Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis
Salem Almaani, Huijuan Song, Meshora Suthanthira, Christopher Toy, Lynn A. Fussner, Alexa Meara, Haikady N. Nagaraja, David Cuthbertson, Nader Khalidi, Curry L. Koening, Carol A. Langford, Carol A. McAlear, Larry W. Moreland, Christian Pagnoux, Philip Seo, Ulrich Specks, Antoine G. Sreih, Kenneth J. Warrington, Paul A. Monach, Peter A. Merkel, Brad H. Rovin, Daniel J. Birmingham
Abstract
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.