普乐可复预防同种肾移植排斥反应的研究

目的 评价并比较新型免疫抑制普乐可复（ＦＫ５０６）对预防同种肾移植受者排斥反应的疗效及安全性。方法 随机将９８例肾移植受者分成２组。（１）ＦＫ５０６组（ｎ＝４０）;主要用药为ＦＫ５０６＋霉酚酸酯（ＭＭＦ）＋泼尼松（Ｐｒｅｄ）;（２）环孢素９Ａ（ＣｓＡ组）（ｎ＝５８）;主要用药为;ＣｓＡ＋ＭＭＦ＋Ｐｒｅｄ。结果 ２组受者平均随访时间为１２．５个月。     

普乐可复替换环孢素A治疗肾移植术后“爬行肌酐”的疗效观察

目的:观察用普乐可复(以下简称FK506)替换环孢素A(以下简称CsA)治疗肾移植术后"爬行肌酐"的临床效果。方法:回顾性分析我院30例肾移植术后"爬行肌酐"的患者,观察患者由CsA转换为FK506治疗方案后肾功能的变化及其不良反应。结果":爬行肌酐"患者采用FK506替换CsA半年后,移植肾功能较前明显好转,血肌酐下降明显(P<0.05),同时降低了血脂水平并减少降脂药物及抗高血压药物的使用。结论:肾移植术后"爬行肌酐"患者采用FK506替换CsA可以提高移植肾的长期存活率。     

供者骨髓输注在临床肾移植中的应用

目前器官移植术后所采用的免疫抑制治疗均为非特异性地全面抑制机体的免疫功能，有许多缺点，如发生感染、肿瘤发病率上升及其它毒副作用。有报道，受者接受供者的骨髓可降低肾移植后急性排斥反应的发生率。本研究旨在通过输注供者骨髓，观察肾移植患者术后排斥反应的发生情况。     

普乐可复在异种小肠移植中的作用

目的探讨免疫抑制剂普乐可复(FK506)对于异种小肠移植后迟发异种移植物排斥反应和细胞介导的异种移植物排斥反应的作用。方法采用仓鼠-大鼠动物实验模型,分为对照组和治疗组。治疗1组为单纯用FK506组;治疗2组为FK506加脾切除组。观察移植肠管吸收功能、体重、生存时间、FK506血药浓度及移植肠管苏木精-伊红染色。结果治疗1、2组的生存时间分别为(29.5±2.4)d和(106.6±26.3)d,与对照组(4.3±0.5)d相比显著延长(P<0.01);且治疗1、2组之间相比,差异亦有非常显著性意义(P=0.006)。术后第4d对照组苏木精-伊红染色可见绒毛萎缩,有大量炎性细胞浸润。治疗组小肠黏膜显示高分泌状态。术后126d治疗2组小肠肌层明显增厚、绒毛萎缩、肠壁小动脉壁纤维化。结论FK506可抑制异种小肠移植后迟发异种移植物排斥反应和细胞介导的异种移植物排斥反应;加脾切除可明显延长异种小肠移植的存活时间;但不能逆转异种小肠移植后所发生的慢性排斥反应。     

普乐可复治疗膜性肾病一例

男,36岁,于2000年8月无诱因出现双下肢水肿到我院治疗。既往无特殊病史。查体血压130/90mmHg,双下肢水肿,胸腹水征阳性,尿蛋白12 g/24 h,血Alb 18 g/L,IgG 16g/L,BUN 81mmol/L,血肌酐92μmol/L,血糖、血常规、ALT、抗“O”、类风湿因子、抗核抗体、抗ds-DNA、狼疮细胞和乙肝两对半均正常。B超示双肾大小正常,胆囊壁水肿,胸腹腔积液。诊为原发性肾病综合征。用泼尼松60 mg qd、雷公藤多甙20 mg tid、     

2007年“普乐可复杯”有奖征文通知

为了感谢广大器官移植工作者数年来对普乐可复的关心、支持和指导，为推动我国器官移植事业贡献一分力量，《中华器官移植杂志》和安斯泰来制药（中国）有限公司将继续联合举办2007年“普乐可复杯”有奖征文活动。现将有关事项通知如下：     

肾移植术后免疫抑制剂应用的策略

肾移植虽已取得长足进步,患者的预后也得到了一定程度的改观,但现今患者仍然需要长期服用免疫抑制剂.肾移植术后的诸多并发症当中,大多数与免疫抑制剂有关,严重影响了移植肾的长期存活.因此,如何调整免疫抑制方案,使其达到低毒化、个体化,成为目前移植工作者急需解决的问题.     

两种免疫抑制方案在乙肝病毒感染的肾移植受者中的应用

目的:比较乙肝病毒感染的肾移植受者应用普乐可复(FK506)或环孢素A(CsA)为基础的两种免疫抑制方案的抗排斥疗效及肝损害情况.方法:将乙肝病毒感染的肾移植受者随机分为FK506组和CsA组,每组各20例,两组均联合应用霉酚酸酯(MMF)和泼尼松(Pred).结果:观察12个月,FK506组中有3例(15%)患者发生急性排斥,CsA组中有4例(20%)发生急性排斥,均使用甲基泼尼松龙(MP)冲击治疗后逆转,两组急性排斥发生率差异无统计学意义.FK506组中有4例(20%)出现肝损害,CsA组中有14例(70%)出现肝功能异常,两组肝功能损害发生率差异有统计学意义.结论:FK506免疫抑制效果与CsA相似,但对肝功能影响较小,适合作为乙肝病毒感染的肾移植受者首选的免疫抑制剂.     

生物制剂在肾移植中的应用进展

多克隆抗体和单克隆抗体等生物制剂应用于肾移植,改善了移植肾的远期存活率.随着新型生物制剂的不断推出,其应用方法也在改进.本文就近几年来生物制剂在肾移植中应用的进展情况综述如下.     

肝移植病人FK506血药浓度与肾功能检测指标相关关系探讨

目的 探讨他克莫司(FK506)血药浓度与尿微量蛋白、血肌酐、血尿素氮等肾功能检测指标之间的相关关系。选择灵敏、准确、及时地反映肾功能损伤的检测指标。方法 ELISA检测FK506血药浓度；速率散射比浊法检测尿微量蛋白；酶法检测血尿素氮，碱性苦味酸法检测血肌酐，动态观察各项检测指标与不同血药浓度的关系。结果 尿微量蛋白、血肌酐、血尿素氮含量与FK506血药浓度呈直线正相关关系。尿α1微球蛋白(A1M)及微量白蛋白(MA)含量与血药浓度呈高度正相关，血肌酐、血尿素氮含量与血药浓度相关程度较低。结论 检测尿A1M及MA含量是监测FK506对肾脏损伤的最为灵敏可靠的指标。     

Long-term use of FK 506 in living related liver transplantation

Abstract FK 506 (Tacrolimus) was used with steroids to treat 61 pediatric patients who received living related partial liver transplantation. Fifty-two recipients survived and 9 died between 6 months and 3 years after transplantation. In the surviving patients, oral doses of Tacrolimus were tapered from 0.298 ± 0.277 mg/kg daily at 1 month after transplantation to 0.078 ± 0.054 at 24 months after transplantation. The 12 h trough levels of Tacrolimus were 12.6 ± 7.1 ng/ml and 4.1 ± 2.4 at 1 and 24 months after transplantation, respectively. The percentage of recipients free from steroids was 77%, 97%, and 94% at 6, 12, and 24 months after transplantation, respectively. Liver allograft rejection was encountered in seven recipients, five of whom were treated by steroid pulse therapy and a dose increase of Tacrolimus; the remaining two required OKT3. However, there was no episode of rejection that required retransplantation. Infectious complications encountered in 34 patients included 12 bacterial, 3 fungal, and 19 viral infections. Two recipients died one of fungal pneumonia and one of Epstein-Barr virus-associated lymphoproliferative disorder. Regarding adverse reactions of Tacrolimus, hypertension was observed in 28 patients, diabetes mellitus in 3, pancreatitis in 3, convulsion in 1, tremor in 12, itching in 5, and pigmentation in the oral mucosa in 2. Slightly increased values of creatinine were observed in most of the patients; however, an abnormal increase of serum of serum creatinine (> 1.0 mg/dl) was confined to the complicated cases. Improvement of somatic growth was observed in 21 patients (62%) and 13 (75%) at 12 and 24 months after transplantation, respectively. The long-term use of Tacrolimus is highly effective in terms of its immunosuppressive potential and reduced adverse reaction. Steady growth development can be expected in pediatric recipients free from steroids.     

Conversion from cyclosporin to FK 506 after liver transplantation

Thirty-seven liver-grafted patients with steroid-resistant acute or chronic graft rejection or with cyclosporin-related complications were converted from CyA to FK 506. The clinical outcome of the patients primarily depended on the degree of liver dysfunction present at initiation of FK 506 treatment. In patients switched to FK 506 for treatment of acute or early chronic graft rejection, CyA nephrotoxicity, or CyA malabsorption, the FK 506 therapy was associated with a clear improvement in the clinical course. In contrast, in patients with advanced chronic graft rejection, a lower response rate to the conversion in immunosuppression was observed. The lower response rate was associated with a higher patient mortality. These studies demonstrate that FK 506 represents a valuable alternative immunosuppressant for liver-grafted patients. The conversion from CyA to FK 506 should take place before serious — and potentially irreversible — disturbances in liver function are observed.     

Low-dose tacrolimus (FK506)-based immunosuppressive protocol in living donor renal transplantation

Abstract In order to avoid the side effects of tacrolimus (FK506), a low-dose FK506-based regimen was started from 1 June 1991. The dose was adjusted to maintain the FK506 whole blood trough level at 15–20 ng/ml for 7 days postoperatively, at 10–15 ng/ml for 2 months, and under 10 ng/ml thereafter. The graft survival rates at 3 years and 5 years were 87.8 and 82.3 % (FK506) vs 86.8 and 86.8% [cy-closporine (CyA)]. The incidence of acute rejection within the first 90 days was 31.6% in the FK506 group which was lower than the 57.1% of the CyA group ( P - 0.0585). Grades of acute rejection episodes over IIA in the FK506 group were 20 %, which was lower than the 37 % in the CyA group. The mean oral dosages of FK506 were 0.061 and 0.04 mg/kg per day at 3 and 5 years, respectively. The incidence of new onset diabetes was 27.8% in the FK506 group and 17.1 % in the CyA group. However, insulin therapy was withdrawn in all patients of the FK506 group within 5 months. The percentage of patients who required an antihypertensive agent was 28.6 % and 40 % in the FK506 group and 73.2% and 88 % in the CyA group at 1 and 3 years, respectively ( P < 0.05). Nephrotoxicity was seen in 20% of the FK506 group and 14.3 % of the CyA group. Hypercholesterolemia was less frequent in the FK506 group than the CyA group. The FK506-based regimen described here is a protocol with the potential to reduce its adverse effects. The whole blood concentration of FK506 should be monitored and blood levels maintained in the range of 5–10 ng/ml after 90 postoperative days for optimal efficacy and minimal toxicity.     

Two-year follow-up study of the efficacy and safety of FK 506 in kidney transplant patients

Abstract We conducted a 2-year follow-up study of the efficacy and safety of FK 506 in 104 kidney transplant patients at 32 sites in Japan. The initial daily oral dose of FK 506 was 0.3 mg/kg, which was gradually reduced to 0.15 mg/kg by month 10 and remained stable thereafter. The mean trough level of FK 506 in whole blood and the mean serum creatinine level in year 2 were 7.9 ng/ml and 1.9 mg/dl, respectively. Patient and graft survival rates for all patients were 97% and 92%, respectively. Forty-ix patients (44%) experienced rejection episodes, and 84% of these episodes occurred within 3 months after transplantation. The principal adverse reactions to FK 506 therapy were hyperglycaemia, renal dysfunction and hyperkalaemia. Most of these events were dose-dependent, and disappeared or ameliorated following reduction of the FK 506 dose.     

心脏移植受者FK506治疗窗的临床初探

目的 寻求适合中国人心脏移植受者FK506理想治疗窗谷浓度范围。方法 应用微粒子酶免疫分析法（MEIA）测定6例心脏移植受者口服FK506后全血谷浓度,以FK506谷浓度结合病人临床疗效及不良反应的情况,总结FK506在心脏移植术后的治疗窗。结果 术后1年病人的FK506谷浓度控制在5-25ng/ml,未出现严重的排异反应和肾毒性,但术后早期曾出现头痛和震颤等不良反应。结论 FK506具有良好的免疫抑制效果,其治疗窗谷浓度范围,术后第1个月内为：15-20ng/ml,第2-3个月10-15ng/ml,第4-6个月8-12ng/ml,6个月后5-8ng/ml。此浓度范围即可有满意的免疫抑制效果。又可减少FK506的肾毒性。     

A comparative study of FK506 granules and capsules in renal transplant recipients

Nine renal transplant recipients in stable systemic condition on FK506 capsules were converted to FK506 granules in order to investigate the safety, efficacy, and pharmacokinetics of the granular formulation of FK506. The study period for the administration of FK506 granules was 4 weeks, and in principle, the oral dose was the same as that of the FK506 capsules. Renal graft function remained stable and no rejection signs were noticed while the patients were taking the granules. The area under the blood concentration-time curve (AUC), the maximum blood level (C_max), and the time to reach C_max (T_max) after FK506 capsules and FK506 granules were, respectively, 93.1 ± 66.4 and 97.0 ± 89.1 ng · h/ml (P = 0.81), 12.7 ± 7.1 and 15.2 ± 11.7 ng/ml (P = 0.39), and 2.0 ± 1.7 and 1.3 ± 0.6 h (P = 0.29). The mean trough blood level during FK506 medication was 4.25 ± 3.42 and 4.02 ± 3.83 ng/ml, respectively, for the capsules and the granules. FK506 granules, a new formulation, showed an efficacy comparable to that of the FK506 capsular formulation. Received: 28 July 1997 Received after revision: 25 November 1997 Accepted: 14 January 1998     

FK506 conversion for intractable rejection of the liver allograft

Twenty-seven liver transplant recipients with intractable, biopsy-proven, acute or chronic rejection (defined as vanishing bile duct syndrome) were conerted from cyclosporin to FK506. Successful conversion was achieved in 9 of 15 patients with acute rejection and in 6 of 12 patients with vanishing bile duct syndrome. A normal bilirubin was achieved more quickly in those with acute rejection (within 1 moth) than in those with chronic rejection (within 3 months). A preconversion total bilirubin of less than 12 mg/dl was considered significant with regard to a successful outcome (P=0.002). Graft survival was 66.7% and patient survival 73% in the case of acute rejection, and 50% and 66.7%, respectively, in the case of chronic rejection. Nephrotoxicity, neurotoxicity, and gastroitestinal side effects were the most serious complications of FK506 conversion. Six of ten patients had a drop in GFR that was 50% or greater a minimum of 1 month of FK506 exposure. The mean maintenance dose of FK506 to maintain FK506 serum levels of 0.5–1.5 ng/ml was 0.07 mg/kg per 12 h for adults (half the recommended dose), compared to 0.15 mg/kg per 12 h for pediatric patients. This study demonstrates that FK506 can be used successfully to convert patients with intractable acute and chronic rejection. Careful adjustments of FK506 dosages and levels are required to minimize side effects.     

Japanese study of FK 506 on kidney transplantation: 2. Follow-up study of FK 506-treated patients

Thirty-seven primary renal transplant patients were enrolled in the early phase II study on kidney transplantation. All grafts survived during the follow-up period. However, 10 of the 37 patients were changed from FK 506 to conventional drugs, and 3 were treated concomitantly with azathioprine (AZA) or mizoribine (MZR) in the 3-month period of observation. After 3 months posttransplantation, an additional 10 patients were treated continuously with AZA or MZR. In addition, 3 were converted from FK 506 to conventional drugs. No additional conversion was observed after 4 months. Trough level monitoring was effective enough to regulate the FK 506 dosage. Nephrotoxicity and hyperglycemia were associated with a high trough level of FK 506 (whole blood, > 20 ng/ml).