Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro

Purpose: To compare the cytotoxic effects of dimeric and monomeric iodinated contrast media on renal tubular cells in vitro with regard to osmolality.

Materials and methods: LLC-PK1 cells were incubated with ioxithalamate, ioversol, iomeprol-300, iomeprol-150, iodixanol, iotrolan, and hyperosmolar mannitol solutions for 1-24 hours at concentrations from 18.75 to 150 mg of iodine per milliliter. Cytotoxic effects were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Data were analyzed with one-way analysis of variance; post hoc tests were performed.

Results: At equal iodine concentrations, ioxithalamate showed stronger cytotoxic effects than did other contrast media (MTT conversion for ioxithalamate was 4% vs that for ioversol of 32%, that for iomeprol-300 of 34%, that for iodixanol of 40%, and that for iotrolan of 41% of undamaged control cells at 75 mg of iodine per milliliter, n = 61-90, P < .001); there was no significant difference between low-osmolar monomeric and iso-osmolar dimeric contrast media (P > .05). At equal molarity, dimeric contrast media induced significantly stronger cytotoxic effects than did low-osmolar monomeric contrast media (40% for iodixanol and 41% for iotrolan vs 64% for ioversol and 59% for iomeprol-300 at 98.5 mmol/L, n = 61-75, P < .001). At equimolar concentrations, both dimeric contrast media showed stronger cytotoxic effects than did iso-osmolar formulation of iomeprol-150 (51% for iodixanol and 50% for iotrolan vs 77% for iomeprol-150 at 98.5 mmol/L, n = 35-40, P < .001). Mannitol solutions induced weaker cytotoxic effects than did corresponding contrast media compounds (74% for mannitol-520 vs 34% for iomeprol-300 and 41% for mannitol-1860 vs 4% for ioxithalamate, P < .001).

Conclusion: Besides hyperosmolality, direct cytotoxic effects of contrast media molecules contribute to their cytotoxic effects. Results of this study indicate that dimeric contrast media molecules have a greater potential for cytotoxic effects on proximal renal tubular cells in vitro than do monomeric contrast media molecules.