西罗莫司在肝移植后并发他克莫司所致肾功能损害患者中的应用

目的探讨肝移植后并发他克莫司(FK506)所致肾功能损害时使用西罗莫司的有效性和安全性。方法13例患者肝移植术后均采用以FK506为主的免疫抑制方案预防排斥反应,发生肾功能损害后,停用FK506,或FK506用量减半,同时加用西罗莫司。治疗期间监测患者的血肌酐和尿素氮水平、血西罗莫司和,FK506浓度、肝脏功能及排斥反应的发生情况。结果所有患者在使用西罗莫司后肾脏功能迅速改善,血肌酐水平由(147.6±92.8)μmol/L降到(106.1±71.6)μmol/L(P <0.05);除1例发生急性排斥反应外,其余患者在治疗期间均未发生排斥反应;用药期间的不良反应有高脂血症(4例)及白细胞减少(2例),经对症处理好转。迄今随访4～15个月,肾功能未再出现异常。结论肝移植术后发生药物性肾功能损害时,使用西罗莫司治疗是安全和有效的。     

肝移植术后长期存活慢性肾功能损害受者的免疫抑制方案个体化应用

目的探讨肝移植术后长期存活慢性肾功能损害受者应用个体化免疫抑制方案的疗效。方法选择18岁以上、肝移植术后2年以上、入组前采用以他克莫司(FK506)为基础免疫抑制方案、肝功能正常而肾功能损害的受者,共32例。根据免疫功能评分和白细胞计数制定个体化免疫抑制方案,以FK06用量最小化为原则,转换为麦考酚吗乙酯(MMF)或西罗莫司,并调整其用量。调整后至少每个月随访1次,进行肝功能、肾功能、血常规检查和免疫功能评估。结果 32例受者经个体化免疫抑制方案治疗,随访(24.3±7.6)个月,个体化治疗后各时段的肾小球滤过率(GFR)均较此前有明显提高(均为P<0.01),以调整用药后1个月最明显。无发生排斥反应。结论根据免疫功能评分和白细胞计数制定个体化免疫方案,使FK506用量最小化,可以有效改善肝移植术后长期存活的受者的肾功能,并不增加排斥反应的发生率。     

西罗莫司在肝移植中的临床应用

西罗莫司(sirolimus,SRL)是一种大环内酯类免疫抑制剂,具有抗增殖、抗肿瘤及无肾毒性等特性.其作用机制与传统免疫抑制剂FK506和CsA不同且互补,丰富了肝移植术后免疫抑制方案的选择,使临床获得了防治肝移植术后肾功能不全、慢性排斥反应、肿瘤复发和提高移植物长期存活的新途径.     

肝移植术后糖尿病的诊治策略

目的探讨肝移植术后糖尿病(PTDM)的临床特征和诊治措施。方法回顾性分析我院自2003年10月到2008年8月的58例PTDM患者的临床资料。70.7%(41/58)的患者予胰岛素治疗,激素组23例口服激素的PTDM患者中有15例激素减量或停用;FK506组16例使用单药他克莫司(FK506)免疫抑制方案的PTDM患者,转换为霉酚酸酯(MMF)或西罗莫司(RPM)为主的免疫抑制方案,随访3个月,观察改变免疫抑制方案对PTDM的影响。结果 89.7%(52/58)的PTDM患者临床症状不典型,激素组有5例患者空腹血糖正常,出现糖尿病逆转;11例患者胰岛素用量显著降低或停用,无一例发生急性排斥反应。FK506组有2例患者糖尿病逆转,10例患者胰岛素用量显著降低或停用,1例患者发生急性排斥反应,在FK506加量后排斥反应得以控制。结论肝移植术后PTDM的临床症状不典型,胰岛素治疗占主体。减低激素和FK506用量,转换MMF或RPM为主的免疫抑制方案,可能是防治PTDM的有效手段。     

治疗肝移植术后顽固性排斥反应的新尝试

目的探讨一种治疗肝移植术后顽固性排斥反应的新方法。方法经病理证实的肝移植术后急性排斥反应2例、慢性排斥反应2例，这4例患者在应用常规治疗方法无效的情况下，应用低剂量他克莫司（FK506）＋西罗莫司（SRL）进行治疗，FK506和SRL的血药浓度分别控制在3～5μg／L和6～12μg／L。排斥反应纠正后停用SRL，并将FK506调整至常规用量。结果4例患者的排斥反应均得以纠正，在应用本方案的过程中出现巨细胞病毒性肺炎1例，经抗病毒治疗后痊愈；原有糖尿病加重1例，新发生糖尿病1例，停用SRL同时应用胰岛素控制血糖，治疗后血糖恢复正常水平。结论肝移植术后经常规治疗方法无效的急、慢性排斥反应，应用低剂量FK506＋SRL进行治疗，排斥反应可以得到逆转。     

肝移植术后西罗莫司的替换治疗

目的 探讨肝移植术后应用西罗莫司的抗排斥替换治疗效果。方法 回顾性分析50例肝移植或肝肾联合移植患者替换西罗莫司前后肝肾功能的改善情况及副作用和排斥反应的发生率。34例联合应用小剂量FK506，9例联合应用骁悉，2例联合应用新山地明。5例术后远期患者，替换前仅用FK506，替换后单用西罗莫司。结果 24例患者因肝功能不良而替换西罗莫司，其中16例（66．7％）肝功能明显改善；18例患者肾功能不良，其中13例（72．2％）在2个月内肾功能明显好转；8例患者因大剂量应用FK506但其浓度未达到6ng／ml而替换西罗莫司，移植术后肝肾功能恢复良好，未出现排斥反应。本组中应用西罗莫司后出现急性排斥反应3例（6％），改用FK506后急性排斥反应治愈。11例（22％）出现白细胞及血小板减少，9例（18％）胆固醇和甘油三酯升高。这些副作用均在西罗莫司应用1月后出现，当停药或对症处理后消失。本组中未出现肝动脉血栓形成、伤口愈合不良等并发症。结论 肝移植术后应用钙调磷酸酶抑制剂发生肝肾功能不良或不能达到理想药物浓度时，西罗莫司是有效的抗排斥替代药物。     

西罗莫司治疗心脏死亡器官捐献肾移植术后急性排斥反应(附1例报告并文献复习)

目的探讨西罗莫司在心脏死亡器官捐献(donation after cardiac death,DCD)肾移植术后急性排斥反应中的应用。方法回顾性分析1例接受同种异体DCD供肾受者肾移植术后发生急性排斥反应,早期应用西罗莫司治疗的临床资料并复习相关文献。结果 1例DCD供肾肾移植受者,采用他克莫司(FK506)+吗替麦考酚酯(MMF)+泼尼松三联抗排斥免疫方案(FK506每次3mg,每日2次;MMF每次750mg,每日2次;泼尼松每次15mg,每日1次),术后即出现无尿,诊断为移植物功能延迟恢复(DGF)。行血液透析治疗,每周3次。术后35d发现尿量减少,移植肾彩色多普勒超声提示急性排斥反应,经肾上腺皮质激素冲击治疗无效后,血清肌酐(Scr)升高,提示治疗无效,改为西罗莫司+FK506+MMF+泼尼松的四联方案(西罗莫司每次0.5mg,每日1次;FK506每次2mg,每日2次;MMF每次250mg,每日2次;泼尼松每次15mg,每日1次),并减少他克莫司剂量。改用方案后3d患者Scr逐渐下降至正常,至出院后未再出现排斥反应。患者随访至2013年4月移植肾功能稳定,生活质量良好。结论西罗莫司有利于DCD供肾肾移植患者肾功能早期恢复,对术后急性排斥反应有一定疗效。     

肝移植术后免疫抑制剂的个体化治疗

目的 总结肝移植术后免疫抑制剂个体化治疗经验.方法 回顾性分析32例肝移植患者免疫抑制剂使用与排斥反应防治情况,除外术后早期3例因非排斥反应原因死亡,共随访观察29例患者不同时期采用不同的免疫抑制方法的效果.结果 1例术后1年半自行停药,6个月后因免疫因素相关的慢性排斥死亡.术后1个月内轻微急性排斥反应3例,1例1个月后急性排斥反应,所有排斥反应均因药物浓度低或长时间停药造成,均早期发现,经加用FK506及激素后控制,现存活的11例中,CsA最低用量为2 mg/(kg·d),FK506最低用量为0.02 mg/(kg·d).结论 应根据受体免疫状态、术后不同时期、合并的特殊病情及对免疫抑制剂的个体差异等来决定免疫抑制剂方案及用量.     

肝移植术后他克莫司导致双下肢疼痛综合征的治疗经验

目的总结肝移植术后他克莫司(FK506)导致的下肢疼痛综合征的治疗经验。方法 1例男性52岁患者,因乙型病毒性肝炎(乙肝)、肝炎后肝硬化失代偿期、肝脏恶性肿瘤行肝移植手术后应用FK506免疫抑制剂治疗后出现双下肢疼痛综合征,经排除血管神经性疼痛后,停用FK506并转化为西罗莫司(SRL)治疗,血药浓度早期维持在6～8 ng/mL,后根据移植物存活时间逐步调整。结果经转化治疗2周后,患者双下肢肿胀疼痛逐步减轻、皮肤瘙痒逐步消退,1个月后基本恢复正常活动功能,随访至投稿日无反复。结论 FK506不良反应导致的双下肢疼痛综合征较为罕见,改用SRL可规避这一不良反应。     

大鼠移植肝组织中一氧化氮合酶的表达及其抑制剂的作用

目的 观察大鼠移植肝组织中一氧化氮合酶(iNOS)的表达及iNOS抑制剂氨基胍和免疫抑制剂他克莫司(FK-506)对肝移植术后急性排斥反应的影响。方法 实验分为4组：同基因组(供、受者均为LEW大鼠)；急性排斥组(供者为BN大鼠，受者为LEW大鼠)；氨基胍组、FK506组在异基因大鼠肝移植后分别应用氨基胍和FK506。用免疫组织化学法检测各组移植肝组织中iNOS表达水平。结果 急性排斥组iNOS表达呈强阳性，与氨基胍组、FK506组、同基因组比较，差异显著。结论 在大鼠原位肝移植发生急性排斥反应时，iNOS增高程度与排斥反应的强度有明显关系。氨基胍和FK506可以抑制iNOS的表达，明显减轻移植肝组织的急性排斥反应。     

Focus on intractable rejection: 6-month results of the European multicentre liver study of FK 506 and cyclosporin A

Abstract The incidence of intractable rejection was evaluated during the course of a multicentre, randomised, parallel-group study comparing the efficacy and safety of FK 506 and conventional cyclosporin A-based immunosuppressive regimens in patients undergoing primary liver transplantation. A diagnosis of intractable rejection was made if there was histological evidence of unchanged or worsening acute rejection, or chronic rejection after two discrete courses of antirejection therapy. Antirejection regimens were specific to each centre. Patients who experienced intractable rejection could be withdrawn from the study. Patients who were withdrawn from the cyclosporin A treatment group could subsequently receive FK 506 therapy and vice-versa. Intractable rejection was diagnosed in 32/540 patients (5.9%): 7/267 patients (2.6%) in the FK 506 treatment group and 25/273 patients (9.2%) receiving cyclosporin A therapy ( P < 0.01). Of these 32 patients, 25 were withdrawn from the study: 3 and 22, from the FK 506 and cyclosporin A treatment groups, respectively. All three patients withdrawn from the FK 506 treatment group are alive: two having undergone retransplantation. Of the 22 patients withdrawn from the cyclosporin A group and converted to FK 506 therapy, 6 were retransplanted, 4 of whom subsequently died. A further two patients died without retransplantation. Thus, in 14 of the 16 patients who were still alive at 6 months, the liver graft was saved after conversion to FK 506 treatment. The reduced incidence of intractable rejection in patients receiving treatment with FK 506, together with the successful rescue of patients developing intractable rejection while receiving cyclosporin A, suggests that FK 506 is an effective immunosuppressive agent following orthotopic liver transplantation.     

Corticosteroids and concomitant medication in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation

Abstract The steroid-paring effect and the use of concomitant medication during the treatment of liver transplant patients with the novel immunosuppressant FK 506 were evaluated within the European multicentre, randomized, parallel-group study in liver transplantation. Patients undergoing primary liver transplantation were randomized to treatment with FK 506 ( n = 267) or with a cyclosporin-based immunosuppressive regimen ( n = 273). The total cumulative steroid usage was significantly reduced in the FK 506 treatment group, which is likely to have resulted from the lower incidence of acute rejection in these patients. The number of patients receiving antidiabetic, diuretic and antihypertensive therapy did not differ between the two treatment groups, even though the incidence of diabetes mellitus and oliguria was significantly higher in the FK 506 group. It can, therefore, be assumed that in a number of such cases the severity of these events was very mild necessitating no specific therapy.     

普乐可复在肾移植中的临床应用

目的 研究普乐可复（ＦＫ５０６）对肾移植患者免疫抑制的疗效与安全性。方法 肾移植术后应用ＦＫ５０６免疫抑制治疗８２例,分为临床验证组４２例和切换治疗组４０例。结果 临床验证组有４０例（９５．２％）肾功能在１４ｄ内恢复正常,１例（２．４％）发生急性排斥反应,经治疗逆转。切换治疗组有２４例肝功能正常;３例移植肾发生急性肾小管坏死（ＡＴＮ）伴急性排斥反应,６例发生慢性排斥反应,４例发生难治性排斥反应,均     

环孢素A和他克莫司在高危肾移植患者中的应用比较

目的　比较高危肾移植患者术后应用环孢素 A(CsA)和他克莫司(FK506)的疗效和安全性。方法　将58例高危肾移植患者随机分为CsA组(30例)和FK506组(28 例),观察肾移植后 1年内两组的急性排斥发生率和药物逆转率、药物毒副作用及感染发生情况。结果　 FK506组和 CsA组的人/肾存活率分别为100%/100%和93.3%/86.7%;急性排斥反应发生率分别为14.3%和16.7%;抗排斥治疗的逆转率分别为100%和60%。FK506组药物毒副作用也较 CsA组小。结论　在高危肾移植患者的免疫抑制治疗中FK506应为首选。     

乙型肝炎相关性肝病肝移植术后的急性排斥反应

目的 研究乙型肝炎相关性肝病肝移植术后急性排斥反应的发病率、治疗和预防。方法前瞻性地研究用肝移植术治疗乙型肝炎相关性肝病100例，分析急性排斥反应的发病相关因素，急性排斥反应和免疫抑制剂治疗的动态监测及二者间的联系。结果临床型急性排斥反应的发病率为12％，急性排斥反应发生前3～5d，有明显的免疫抑制剂浓度降低的过程。FKS06为基础的免疫抑制方案，加用骁悉，可有效地终止、逆转急性排斥反应；和以甲基强的松龙冲击治疗急性排斥反应相比较，副作用少，但肝功能的完全恢复时间相对较慢。结论乙型肝炎相关性肝病的肝移植术后急性排斥反应的发生率相对较低；和急性排斥反应发生相关的免疫抑制剂低浓度是诱导急性排斥反应的重要相关因素；FK506为基础的免疫抑制方案，可有效地终止、逆转急性排斥反应，且副作用少。     

肾移植术后患者应用西罗莫司对他克莫司剂量的影响

目的观察肾移植术后联合应用西罗莫司(雷帕霉素)对他克莫司(FK506)剂量的影响。方法60例肾移植术后患者随机分为两组,研究组30例,免疫抑制方案采用西罗莫司+他克莫司+泼尼松;对照组30例,采用麦考酚吗乙酯(MMF)+他克莫司+泼尼松联合治疗。术后随访2年,比较两组的人、肾存活率,急性排斥反应率,他克莫司用量,肾功能变化和不良事件发生率。结果研究组、对照组全部如期完成观察,两组的人肾存活率均为100%,研究组、对照组急性排斥反应发生率分别为7%(2/30)、10%(3/30),经肾上腺皮质激素(激素)冲击治疗后逆转;研究组在维持他克莫司血药浓度与对照组相当情况下,其用量低于对照组,比较差异有统计学意义(P0.05)。两组的不良事件发生率相近(60%比70%,P0.05)。结论联合西罗莫司+他克莫司+泼尼松方案用作肾移植术后免疫抑制治疗是安全有效的,且能减少他克莫司的剂量。     

Patient and graft survival in the European Multicentre Liver Study - FK 506 vs cyclosporin A

Abstract A prospective randomised study was conducted to evaluate the efficacy and safety of FK 506 administered with corticosteroids compared with a cyclosporin A-based immunosuppressive regimen in patients undergoing primary liver transplantation. 545 patients were recruited in eight European centres, of whom 267 were randomised to FK 506 therapy and 273 to cyclosporin A-based therapy. The estimated Kaplan-Meier patient and graft survival figures of 82.9% and 77.5% respectively in the FK 506 group were higher than the comparable figures in the cyclosporin A group (77.5% and 72.6%, respectively). These differences did not reach statistical significance. Retransplantation rates, time to first rejection episode and number of rejection episodes were all lower ( P < 0.001) in the FK 506 group. The infection rates were comparable between the two groups. During the study, the dose of FK 506 was reduced; this did not compromise efficacy and reduced the associated toxicity. FK 506 provides effective immunosuppression in patients undergoing primary liver transplantation and is associated with a lower incidence of rejection.     

他克莫司与环孢素A在尸肾移植中应用的长期疗效和安全性比较

目的　比较他克莫司 (FK5 0 6 )和环孢素A(CsA)在尸肾移植中应用的长期疗效和安全性。方法　 2 10例尸肾移植患者分为FK5 0 6组和CsA组 ,随访 12～ 32个月 ,观察两个组血药浓度变化、急性排斥和慢性排斥反应发生率、人 /肾 1年存活率、血肌酐、肝功能、血糖及血脂水平、药物不良反应、感染发生率以及FK5 0 6逆转顽固性急性排斥反应的效果。结果　血中FK5 0 6和CsA浓度谷值的变化趋势基本相同。FK5 0 6组与CsA组相比 ,急、慢性排斥反应发生率明显降低 (P <0 .0 5 ) ;肝功能异常发生率、高脂血症和牙龈增生发生率以及术后 3个月血肌酐水平均明显降低 (P <0 .0 5 ) ;高血糖和震颤发生率明显升高 (P <0 .0 5 ) ;感染发生率及人 /肾 1年存活率的差异无显著性。结论　与CsA相比 ,FK5 0 6是一种更高效的免疫抑制剂 ,长期使用可以有效降低肾移植后急、慢性排斥反应的发生率 ,有利于移植肾功能的恢复。     

Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression.

OBJECTIVE: The efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined. SUMMARY BACKGROUND DATA: After 3 years of preclinical research, a clinical trial of FK 506 for orthotopic liver transplantation was begun in February 1989, first as a rescue therapy for patients with intractable rejection with conventional immunosuppression, then as a primary drug. METHODS: Between August 1989 and December 1993, 1391 recipients (1188 adult and 203 pediatric) of primary liver allografts were treated with FK 506 from the outset. Results from these patients were analyzed and compared with those of 1212 historical control patients (971 adult and 241 pediatric) given cyclosporine-based immunosuppression. RESULTS: Actuarial survival at 4 years was 86.2% with FK 506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and 71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was reduced significantly for FK 506 patients. Four-year graft survival was 77.0% with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p < 0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult recipients (p < 0.0000). Regression analysis revealed that reduction in mortality or graft loss from uncontrollable rejection, sepsis, technical failure, and recurrent original liver disease were responsible for the improved results with FK 506 therapy. CONCLUSIONS: FK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation.     

肾移植术后应用他克莫司的临床观察

目的 观察他克莫司（ＦＫ５０６）作为免疫抑制剂的有效性和安全性。方法 将首次接受同种异体肾移植的３５例患者随机分为２组,一组给予他克莫司,硫唑嘌呤（或霉酚酸酯）和泼尼松（ＦＫ５０６组）,另一组给予环孢素Ａ、硫唑嘌呤（或霉酚酸酯）及泼尼松（ＣｓＡ组）,观察２个组的免疫抑制效果及药物的副作用。结果 ＣｓＡ组和ＦＫ５０６组的人／肾１年存活率分别为１００．０％／９３／３％和９５．０％／９５．０％;两组肝和