Urinary TWEAK reflects disease activity in ANCA-associated vasculitis.

BACKGROUND: The aim of the study was to investigate urinary and serum tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as potential biomarkers in a longitudinal cohort of patients with ANCA-associated vasculitis (AAV). METHODS: Patients with active AAV were included in the study. The Birmingham Vasculitis Score 2003 (BVAS) was used for assessment of disease activity and C-reactive protein (CRP), creatinine, albuminuria, and serum (s) and urinary (u) TWEAK levels were measured at baseline and 6-month follow-up. sTWEAK was measured in population-based controls for comparison. Kidney biopsies from AAV patients were stained for TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) using immunohistochemistry (IHC). RESULTS: sTWEAK was measured in 74 patients and uTWEAK in 69 patients, 42 of whom had kidney involvement. uTWEAK-to-creatinine ratio (uTWEAK/Cr) was significantly higher at baseline compared with follow-up (median 7.21 vs 4.94 ng/mmol, P < .0001). Patients with kidney involvement had higher uTWEAK/Cr levels compared with those without (P = .03). A correlation was found between uTWEAK/Cr and BVAS (P = .006), albuminuria (P = .022) and crescentic changes (P = .03). sTWEAK levels were higher in patients at inclusion than at follow-up (P = .009) but no difference was found when comparing patients and controls, nor did sTWEAK correlate with BVAS. IHC staining showed a clear expression of TWEAK but a fainter pattern of Fn14 in kidney biopsies from AAV patients. CONCLUSIONS: uTWEAK/Cr correlated with BVAS, albuminuria and number of crescents in active AAV and may be a useful biomarker in assessing disease activity in patients with AAV, whereas sTWEAK level is not.