Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis
Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis
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DOI：
10.1093/rheumatology/kep468
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发表时间：
2010-05-01
期刊：
影响因子：
5.5
通讯作者：
Putterman, Chaim
中科院分区：
文献类型：
--
作者：
Rubinstein, Tamar;Pitashny, Milena;Putterman, Chaim
目标.目前使用的临床和实验室标志物对预测狼疮患者肾脏疾病的发展具有有限的特异性和敏感性。在这项纵向研究中，我们研究了尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）是否能预测有和无活检证实的狼疮性肾炎病史的狼疮患者的活动性肾炎和肾耀斑。通过SLEDAI和BILAG评分确定肾脏疾病活动和发作状态。随机效应模型用于确定uNGAL是否是SLE患者肾脏疾病活动性的重要预测因子，以及是否是已确诊肾炎患者肾脏疾病发作的重要预测因子。为了评估uNGAL的预测性能，使用先前访问的uNGAL水平构建受试者工作特征（ROC）曲线。然后将这些曲线与用目前使用的生物标志物构建的曲线进行比较。ROC曲线确定的临界值在一个独立的验证队列中进行检验。在校正年龄、种族、性别和抗双链（ds）DNA抗体滴度的多变量模型中，发现uNGAL是所有SLE患者中肾脏疾病活动性的显著预测因子，并且是具有活检证实的肾炎病史的患者中发作的显著预测因子。作为经活检证实的肾炎患者中肾功能恶化的预测因子，uNGAL优于抗dsDNA抗体滴度。这些结果在一个独立的验证队列中得到证实。uNGAL预测有活检证实的肾炎病史的患者的肾闪辉具有高敏感性和特异性。此外，uNGAL比抗dsDNA抗体滴度更敏感和特异性地预测有狼疮肾炎病史的患者的肾功能恶化。
Objectives. Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis.Methods. Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort.Results. uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort.Conclusions. uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.