Idée J M, Santus R, Beaufils H, Balut C, Huntsman A M, Bourbouze R, Koeltz B, Jouanneau C, Bonnemain B
Laboratoire Guerbet, Aulnay-sous-Bois, France.
Am J Nephrol. 1995;15(1):66-74. doi: 10.1159/000168803.
The nephrotoxic potentials of a high-osmolar contrast medium, diatrizoate, and of a low-osmolar contrast medium, ioxaglate, were compared during early degenerative gentamicin-induced nephropathy in the rat. Male rats (13-22/group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery, and either diatrizoate or ioxaglate was administered (1 ml/min for 3 min) via an aortic puncture into the remaining kidney. Some of the rats received chronic treatment with gentamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and ending 1 day after contrast medium administration. Two control groups, only one of which received gentamicin, were subjected to a 3-min renal ischemia. The creatinine clearance (CrCl) per 100 g body weight was determined before and 24 and 48 h after contrast medium injection. A second study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and the histologic appearance of the kidneys (blinded analysis) in the same experimental groups. Gentamicin induced a significant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p < 0.01) and an increase in urinary NAG (128 +/- 92 vs. 39 +/- 57 mumol/h/mmol creatinine; p < 0.01). Taking into account these differences at baseline, univariate repeated-measures analysis showed that on day 1 diatrizoate caused a more marked decrease in CrCl than ioxaglate (p < 0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamicin persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of diatrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
在大鼠早期庆大霉素诱导的肾病模型中，比较了高渗性造影剂泛影葡胺和低渗性造影剂碘克沙醇的肾毒性。将雄性大鼠（每组13 - 22只）进行单侧肾切除。6天后，夹闭肾动脉上方的主动脉，通过主动脉穿刺向剩余肾脏注入泛影葡胺或碘克沙醇（1 ml/分钟，共3分钟）。部分大鼠在造影剂注射前2天开始并在注射后1天结束接受庆大霉素慢性治疗（50 mg/kg/天，肌肉注射，共4天）。两个对照组，其中只有一组接受庆大霉素治疗，均经历3分钟的肾脏缺血。在造影剂注射前、注射后24小时和48小时测定每100克体重的肌酐清除率（CrCl）。第二项研究（每组6只大鼠）评估了相同实验组中尿N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）排泄情况和肾脏的组织学表现（盲法分析）。庆大霉素使基线时的CrCl显著降低（0.35 ± 0.19对0.41 ± 0.19 ml/分钟；p < 0.01），并使尿NAG增加（128 ± 92对39 ± 57 μmol/小时/毫摩尔肌酐；p < 0.01）。考虑到基线时的这些差异，单变量重复测量分析表明，无论是否给予庆大霉素，在第1天泛影葡胺导致的CrCl降低比碘克沙醇更显著（p < 0.05）。在第2天，与庆大霉素相关的泛影葡胺的抑制作用持续存在（CrCl与第0天相比 = -0.19 ± 0.10 ml/分钟），而单独使用泛影葡胺的抑制作用恢复到基线水平（-0.05 ± 0.24 ml/分钟）。（摘要截断于250字）
