Abstract
Identification of novel biomarkers for acute kidney injury (AKI) is important to replace renal biopsies. Recently, several serum and urinary biomarkers have been identified for detection of AKI. In this study, we compared the sensitivity of biomarkers using NMR-based metabolites with conventionally used biomarkers of AKI. The animals were allocated to several groups. A single dose of cisplatin (20 mg/kg, i.p.), cyclosporin A (50 mg/kg, i.p.) and D-galactosamine (20 mg/kg, i.p.) was administered to Sprague-Dawley rats. Urine and plasma samples were collected at 1 and 3 days after drug injection. Measurement of urinary indexes and blood biochemical parameters were performed. 3-Indoxyl sulfate and trigonelline levels were measured in the serum, urine, kidney, and liver. In the cisplatin-treated rats, urinary blood urea nitrogen (BUN) and creatinine levels were dramatically decreased and protein, glucose and LDH levels were significantly increased, which were thought to be caused by the dysfunction of proximal tubule injury. However, no significant differences in urinary biomarkers were observed in D-galactosamine-treated rats. 3-Indoxyl sulfate was significantly reduced in urine of Sprague-Dawley rats treated with cisplatin and cyclosporin A, whereas it's levels were significantly elevated in the serum and kidney. These results suggest that serum 3-indoxyl sulfate and trigonelline may be used as an early biomarker for detecting AKI. It may be possible for measurement of serum and urinary 3-indoxyl sulfate level to replace renal biopsies in evaluation of drug-induced renal toxicity. This research was support by a grant (10182KFDA992-1203) from Korea Food & Drug Administration.
