title: Neutrophil gelatinase-associated lipocalin, a sensitive urinary biomarker of acute kidney injury in dogs receiving gentamicin.
abstract: A sensitive urinary biomarker for acute kidney injury (AKI) was investigated in beagle dogs with nephrotoxicity induced by gentamicin. Gentamicin sulphate at 25 or 50 mg/kg was injected (s.c.) for 9 days, and conventional urinalysis, ELISA assay of neutrophil gelatinase-associated lipocal (NGAL) in urine, blood chemistry, and pathological examinations were performed. The dog given gentamicin at 25 mg/kg only showed slight deposition of lysosomal granules in the proximal tubular epithelium of the kidneys without any other significant changes even though urinary NGAL was elevated on Day 10 (day of necropsy). In the dog receiving gentamicin at 50 mg/kg, increases in urinary NGAL were observed on Days 3 and 5, and absence of urination, marked increases in serum urea nitrogen and creatinine, enlargement and discoloration of the kidneys with marked necrosis, and swelling of proximal epithelium were observed. In conclusion, urinary NGAL is considered to be a candidate as a sensitive predictable biomarker of AKI in the gentamicin-induced nephrotoxicity model in dogs.
authors.affiliation: Medical Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan. kai.kiyonori.xb@daiichisankyo.co.jp
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Kai
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yu
authors.initials: Y
authors.lastname: Yoshimatsu
authors.forename: Junzo
authors.initials: J
authors.lastname: Kinoshita
authors.forename: Munehiro
authors.initials: M
authors.lastname: Teranishi
authors.forename: Wataru
authors.initials: W
authors.lastname: Takasaki
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis* / Q000473:pathology; D000209:Acute-Phase Proteins / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D001806:Blood Urea Nitrogen; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011933:Reagent Kits, Diagnostic
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D005839:Gentamicins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D011933:Reagent Kits, Diagnostic