Abstract 510: Neuronal Voltage-Dependent Calcium Channel 2.1 RNA Increased in Animal Models With Contrast-Induced Nephropathy

Abstract

Objectives: Contrast media has been widely used in imaging studies and endovascular procedures. However, contrast induced nephropathy (CIN) has been a major concern in the patients undergoing angiography and less invasive endovascular surgery. The current available main test for the diagnosis of CIN is to measure serum creatinine (Cr); however, It is non-specific and maybe due to underline renal disease. The objectives of this study were to analyze the changes of different proteins in CIN animal models, and to discover potential biomarker(s) for the early diagnosis of CIN. Materials & Methods: C57B1/6J mice were used to create CIN model. A prostaglandin synthesis inhibitor (indomethacin, 10 mg/kg) and a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine methyl ester, L-NAME, 10mg/kg) were injected intraperitoneally (ip) before giving Iodixanol, a commonly-used intravenous contrast, (320 mg iodine/ml, 4.9 g iodine/kg ip). Sham mice received ip injections of normal saline instead of Iodixanol. Mice kidneys were harvested at day1, day2 and day3 in different groups. RNA was extracted from half of the kidney specimen. qRT -PCR were used to quantify Kidney Injury Molecule-1 (KIM-1), neuronal voltage-dependent calcium channel 2.1 (CaV 2.1) and Cystatin C RNA expression, using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as endogenous control. The other half of the specimen was fixed with formalin, embedded in paraffin, and then stained with Hematoxylin and Eosin (H&E) for histopathology evaluation. Results: H&E staining demonstrated histological damages in Iodixanol-treated groups but not in controls. KIM-1 and Cystatin C expressions were not increased after receiving Iodixanol. CaV 2.1 RNA levels were significantly increased on day 3 in Iodixanol group (p < 0.05), which was consistent with the contrast-induced damage based on histological examination. CaV 2.1 levels were also elevated on Day1 and Day 2 following iodixanol administration, although not statistically significant. Conclusions: Cav 2.1 gene expression is significantly increased in CIN animal models. Cav 2.1 may be involved in the mechanisms of CIN development, and could be a potential biomarker for the diagnosis of CIN. Further clinical investigation is needed.