Complement inhibition in C3 glomerulopathy

•Dysregulation of the alternative pathway of complement plays a critical role in C3 glomerulopathy.•Ultra-rare variants in complement genes are identified in about 40% of C3 glomerulopathy patients.•C3 nephritic factors are present in the majority of patients with C3 glomerulopathy.•Complement biomarker abnormalities are common in C3 glomerulopathy.•Complement inhibitors provide a targeted approach to the treatment of C3 glomerulopathy.

C3 glomerulopathy (C3G) describes a spectrum of glomerular diseases defined by shared renal biopsy pathology: a predominance of C3 deposition on immunofluorescence with electron microscopy permitting disease sub-classification. Complement dysregulation underlies the observed pathology, a causal relationship that is supported by well described studies of genetic and acquired drivers of disease. In this article, we provide an overview of the features of C3G, including a discussion of disease definition and a review of the causal role of complement. We discuss molecular markers of disease and how biomarkers are informing our evolving understanding of underlying pathology. Research advances are laying the foundation for complement inhibition as a targeted approach to treatment of C3G.