Kim Kijun, Kim Sung Hoon, Yang Chul Woo, Li Can, Chung Yong An, Lee Sung Yong, Sohn Hyung Sun, Chung Soo Kyo
Department of Radiology, The Catholic University of Korea, Seoul, Korea.
Invest Radiol. 2003 Aug;38(8):473-81. doi: 10.1097/01.rli.0000065696.41011.ce.
Acute cyclosporine (CsA) nephrotoxicity cannot be easily differentiated from other renal parenchymal complications, such as acute tubular necrosis (ATN), that cause renal function impairment at the early posttransplantation period. The purpose of this study was to differentiate acute CsA nephrotoxicity from ATN using enalaprilat renal scintigraphy in rats.
Twenty-six rats were divided into 4 experimental groups: CsA group, who were treated with CsA (50 mg/kg/d) for 2 days; ATN group, who received clamping of both renal arteries for 45 minutes; vehicle group, who were treated with olive oil (1 mL/kg/d) for 2 days; and sham-operated group, who received the same surgical procedure as ATN group without clamping of renal arteries. The baseline study was performed with 300 microCi of technetium-99m diethylenetriaminepentaacetic acid and enalaprilat scintigraphy with 2 mCi of technetium-99m diethylenetriaminepentaacetic acid 5 minutes after intravenous enalaprilat injection (30 microg/kg). The changes of renogram grade and the renal function indices such as T(max), T(1/2), residual cortical activity, and mean transit time between 2 studies were analyzed. Immediately after renal scintigraphy, blood urea nitrogen and serum creatinine levels were measured and renal tissues stained by periodic acid Schiff reaction were examined in each group.
Blood urea nitrogen and serum creatinine levels in the CsA and ATN groups were higher than their control groups (P < 0.05). Histologic study revealed severe ischemic necrosis of tubular epithelium in ATN group, but the other groups remained with essentially normal morphology. After enalaprilat injection, renal function indices became improved in CsA group, whereas they deteriorated in ATN group. The renogram grade was decreased in CsA group and increased or unchanged in ATN group after enalaprilat injection. The T(max), residual cortical activity, and mean transit time ratio were statistically different between the 2 groups on enalaprilat study (P < 0.05).
These results suggest that enalaprilat renal scintigraphy could be used clinically in differentiating acute CsA nephrotoxicity from ATN after renal transplantation.
急性环孢素（CsA）肾毒性不易与其他肾实质并发症相区分，如急性肾小管坏死（ATN），后者在移植后早期会导致肾功能损害。本研究的目的是利用依那普利拉肾闪烁扫描术在大鼠中区分急性CsA肾毒性与ATN。
26只大鼠分为4个实验组：CsA组，给予CsA（50mg/kg/d）治疗2天；ATN组，双侧肾动脉夹闭45分钟；溶剂组，给予橄榄油（1mL/kg/d）治疗2天；假手术组，接受与ATN组相同的手术操作，但不夹闭肾动脉。基础研究采用300微居里的锝-99m二乙三胺五乙酸进行，静脉注射依那普利拉（30微克/千克）5分钟后，采用2毫居里的锝-99m二乙三胺五乙酸进行依那普利拉闪烁扫描。分析两次研究之间肾图分级的变化以及肾功能指标，如T（max）、T（1/2）、残余皮质活性和平均通过时间。肾闪烁扫描后立即测量每组的血尿素氮和血清肌酐水平，并对肾组织进行高碘酸希夫反应染色检查。
CsA组和ATN组的血尿素氮和血清肌酐水平高于各自的对照组（P<0.05）。组织学研究显示ATN组肾小管上皮严重缺血坏死，但其他组形态基本正常。依那普利拉注射后，CsA组的肾功能指标得到改善，而ATN组则恶化。依那普利拉注射后，CsA组肾图分级降低，ATN组升高或不变。依那普利拉研究中两组的T（max）、残余皮质活性和平均通过时间比有统计学差异（P<0.05）。
这些结果表明，依那普利拉肾闪烁扫描术可在临床上用于区分肾移植后急性CsA肾毒性与ATN。
