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Published online before print April 21, 2005, 10.1148/radiol.2353040726

(Radiology 2005;235:843.)

A more recent version of this article appeared on June 1, 2005
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© RSNA, 2005

Experimental Studies

Cytotoxic Effects of Ionic High-osmolar, Nonionic Monomeric, and Nonionic Iso-osmolar Dimeric Iodinated Contrast Media on Renal Tubular Cells in Vitro1

Marc C. Heinrich, MD, Martin K. Kuhlmann, MD, Aleksandar Grgic, MD, Martina Heckmann, MD, Bernhard Kramann, MD and Michael Uder, MD

1 From the Department of Diagnostic Radiology (M.C.H., A.G., M.H., B.K.) and Department of Medicine, Division of Nephrology and Hypertension (M.K.K.), University Hospital of Saarland, Homburg/Saar, Germany; and Department of Diagnostic Radiology, University Hospital of Erlangen, Maximiliansplatz 1, 91054 Erlangen, Germany (M.U.). From the 2004 RSNA Annual Meeting. Received April 22, 2004; revision requested June 29; revision received July 21; accepted August 18. Address correspondence to M.U. (e-mail: michael.uder@idr.imed.uni-erlangen.de).

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.

© RSNA, 2005




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