title: Usefulness of urinary kidney injury molecule-1 (Kim-1) as a biomarker for cisplatin-induced sub-chronic kidney injury.
abstract: We explored biomarkers suitable for monitoring sub-chronic kidney injury using the three rat models of cisplatin (CDDP)-induced kidney injury, which were designed to extend the current knowledge beyond the sub-acute exposure period. In the pilot study, a single intravenous administration of 1.5 mg kg(-1) CDDP to rats was confirmed to result in no histopathological changes. Subsequently, CDDP was intravenously administered to rats at a dose of 1.5 mg kg(-1) for 4 days at 24-h intervals (Experimental model 1) and for up to 10 weeks at weekly intervals (Experimental models 2 and 3), and the changes in blood and urine components, such as recently recommended urinary biomarkers (Kim-1, clusterin and so on) and traditional blood biomarkers (blood urea nitrogen and serum creatinine), were examined together with the histopathological changes in renal tissues during the development of the kidney injury in each model. In these experimental models, a significant increase in urinary Kim-1 was observed prior to the histopathological changes in renal tissues, and these changes were retained after the adverse histopathological changes. Significant changes in all of the other urinary biomarkers examined occurred along with the histopathological changes. In addition, the increase in urinary Kim-1 after weekly treatment with CDDP for 4 weeks was reduced in a time-dependent manner after cessation of the drug. The present findings indicate that urinary Kim-1 is the most useful biomarker for CDDP-induced rat sub-chronic kidney injury among the biomarkers examined.
authors.affiliation: Drug Discovery Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8731, Japan; Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Nan-Ya
authors.forename: Masatomo
authors.initials: M
authors.lastname: Kajihara
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kojima
authors.forename: Masakuni
authors.initials: M
authors.lastname: Degawa
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D001806:Blood Urea Nitrogen; D015815:Cell Adhesion Molecules / Q000652:urine*; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology / Q000652:urine
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D002945:Cisplatin; D003404:Creatinine; C110936:Havcr1 protein, rat
keywords: Kim-1; cisplatin; rat; sub-chronic kidney injury; urinary biomarkers