Kidney Week Educational Symposia-Mechanisms and Advances in ANCA-Associated Vasculitis

Video Transcription

Video Summary

The symposium reviewed advances in ANCA-associated vasculitis (AAV), linking clinical organ manifestations to immune mechanisms and evolving therapies. ANCA autoantibodies (PR3 or MPO) activate neutrophils/monocytes, driving endothelial injury via broader innate–adaptive immune interactions. Despite standard induction with glucocorticoids plus cyclophosphamide or rituximab, trials show suboptimal long-term survival and frequent relapses, highlighting unmet need.<br /><br />Newer approaches include complement inhibition: mouse models show C5a receptor deletion prevents necrotizing crescentic GN, supporting C5aR blockade (avacopan) to interrupt the ANCA–complement amplification loop. Future concepts discussed include gene editing to delete autoantigens (e.g., PR3 disruption in stem-cell–derived neutrophils), CAR-T strategies, plasma-cell targeting (e.g., anti-CD38), and other novel agents.<br /><br />Treatment updates emphasized guideline-based induction (rituximab or cyclophosphamide with reduced-dose steroids; rituximab preferred in relapsing/PR3 disease; cyclophosphamide favored with very high creatinine). Avacopan reduces steroid exposure and improved sustained remission and eGFR recovery in ADVOCATE. Plasma exchange remains controversial; meta-analyses suggest possible kidney benefit in high-risk patients but increased infection risk.<br /><br />A third talk proposed endothelin as a cardiovascular risk mechanism in AAV remission: patients showed increased arterial stiffness, impaired endothelial vasodilation and fibrinolysis (TPA release), higher endothelin-1 levels, and acute improvement with endothelin receptor blockade—supporting trials of endothelin-targeted therapy and eye imaging as a vascular biomarker.

Asset Subtitle

Moderator(s): Ralph Kettritz

Presentation(s):

Introduction - Ralph Kettritz
Treatment of ANCA-Associated Vasculitis - Duvuru Geetha
The Role of Endothelin in ANCA-Associated Vasculitis - Neeraj Dhaun

This activity is supported by educational funding provided by Amgen.

Meta Tag

Date 10/24/2024

Pathway 1 Glomerular Diseases

Pathway 2 Pathology

Session ID 494158

Session Type ES - Educational Symposium

Keywords

ANCA-associated vasculitis (AAV)

PR3-ANCA and MPO-ANCA

neutrophil activation and endothelial injury

complement C5a receptor (C5aR) blockade

avacopan (ADVOCATE trial)

rituximab vs cyclophosphamide induction therapy

relapse prevention and sustained remission

plasma exchange (PLEX) in severe AAV

endothelin-1, arterial stiffness, and cardiovascular risk biomarkers