%0 Journal Article %T Novel genomic biomarkers for acute gentamicin nephrotoxicity in dog %A James Eric McDuffie %A Jingjin Gao %A Jingying Ma %A David La %A Anton Bittner %A Manisha Sonee %A Matthew Wagoner %A Sandra Snook %J Open Journal of Molecular and Integrative Physiology %P 125-133 %@ 2162-2167 %D 2013 %I Scientific Research Publishing %R 10.4236/ojmip.2013.33018 %X
Objectives: Novel biomarkers indicative of drug-induced kidney injury (DIKI) in dogs would have significant application in preclinical drug development. We conducted a feasibility study to identify genomic expression profiles for monitoring progressive, acute DIKI in dogs. Materials and Methods: Animals were intramuscularly administered either 0.9% physiological saline or gentamicin (40 mg/kg/day) for 10 consecutive days and euthanized on day 11. Serum and urine samples were collected at various time points and kidney samples were collected at necropsy for biomarker measurements. Results: Acute gentamicin-induced renal histopathology changes were localized to the proximal convoluted tubules and characterized as slight-to-marked, diffuse cortical-medullary tubular epithelial degeneration/necrosis. Serum creatinine (sCr) and blood urea nitrogen (BUN) elevations suggestive of mild renal dysfunction were first observed on days 7 to 8. Gentamicin-induced increased urinary kidney injury molecule-1 (KIM-1) mRNA was observed on day 6 preceding detectable elevations of sCr and/or BUN. Increased urinary KIM-1 mRNA correlated with multifocal KIM-1 immunostaining in the corticomedullary tubular epithelial cells. Microarray analysis revealed changes in additional mRNA expression products detected in urine and/or kidney that should be further investigated for use as potential biomarkers for acute gentamicin related nephrotoxicity in dogs. Conclusion: These findings suggested the utility of non-invasive urinary genomic parameters for monitoring acute DIKI in dogs.
%K Biomarker %K Gentamicin %K Nephrotoxicity %K Dog %U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=36335