Ma Jingyuan, Yiu Wai Han, Tang Sydney C W
Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Diabet Med. 2025 Feb;42(2):e15427. doi: 10.1111/dme.15427. Epub 2024 Aug 27.
Diabetic kidney disease (DKD) is the most common cause of kidney failure, characterized by chronic inflammation and fibrosis. The complement system is increasingly implicated in the development and progression of diabetic nephropathy. The important complement anaphylatoxins C3a and C5a are key mediators of the innate immune system, which regulates cellular inflammation, oxidative stress, mitochondrial homeostasis and tissue fibrosis. This review summarizes the involvement of anaphylatoxins in the pathogenesis of diabetic kidney disease, highlights their important roles in the pathophysiologic changes of glomerulopathy, tubulointerstitial damage and immune cell infiltration, and discusses the modulatory effects of new anti-diabetic drugs acting on the complement system. Based on available clinical data and findings from the preclinical studies of complement blockade, anaphylatoxin-targeted therapeutics may become a promising approach for patients with DKD in the future.
糖尿病肾病（DKD）是肾衰竭最常见的病因，其特征为慢性炎症和纤维化。补体系统在糖尿病肾病的发生发展中所起的作用越来越受到关注。重要的补体过敏毒素C3a和C5a是先天免疫系统的关键介质，可调节细胞炎症、氧化应激、线粒体稳态和组织纤维化。本综述总结了过敏毒素在糖尿病肾病发病机制中的作用，强调了它们在肾小球病变、肾小管间质损伤和免疫细胞浸润的病理生理变化中的重要作用，并讨论了作用于补体系统的新型抗糖尿病药物的调节作用。基于现有的临床数据和补体阻断的临床前研究结果，针对过敏毒素的治疗方法可能在未来成为DKD患者的一种有前景的治疗手段。
