Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury
Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury
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DOI：
10.1128/aac.00079-19
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发表时间：
2019-07-01
影响因子：
4.9
通讯作者：
Scheetz, Marc H.
中科院分区：
文献类型：
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作者：
Pais, Gwendolyn M.;Avedissian, Sean N.;Scheetz, Marc H.
尿液生物标志物在确定肾脏损伤的开始和程度方面优于血肌酐。本研究将生物标记物对万古霉素所致肾损伤(VIKI)的时间预测能力进行分类，根据组织病理学损害的定义进行分类。雄性SD大鼠(n=125)按体重150~400 mg/kg/d腹腔注射万古霉素1~2次，连续1、3、6天。安乐死前24小时取尿1次，治疗6天后取尿2次。受试者操作特征(ROC)曲线用于评估肾脏损伤分子1(Kim-1)、聚集素(Clusterin)、骨桥蛋白(OPN)、胱抑素C(Cystatin C)和中性粒细胞明胶酶相关脂蛋白(NGAL)的尿液生物标志物性能，以预测组织病理学定义的Viki(使用苏木精-伊红染色的国家标准病理评估方案)。尿Kim-1、Clusterin和OPN在敏感性和特异性方面优于Cystatin C和NGAL。对于最早的损伤，尿KIM-1(受试者工作特征曲线下面积[AuC]，0.662；P<；0.001)和Clusterin(AuC，0.706；P<；0.001)是最敏感的，与NGAL相比，24 h时即使是低水平的组织病理损伤也是最敏感的。Kim-1和Clusterin是VIKI最早和最敏感的预测指标。随着损伤的进展，Kim-1、Clusterin和OPN最能确定损伤的程度。
Urinary biomarkers are superior to serum creatinine for defining onset and extent of kidney injury. This study classifies the temporal predictive ability of biomarkers for vancomycin-induced kidney injury (VIKI) as defined by histopathologic damage. Male Sprague-Dawley rats (n = 125) were randomized to receive 150 to 400 mg/kg of body weight/day vancomycin via once or twice daily intraperitoneal injection over 1, 3, or 6 days. Urine was collected once during the 24 h prior to euthanasia or twice for rats treated for 6 days. Receiver operating characteristic (ROC) curves were employed to assess the urinary biomarker performances of kidney injury molecule 1 (KIM-1), clusterin, osteopontin (OPN), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) to predict histopathologically defined VIKI (using a national standard pathological assessment scheme from hematoxylin and eosin stained kidneys). Urinary KIM-1, clusterin, and OPN outperformed cystatin C and NGAL with regard to sensitivity and specificity. For the earliest injury, urinary KIM-1 (area under the receiver operating characteristic curve [AUC], 0.662; P < 0.001) and clusterin (AUC, 0.706; P< 0.001) were the most sensitive for predicting even low-level histopathologic damage at 24 h compared to NGAL. KIM-1 and clusterin are the earliest and most sensitive predictors of VIKI. As injury progresses, KIM-1, clusterin, and OPN best define the extent of damage.