227. Urine and Plasma Complement Ba Levels During Flares of Nephritis in Patients with ANCA-Associated Vasculitis

Background: The alternative complement pathway has been implicated in the pathogenesis of ANCA-associated vasculitis (AAV). This knowledge has been leveraged therapeutically and incorporated in the management of AAV. However, it is not clear whether activation of complement primarily occurs systemically or in affected organs such as the kidney. This study measured levels of urinary and plasma complement fragment Ba (uBa and pBa respectively) at multiple time points in patients with AAV.

Methods: The complement fragment Ba was measured by ELISA in serial samples of urine (uBa) and plasma (pBa) from 21 AAV patients who developed a renal flare, 19 who developed a non-renal flare, and 20 in long-term remission. Because the timing of visits prior to a flare differed from patient to patient, visit number was used as a time variable, where visit 0 represents a disease flare in the renal flare and non-renal flare groups. uBA levels were corrected for concentration and uBa-to-creatinine ratios (uBa/uCr) were used for analysis. uBa/uCr levels were correlated to markers of disease activity. Changes in Ba levels were modeled using mixed linear effect models. A logistic regression model was fit to predict a renal flare using Ba/Cr ratio at the visit 0 vs. the non-renal flare and long-term remission groups.

Results: Data from 60 patients were used for this analysis; 32 (53%) were male, 56 (93%) were Caucasian, and 34 (74% with antigen-specific testing) had PR3-AAV. uBa levels increased at renal flare (p<0.001), but did not increase at non-renal flare (p=0.956), and remained stable in long-term remission (p=0.337) (Figure 1a). pBa levels were stable over time in all groups (Figure 1b). uBa correlated with renal AAV activity measured as the renal component of the BVAS score (R²= 0.33, p<0.01) (Figure 2a), but did not correlate with the overall BVAS score during renal flare (R²= 0.13, p=0.12) or non-renal flare (R²= 0.10, p=0.22) (Figure 2b,c). The logistic regression model using Ba/Cr ratio to predict a renal flare had an AUC of 0.76. At a Ba/Cr cutoff of 4160 ng/mg, the sensitivity and specificity for detecting a renal flare were 76.2% and 68.4% respectively.

Conclusions: Urine, but not plasma, Ba levels increase at the time of a flare of renal disease in AAV, suggesting intra-renal alternative complement pathway activation. uBa levels increase at the time of a renal flare but remain stable in patients with a non-renal flare or those in remission, suggesting its potential for use as a surveillance biomarker of renal vasculitis.

Disclosures: This work was supported by the Vasculitis Clinical Research Consortium and the Columbus Medical Research Foundation.