Complement inhibitors for kidney disease

A refined understanding of the role of complement in the pathogenesis of glomerular and other kidney diseases has, over the past two decades, been matched by the development of novel, complement-targeting therapies. As we increasingly recognize the important role that complement activation across all three pathways-classical, lectin and alternative-plays in glomerular lesions both rare (e.g. C3 glomerulopathy) and common (e.g. immunoglobulin A nephropathy), we can identify avenues for precise, targeted approaches to modifying the natural history of these kidney diseases. In this review, we survey the evidence on using complement inhibition from the earliest, small-scale studies focusing on C5-targeting agents to more recent, large, multicenter, randomized trials utilizing complement blockade higher up in the complement pathway at the level of C3. We conclude by examining where the field of complement targeting therapy may be headed in light of these studies.

Automated summary

Over the past two decades, there has been an improved understanding of the role of complement in kidney diseases, leading to the development of new complement-targeting therapies. The activation of complement across all three pathways has been recognized to play a significant role in both rare and common glomerular lesions, providing opportunities for precise interventions. This review examines the evidence on complement inhibition, from small-scale studies focusing on C5-targeting agents to recent large, randomized trials targeting the complement pathway at the C3 level, and discusses future directions in complement targeting therapy.