Comparison of the Effects of Iodixanol and Iopamidol on Urine Flow, Urine Viscosity, and Glomerular Filtration in Rats

Dehydration is a major risk for contrast media (CM) induced acute kidney injury, yet prospective studies in human patients without ample hydration are not feasible. The freely drinking rat can serve as a model for hydropenic humans. We compared the effects of two CM, iso-osmolar iodixanol and lowosmolar iopamidol, on urine flow, urine viscosity and glomerular filtration rate (GFR) in non-hydrated rats, and studied the impact of hydration by saline. In four groups of rats, either iodixanol 320 mg iodine/mL or iopamidol 370 mg iodine/mL was injected as 1.5 mL bolus into the thoracic aorta. Two groups had access to drinking water only and two groups received additional saline infusion (4 mL/hour per kg) starting 60 min before CM injection. Urine was collected (10 min sampling periods), urine viscosity measured, and GFR determined by creatinine clearance. In nonprehydrated rats, iodixanol led to a massive increase in urine viscosity and a transient 50% drop in GFR. Iopamidol had a much stronger diuretic effect than iodixanol, urine viscosity increased much less and GFR was unaffected. Saline infusion blunted the viscosity rise and transient decline in GFR caused by iodixanol. It is concluded that the choice of CM and ample hydration are important elements in the prevention of CM induced kidney injury. Low-osmolar iopamidol has a better renal safety profile than iso-osmolar iodixanol, at least in non-hydrated subjects. Hydration by saline counteracts the renal tubular concentration of CM thereby alleviating the increase in urine viscosity and the decline in GFR.