-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.Key words: NGAL, Dogs, Acute kidney injury, Urinary biomarker, Gentamicin Correspondence: Kiyonori Kai (E-mail: kai.kiyonori.xb@daiichisankyo.co.jp)
LetterThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.38, No.2, 269-277, 2013 Vol. 38 No. 2 269 addition to these biomarkers, neutrophil gelatinase-associated lipocal (NGAL), a member of the lipocalin superfamily, has been proposed as a candidate for a sensitive urinary biomarker to detect AKI Mori, 2005;Mori and Nakao, 2007). Unfortunately, in part due to the lack of commercially available assays for non-rodents, limited data comparing the performance of the exploratory and approved markers are publicly available so far.In this study, we selected gentamicin, a well-known nephrotoxic agent that induces AKI in experimental animals and humans, and injected it subcutaneously to beagle dogs for 9 days and evaluated urinary NGAL using a commercial ELISA kit as a sensitive urinary biomarker in comparison with conventional blood and urinary toxicity makers and pathological examinations.
MATERIALS AND METHODS
Test articleELTACIN injection, an injectable product of gentamicin sulfate was purchased from FujiPharma (Shizuoka, Japan).
Animals and housing conditionsTwo male beagle dogs were purchased from Narc Corporation (Chiba, Japan) for gentamicin treatment, and 6 males and 6 females were additionally obtained from Marshall BioResources, Japan (Ibaraki, Japan) for collection background data of urinalysis. The dogs were individually housed in stainless steel cages (W93.5 cm × W80 cm × H78.5 cm) in an air-conditioned room (temperature, 18 to 28°C; relative humidity, 30 to 70%). A light/dark cycle of 12 hr and ventilation rate of 10 to 20 air changes/ hr were used in the animal rooms. Two hundred and twenty grams of basal diet (Certified Canine Diet 5007, PMI Nutrition International, Inc., St. Louis, MO, USA) was given to each dog in the morning and tap water was available ad libitum. All experimen...