视角

An Update on Targeted Treatment of IgA Nephropathy: An Autoimmune Perspective.

作者信息

Huang Xin, Xu Gaosi

机构信息

Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Front Pharmacol. 2021 Aug 23;12:715253. doi: 10.3389/fphar.2021.715253. eCollection 2021.

Abstract

Immunoglobulin (Ig) A nephropathy (IgAN) is the commonest form of primary glomerulonephritis worldwide and is, considered a significant cause of end-stage renal disease in young adults. The precise pathogenesis of IgAN is unclear. The clinical and pathological features vary significantly between individuals and races, which makes treating IgAN difficult. Currently, the therapeutic strategies in IgAN are still optimal blood pressure control and proteinuria remission to improve the renal function in most cases. Immunosuppressive drugs such as corticosteroids can be considered in patients with persistent proteinuria and a high risk of renal function decline; however, they include a high toxicity profile. Therefore, the safety and selectivity of medications are critical concerns in the treatment of IgAN. Various pharmacological therapeutic targets have emerged based on the evolving understanding of the autoimmune pathogenesis of IgAN, which involves the immune response, mucosal immunity, renal inflammation, complement activation, and autophagy; treatments based on these mechanisms have been explored in preclinical and clinical studies. This review summarizes the progress concerning targeted therapeutic strategies and the relevant autoimmune pathogenesis in IgAN.

摘要

免疫球蛋白A肾病(IgAN)是全球原发性肾小球肾炎最常见的形式,被认为是年轻成年人终末期肾病的重要病因。IgAN的确切发病机制尚不清楚。其临床和病理特征在个体和种族之间差异很大,这使得IgAN的治疗很困难。目前,IgAN的治疗策略在大多数情况下仍然是优化血压控制和缓解蛋白尿以改善肾功能。对于持续性蛋白尿和肾功能下降风险高的患者,可以考虑使用皮质类固醇等免疫抑制药物;然而,它们具有较高的毒性。因此,药物的安全性和选择性是IgAN治疗中的关键问题。基于对IgAN自身免疫发病机制不断发展的认识,出现了各种药理学治疗靶点,其涉及免疫反应、黏膜免疫、肾脏炎症、补体激活和自噬;基于这些机制的治疗方法已在临床前和临床研究中进行了探索。本综述总结了IgAN靶向治疗策略及相关自身免疫发病机制的研究进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/764a/8419281/a7730bffd47f/fphar-12-715253-g003.jpg

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