Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury

Drug-induced nephrotoxicity is a serious problem in cases with hospital-acquired acute kidney injury (AKI). New renal biomarker is needed because traditional markers are not sensitive for early detection of drug-induced AKI. Recently, we have demonstrated that vanin-1 is a novel candidate biomarker of nephrotoxicant-induced kidney injury. Objective of the present study is to determine whether the increase of urinary vanin-1 is detected before the elevations of serum creatinine, or urinary N -acetyl-beta-glucosaminidase (NAG), Kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the two well-established animal models of drug-induced AKI. After the dosing of a higher cisplatin (10 mg/kg, a single i.p. dosing) or gentamicin (120 mg/kg/day, once daily i.p. dosing for 9 days), urinary vanin-1 was detected earlier than the other biomarkers. In rats treated with a lower cisplatin (5 mg/kg, a single i.p. dosing) or gentamicin (40 mg/kg/day, once daily i.p. dosing for 9 days), serum creatinine and urinary NAG were not changed throughout the study period, whereas urinary vanin-1, Kim-1 and NGAL were significantly increased. The renal vanin-1 protein levels were significantly decreased in rats treated with the higher dose of cisplatin on day 5 and gentamicin on day 9, and the immunofluorescence analyses confirmed that vanin-1 immunoreactivity in tubular cells was reduced with the time after the dosing of cisplatin, indicating that urinary vanin-1 was leaked from tubular cells. These results suggest that compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally sensitive biomarker for drug-induced AKI.