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Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study

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 me...

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Autores principales: Suttichet, Thitima Benjachat, Kittanamongkolchai, Wonngarm, Phromjeen, Chutipha, Anutrakulchai, Sirirat, Panaput, Thanachai, Ingsathit, Atiporn, Kamanamool, Nanticha, Ophascharoensuk, Vuddhidej, Sumethakul, Vasant, Avihingsanon, Yingyos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519400/
https://www.ncbi.nlm.nih.gov/pubmed/31168397
http://dx.doi.org/10.1136/lupus-2018-000298
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author Suttichet, Thitima Benjachat
Kittanamongkolchai, Wonngarm
Phromjeen, Chutipha
Anutrakulchai, Sirirat
Panaput, Thanachai
Ingsathit, Atiporn
Kamanamool, Nanticha
Ophascharoensuk, Vuddhidej
Sumethakul, Vasant
Avihingsanon, Yingyos
author_facet Suttichet, Thitima Benjachat
Kittanamongkolchai, Wonngarm
Phromjeen, Chutipha
Anutrakulchai, Sirirat
Panaput, Thanachai
Ingsathit, Atiporn
Kamanamool, Nanticha
Ophascharoensuk, Vuddhidej
Sumethakul, Vasant
Avihingsanon, Yingyos
author_sort Suttichet, Thitima Benjachat
collection PubMed
description 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.
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spelling pubmed-65194002019-06-05 Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study Suttichet, Thitima Benjachat Kittanamongkolchai, Wonngarm Phromjeen, Chutipha Anutrakulchai, Sirirat Panaput, Thanachai Ingsathit, Atiporn Kamanamool, Nanticha Ophascharoensuk, Vuddhidej Sumethakul, Vasant Avihingsanon, Yingyos Lupus Sci Med Biomarker Studies 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. BMJ Publishing Group 2019-04-09 /pmc/articles/PMC6519400/ /pubmed/31168397 http://dx.doi.org/10.1136/lupus-2018-000298 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. 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/.
spellingShingle Biomarker Studies
Suttichet, Thitima Benjachat
Kittanamongkolchai, Wonngarm
Phromjeen, Chutipha
Anutrakulchai, Sirirat
Panaput, Thanachai
Ingsathit, Atiporn
Kamanamool, Nanticha
Ophascharoensuk, Vuddhidej
Sumethakul, Vasant
Avihingsanon, Yingyos
Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
title Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
title_full Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
title_fullStr Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
title_full_unstemmed Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
title_short Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
title_sort urine tweak level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
topic Biomarker Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519400/
https://www.ncbi.nlm.nih.gov/pubmed/31168397
http://dx.doi.org/10.1136/lupus-2018-000298
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