Introduction and Aims: Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes. We particularly analysed the association between C3 levels and renal histological features.
Methods: The study included 45 patients diagnosed with AAV between January 2000 and December 2014 in the Nephrology Department of Angers University Hospital, France. All patients had serum C3 level determination at diagnosis, and a renal biopsy was performed on 34 patients at AAV diagnosis. Patients’ charts and kidney biopsies were reviewed for the purpose of the study.
Results: Two groups of patients were defined according to the median C3 level value of the cohort. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P=0.008) and lower eGFR (P=0.002) at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P=0.047 and P=0.001, respectively) (Figure A&B). We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P=0.017, r=-0.407). According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01). Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p=0.046).
Conclusions: A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.
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