Background TNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory molecule that plays a key role in active inflammation of lupus nephritis (LN). Urine TWEAK (uTWEAK) levels were found to be associated with renal disease activity among patients with LN. Here, we determined whether serial measurements of uTWEAK during induction therapy could predict treatment response or not.
Methods Spot urine samples were collected from patients with biopsy-proven active LN at time of flare, and 3 and 6 months after flare to assess the uTWEAK levels. All patients received standard immunosuppressive therapy and treatment response was evaluated at 6 months. The performance of uTWEAK as a predictor for treatment response was compared with clinically used biomarkers for patients with LN.
Results Among 110 patients with LN, there were 29% complete responders (CR), 34% partial responders (PR) and 37% non-responders (NR). On average, uTWEAK level was consistently low in CR, trended down by 3 months in PR and persistently elevated in NR. uTWEAK levels at month 3 were able to predict complete response at month 6 (OR adjusted for age, sex and creatinine=0.34 [95% CI 0.15 to 0.80], the area under the receiver operating characteristic curve [ROC-AUC]=0.68, p=0.02). The optimal threshold for uTWEAK level at month 3 was 0.46 pg/mgCr, discriminating complete response with 70% sensitivity and 63% specificity. Combining uTWEAK and urine protein at month 3 improved predictive performance for complete response at 6 months (ROC-AUC 0.83, p<0.001).
Conclusions In addition to urine protein, uTWEAK level at 3 months after flare can improve the accuracy in predicting complete response at 6 months of induction therapy.
- lupus nephritis
- urine protein
- response prediction
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Presented at Part of this study was presented at the 12th International Congress on Systemic Lupus Erythematosus (LUPUS 2017) and the 7th Asian Congress on Autoimmunity (ACA 2017), held in Melbourne, Australia, on 28 March 2017.
Contributors TBS and WK performed data analysis and drafted the manuscript. CP did sample handling and measurement. SA, TP, AI, NK and VO recruited volunteers and performed clinical trials. VS drafted the clinical trial. YA drafted the study concept and biomarker project and finalised the manuscript.
Funding This study was supported by a grant from the National Science and Technology Development Agency (NSTDA) (P-13-00505) and International Network for Lupus Research (IRN59W0004), the Thailand Research Fund (TRF). TBS received support from the Post-Doctoral Scholarship, Ratchadaphiseksomphot Fund, Chulalongkorn University.
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval The study was approved by the Joint Research Ethics Committees, Thailand (JREC017/55, COA-JREC: 012/2012) and the Ethics Committee for Human Research of the Faculty of Medicine, Chulalongkorn University (IRB No 122/55).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data, protocols and materials will be made available to researchers upon request and disclosed where restrictions apply.
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