title: Age-related differences in kidney injury biomarkers induced by cisplatin.
abstract: Acute kidney injury (AKI) occurs in a half of cisplatin (CDDP)-treated patients. Traditional biomarkers including blood urea nitrogen (BUN) and serum creatinine (SCr) are still used for detection of CDDP-induced AKI, but these biomarkers are not specific or sensitive. The aim of this study was to identify the specific and sensitive biomarkers against CDDP-induced renal injury between young (3-week-old) and old (20-week-old) rats. All animals were intraperitoneally injected once with CDDP (6 mg/kg). After 3 days, all animals were sacrificed and serum, urine, and kidney tissues were collected. Urinary and serum biomarkers as well as histological changes were measured. CDDP-induced proximal tubular damage was apparent from histopathological examination, being more severe in 3-week-old rats accompanied by increased number of TUNEL-positive apoptotic cells. This was associated with elevated urinary kidney injury molecule-1 (KIM-1), glutathione-S-transferase alpha (GST-α), vascular endothelial growth factor (VEGF), and tissue inhibitor of metalloproteinases-1 (TIMP-1). In contrast, the levels of neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were significantly increased in 20-week-old rats after CDDP treatment. These results indicate that the use of age-specific urinary biomarkers is necessary to diagnosis of CDDP-induced AKI. Especially, urinary KIM-1, GST-α, TIMP-1, and VEGF levels may help in the early diagnosis of young patients with CDDP-induced AKI.
authors.affiliation: MRC Center, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, South Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: MRC Center, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, South Korea.
authors.forename: A Jin
authors.initials: AJ
authors.lastname: Won
authors.affiliation: National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Oh-song, South Korea.
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Health Science, Changwon National University, Gyeongnam 641-773, South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Kacew
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, South Korea. Electronic address: hkims@skku.edu.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000652:urine*; D000375:Aging / Q000378:metabolism / Q000652:urine*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000652:urine; D002945:Cisplatin / Q000633:toxicity*; D005982:Glutathione Transferase / Q000652:urine; D024243:HMGB1 Protein / Q000652:urine; D007527:Isoenzymes / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009414:Nerve Growth Factors / Q000652:urine; D000075388:Netrin-1; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000652:urine; D042461:Vascular Endothelial Growth Factor A / Q000652:urine
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D002945:Cisplatin; D005982:Glutathione Transferase; D024243:HMGB1 Protein; D007527:Isoenzymes; D009414:Nerve Growth Factors; D000075388:Netrin-1; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C110936:Havcr1 protein, rat; C104200:Hbp1 protein, rat; C467498:vascular endothelial growth factor A, rat; C119995:glutathione S-transferase alpha
keywords: Acute kidney injury; Age-specific biomarkers; Cisplatin; KIM-1