title: The effect of iodinated contrast agent properties on renal kinetics and oxygenation.
abstract: OBJECTIVE
  We analyzed renal kinetics and renal oxygenation in rats after administration of several classes and formulations of contrast agents (CAs) with a focus on the influence of osmolality and substance-specific properties.
  
  
  METHODS
  We investigated the renal kinetics of a nonionic, dimeric CA (iodixanol) formulated in 3 different osmolalities (hypo-osmolar, iso-osmolar, low-osmolar) and compared it to nonionic, low-osmolar (iopromide), and ionic, low-osmolar CAs (ioxaglate) using computed tomography for a period of 24 hours. The CAs were administered intravenously at a dosage of 4 g iodine/kg body weight. The average exposure was calculated, and urine viscosities were compared before the injection and during the time intervals of 0 to 60 minutes and 60 to 120 minutes after the injection. Renal oxygenation levels of the renal cortex and medulla were estimated using blood-oxygen-level-dependent magnetic resonance imaging. We used histologic methods to systematically analyze the gravity of vacuole formation based on the physicochemical and substance-specific properties of each CA.
  
  
  RESULTS
  Iso-osmolar and hypo-osmolar iodixanol and, to a lesser extent, iodixanol/mannitol accumulated rapidly in the kidneys during the first 5 minutes of the injection and remained higher 2, 4, 6, and 24 hours after the injection compared with iopromide and ioxaglate, which showed fast iodine excretion. Similarly, lower renal blood oxygen levels were estimated for all iodixanol formulations as compared with ioxaglate and iopromide. The incidence of vacuole formation was high for all iodixanol formulations and for ioxaglate (6 of 6 rats) and low for iopromide (1 of 6 rats). Moderate severity of vacuoles was determined for the iodixanol solutions; minimal severity, for ioxaglate and iopromide.
  
  
  CONCLUSIONS
  We identified a superior profile for the low-osmolar CAs compared with the iso-osmolar CAs regarding rapid excretion, short-term renal exposure, and renal oxygenation.
authors.affiliation: MR and CT Contrast Media Research, Bayer Healthcare, Berlin, Germany. diana.lenhard@bayer.com
authors.forename: Diana Constanze
authors.initials: DC
authors.lastname: Lenhard
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Frisk
authors.forename: Philipp
authors.initials: P
authors.lastname: Lengsfeld
authors.forename: Hubertus
authors.initials: H
authors.lastname: Pietsch
authors.forename: Gregor
authors.initials: G
authors.lastname: Jost
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D007472:Iohexol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D007485:Ioxaglic Acid / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009994:Osmolar Concentration; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007472:Iohexol; C038192:iopromide; C044834:iodixanol; D010100:Oxygen; D007485:Ioxaglic Acid