#2335 Associations of systemic complement, kidney deposition and gene polymorphisms with patient and renal outcomes in ANCA-associated vasculitis—a systematic review

Abstract Background and Aims Complement activation leads to inflammation and organ damage in ANCA-associated vasculitis (AAV). However, the impact of systemic and kidney-specific complement markers, as well as complement gene polymorphisms on patient and kidney outcomes is unclear. We conducted a systematic review to assess the associations of systemic and kidney complement markers, and complement gene polymorphisms, with clinical severity, and prognosis in AAV. Method We conducted a literature search using the Pubmed/ MEDLINE database for publications from inception to January 2024 using pre-defined search criteria (PROSPERO registration CRD42023489422). Two researchers independently reviewed the titles and abstracts of the articles. Studies were included if they involved human subjects with AAV (including microscopic polyangiitis (MPA), granulomatous polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA)) and assessed the impact of markers in complement activation such as complement levels in systemic circulation, complement deposition in kidney biopsies, or complement gene polymorphisms. Studies were excluded if they were non-human studies, did not include AAV and/or complement, not published in English, or were reviews, case reports, or case series with fewer than 5 patients. Results Among 593 articles screened, 41 publications from 40 studies fulfilled the inclusion criteria. AAV was defined according to the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides or the 1990/2021 American College of Rheumatology criteria (34 studies) and/or by kidney histology (11 studies). Complement markers evaluated included levels of C3, C4, and/or C5 (including C5a and C5b-9) in the systemic circulation (31 studies) and urine (3 studies), deposition of C3, C4, C5, and/or C1q in the kidney biopsy (10 studies), and complement gene polymorphisms (2 studies). The outcomes included all-cause mortality or patient survival (18 studies), kidney survival (23 studies), AAV relapses (17 studies), kidney function (14 studies), and kidney histology (9 studies). Low plasma C3 levels were associated with higher risk of all-cause mortality in 11 of 15 studies and higher risk of end-stage kidney disease (ESKD) or dialysis in 14 of 19 studies. The presence of C3 in the glomeruli was associated with higher risk of ESKD or dialysis in 5 of 7 studies. Conclusion Markers of complement activation may be associated clinical outcomes for patients with AAV.