Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

ObjectiveAlthough the alternative complement pathway has been implicated in the pathogenesis of ANCA-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV.MethodsThe complement fragment Ba was measured by ELISA in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a non-renal flare, and 20 in long-term remission. Urine Ba levels were corrected for urine creatinine (uCr) concentration. Changes in Ba levels were modeled using mixed linear-effect models. A logistic regression model was fit to predict a renal flare using Ba levels at the time of flare versus the non-renal flare and long-term remission groups.ResultsData from 60 patients with AAV were used for this analysis; 53% were male, 93% were White, and 74% had antiproteinase3-ANCA. Urine Ba levels increased at renal flare (p<0.001) but remained stable during a non-renal flare or long-term remission. Plasma Ba levels were stable over time in all groups. Urine Ba levels predicted a renal flare with an area under the curve of 0.76 (p<0.001), with a cutoff of 12.53 ng/mg uCr yielding a sensitivity of 76.2% and a specificity of 68.4%.ConclusionUrine Ba levels, but not plasma Ba levels, are increased at the time of a renal flare in AAV, suggesting intra-renal complement activation, and highlighting the potential use of this biomarker for surveillance of active renal vasculitis.