C3 glomerulopathy: advancements in diagnostics and therapeutics

C3 glomerulopathy is a complex, relatively recently elucidated topic with many diagnostic and therapeutic developments over the last 10 years. The authors aim to update the general, glomerular disease, and transplant nephrology audience regarding these new discoveries.

C3 glomerulopathy (C3G) includes a spectrum of disorders both etiologically, and morphologically, like dense deposit disease. Further developments in related glomerular pathologies like immune complex mediated membranoproliferative glomerulonephritis (ICMPGN), C3 monoclonal immunoglobulin deposition disease (C3-MIDD), and post infectious glomerulonephritis (PIGN) are emerging. Increases in molecular testing have revealed genetic links to alternative complement and acquired nephritic and anticomplement antibodies as playing an etiologic role. This alongside new pharmaceutical developments have moved the field forward significantly. There are also two new pivotal pharmacological agents approved by the United States Food and Drug Administration (USFDA). The new pharmacological pathways involve Factor B blockade (iptacopan) and C3 blockade (pegetacoplan).

The new diagnostic, genetic, and molecular developments are discussed; changes in nomenclature and taxonomy are reviewed. Finally, landmark trials (such as the APPEAR-C3G and VALIANT, respectively) are reviewed to provide clinicians and clinician researchers with a timely update of new events in C3G.