Kidney Week 2025 Annual Meeting-Role of Complement in ANCA-Associated Vasculitis

Video Transcription

Video Summary

The session opens with housekeeping announcements (industry support, disclosures, recording, evaluations, and how to claim continuing education credit). Moderator Corey Cavanaugh introduces two talks on the role of complement in ANCA-associated vasculitis (AAV).<br /><br />Prof. Andreas Kronbichler reviews how complement—especially the alternative pathway—drives AAV. C5a is highlighted as a potent neutrophil chemoattractant that amplifies inflammation, NET formation, platelet activation, and endothelial injury. Genetic and biomarker studies suggest complement activation correlates with disease severity: some patients have low serum C3 (a minority, but associated with worse renal and overall outcomes), and kidney biopsies often show complement deposits (challenging the “pauci-immune” concept). Proteomic data suggest ANCA-negative crescentic GN may be particularly complement-driven. Animal models show strong protection from glomerular injury with C5/C5aR1 or factor B blockade, though lung disease responses differ between mice and humans. C5aR1 blockade avoids meningococcal prophylaxis concerns seen with terminal C5 inhibition.<br /><br />Prof. Annette Bruchfeld places complement inhibition into clinical practice, focusing on avacopan (C5aR1 antagonist). Trials (notably ADVOCATE) show steroid-sparing benefits, improved sustained remission at 52 weeks, better renal recovery and proteinuria reduction, and improved quality of life. Real-world data include use in patients with very low eGFR, but key questions remain: optimal duration beyond 52 weeks, role in maintenance, cost/access, and long-term safety (being studied in post-authorization cohorts).

Asset Subtitle

Moderator(s): Corey Cavanaugh

Presentation(s):

Introduction - Corey Cavanaugh
Pathophysiology of Complement Activation and Glomerular Injury in ANCA-Associated Vasculitis - Andreas Kronbichler
Where Does Complement Inhibition Fit Within the Treatment Paradigm for ANCA-Associated Vasculitis? - Annette Bruchfeld

This activity is supported by educational funding provided by Amgen.

Meta Tag

Date 11/6/2025

Pathway 1 Glomerular Diseases

Pathway 2 AKI and Critical Care

Session ID 519080

Keywords

ANCA-associated vasculitis

complement system

alternative complement pathway

C5a

C5aR1

avacopan

pauci-immune crescentic glomerulonephritis

renal outcomes and proteinuria

steroid-sparing therapy