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


METHODS
HK-2 cells (human proximal renal tubular cell line) were incubated at different time points (10 min-2 h) with increasing concentrations (20-120 mg/ml iodine) of iodixanol or of iopromide. Oxidative DNA damage to renal tubular cells was measured by alkaline comet assay (single-cell gel electrophoresis).


RESULTS
Both iso- and low-osmolar contrast agents induced time- and concentration-dependent DNA fragmentation. DNA fragmentation was maximal at 2 h with 120 mg/ml iodine for iopromide (32 ± 27 tail moments) and iodixanol (46 ± 41 tail moments); both were significantly different from the control value with 3.15 ± 1.6 tail moments (Student's t test; p < 0.001). After 1 and 2 h and for all concentrations, iodixanol produced significantly higher DNA fragmentation than iopromide (ANOVA for 1 h p = 0.039 and 2 h p = 0.025, respectively).


CONCLUSIONS
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.
Division of Nephrology, Internal Medicine I, University of Ulm, Albert-Einstein Allee 23, 89081, Ulm, Germany, ulla.ludwig@uniklinik-ulm.de.
Ulla
U
Ludwig
Julia
J
Connemann
Frieder
F
Keller
D058186:Acute Kidney Injury / Q000139:chemically induced; D002460:Cell Line; D003287:Contrast Media / Q000009:adverse effects*; D053938:DNA Fragmentation; D006801:Humans; D007472:Iohexol / Q000009:adverse effects / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects; D009994:Osmolar Concentration; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007472:Iohexol; C038192:iopromide; C044834:iodixanol