title: Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media.
abstract: Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.
authors.affiliation: Division of Drug Safety Research, Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Rouse
authors.forename: Sharron R
authors.initials: SR
authors.lastname: Stewart
authors.forename: Karol L
authors.initials: KL
authors.lastname: Thompson
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001806:Blood Urea Nitrogen; D003287:Contrast Media / Q000737:chemistry; D003920:Diabetes Mellitus / Q000097:blood* / Q000652:urine*; D006973:Hypertension / Q000097:blood* / Q000652:urine*; D007472:Iohexol / Q000737:chemistry; D007674:Kidney Diseases / Q000097:blood* / Q000139:chemically induced / Q000473:pathology / Q000652:urine*; D007677:Kidney Function Tests; D008297:Male; D012372:ROC Curve; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D007472:Iohexol
keywords: acute kidney injury; contrast media; contrast nephropathy; kidney injury biomarkers.; risk factors