Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy.
OBJECTIVE
The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats.


METHODS
Urine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats' kidneys were removed for examination by light microscopy and electron microscopy.


RESULTS
Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not.


CONCLUSIONS
High doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.
Thomsen
H S
HS
Department of Diagnostic Radiology, Herlev Hospital, University of Copenhagen, Denmark.
Dorph
S
S
Larsen
S
S
Horn
T
T
Hemmingsen
L
L
Skaarup
P
P
Golman
K
K
Svendsen
O
O
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D003973:Diatrizoate / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000009:adverse effects; D007275:Injections, Intravenous; D007472:Iohexol / Q000008:administration & dosage / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000652:urine*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011859:Radiography / Q000379:methods*; D051381:Rats
D000970:Antineoplastic Agents; D003287:Contrast Media; D003973:Diatrizoate; D007472:Iohexol; C064925:gadodiamide; D019786:Gadolinium DTPA; D002945:Cisplatin