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Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
  1. Thitima Benjachat Suttichet1,
  2. Wonngarm Kittanamongkolchai2,3,
  3. Chutipha Phromjeen2,
  4. Sirirat Anutrakulchai4,
  5. Thanachai Panaput5,
  6. Atiporn Ingsathit6,
  7. Nanticha Kamanamool7,
  8. Vuddhidej Ophascharoensuk8,
  9. Vasant Sumethakul9 and
  10. Yingyos Avihingsanon1
  11. On behalf of the CONTROL and Thai Tacrolimus Trials investigators
  1. 1Department of Medicine, Faculty of Medicine, Center of Excellence in Immunology and Immune-mediated Diseases, Chulalongkorn University, Bangkok, Thailand
  2. 2Chula Clinical Research Center and Renal Immunology and Transplantation Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  3. 3Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  4. 4Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
  5. 5Department of Medicine, Khon Kaen Regional Hospital, Khon Kaen, Thailand
  6. 6Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  7. 7Department of Preventive and Social Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand
  8. 8Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  9. 9Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  1. Correspondence to Dr Wonngarm Kittanamongkolchai; wonngarm.k{at}gmail.com

Abstract

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.

  • biomarker
  • lupus nephritis
  • TWEAK
  • urine protein
  • response prediction

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Footnotes

  • 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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