Novel genomic biomarkers for acute gentamicin nephrotoxicity in dog

• 作者: Anton Bittner David La James Eric McDuffie Jingjin Gao Jingying Ma Manisha Sonee Matthew Wagoner Sandra Snook
• 来源期刊: 分子和综合生理学期刊(英文)
• 学科: 医学
• 关键词: BIOMARKER GENTAMICIN NEPHROTOXICITY DOG
• 年，卷（期）: 2013,（3）
• 页码范围: 125-133
• 页数: 9页
• 分类号: R73

摘要

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.