Effect of low-osmolar contrast medium iopromide and iso-osmolar iodixanol on DNA fragmentation in renal tubular cell culture

Abstract

Intravascular administration of iodinated contrast media continues to be a common cause of hospital-acquired acute kidney injury. Accumulating evidence suggests that radiocontrast agent-induced nephrotoxicity is associated with increased oxidative stress, which leads to renal tissue damage with DNA fragmentation. We therefore tested whether an iso-osmolar contrast medium (iodixanol) causes less oxidative DNA damage to renal tubular cells than a low-osmolar contrast medium (iopromide). HK-2 cells (human proximal renal tubular cell line) were incubated at different time points (10min-2h) with increasing concentrations (20-120mg/ml iodine) of iodixanol or of iopromide. Oxidative DNA damage to renal tubular cells was measured by alkaline comet assay (single-cell gel electrophoresis). Both iso- and low-osmolar contrast agents induced time- and concentration-dependent DNA fragmentation. DNA fragmentation was maximal at 2h with 120mg/ml iodine for iopromide (32±27tail moments) and iodixanol (46±41tail moments); both were significantly different from the control value with 3.15±1.6tail moments (Student's t test; p<0.001). After 1 and 2h and for all concentrations, iodixanol produced significantly higher DNA fragmentation than iopromide (ANOVA for 1h p=0.039 and 2h p=0.025, respectively). We were able to demonstrate for the first time that an iso-osmolar contrast medium induced even greater oxidative stress and DNA damage than a low-osmolar agent in HK-2 cells. This could provide an explanation for the nephrotoxicity that also is observed with iodixanol in clinical practice.