Advances in Complement-Targeted Therapy for IgA Nephropathy.

Background: IgA nephropathy (IgAN) is a common cause of renal failure among young people in China. The heterogeneity of the clinical and histological characteristics of this disease is predominant, which limits the development of targeted therapeutic drugs for different patient subgroups. In recent years, there has been increasing attention paid to the role of the complement system in the occurrence and development of IgAN, and the research and development of new drugs targeting complement components have made rapid progress. This article examines the connection between IgAN and the complement system, as well as the most recent advancements in the use of novel complement-targeted medications to treat IgAN. Summary: This paper systematically summarizes the association between the complement system and IgAN, as well as the research advances in complement-targeted therapy. In terms of pathogenesis, the four-hit hypothesis states that complement system is involved in the development of IgAN. Among complement activation pathways, the alternative pathway serves as the dominant one, while other pathways also contribute to the renal injury process. In the field of targeted therapy, a variety of inhibitors targeting key components of the complement cascade have entered clinical trials, exhibiting variable therapeutic efficacies. At present, this therapeutic approach faces challenges such as difficulty in patient selection, unclear long-term efficacy and safety profiles, and high drug costs. It is still necessary to improve the therapeutic system by identifying beneficiary populations, developing biomarkers for monitoring drug responses, and supplementing large-scale clinical evidence. Key Messages: Complement-targeted therapy represents a promising novel approach for IgAN treatment, and overcoming current barriers is essential to facilitate the advancement of individualized precision therapy for the condition.