Background and aims Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that processes via prolonged activation of the NF-κB pathway. TWEAK plays role in autoimmune diseases like lupus nephritis (LN). TWEAK soluble form and its receptor were found in active LN. We determined whether urinary TWEAK (uTWEAK) levels predict response to standard treatment in a multi-centre clinical trial of lupus patients.

Methods Urine samples were collected at baseline, 3 and 6 month of LN patients from a multi-centre randomized-controlled study (Clinicaltrials.gov ID#NCT01015456). The uTWEAK levels were measured with commercially available enzyme-linked immunosorbent assay (ELISA) kits.

Results All subjects (n=49) were biopsy-proven proliferative class III/IV LN. Median (IQR) patient’s age were 32 (29-36) years old. Urine protein creatinine ratio and serum creatinine were 6.32 (6.16–9.20) mg/mg and 0.80 (0.82–1.03) mg/dL. After 6 month treatment of either intravenous cyclophosphamide (IVCY) or mycophenolate sodium (MPS) and steroids, there were 32 responders and 13 non-responders. Baseline uTWEAK levels were higher in non-responder LN compared with responders LN. This was observed in both treatment either IVCY (n=25) or MPS (n=24) (175.50±36.97 vs 57.09±7.40 pg/mL; p=0.018 or 124.90±34.53 vs 55.69±14.22 pg/mL; p=0.038). The area under the ROC curve to predict response to treatment was 0.79 (95% CI=0.64–0.94). The cut-off level of 94.0 pg/dL predict resistant-to-treat at sensitivity and specificity of 64 and 85 percent, respectively.

Conclusions uTWEAK may be a biomarker that guide treatment of lupus nephritis patients. Targeting TWEAK protein in active lupus nephritis is an interesting choice of therapy.