Association of Low Serum Complement C3 with Reduced Patient and Renal Survival in Antimyeloperoxidase-Associated Small-Vessel Vasculitis

Abstract

Objective: This study aimed to determine the value of hypocomplementemia in predicting the renal and patient survival of patients with antineutrophil cytoplasmatic antibody-associated vasculitis (AAV). Methods: A retrospective analysis of 30 consecutive patients who were diagnosed with AAV and followed at our hospital from 1996 to 2011 was performed. Renal outcome was determined by the Modification of Diet in Renal Disease equation. Disease outcome measures included patient survival and accrual of chronic kidney disease (CKD) defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² from the date of diagnosis. Logistic regression analysis was used to identify predictors of survival. Results: At presentation, 6 (20%) patients had a low C3 level, which was significantly associated with older age (p = 0.009), higher C-reactive protein (p = 0.02), a lower eGFR (p = 0.03), and anti-MPO antibody positivity (p = 0.03). A low C3 level at presentation was significantly associated with a reduced eGFR at the last study visit (p = 0.015, OR = 11; 95% CI 1.27-95.15). During a mean follow-up of 9.0 ± 6.2 years, 8 (26.6%) patients had accrued CKD that was significantly associated with low C3 levels at presentation (p = 0.002, OR = 22; 95% CI 2.36-204.7). Mortality was significantly associated with low serum C3 levels at presentation (p = 0.02). Conclusion: We found that a low serum C3 level at the time of diagnosis was significantly associated with reduced renal and patient survival in patients with anti-MPO AAV. Our results suggest a role for complement activation in the pathogenesis of AAV.

Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis

“…In our study, more than one third of the patients with active renal AAV had reduced sC3 levels; this subset of patients had a dramatically worse renal prognosis, an observation that is in line with findings of a recently published study (15).…”

Antineutrophilic cytoplasmic antibody-associated vasculitis with hypocomplementemia has a higher incidence of serious organ damage and a poor prognosis

“…A clinical study of a small number of patients revealed that hypocomplementemia was associated with the patient prognosis and with a poor renal prognosis. [6] …”

Overview of the Pathogenesis of ANCA-Associated Vasculitis

“…The mouse model of anti-MPO IgG-induced NCGN identified an unsuspected role of complement activation [53] that has subsequently been supported by observations in patients [54,55,56,57,58,59]. The NCGN induced by transfer of anti-MPO IgG into wild-type mice or anti-MPO splenocytes into immunodeficient (Rag2-/-) mice could be completely blocked by complement depletion using cobra venom factor [53].…”

“…A number of subsequent observations in AAV patients support a role for complement activation in pathogenesis, including evidence for complement activation at tissue sites of vascular inflammation and detection of biomarkers for complement activation in plasma and urine [54,55,56,57,58,59]. For example, the complement membrane attack complex C3d and factor B are detected in the lesion sites of patients with AAV [54].…”