Comparison of the course of biomarker changes and kidney injury in a rat model of drug-induced acute kidney injury |
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Authors: | Sasaki Daisuke Yamada Atsushi Umeno Hitomi Kurihara Hiroshi Nakatsuji Shunji Fujihira Shiro Tsubota Kenjiro Ono Mihoko Moriguchi Akira Watanabe Kouji Seki Jiro |
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Institution: | Drug Safety Research Labs., Astellas Pharma Inc. , Kashima, Yodogawa-ku, Osaka , Japan. daisuke.sasaki@jp.astellas.com |
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Abstract: | Objective: To aid in evaluating the performance of biomarkers, we measured kidney injury biomarkers in rat models of drug-induced acute kidney injury. Methods and results: 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. Conclusion: These data suggested that establishment of a suitable biomarker panel would facilitate detection of site-specific kidney injury with high sensitivity. |
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