肝肾联合移植患者免疫抑制剂的应用

Application of immunosuppressive agent to patients undergoing combined liver and kidney transplantation

背景:不同单一器官移植后调动机体免疫反应的力度各不相同,故其免疫抑制剂的应用种类及剂量有所差异,多器官联合移植工作中,免疫抑制剂的应用则更为复杂,是移植工作者需要逐步总结的经验之一。目的:探讨肝肾联合移植患者合理的免疫抑制剂应用方案。方法:选择解放军第309医院器官移植中心2002-04/2009-07肝肾联合移植患者10例,以单独肝移植及肾移植患者为对照。3组患者术后早期抗排斥治疗均采用以他克莫司为基础的三联免疫抑制方案,在此方案基础上同时应用巴利昔单抗诱导疗法。肝肾联合移植组和肝移植组患者术中给予甲基泼尼松龙500mg冲击,术后第1天激素用量为160mg,分2次给药,此后每日递减40mg,术后第5天改为20mg泼尼松口服,术后2个月停用激素,术后6个月停用霉酚酸酯,仅应用他克莫司抗排斥治疗;肾移植组术中给予甲基泼尼松龙1000mg冲击,术后前3d应用甲基泼尼松龙500mg,此后每日50mg泼尼松口服,逐渐递减至每日10mg长期维持,术后长期应用他克莫司、霉酚酸酯和糖皮质激素。结果与结论:肝肾联合移植患者术后早期及术后6个月他克莫司用量同肝移植患者相近(P>0.05),但低于肾移植患者(P<0.05,P<0.01);肝肾联合移植和肝移植患者激素和霉酚酸酯用量亦明显低于肾移植患者,并且均在半年内停用激素和霉酚酸酯,肾移植患者需长期应用。3组病例1年后维持用药逐渐体现出个体差异现象。肝肾联合移植组均未出现远期肝功能异常,同时低剂量抗排斥药物对患者免疫系统影响较小,围手术期感染发生率明显减低。说明肝肾联合移植患者免疫抑制剂早期的应用参考单肝移植患者即可达到满意的治疗效果,激素和霉酚酸酯可在6个月内停药,他克莫司用量可低于单肾脏移植患者。

BACKGROUND：Different degrees of immunoreaction are stimulated in different isolated organ transplantation.Thus,the kind and the dose of immunosuppressive agent in different isolated organ transplantation patients are distinguishing.The application of immunosuppressive agent in combined organ transplantation is more complicated,which is one of the experiences that the transplant doctor should master.OBJECTIVE：To explore the suitable immunosuppressive project in combined liver and kidney transplantation（CLKT） patients.METHODS：A total of 10 patients underwent CLKT from the Organ Transplantation Center,the 309 Hospital of Chinese PLA from April 2002 to July 2009.The control groups were comprised of isolated liver transplantation（ILT） patients and isolated kidney transplantation（IKT） patients.The immunosuppressive project,which was based on tacrolimus,was adopted in the early postoperative period in these three groups.Basiliximab was used as immune inducer in these all cases.In the CLKT and ILT patients,500 mg methyllprednisolone was used during the operation,then 160 mg in the first day after the operation.The administration was performed twice.The dose of methyllprednisolone was decreased 40 mg per day in the following days.20 mg prednisone was given from the day 5 and the hormone was withdrawn by the end of the second month.Mycophenolate was also withdrawn in the end of the sixth month and tacrolimus was used only from then on.In the IKT patients,1 000 mg methyllprednisolone was used during the operation,followed by 500 mg/d in the first three days after the operation.Prednisone was decreased from 50 mg/d to 10 mg/d gradually.Tacrolimus,mycophenolate and prednisone were all used perennially in IKT patients.RESULTS AND CONCLUSION：The dose of tacrolimus to patients undergoing CLKT in early period and sixth month was similar to patients undergoing ILT（P 0.05）,and was obviously lower than patients undergoing IKT（P 0.05 and P 0.01）.Mycophenolate and prednisone to CLKT and ILT patients were both withdrawn in the first six months,the doses of which were obviously lower than to IKT patients.Mycophenolate and prednisone were used perennially in IKT patients.Individual difference for drug displayed in some patients of these three groups since 1 year after operation.There was no long-term hepatic insufficiency in the CLKT patients.Low-dose immunosuppressive agent has little effect on the patient＇s immune system,so it brought lower infection rate.A satisfactory therapeutic efficacy to CLKT patients has been got when the immunosuppressive project of ILT patients was used.Mycophenolate and prednisone were withdrawn in the first six months.The dose of tacrolimus was lower than IKT patients.