Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study
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尿液 TWEAK 水平作为活动性狼疮肾炎治疗早期反应的生物标志物：一项前瞻性多中心研究
DOI：
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发表时间：
2019
影响因子：
3.9
通讯作者：
Y. Avihingsanon
中科院分区：
文献类型：
--
作者：
T. B. Suttichet;W. Kittanamongkolchai;Chutipha Phromjeen;Sirirat Anutrakulchai;T. Panaput;A. Ingsathit;Nanticha Kamanamool;Vuddhidej Ophascharoensuk;Vasant Sumethakul;Y. Avihingsanon
背景：肿瘤坏死因子样弱凋亡诱导因子（TWEAK）是一种促炎分子，在狼疮性肾炎（LN）的活动性炎症中起关键作用。发现尿TWEAK（uTWEAK）水平与LN患者的肾脏疾病活动相关。在这里，我们确定了诱导治疗期间uTWEAK的连续测量是否可以预测治疗反应。方法收集经活检证实的活动性LN患者在发作时、发作后3个月和6个月的尿液样本，以评估uTWEAK水平。所有患者均接受标准免疫抑制治疗，并在6个月时评价治疗反应。将uTWEAK作为治疗反应的预测因子的性能与临床上用于LN患者的生物标志物进行比较。结果110例LN患者中，完全缓解（CR）29%，部分缓解（PR）34%，无效（NR）37%。平均而言，CR中的uTWEAK水平始终较低，PR中3个月时呈下降趋势，NR中持续升高。第3个月时的uTWEAK水平能够预测第6个月时的完全缓解（根据年龄、性别和肌酐调整的OR =0.34 [95% CI 0.15 - 0.80]，受试者工作特征曲线下面积[ROC-AUC]=0.68，p=0.02）。第3个月时uTWEAK水平的最佳阈值为0.46 pg/mgCr，以70%的灵敏度和63%的特异性区分完全缓解。在第3个月时将uTWEAK和尿蛋白组合改善了在第6个月时完全反应的预测性能（R 0 C-AUC 0.83，p<0.001）。结论除尿蛋白外，急性发作后3个月的uTWEAK水平可提高预测诱导治疗6个月完全缓解的准确性。
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.
DOI：
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发表时间：
2007
期刊：
Bulletin of the NYU hospital for joint diseases
影响因子：
--
作者：
B. Rovin;D. Birmingham;H. Nagaraja;C. Y. Yu;L. Hebert
通讯作者：
B. Rovin;D. Birmingham;H. Nagaraja;C. Y. Yu;L. Hebert
影响因子：
32.4
作者：
Wiley, SR;Cassiano, L;Fanslow, WC
通讯作者：
Fanslow, WC