Age-related differences in kidney injury biomarkers induced by cisplatin

作者：Shin Yu Jin; Kim Tae Hyung; Won A Jin; Jung Ja Young; Kwack Seung Jun; Kacew Sam; Chung Kyu Hyuck; Lee Byung Mu; Kim Hyung Sik^*

来源：Environmental Toxicology and Pharmacology, 2014, 37(3): 1028-1039.

DOI：10.1016/j.etap.2014.03.014

• Cisplatin
• Acute kidney injury
• Age-specific biomarkers
• KIM-1

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-alpha), 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-alpha, TIMP-1, and VEGF levels may help in the early diagnosis of young patients with CDDP-induced AKI.

• 出版日期2014-5