# Urinary TWEAK reflects disease activity in ANCA-associated vasculitis

## TL;DR

This study shows that urinary TWEAK levels correlate with disease activity in patients with ANCA-associated vasculitis, suggesting it could be a useful biomarker.

## Contribution

The study identifies urinary TWEAK as a novel biomarker for monitoring disease activity in ANCA-associated vasculitis.

## Key findings

- Urinary TWEAK-to-creatinine ratio was significantly higher at baseline compared to follow-up in AAV patients.
- Urinary TWEAK levels correlated with disease activity, albuminuria, and crescentic changes in AAV.
- Serum TWEAK levels did not differ between patients and controls and did not correlate with disease activity.

## Abstract

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).

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).

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.

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.

Graphical Abstract