RATIONALE AND OBJECTIVESThe authors investigate the relative sensitivity of rat mesangial cells to iodinated contrast media (CM) and control solutions versus less differentiated cells(ie, human fibroblasts) and compare the effects of low-osmolar ionic (ioxaglate) and nonionic (iopamidol) and high-osmolar ionic (diatrizoate) CM on rat mesangial cells. METHODSThe cytotoxic effects of ioxaglate and control solutions of sodium chloride and mannitol were assessed by neutral red uptake in isolated rat mesangial cells and human fibroblasts. In a second series of studies, the cytotoxic effects of ioxaglate, iopamidol, and diatrizoate (0 to 100 mg I/mL) on rat mesangial cells were compared. RESULTSRat mesangial cells were more sensitive to the cytotoxic effects of ioxaglate than the less differentiated human fibroblasts between 70 and 100 mg I/mL. A similar discrepancy was observed in the case of control solutions, sodium chloride, and mannitol. Ioxaglate and iopamidol induced a similar level of cytotoxicity in rat mesangial cells whereas the high-osmolar agent diatrizoate was significantly more cytotoxic. However, the calculated inhibitory concentrations of 50% of all three CM were associated with similar osmolalities, suggesting a major role for this parameter in the case of such media. CONCLUSIONSRat mesangial cells are more sensitive to the cytotoxic effects of CM and hyperosmolar solutions than the less differentiated human fibroblasts. High-osmolar CM are more cytotoxic than ionic and nonionic low-osmolar CM to rat mesangial cells. Ionicity seems to play no deleterious role at similar iodine concentrations because ioxaglate and iopamidol had equivalent cytotoxic effects on mesangial cells.