C3 Glomerulopathy

A consensus report in 2013 defined the term C3 glomerulopathy (C3G) to describe a group of glomerular disorders resulting from dysregulation of the complement system's alternative pathway. This condition is characterized by the dominant deposition of C3 in the glomerulus without or with scant immunoglobulin deposition. C3G encompasses 2 major subtypes—C3 glomerulonephritis (C3GN) and dense deposit disease (DDD)—based on different patterns of C3 deposition on electron microscopy. C3GN comprises about 66% of cases and DDD about 33%. Previously, these disease processes were often classified as types of membranoproliferative disease. Clinical manifestations of both can include features of both nephritic and nephrotic syndromes.

C3 glomerulopathy involves intricate complement system dysregulation. A solid understanding of the alternative complement pathway, how it differs from other complement-mediated diseases, and the role of genetic mutations or autoantibodies is essential for accurate diagnosis and management. The diagnosis of C3 glomerulopathy requires the use of advanced diagnostic tools, such as studies for autoantibodies to complement system components, genetic identification of essential complement proteins and regulatory proteins, and histologic analysis of kidney tissue.