title: Retention of iodine and expression of biomarkers for renal damage in the kidney after application of iodinated contrast media in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Jost
authors.forename: Hubertus
authors.initials: H
authors.lastname: Pietsch
authors.forename: Janine
authors.initials: J
authors.lastname: Sommer
authors.forename: Peter
authors.initials: P
authors.lastname: Sandner
authors.forename: Philipp
authors.initials: P
authors.lastname: Lengsfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Seidensticker
authors.forename: Stephan
authors.initials: S
authors.lastname: Lehr
authors.forename: Joachim
authors.initials: J
authors.lastname: Hütter
authors.forename: Martin A
authors.initials: MA
authors.lastname: Sieber
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003287:Contrast Media / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007472:Iohexol / Q000009:adverse effects / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
chemical_list: D015815:Cell Adhesion Molecules; D003287:Contrast Media; D006419:Heme Oxygenase (Decyclizing); D007472:Iohexol; D014283:Triiodobenzoic Acids; C110936:Havcr1 protein, rat; C038192:iopromide; C491523:Hmox1 protein, rat; C044834:iodixanol