RENAL EFFECTS OF IODIXANOL IN EXPERIMENTAL-ANIMALS

The effects of the new nonionic dimeric hexa-iodinated contrast medium (CM) iodixanol on renal function and morphology were investigated in 7 independent studies in rats, rabbits and monkeys and compared with o ther iodinated CM. No significant effect on serum creatinine levels wa s seen at doses up to and including 5 g I/kg in rats and 10.5 g I/kg i n rabbits. An immediate and transient increase in proteinuria was foun d in rabbits when 10.5 g I/kg was administered as a bolus, and when 12 .5 g I/kg was administered as a slow infusion in a comparative study w ith several CM. Increased serum elimination half-life was shown by mea suring serum iodine concentrations after the infusion of 12.5 g I/kg. The effect of a high dose of iodixanol on proteinuria and elimination half-life were in this study in the same range as those of the monomer ic nonionic CM, but less pronounced than those of the monomeric ionic CM. Reduced renal capacity was induced in male rats by performing unil ateral nephrectomy 4 weeks before i.v. injection of iodixanol or iopam idol (2 g I/kg). The administration of CM did not affect renal functio n monitored as serum concentrations of creatinine and urea. The vacuol ation of renal proximal tubular cells and kidney iodine retention were investigated in rats 48 hours after administration of different doses of iodixanol or iotrolan. The no-effect level for vacuolation was 0.5 g I/kg for both CM. Iodine retention was higher in male than female r ats, and was higher for iodixanol than iotrolan at the 2 highest dose levels (3 and 5 g I/kg). No difference in iodine retention was found a t the other dose levels (0.25-1 g I/kg). The reversibility of renal pr oximal tubular vacuolation after administration of iodixanol was studi ed in male rats (1.2 g I/kg) and monkeys (1.2 and 3.6 g I/kg). The vac uolation was more pronounced in rats than in monkeys. Vacuolation was completely reversed in all rats 3 weeks after dosing, and in 2 of 3 mo nkeys 3 days after a dose of 1.2 g I/kg. The degree of vacuolation evi dent in renal percutaneous biopsy specimens from monkeys 14 days after i.v. administration of iodixanol at a dose of 3.6 g I/kg was not sign ificantly different to that in control animals. In conclusion, iodixan ol affected renal function to the same degree as did the nonionic mono meric and dimeric comparative media, but to a lesser degree than the i onic monomers. The degree of renal proximal tubular cell vacuolation i nduced by iodixanol seems to be species-dependent, being less pronounc ed and more quickly reversed in monkeys than rats.