Oxygen free radicals and contrast nephropathy.

Ionic, high-osmolality contrast medium causes nephrotoxicity associated with increased intrarenal adenosine production. To test the hypothesis that oxygen free radicals (produced during intrarenal adenosine catabolism to xanthine) should be implicated in the pathogenesis of ionic, high-osmolality contrast medium nephrotoxicity in humans and to determine whether magnesium protects the kidney from oxygen free radical injury following contrast, 39 patients with mild renal dysfunction were divided into low (LoMg++) and normal (NlMg++) magnesium states and randomized to precoronary angiography oral allopurinol (a xanthine oxidase inhibitor) or placebo. Creatinine clearance and urinary xanthine excretion were measured before and after angiography. Forty-eight hours after contrast medium exposure, placebo-treated LoMg++ and NlMg++ patients had 61%+/-5% and 67%+/-6% increases in urinary xanthine excretion, respectively; however, placebo-treated LoMg++ patients had a greater (79%+/-9% v 35%+/-6%; P < 0.01) decrease in creatinine clearance than placebo-treated NlMg++ patients. Allopurinol-treated LoMg++ and NlMg++ patients had no significant change in urinary xanthine excretion, but did have 40%+/-7% and 33%+/-5% decreases, respectively, in creatinine clearance 48 hours after contrast medium exposure. There was no difference in renal dysfunctional response among placebo-treated NlMg++ patients or allopurinol-treated LoMg++ or NlMg++ patients. These data suggest (1) that oxygen free radicals contribute to ionic, high-osmolality contrast medium nephrotoxicity in hypomagnesemic patients with mild renal disease and (2) that magnesium attenuates the nephrotoxicity mediated by oxygen free radicals.

Nephrotoxicity from contrast media: attenuation with theophylline.

PURPOSE: To determine if depression of creatinine clearance after administration of contrast medium may be prevented with theophylline. MATERIALS AND METHODS: A nonionic, low-osmolality contrast medium (iopamidol) or an ionic, high-osmolality contrast medium (sodium diatrizoate) was administered to 93 patients. Before the examination, these patients were given theophylline or a placebo orally. There were also 30 patients who received an adenosine-uptake inhibitor (dipyridamole). Creatinine clearance and urinary adenosine levels were measured before and after angiography. RESULTS: Creatinine clearance decreased 18% +/- 4 in the placebo-iopamidol group but did not decrease in the theophylline group; urinary adenosine increased 67% +/- 7. Creatinine clearance decreased 42% +/- 5 in the placebo-sodium diatrizoate group and decreased 24% +/- 3 in the theophylline group; urinary adenosine increased 119% +/- 8. In the dipyridamole group in which iopamidol was given, urinary adenosine increased 96% +/- 7 and creatinine clearance decreased 37% +/- 5. CONCLUSION: Intrarenal adenosine can be implicated in the pathogenesis of hypertonic contrast medium nephrotoxicity.

Nephrotoxicity of nonionic low-osmolality versus ionic high-osmolality contrast media: a prospective double-blind randomized comparison in human beings.

To test whether a nonionic, low-osmolality contrast medium (iopamidol) administered for coronary angiography was less harmful to renal function than ionic, high-osmolality medium (sodium diatrizoate), a prospective, double-blind randomized study of 70 patients with normal or mildly depressed renal function (serum creatinine < or = 2.0 mg/dL (175 mumol/L) was performed. Creatinine clearance was determined before coronary angiography and 24 and 48 hours after. There were no significant differences between the low- and high-osmolality groups with regard to age, baseline creatinine clearance, or dose of contrast medium given. In patients receiving low-osmolality medium (n = 35), creatinine clearance decreased by 19% +/- 13 (1 standard deviation) at 24 hours and recovered by 48 hours. In patients receiving high-osmolality medium (n = 35), creatinine clearance decreased by 40% +/- 16 at 24 hours and remained depressed by 47% +/- 14 at 48 hours. In patients with normal or mildly depressed renal function, use of a non-ionic, low-osmolality contrast medium minimized nephrotoxicity as measured by reductions in creatinine clearance after coronary angiography.