%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 <p>
	<b><span style=\"font-size:10.0pt;\">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 <span>urinary </span><span>kidney
injury molecule-1 (KIM-1) mRNA was ob</span>served 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. </span></b><b><span style=\"font-size:10.0pt;\"></span></b> 
</p>
%K Biomarker
%K Gentamicin
%K Nephrotoxicity
%K Dog
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=36335