Hypocomplementemia is associated with more severe renal disease and worse renal outcomes in patients with ANCA-associated vasculitis: a retrospective cohort study

Background The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV. Methods This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared. Results In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years,p = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL,p = 0.006), were more often hemodialysis dependent (64% vs. 19%,p = 0.009) and progressed more often to ESRD (55% vs. 11%,p = 0.01) compared to normo-complementemic patients (n = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI: 1.354-208.62,p = 0.028) and low serum C3 (HR = 2.492; 95% CI: 1.537-11.567;p = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%,p = 0.033), low serum C3 levels (42% vs. 18%,p < 0.001) and serious infections during follow-up (57% vs. 18%,p = 0.047) compared to those with negative (n = 11) IF staining. Conclusion Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.