Urinary complement C3 fragment levels and their clinical relevance in MPO-ANCA-associated vasculitis

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease characterized by systemic small-vessel inflammation. Complement activation, particularly through the alternative pathway, has been implicated in AAV pathogenesis. However, the role and clinical significance of urinary complement C3 fragments as non-invasive biomarkers for disease activity remain unclear. This cross-sectional study enrolled 22 AAV patients and 20 healthy controls. Urinary levels of C3a, C3b, iC3b, C3c, and C3d were measured using enzyme-linked immunosorbent assay (ELISA) and normalized to urinary creatinine. Between-group comparisons were performed using independent t-tests or Mann–Whitney U tests. Correlations and independent predictors of urinary complement fragments were evaluated using Spearman correlation and multivariate linear regression, respectively. All urinary complement C3 fragment levels were significantly elevated in AAV patients compared to healthy controls (all p < 0.01). Among AAV patients, urinary C3 fragments correlated strongly with Birmingham Vasculitis Activity Score (BVAS, r = 0.793–0.900), proteinuria (r = 0.551–0.735), and hematuria (r = 0.643–0.752) (all p < 0.01), but not with serum creatinine (p > 0.05). BVAS was an independent predictor of all C3 fragments (β = 0.458–0.760, all p < 0.05), while proteinuria independently predicted all except iC3b (β = 0.302–0.455, all p < 0.05). Urinary complement C3 fragments are elevated in AAV patients and closely associated with disease activity, independent of renal function. These findings support their potential utility as non-invasive biomarkers for monitoring AAV disease activity.