URINE PROFILES AND KIDNEY HISTOLOGY AFTER IONIC AND NONIONIC RADIOLOGIC AND MAGNETIC-RESONANCE CONTRAST-MEDIA IN RATS WITH CISPLATIN NEPHROPATHY

Rationale and Objectives. The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcin oma frequently undergo examinations with contrast media. We examined w hether ionic and nonionic radiologic and magnetic resonance contrast m edia would have any effect on cisplatin nephropathy in rats. Methods. Urine and serum profiles were monitored for 24 days after intravenous (ni) injections of saline, diatrizoate, iohexol, gadopentetate dimeglu mine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (IF) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rat s injected with both IP and TV saline served as control subjects. Afte r euthanization, rats' kidneys were removed for examination by light m icroscopy and electron microscopy. Results. Light and electron microsc opy showed severe morphologic changes, including tubular dilatation, a trophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dime glumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with IV saline in cisplatin nephropathy, whereas gadodiamide did not, Albuminuria was highest after diatrizoate inject ion. All four contrast media caused an immediate and transient signifi cant increase in the excretion of the brush border enzymes alkaline ph osphatase and gamma-glutamyltransferase (125-500 times) and the cytopl asmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-1 00 times). Compared with saline, the ionic agents significantly increa sed the excretion of both glucose (two times) and sodium (three to fiv e times), whereas the nonionic agents did not. Conclusion. High doses of radiologic and magnetic resonance contrast agents cause temporary d ysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.