Complement anaphylatoxins: Potential therapeutic target for diabetic kidney disease

Abstract

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.