C3 Glomerulopathy: A Current Perspective in an Evolving Landscape

Abstract

Background: C3 Glomerulopathy (C3G) is a heterogenous disease characterized by dysregulation of the complement alternative pathway (AP). Within 10 years of a diagnosis, roughly 50% of patients with C3G will progress to end stage kidney disease (ESKD). Historically, treatment options have been limited to nonspecific immune suppression with suboptimal response rates to recommended therapies. Advances in immunology and the emergence of novel complement targeted therapies have shifted the focus toward identifying the distinct underlying etiologies of C3G. Summary: In this review, we provide a description of the current landscape and challenges faced in tbe classification, evaluation, and treatment of patients with C3G. Key Message: C3G can be broadly separated into four distinct groups: (1) Genetic mutations/variants, (2) Autoimmune/Acquired auto-antibodies, (3) Monoclonal immunoglobulin associated C3G (MIg-C3G), and (4) C3G without an identified cause. Therapy directed towards the underlying pathogenetic cause of disease may improve outcomes in a disease in which current treatment options are largely ineffective.