Nephrology Dialysis Transplantation, Vol 14, Issue 2 342-347, Copyright © 1999 by Oxford University Press
C Schick and C Haller
Background: Intravascular radiocontrast agents may
cause acute renal failure, particularly in patients with pre-existing renal
insufficiency. Direct cytotoxic effects of radiocontrast agents on renal
tubular cells may contribute to the pathogenesis of radiocontrast-induced
nephropathy. Methods: We analysed the cytotoxicity of
the ionic radiocontrast agents diatriozoate (monomeric) and ioxaglate
(dimeric), as well as of the non-ionic radiocontrast agents iohexol
(monomeric) and iodixanol (dimeric) on the renal epithelial Madin Darby
Canine Kidney (MDCK) cell line grown on permeable supports. The toxicity
assays assessed cell viability, transmonolayer resistance and inulin
permeability between the apical and basal cell culture compartment. In
addition, the distribution of the tight-junction-associated membrane
proteins ZO-1 and occludin was analysed using immunofluorescence
microscopy. Results: In all assays the high osmolal
ionic compound diatrizoate had significant cytotoxic effects that included
the partial redistribution of the tight-junction-associated membrane
proteins into a cytoplasmic compartment. To a lesser extent this
redistribution also occurred with the dimeric ionic compound ioxaglate, but
not with the non-ionic radiocontrast agents. With regards to cell
viability, transmonolayer resistance and inulin permeability the
radiocontrast agents with reduced osmolality were significantly less toxic
than diatrizoate, independent of their ionic strength.
Conclusions: Physicochemical factors contribute to the
cytotoxicity of radiocontrast agents in vitro. The
redistribution of tight-junction-associated membrane proteins by the ionic
radiocontrast agents corresponds with the loss of the barrier function of
the epithelial cell monolayer, which is a major pathophysiological
mechanism in acute renal failure. The radiocontrast agents with reduced
osmolality are less cytotoxic than diatrizoate, independent of their
ionicity. Hyperosmolality appears to be a more important determinant of the
cytotoxicity of diatrizoate than ionic strength. Key
words: inulin permeability; MDCK; radiocontrast; renal failure;
transmonolayer
ORIGINAL ARTICLES
Comparative cytotoxicity of ionic and non-ionic radiocontrast agents on MDCK cell monolayers in vitro
Department of Internal Medicine, University of Heidelberg, Bergheimstrasse 58, D-69115, Germany; Corresponding author
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