title: Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury.
abstract: Drug-induced nephrotoxicity is a serious problem in patients with hospital-acquired acute kidney injury (AKI). A new renal biomarker is needed because traditional markers are not sensitive for early detection of drug-induced AKI. In a recent study, we demonstrated that vanin-1 is a novel candidate biomarker of nephrotoxicant-induced kidney injury. The objective of the present study is to determine whether the increase in urinary vanin-1 is detected before the elevations of serum creatinine or urinary N-acetyl-β-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 administration of a higher dose of cisplatin (10 mg/kg, a single intraperitoneal dose) or gentamicin (120 mg/kg per day, once daily intraperitoneal dose for 9 days), urinary vanin-1 was detected earlier than the other biomarkers. In rats treated with a lower dose of cisplatin (5 mg/kg, a single intraperitoneal dose) or gentamicin (40 mg/kg per day, once daily intraperitoneal dose 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 dose 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.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Hosohata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000581:Amidohydrolases / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D015815:Cell Adhesion Molecules / Q000652:urine; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D042241:Early Diagnosis; D058851:GPI-Linked Proteins / Q000652:urine; D005839:Gentamicins / Q000633:toxicity; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D051379:Mice; D023421:Models, Animal; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D048828:beta-N-Acetyl-Galactosaminidase / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D000581:Amidohydrolases; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D002945:Cisplatin; D003404:Creatinine; D058851:GPI-Linked Proteins; D005839:Gentamicins; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D048828:beta-N-Acetyl-Galactosaminidase; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat; C022314:pantetheinase