Nephrotoxic effects of ionic and nonionic contrast media on rat and human renal cortical slices

Abstract

Background. Nephrotoxicity is a well-known adverse effect of radiographic contrast medium (CM). Recently, several kinds of low- osmolality nonionic CM have been developed. However, the nephrotoxic effects of nonionic CM compared with those of ionic CM have not been well evaluated.

Methods. To compare the direct nephrotoxic effects of ionic and nonionic CM on renal epithelial cells, rat and human renal cortical slices were incubated with CM at 37°C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol, iohexol, iomeprol, ioversol, iopromide, and ioxilan were employed as nonionic CM. Direct toxicity of CM was evaluated by the activities of N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyl-transferase (GGT) released from the renal slices into the incubation buffer.

Results. In the experiment with rat renal slices, NAG and GGT activities in buffer solutions were increased dose-dependently by 30, 60, and 90 mg I/ml of CM. There was no significant difference in NAG or GGT release between ionic and nonionic CM at the concentration of 60 mg I/ml. In the experiment with human renal slices, incubation with 60 mg I/ml of diatrizoate, iothalamate, iomeprol, and iopromide did not affect NAG levels. Significantly greater increases in NAG levels, compared with the control, were observed after incubation with iopamidol, iohexol, ioxilan and ioversol. Nevertheless, the increases in NAG caused by some of the nonionic CM were very slight. GGT release from human renal slices was significantly greater than that of the control in all experimental groups. Again, there was no significant difference in renal toxicity between ionic and nonionic CM.

Conclusions. Newly developed nonionic CM had almost the same degree of nephrotoxicity against rat and human renal epithelial cells as conventional ionic CM, when direct renal toxicity was evaluated by enzyme release in an in-vitro experimental system using renal cortical slices.