What’s New in the Management and Treatment of Glomerulonephritis: Dissecting the Role of Complement in Glomerulonephritis with a Focus on C3G

C3 glomerulopathy (C3G), is a prototypical disorder of complement over activation with prominent C3 deposition on the renal biopsy. Complement dysregulation occurs predominantly in the fluid phase but also in the glomerular microenvironment. The alternative pathway is the key driver of pathology in C3G with terminal pathway recruitment also seen. The disease is largely acquired with activating autoantibodies (e.g. nephritic factor) and only rarely genetic.  This detailed understanding of the underlying pathophysiology of disease has led to ongoing clinical trials of the next generation of alternative pathway complement inhibitors. 

Learning Objectives

1.C3G is a disorder of the alternative pathway of complement 

2.C3G is predominantly driven by autoantibodies such as nephritic factors 

3. Pathogenic genetic variants in complement genes can cause disease but are rare