The impact of the viscosity and osmolality of iodine contrast agents on renal elimination.
OBJECTIVE
The iodinated contrast agents (CAs) that are currently used in radiographic procedures possess special physicochemical properties and a high safety profile; however, according to a large retrospective study (Swedish registry), the viscosity of CAs may have an underestimated impact on renal failure. The aim of our study was to investigate the possible consequences of CA viscosity differences, such as CA retention in the kidney.


METHODS
Five Göttingen minipigs were each intravenously injected in a crossover setting at intervals of at least 7 days with monomeric (Iopromide) and dimeric (Iodixanol) CAs at 2 doses (1 and 2 g iodine/kg bodyweight), and the retention of the CA in the kidneys was determined during the first 6 hours postinjection using a 64-slice computed tomography scanner. Additionally we performed in vitro dialysis of the monomeric and dimeric CAs across the various physiological osmolalities of the renal tubulus (300, 600, 800, and 1200 mOsm/kg H(2)O) to estimate CA viscosity in vivo. Following the dialyzes, iodine concentrations and CA viscosities were determined.


RESULTS
A different exposure of the kidneys to iodine and a different elimination kinetics from the kidneys was observed after the administration of monomeric and dimeric CAs. The monomeric agent was observed to clear from the kidney immediately after administration. In contrast, after administration of the dimeric CA an increase in iodine concentration in the kidney was observed up to 180 minutes postinjection, before the CA was observed to begin clearing; however, no difference was observed between the plasma half-lives of the 2 investigated CAs. In vitro dialysis of the dimeric CA increased iodine concentrations and strongly increased viscosity at all of the tested osmolalities. In contrast, the monomeric agent only demonstrated increases in iodine concentration and viscosity at 800 and 1200 mOsm/kg, and these changes were smaller than those observed for the dimeric CA. In summary, dialysis strongly enhanced the viscosity differences between the 2 investigated CAs.


CONCLUSIONS
The viscosity differences between the investigated monomeric and dimeric CAs are strongly enhanced by concentration processes, such as the process taking place in the tubular system. These viscosity differences may be the cause of the prolonged retention and the different elimination kinetics from the kidney observed after application of the dimeric CA relative to the monomeric CA.
Jost
Gregor
G
TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin, Germany.
Pietsch
Hubertus
H
Lengsfeld
Philipp
P
Hütter
Joachim
J
Sieber
Martin A
MA
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D003956:Dialysis; D005260:Female; D006207:Half-Life; D007455:Iodine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007472:Iohexol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007668:Kidney / Q000000981:diagnostic imaging / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D013552:Swine; D013556:Swine, Miniature; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000493:pharmacokinetics; D014783:Viscosity
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007472:Iohexol; C038192:iopromide; D007455:Iodine; C044834:iodixanol