Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro.
OBJECTIVE
To compare the cytotoxic effects of dimeric and monomeric iodinated contrast media on renal tubular cells in vitro with regard to osmolality.


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).


CONCLUSIONS
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.
Heinrich
Marc C
MC
Department of Diagnostic Radiology, Division of Nephrology and Hypertension, University Hospital of Saarland, Homburg/Saar, Germany.
Kuhlmann
Martin K
MK
Grgic
Aleksandar
A
Heckmann
Martina
M
Kramann
Bernhard
B
Uder
Michael
M
D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D007479:Iopamidol / Q000009:adverse effects / Q000031:analogs & derivatives*; D007483:Iothalamic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D008353:Mannitol / Q000009:adverse effects; D009994:Osmolar Concentration; D013552:Swine; D014283:Triiodobenzoic Acids / Q000009:adverse effects
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007483:Iothalamic Acid; C033300:iotrolan; C057937:iomeprol; D008353:Mannitol; C002587:ioxitalamic acid; C044834:iodixanol; D007479:Iopamidol; C054871:ioversol