Drug Safety Research Labs., Astellas Pharma Inc. , Kashima, Yodogawa-ku, Osaka , Japan.
Biomarkers. 2011 Nov;16(7):553-66. doi: 10.3109/1354750X.2011.613123. Epub 2011 Sep 28.
To aid in evaluating the performance of biomarkers, we measured kidney injury biomarkers in rat models of drug-induced acute kidney injury.
Rats were treated with site-specific nephrotoxins, puromycin, gentamicin, cisplatin, or 2-bromoethylamine. Fifteen biomarkers (β-2-microglobulin, calbindin, clusterin, cystatin-C, KIM-1, GST-α, GST-μ, NGAL, osteopontin, EGF, TIMP-1, VEGF, albumin, RPA-1, and urinary total protein) were examined in comparison with BUN, serum creatinine, and NAG. Some biomarkers, which were different depending in each nephrotoxin, showed ability to detect the prodromal stage of drug-induced kidney injury. Characteristic changing patterns of biomarkers were also found depending on the specific lesion site in the kidney.
These data suggested that establishment of a suitable biomarker panel would facilitate detection of site-specific kidney injury with high sensitivity.
为了帮助评估生物标志物的性能，我们在药物诱导的急性肾损伤的大鼠模型中测量了肾损伤生物标志物。
用局灶性肾毒物、嘌呤霉素、庆大霉素、顺铂或 2-溴乙胺处理大鼠。比较了 15 种生物标志物（β-2-微球蛋白、钙结合蛋白、簇集素、胱抑素-C、肾损伤分子 1、谷胱甘肽 S-转移酶-α、谷胱甘肽 S-转移酶-μ、中性粒细胞明胶酶相关脂质运载蛋白、骨桥蛋白、表皮生长因子、金属蛋白酶组织抑制剂-1、血管内皮生长因子、白蛋白、核仁素相关蛋白 1 和尿总蛋白）与 BUN、血清肌酐和 NAG 的相关性。一些生物标志物在每种肾毒物中都有所不同，它们具有检测药物诱导的肾损伤前驱期的能力。还发现生物标志物的特征变化模式取决于肾脏的特定损伤部位。
这些数据表明，建立合适的生物标志物谱将有助于高灵敏度地检测特定部位的肾损伤。
