Renal tolerance of AMI 25.
The objective of this study was to evaluate the renal tolerance of a new magnetic resonance contrast agent, AMI 25. This agent has an affinity for the reticuloendothelial system and is used for the detection of focal liver lesions. A combination of renal ischemia and intra-arterial iodinated contrast agent infusion (diatrizoate) leads to a reproducible and reversible model of acute renal failure in the rat. Using this model, AMI 25 was perfused directly into the aorta at the dose of 1 ml/kg--ten times the dose used in humans. AMI 25 induced no change in serum creatinine (45 +/- 7, 40 +/- 6, 40 +/- 9 mumol/L before infusion and at 24 and 48 hours, respectively), in creatinine clearance (2.1 +/- 0.6, 2.1 +/- 0.6, 2.1 +/- 0.6 mL/mn), or in urinary N-acetyl glucosaminidase (NAG) excretion (72 +/- 16, 98 +/- 12, 58 +/- 9.8 mumol hour-1/mmol creatinine). Blinded histologic analysis of 11 kidneys perfused with AMI 25 revealed no abnormalities, whereas diatrizoate induced acute tubular necrosis in four of the seven kidneys examined. In our animal model, AMI 25 has no nephrotoxicity, even at ten times the expected clinical dose for humans.
Brillet
G
G
Department of Nephrology, Hôpital de la Pitie, Paris, France.
Dubois
M
M
Beaufils
H
H
Bourbouze
R
R
Deray
G
G
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D003911:Dextrans; D003973:Diatrizoate / Q000633:toxicity; D052203:Ferrosoferric Oxide; D007501:Iron / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D010087:Oxides / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D003973:Diatrizoate; D003404:Creatinine; D007501:Iron; D000118:Acetylglucosaminidase; C065507:ferumoxides; D052203:Ferrosoferric Oxide