Brillet G, Dubois M, Beaufils H, Bourbouze R, Deray G
Department of Nephrology, Hôpital de la Pitie, Paris, France.
Invest Radiol. 1991 Oct;26(10):879-81. doi: 10.1097/00004424-199110000-00008.
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.
本研究的目的是评估新型磁共振造影剂AMI 25的肾脏耐受性。该造影剂对网状内皮系统具有亲和力，用于检测肝脏局灶性病变。肾缺血与动脉内注入碘化造影剂（泛影葡胺）相结合可在大鼠中建立一种可重复且可逆的急性肾衰竭模型。利用该模型，将AMI 25以1 ml/kg的剂量直接灌注到主动脉中——该剂量是人类所用剂量的10倍。AMI 25并未引起血清肌酐（输注前、输注后24小时和48小时分别为45±7、40±6、40±9 μmol/L）、肌酐清除率（2.1±0.6、2.1±0.6、2.1±0.6 mL/min）或尿N - 乙酰葡糖胺酶（NAG）排泄量（72±16、98±12、58±9.8 μmol·小时-1/mmol肌酐）发生变化。对11个灌注了AMI 25的肾脏进行的盲法组织学分析未发现异常，而在检查的7个灌注了泛影葡胺的肾脏中，有4个出现了急性肾小管坏死。在我们的动物模型中，即使给予AMI 25相当于人类预期临床剂量10倍的剂量，它也没有肾毒性。
