Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.
OBJECTIVE
Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.


METHODS
Dog kidney cells were incubated with 5- and 30-mmol/L glucose solutions and no glucose and then exposed for 2 hours to three types of contrast media-high osmolar (370 mg I/mL), low osmolar (300 mg I/mL), and isoosmolar (320 mg I/mL)-and a mannitol control solution. In an identical experiment, each group of cells was pretreated with an antioxidant-N-acetylcysteine or taurine-to evaluate the protective effect, if any. Apoptosis was assessed with fluorescence-activated cell sorter flow cytometry.


RESULTS
The high-osmolar contrast medium was associated with significantly elevated levels of apoptosis compared with the mannitol control (percentage apoptosis, 27.98 +/- 1.08 vs 6.19 +/- 0.771; p < 0.001). This effect was less pronounced after incubation with the low-osmolar agent but was still significant (percentage apoptosis, 20.19 +/- 0.3665 vs 6.19 +/- 0.771; p < 0.001). The isosmolar agent did not have a significant effect. Both the high- and low-osmolar contrast media coupled with hyperglycemia (30-mmol/L glucose) were associated with a significantly increased level of apoptosis. In all contrast medium groups, taurine had a greater protective effect on attenuation of cell apoptosis than did N-acetylcysteine.


CONCLUSIONS
The combination of contrast medium and an elevated glucose level has a synergistic effect on apoptosis. Taurine may be a more effective prophylactic antioxidant than the currently advocated antioxidant, N-acetylcysteine.
O'Donnell
David H
DH
Department of Radiology and Vascular Surgery, Beaumont Hospital, The Royal College of Surgeons in Ireland, Dublin, Ireland. davidhodonnell@hotmail.com <davidhodonnell@hotmail.com>
Moloney
Michael A
MA
Bouchier-Hayes
David J
DJ
Lee
Michael J
MJ
D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D003287:Contrast Media / Q000009:adverse effects*; D004285:Dogs; D006943:Hyperglycemia / Q000150:complications*; D007674:Kidney Diseases / Q000139:chemically induced / Q000209:etiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D009994:Osmolar Concentration; D018384:Oxidative Stress; D013654:Taurine / Q000494:pharmacology
D003287:Contrast Media; D013654:Taurine; D000111:Acetylcysteine