CYTOTOXICITY OF RADIOCONTRAST AGENTS ON POLARIZED RENAL EPITHELIAL-CELL MONOLAYERS

Objective: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of radi ocontrast-induced renal dysfunction are not clear. Since tubular trans port functions depend on the polarity of renal epithelial cells, we in vestigated the effects of radiocontrast agents on polarized tubular ce lls in vitro. Methods: We studied the effects of iso-iodine concentrat ions (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ioni c (iopamidol) monomeric radiocontrast agent and of hyperosmolal mannit ol control solutions on filter-grown renal epithelial cell (MDCK, LLCP K) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and ( polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofl uorescence microscopy using monoclonal antibodies against specific api cal (gp135) and basal (gp60, uvomorulin) MDCK surface markers. Results : The radiocontrast agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate w as more toxic than iopamidol. LLCPK cells were more susceptible to rad iocontrast cytotoxicity than MDCK cells. This cytotoxicity was associa ted with an alteration of MDCK cell polarity as assessed by the redist ribution of surface marker proteins. Conclusions: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality . The cytotoxicity of radiocontrast agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysio logy of radiocontrast-induced nephropathy.