肾移植后雷帕霉素免疫抑制剂转换方案应用12例

目的:总结分析肾移植后转换为雷帕霉素免疫抑制方案的初步经验.方法:回顾性分析2008-01/2009-03 12例因急性排斥反应、移植肾肾病、肝功能损害及齿龈增生等因素,由神经钙蛋白抑制剂为主的免疫抑制方案转换为以雷帕为主的免疫抑制方案的临床资料,转换方案的选择:①方案1,快速转换方式:第1天神经钙蛋白抑制剂减50%,1周完全停用神经钙蛋白抑制剂;雷帕霉素4 mg起,2 mg维持.②方案2:第1天停用霉酚酸酯,神经钙蛋白抑制剂不调整或减半,雷帕霉素4 mg起,2 mg维持,5 d后复查血药浓度,调整排斥用药.结果:快速代谢性患者5例,4例选用第2种方案,血肌酐平均下降30 μmol/L,且他克莫司/环孢素A+雷帕霉素可调整到目标浓度,无排斥反应再次发生,1例出现肺部感染后治愈;1例选用第1种方案,转换后短期血肌酐下降明显,后出现严重腹泻,且就医意识差,未及时诊治致移植肾失功.1例因肝功能持续异常选用第1种转换方案,转换后肝功能在2个月后完全正常.3例因血肌酐爬行性升高选用第1种转换方案,转换2个月后血肌酐平均下降23 μmol/L,且稳定在该水平,但1例蛋白尿显著增加.2例因齿龈增生明显选用第1种方案转换后,复查3个月症状明显好转,血肌酐稳定.1例因既往有脾功能亢进,术后口服环孢素或他克莫司达目标浓度后,均出现严重的骨髓抑制选用第1种方案转换后,复查3个月症状明显好转,血肌酐稳定.3例有不同程度血脂升高,9例未见明显血脂升高现象.结论:对于快速代谢型肾移植患者,转换为雷帕霉素为较好的选择,主要通过早、中、晚3次口服抗排斥药物保持有效的抗排斥药物浓度,同时增加神经钙蛋白抑制剂类抗排斥药物的浓度,有利于排斥的纠正和预防.急性排斥不是转换雷帕霉素的绝对禁忌证,但转换雷帕霉素后,神经钙蛋白抑制剂浓度应保持在相对较高的浓度,保持有效的抗排斥作用.

Rapamycin combined immunosuppression for 12 renal transplant recipients

OBJECTIVE:To analyze and summarize the initial experience of rapamycin combined immunosuppression(SRL)used in renal transplant recipients.METHODS:A retrospective analysis was performed on 12 cases who were cured by SRL-based immunosuppression instead of calcineurin(CNI)-based immunosuppression due to acute rejection,allograft nephropathy,liver dysfunction,and gingival hyperplasia between January 2008 and June 2009.The selection of immunosuppression was as follows:①rapid conversion:calcineurin was reduced by 50%at the first day,and terminated at 1 week;4 mg SRL and maintained to 2 mg;②mycophenolate was terminated at the first day,while calcineurin was maintained or reduced by 50%;4 mg SRL and maintained to 2 mg;blood drug level was detected 5 days later to adjust drugs.RESULTS:Four of five patients with rapid metabolism were subjected to strategy 2,and creatinine was reduced 30 μmol/L;FK/CsA+SRL were adjusted to the target concentration,with no rejection.One of them was cured after lung infection.One case,who was treated by CNI-based immunosuppression,showed the visible short-term decline in creatinine after the conversion and then severe diarrhea and bad sense of treatment,ultimately resulting in the renal graft failure.One case was subjected to the first conversion strategy due to abnormal liver function.The liver function recovered after 2 months;3 cases was subjected to the first conversion strategy due to increasing creatinine,and the creatinine reduced 23 μmol/L fter 2 months and maintained at that level,but proteinuria of one cases was significantly increased.Two cases selected the first conversion strategy due to gingival hyperplasia,and the symptoms were significantly improved after 3 months with stable serum creatinine;1 case showed hypersplenism,and developed severe bone marrow suppression following oral administration of cyclosporine or tacrolimus at target concentration.The symptom was improved,and serum creatinine kept stable after 3 months of the first conversion strategy.Three cases had varying elevated degrees of blood lipids,and 9 cases had no significant increase in blood lipids.CONCLUSION:For renal transplant patients with rapid metabolism,the conversion to SRL is recommended.An effective anti-rejection drug concentration was mainly maintained through three times of oral anti-rejection drugs;meanwhile,the concentration increase of CNI-type anti-rejection drug is conducive to correcting and preventing rejection.Acute rejection is not an absolute contraindication after conversion to SRL,but after converted to SRL,CNI concentration should be maintained at a relatively high concentration,to maintain effective anti-rejection effect.