Jost Gregor, Pietsch Hubertus, Sommer Janine, Sandner Peter, Lengsfeld Philipp, Seidensticker Peter, Lehr Stephan, Hütter Joachim, Sieber Martin A
TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin, Germany.
Invest Radiol. 2009 Feb;44(2):114-23. doi: 10.1097/RLI.0b013e318190fbd2.
Commercially available iodinated contrast media (CM) show significantly different physico-chemical properties. The relevance of the viscosity of CM may be underestimated as a contributing factor for clinically relevant renal failure as suggested by a large registry data analysis (Swedish registry study). The objective of this preclinical study is to assess differences of a low and high-viscous CM regarding their retention time in the kidney. Furthermore, we investigated the expression of marker genes for renal damage and hypoxia to evaluate a potential renal damage and hypoxia after application of iodinated CM.
After application of Iopromide 300 and Iodixanol 320 CM, the iodine concentration over time was determined using computed tomography and x-ray fluorescence analysis in healthy Han Wistar and renally impaired ZSF1 rats. The latter served as a model for age and diabetes-related renal impairment. X-ray attenuation (Hounsfield units) in the renal cortex was analyzed by 2 independent blinded readers. Furthermore, the expression of kidney injury molecule 1 (Kim-1/Havcr1) and heme oxygenase I (HO-1/HMOX1) was measured by quantitative reverse transcription-polymerase chain-reaction.
Computed tomography and x-ray fluorescence analysis in the kidneys of animals treated with Iodixanol revealed significantly prolonged retention of iodine in the kidney as compared with animals treated with Iopromide. This difference was even more pronounced in renally impaired rats. Twenty-four hours after Iodixanol treatment, significantly increased levels of Kim-1/Havcr1 and HO-1/HMOX1 transcript levels were observed compared with the saline and Iopromide treatment.
A prolonged retention of contrast media in the kidney was observed after administration of dimeric CM (Iodixanol 320). One possible explanation for this effect could be the high viscosity of the dimeric CM (Iodixanol 320) and the lack of dilution by osmotic diuresis. This prolonged exposure is possibly associated with higher renal toxicity as indicated by the elevated expression of biomarkers for hypoxia and renal injury.
市售碘化造影剂（CM）显示出显著不同的物理化学性质。正如一项大型注册数据分析（瑞典注册研究）所表明的，CM粘度作为临床相关肾衰竭的一个促成因素，其相关性可能被低估。这项临床前研究的目的是评估低粘度和高粘度CM在肾脏中的滞留时间差异。此外，我们研究了肾脏损伤和缺氧标志物基因的表达，以评估应用碘化CM后潜在的肾脏损伤和缺氧情况。
在健康的Han Wistar大鼠和肾损伤的ZSF1大鼠中，应用碘普罗胺300和碘克沙醇320 CM后，使用计算机断层扫描和X射线荧光分析来测定随时间变化的碘浓度。后者作为年龄和糖尿病相关肾损伤的模型。由2名独立的盲法读者分析肾皮质中的X射线衰减（亨氏单位）。此外，通过定量逆转录-聚合酶链反应测量肾损伤分子1（Kim-1/Havcr1）和血红素加氧酶I（HO-1/HMOX1）的表达。
与接受碘普罗胺治疗的动物相比，接受碘克沙醇治疗的动物肾脏的计算机断层扫描和X射线荧光分析显示碘在肾脏中的滞留时间显著延长。这种差异在肾损伤大鼠中更为明显。与生理盐水和碘普罗胺治疗相比，碘克沙醇治疗24小时后，观察到Kim-1/Havcr1和HO-1/HMOX1转录水平显著升高。
给予二聚体CM（碘克沙醇320）后，观察到造影剂在肾脏中的滞留时间延长。这种效应的一种可能解释可能是二聚体CM（碘克沙醇320）的高粘度以及缺乏渗透性利尿的稀释作用。如缺氧和肾损伤生物标志物表达升高所示，这种延长的暴露可能与更高的肾毒性有关。
