Urinary Complements as a Predictor of Kidney Outcomes in Patients with ANCA-Associated Vasculitis

Background: Anti-Neutrophil Cytoplasmic Antibody (ANCA) -associated vasculitis (AAV) is a systemic vasculitis characterized by inflammation of small blood vessels that can lead to rapidly progressive glomerulonephritis. Recent research has underscored the significance of C5a in the pathogenesis of this condition. Although there are reports of elevated urinary complement levels during the active phase of AAV, the exact relationship between elevated complement and renal outcome is unclear. Methods: This study included 36 patients (median age 73 [69, 78] years, 38.9% male, serum Cr 2.26 [1.2, 5.5] mg/dL) with newly diagnosed MPO-ANCA positive AAV with renal involvement who were admitted to our hospital from March 2019 to November 2023. Urine samples were collected at the beginning of treatment and stored in a -30 °C freezer. Urinary complement levels (specifically C5a and C3a) were measured using each ELISA kits (Becton, Dickinson and Company, Franklin Lakes, NJ). Patients were classified into three groups (low, intermediate, and high) based on their respective C5a/Cr and C3a/Cr ratios and their progression to end-stage kidney disease (ESKD) was evaluated. In addition, the relationship between urinary complement levels and renal biopsy findings was also examined (n=32). Results: Five patients developed ESKD during the 2-year follow-up period, and Kaplan-Meier analysis showed no significant difference among the three groups in C5a/Cr ratio (P=0.053), but there was a significant difference in C3a/Cr ratio among the groups (P=0.025). Histopathological examination showed an associations between C3a/Cr ratio and cellular crescent formation (|ρ|=0.3947, P=0.025) and tubulointerstitial lesions (|ρ|=0.4002, P=0.023), while C5a/Cr ratio was correlated with tubulointerstitial lesions (|ρ|=0.4563, P=0.010). Conclusion: Urinary complement levels in newly diagnosed AAV patients may be a useful biomarker for assessing the risk of developing ESKD. It also correlates with renal involvement in patients with AAV and may be an alternative to kidney biopsy.