Sakuma T, Ogawa O, Kawamura T, Hasegawa A, Kamidono S
Department of Urology, Tokyo Metropolitan Children's Hospital.
Nihon Hinyokika Gakkai Zasshi. 1995 Sep;86(9):1450-9. doi: 10.5980/jpnjurol1989.86.1450.
Results of a total of 46 pediatric (mean age; 9.0 years), living-related, cyclosporine-treated renal allograft recipients were analyzed retrospectively to study 1), the effects of an acute rejection on the long-term allograft function and 2), the relationship between the cyclosporine blood levels and the frequency of acute rejections. In addition, sequential allograft biopsies (100 days, one, two and three years post-transplant) were performed in all cases to see if clinical symptoms correlated with histological changes.
After a mean follow up of 3.3 (range 1-6) years, 15 of 22 (68%) recipients who had no signs of acute rejection, 6 of 12 (50%) who had acute rejections but responded completely to therapy, and none of the remaining 12 cases who failed to recover completely from acute rejections showed good allograft functions and normal histology on biopsy. Thirty-four of 46 cases had no clinical signs of rejection at 100-day allograft biopsy. Yet, histological changes compatible with acute rejection were noted in 11 of 34. Treatments of the rejection were promptly started on these patients and the prognosis was excellent in six cases. The mean blood trough levels of cyclosporine were significantly lower in patients who developed an acute rejection during the first week following transplantation as compared to those without rejection episodes during the same period, 165.5 ng/ml and 204.1 ng/ml, respectively. Furthermore, the mean blood cyclosporine trough levels in patients who experienced rejections during two, three and five weeks after transplantation were definitely lower than those who did not experience such episodes; 124.5 ng/ml, 101 ng/ml and 149.3 ng/ml versus 241.7 ng/ml, 217.7 ng/ml and 201.1 ng/ml respectively, although the number of the cases was too small to reach statistical significance.
The results indicate that the long-term allograft function would depend on whether there were episodes of acute rejections, and/or how the allograft responded to the treatments. Since the introduction of cyclosporine has made it difficult to detect acute rejections by clinical findings alone such as blood chemistry or urinalysis, the role of routine allograft biopsies is very important in renal transplantation. It seems likely that low blood levels and/or acute decline of cyclosporine during early postransplant period could increase the possibility of episodes of acute rejection. Since it is well documented that cyclosporine induces less renal parenchymal damages in children, the blood through levels of the drug should be kept at between 200 and 300 ng/ml within 5 weeks of transplantation in order to reduce the risk of acute rejections and to improve the chance of long-term allograft survival.
对46例儿科（平均年龄9.0岁）活体亲属供肾、接受环孢素治疗的肾移植受者的结果进行回顾性分析，以研究：1）急性排斥反应对移植肾长期功能的影响；2）环孢素血药浓度与急性排斥反应发生率之间的关系。此外，对所有病例均在移植后100天、1年、2年和3年进行了系列移植肾活检，以观察临床症状与组织学变化是否相关。
平均随访3.3年（范围1 - 6年），22例无急性排斥反应迹象的受者中，15例（68%）移植肾功能良好且活检组织学正常；12例发生急性排斥反应但对治疗完全反应的受者中，6例（50%）情况良好；其余12例未从急性排斥反应中完全恢复的受者，均未表现出良好的移植肾功能和正常的组织学。46例中有34例在移植后100天的移植肾活检时无排斥反应的临床体征。然而，34例中有11例发现有与急性排斥反应相符的组织学变化。对这些患者立即开始进行排斥反应治疗，6例预后良好。与移植后第一周内未发生排斥反应的患者相比，发生急性排斥反应的患者环孢素血药谷浓度显著较低，分别为165.5 ng/ml和204.1 ng/ml。此外，移植后第2周、第3周和第5周发生排斥反应的患者，其环孢素血药谷浓度肯定低于未发生此类情况的患者；分别为124.5 ng/ml、101 ng/ml和149.3 ng/ml，而未发生排斥反应的患者分别为241.7 ng/ml、217.7 ng/ml和201.1 ng/ml，尽管病例数太少，未达到统计学意义。
结果表明，移植肾的长期功能取决于是否发生急性排斥反应以及移植肾对治疗反应如何。由于环孢素的应用使得仅通过血生化或尿液分析等临床检查难以发现急性排斥反应，因此常规移植肾活检在肾移植中非常重要。移植早期环孢素血药浓度低和/或急剧下降似乎可能增加急性排斥反应的发生可能性。鉴于有充分证据表明环孢素对儿童肾实质损害较小，为降低急性排斥反应风险并提高移植肾长期存活几率，移植后5周内环孢素血药谷浓度应维持在200至300 ng/ml之间。
