Kidney Week 2025 Early Program - Glomerular Diseases: 2025 Update-Targeting the Complement Pathway in Glomerular Disease Management

Video Transcription

Video Summary

Dr. Joshua Turman reviews complement-targeting drugs in glomerular disease and how to choose among them based on pathophysiology and approvals. He simplifies complement into three activation pathways (classical, lectin, alternative) that converge on C3, producing downstream inflammatory mediators (C3a, C5a) and the membrane attack complex (C5b-9). The alternative pathway is continuously “ticking over” and normally restrained by regulators; defects in these regulators can preferentially injure the kidney.<br /><br />He groups diseases into: (1) “pure” complement-mediated (atypical HUS/TMA, C3 glomerulopathy), where complement inhibition is central; (2) immune-complex diseases (e.g., lupus, membranous), where complement inhibitors may complement B-cell/plasma-cell therapy by rapidly suppressing kidney inflammation and bridging the delay while immune complexes clear; and (3) “unclear” diseases (IgA nephropathy, ANCA vasculitis) where complement involvement was unexpected but supported by biomarkers, genetics, and trials.<br /><br />Key FDA-approved agents discussed: C5 blockade (eculizumab/ravulizumab) for atypical HUS; C3 blockade (pegcetacoplan) and alternative pathway blockade (iptacopan) for C3G (and pegcetacoplan also for immune-complex MPGN); iptacopan for IgA nephropathy; and C5a receptor blockade (avacopan) for ANCA vasculitis as a steroid-sparing strategy.<br /><br />Main risk is infection with encapsulated bacteria, requiring vaccination (meningococcus, H. influenzae, pneumococcus) and sometimes prophylactic antibiotics. Complement biomarkers may help monitor drug effect and guide future therapy selection. He notes complement is mainly liver-derived but can also be produced locally in the kidney.

Asset Subtitle

Joshua Thurman

Meta Tag

Module GLOM

Speaker Joshua Thurman

Keywords

complement-targeting therapies

glomerular disease

alternative complement pathway dysregulation

C3 glomerulopathy (C3G)

atypical hemolytic uremic syndrome (aHUS)

IgA nephropathy

ANCA-associated vasculitis (avacopan)