The effect of graft function on FK506 plasma levels, dosages, and renal function, with particular reference to the liver.

Plasma FK506 was studied in 49 liver, 13 heart, 3 double-lung or heart-lung, and 21 kidney recipients. The levels were correlated with the drug doses used, kidney function, and liver function. In all varieties of recipients, there was an early rise in the FK506 plasma levels that occurred at the time of intravenous administration of the drug. At the same time or shortly after, there were increases in serum creatinine that were transitory except in liver recipients with continuing suboptimal graft function. The quality of hepatic function dominated all aspects of FK506 management in the liver recipients. Those who received well-functioning grafts could be given about the same drug doses as recipients of kidneys and the thoracic organs. Liver recipients with defective grafts had astronomical rises in plasma FK506, a high incidence of renal failure, and probably increased neurotoxicity. In kidney transplant recipients, the FK506 plasma levels and doses were essentially the same in patients with prompt versus delayed renal function. These studies have highlighted the necessity, first, of close pharmacologic monitoring of patients who are given FK506 in the presence of abnormal liver function, and second, of using smaller intravenous induction doses than in past practice.     

Neurological complications in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation

Abstract Neurological complications were examined in a multi-centre, randomized, parallel-group study of 545 patients undergoing primary liver transplantation to compare the efficacy and safety of FK 506- and cyclosporin A-based immunosuppressive regimens (CBIR). In an additional analysis, patients were divided into early and late randomized cohorts to detect the influence of protocol amendements that allowed for FK 506 dose reductions. Initial follow-up was for 6 months. Tremor, headache and insomnia were the most frequently reported adverse events involving the neurological system. Whereas these neurological symptoms were observed significantly more often in FK 506-treated patients ( P < 0.05 vs. CsA for the overall population), this was no longer the case for the late FK 506 and CBIR cohorts. The risk of FK 506-treated patients developing tremor was related to the initial i. v. dose, the rate of administration of the i.v. dose and the daily dose ( P < 0.01). Headache was significantly correlated with the FK 506 dose ( P < 0.05), and insomnia was not related to any dosing variable. Major neurological symptoms, including psychosis, convulsion, coma, aphasia and intracranial haemorrhage, were reported with a low frequency (0.4–5.2%), and differences between both treatment groups were neither significant for the overall population nor for the early and late cohorts of FK 506 and CBIR. Data from the late cohorts showed no differences in the overall incidence of neurological adverse events between FK 506-and CBIR-treated patients.     

FK 506 versus cyclosporin in the prevention of renal allograft rejection — European pilot study: six-week results

FK 506 was compared with cyclosporin in a randomised trial in good-risk cadaveric renal transplant recipients. The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10–20 ng/ml would prove to be practical. Thirty-one adult patients were randomised to FK 506 and 16 to cyclosporin. Both groups received an identical regimen of azathioprine and corticosteroids. Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mol/l within 2 weeks. One graft in the cyclosporin group was lost due to renal vein thrombosis. During the 6-week study period, 19.4% of patients on FK 506 and 31.3% on cyclosporin experienced acute rejection. One patient in each group experienced corticosteroidresistant rejection that responded to anti-lymphocyte therapy. Infections were reported in 51.6% of the FK 506 group compared with 37.5% of the cyclosporin group. The spectrum of adverse events was similar in both groups. However, minor neurological disorders were more common in the FK 506 group (54.8% versus 6.3%) whereas hypertension was less common (48.8% versus 75.0%). The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients.     

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。     

FK506与CsA在肾移植术后抗排斥的临床应用

目的 比较他克莫司(FK506)与环孢素A(CsA)预防肾移植术后排斥反应的效果和安全性。方法 肾移植患者53例分成两组,FK506组为28例,CsA组为25例。其中CsA组因肝功能损害3例,难治性急性排斥反应1例而改换成FK506。FK506起始用0.2mg·kg~(-1)·d~(-1),CsA起始用6mg·kg~(-1)·d~(-1),同时分别联合应用MMF0.75g,每日2次口服,以及术后三天大剂量甲基强的松龙(MP)静滴,第三天改强的松口服,所有病例均严密观察并行血、尿等生化分析。结果 FK506组移植肾功能好,平均7.5天脱酐水平降至平均99.5μmol/L,2例出现排斥反应,经MP连续3d冲击后治愈。CsA组19例移植肾功能良好,6例出现急性排斥,其中3例经MP连续3d冲击后治愈,2例应用OKT3后急性排斥逆转,1例术后3d出现急性排斥经MP与OKT3治疗后改换成FK506,另3例肝损害呈进行性转氨酶升高改换成FK506。FK506组有血糖升高6例(18.8%),高血压5例(15.6％),感染7例(21.9％)。CsA组血糖升高2例(9.5％),高血压5例(23.8％),感染4例(19.0%)。结论肾移植术后应用FK506疗效确切,能有效防治难治性排斥的发生、发展,降低急性排斥的发生率,特别是在乙肝抗原阳性、肝功能受损者比CsA优越。     

Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European multicentre study

Abstract From September 1990 to January 1992, 545 liver transplant patients were randomised to treatment with either FK 506 and prednisolone or a conventional cyclosporin-based immunosuppressive regimen (CBIR). Eight European centres participated in the study. Adverse events were reported as defined by each centre. Hyperglycaemia was reported as an adverse event in 30.7% of patients receiving FK 506 compared with 20.5% in the CBIR group ( P < 0.01). Diabetes mellitus was reported in 17.2% of patients treated with FK 506 and 9.5% of CBIR-treated patients ( P < 0.05). Treatment with insulin was required in 12.0% of patients in the DK 506 treatment group and in 5% in the CBIR group at 6 months. Initially, higher doses of FK 506 were used. During the study, the protocol was changed to allow a lower dose of FK 506. When the early and late cohorts of patients were compared, the incidence of diabetes mellitus fell from 23.9% to 10.5% in FK 506-treated patients but remained relatively constant in the CBIR group (10.4% to 8.7%). The median cumulative doses of i.v. and p. o. corticosteroids were significantly greater in the CBIR group. Thus, in the overall series, the incidence of diabetes mellitus was significantly greater in the FK 506 group as compared with the CBIR group. However, when a lower FK 506 dose was used during the second half of the study, the difference in the incidence of diabetes mellitus disappeared.     

862例肾移植患者应用他克莫司的临床经验

目的 探讨肾移植患者术后长期应用他克莫司（FK506）的疗效和安全性。方法 （1）选取1997至2005年肾移植术后长期应用FK506的患者862例，根据患者的年龄分为儿童组（〈18岁）18例，成人组（≥18岁，≤60岁）692例，高龄组（〉60岁）152例；根据术前是否有糖尿病分为糖尿病组（164例）和非糖尿病组（698例），比较各组间1、3、5年的人／肾存活率、排斥反应率及毒副反应发生率。（2）选择上述应用FK506的糖尿病患者164例（FK506组），另选同期肾移植术后应用环孢素A（CsA）的糖尿病患者126例（CsA组），比较两组1年内高血糖发生率及胰岛素的应用情况。结果 （1）儿童组、成人组和高龄组的1年人／肾存活率（％）分别为93．8／93．8、98．8／97．2和97．8／95．7；3年人／肾存活率（％）分别为91．7／83．3、96．5／87．3和94．7／93．3；儿童组1、3年人／肾存活率略低于成人组和高龄组，但三组间比较，差异均无统计学意义（P〉0.05）。儿童组有3例患者均带肾存活超过5年，成人组和高龄组的5年人／肾存活率（％）为87．5／84．4和90．4／85．7。糖尿病组1、3、5年人／肾存活率（％）分别为96．5／94．4、91．5／84．1和88．2／82．4，非糖尿病组为98．2／97．3、97．1／89．1和89．7／87．2，两组比较，差异无统计学意义（P〉0．05）。862例患者的1、3、5年的急性排斥反应发生率分别为9．9％、12．69％和16．07％；3、5年的慢性排斥反应发生率分别为5．25％和12．5%。FK506的毒副作用有肝功能损害、肾中毒、感染等，其发病率分别为7．54％、5．33％和12．41%，神经、精神毒性和脱发的发生率为15．89％和4．76％。非糖尿病组的糖代谢紊乱发生率为16．7％。（2）FK506组术后1个月有112例（68．3％）使用胰岛素，平均剂量为32．72IU／d，术后1年有63例（38．4%）使用胰岛素，平均剂量为13．46IU／d；CsA组术后1个月有78例（61．9％）使用胰岛素，平均剂量为29．08IU／d，术后1年有40例（31．79／）使用胰岛素，平均剂量为12．29IU／d。结论 肾移植术后长期应用FK506可降低排斥反应发生率，提高移植肾存活率。FK506是一种安会有效的基础免疫抑制剂，也适用于儿童和高龄患者。     

A 39-month follow-up study to evaluate the safety and efficacy in kidney transplant recipients treated with modified-release tacrolimus (FK506E)-based immunosuppression regimen

Background

We initially performed a study to evaluate the safety and efficacy of modified-release tacrolimus (FK506E) in a phase 3, 2-arm, 6-month, randomized, open-label, multicenter trial in Korean living donor de novo kidney transplant recipients. We then performed an extended study to evaluate the long-term safety and efficacy of a FK506E-based regimen up to 45 months posttransplantation in recipients already treated with FK506E.

Methods

Initial study was designed as a randomized, open-label, comparative, multicenter study in de novo living donor kidney transplant recipients. The patients were randomized to an FK506E versus a control (FK506) group (1:1). Recipients who completed a 6-month FK506E treatment study were enrolled in the 39-month follow-up study. Primary end-points were patient and graft survivals at posttransplantation 45 months. Secondary end-point was the incidence of a clinical or biopsy-proven acute rejection episode between 6 and 45 months posttransplantation.

Results

In the initial 6-month de novo study 124 enrolled patients were randomized into either the FK506E (n = 62) or the control group (n = 62). The incidence of an acute rejection episode was 19.4% (n = 12) in the FK506E versus 16.1% (n = 10) in the control group (P = .638). There was no mortality or graft failure among the 44 recipients enrolled in this additional 39-month follow-up study. There was 1 patient with biopsy-proven acute cellular rejection episode (2.3%) who underwent steroid pulse therapy with renal function recovery. At the time of study completion 40/44 recipients (90.9%) maintained FK506E treatment.

Conclusion

This 39-month study following the initial 6-month FK506E study period showed an FK506E-based immunosuppressive regimen in living donor kidney transplantation recipients to be safe and effective.     

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。     

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     

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。     

尸体肾移植术后应用他克莫司的体会

目的：观察肾移植患者应用他克莫司（FK506）进行免疫抑制治疗的效果和副作用。方法：对肾移植术后应用FK506的64例患者的临床资料进行回顾性分析。结果：肾移植术后应用FK506,霉酚酸酯（MMF）及泼尼松的24例患者,术后未发生急性排斥反应;先用环孢素A,后因肝功能异常,急性排斥反应及慢性排斥反应而改用FK506的40例患者,大部分排斥缓解,肝功能改善;FK506的主要副作用有血糖升高（10．9％）和肾毒性（4．7％）,结论：FK506是一种强效的免疫抑制剂,其用量的个体差异很大。     

乙型肝炎病毒携带者肾移植后应用他克莫司和环孢素A对肝功能影响的比较

目的 探讨乙型肝炎病毒携带者肾移植术后应用他克莫司（FK506）和环孢素A（CsA）对肝功能的影响。方法 73例乙型肝炎病毒（HBV）携带者接受肾移植，术前患者的肝功能正常，HBVDNA阴性。术后将患者分为两组：FK506组40例，术后服用FK506、霉酚酸酯（MMF）及泼尼松（Pred）预防排斥反应；CsA组33例，术后服用CsA、MMF及Pred预防排斥反应。术后追踪随访1～6年，观察两个组患者肝功能损害情况以及HBVDNA阳性率，发生肝功能损害时，调整免疫抑制剂的用量，并给予护肝治疗。结果 术后FK506组有4例（10．0％）、CsA组有16例（48．5％）发生肝功能损害，FK506组有2例（5．0％）、CsA组有9例（27．3％）HBVDNA转阳性，两组比较，差异均有统计学意义（P＜0.05）。CsA组肝功能损害的16例中，10例将CsA切换为FK506，另6例治疗方案不变，结果转换药物者肝功能恢复正常的时间明显短于未转换者（P〈0．01），且治疗1～2周时的丙氨酸转氨酶、天冬氨酸转氨酶和胆红素总量的水平也明显低于未转换者（P＜0．05，P＜0．01）。结论 与CsA相比，乙型肝炎病毒携带者肾移植术后应用FK506可降低肝功能损害的发生率，减少乙型肝炎复发。     

Comparison of short and long-term renal function in liver transplant patients receiving cyclosporin or FK 506

Abstract Long-term renal function was compared in 49 liver recipients [25 patients received cyclosporin (CyA) and 24 patients received FK 5061 followed for a period of 1 year. Creatinine (CR) and glome-rular filtration rate (GFR) pre-transplantation (pre-Tx) and at 1, 3, 5, and 12 months post-Tx were recorded, as well as incidences of hyperkalemia, post-Tx hypertension, and insulin-dependent diabetes mellitus (IDDM) in the two groups. At 1 year post-Tx, the mean Cr had risen from baseline by 56% and 60% in the FK and CyA groups, respectively; the mean GFR had dropped by 32% in FK patients and by 27 % in CyA patients. Acute nephrotoxicity occurred in 1/25 CyA patients (217 required dialysis) and 9/26 FK patients (7/9 required dialysis; 211 were switched to CyA). None remained on dialysis at 3 months. Renal insufficiency persisted at 1 year in 7/16 patients with early toxicity (CyA, 4; FK, 3) and in 3 of the remaining 36 pts ( P < 0.001). Hyperkalemia occurred in 4/25 CyA, and in 12/24 FK patients ( P < 0.025), post-Tx hypertension occurred in 15 CyA, and 7 FK patients ( P < 0.05), and IDDM occurred in 4 CyA and 7 FK patients ( P = ns). FK 506 and CyA, thus, exerted similar chronic renal effects. Although acute renal insufficiency improved upon dose reduction, renal impairment was permanent in some cases.     

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。     

FK 506 primary immunosuppression following emergency liver transplantation for fulminant hepatic failure

Abstract The efficacy and safety of an FK 506-compared to a cyclosporin A based immunosuppression regimen was examined in liver recipients who underwent transplantation for fulminant hepatic failure in the European FK 506 liver study. A consistent trend towards improved patient and graft survival noted in the FK 506-treated patients was apparent from the first postoperative week (e. g. patient survival: day 7, 95.5% vs. 82.1% and month 6, 72.7% vs. 60.7%). Acute (in particular intractable) rejection was less frequent in the FK 506 group (e. g. cumulative intractable rejection rate at 6 months, 6.2% vs. 22.6%). In a single centre (Kings College Hospital), 17 patients were studied in more detail. The FK 506 treatment group had improved graft function, lower steroid requirments and episodes of infection. Accompanying these benefits, apache 111 and TISS scores were lower in this group in the early posttransplant period. Intensive care discharge was earlier and both treatment groups experienced similar toxicity.     

Tacrolimus reversibly reduces insulin secretion in paediatric renal transplant recipients.

BACKGROUND: Conflicting reports exist about the mechanism of tacrolimus-induced post-transplant diabetes mellitus. METHODS: We analysed intravenous glucose tolerance tests (IVGTT) of 14 paediatric renal transplant recipients on cyclosporin (CsA) microemulsion and 15 patients on tacrolimus (FK506). The groups were similar in age (13.2+/-4.2 vs 13.0+/-3.7 years), body mass index, serum creatinine concentrations (96+/-60 vs 97+/-44 micromol/l), time after renal transplantation, and cumulative steroid dose over 12 weeks prior to the test (3.4 vs 3.5 mg/m(2)/day, NS, Mann-Whitney). Parameters of glucose tolerance included glucose, insulin, C-peptide concentrations, and HbA1c. The mean concentrations of the primary immunosuppressant were similar to treatments employed in other centres (CsA 165+/-59 ng ml and FK506 7. 5+/-2.2 ng ml). RESULTS: Baseline glucose concentrations were significantly higher on FK506 therapy compared with CsA microemulsion therapy. Baseline insulin concentrations and C-peptide concentrations were identical in both treatment groups. FK506 trough levels correlated negatively with k values (glucose constant decay) in the FK506 group. There was a significant reduction of the insulin first-phase concentrations, both after 1 min and after 3 min in the FK506 group compared with the CsA group (112+/-17 vs 237+/-57 microU/ml, P=0.034). In patients with repetitive IVGTTs, glucose constant decay and insulin production improved after lowering FK506 whole-blood trough levels. CONCLUSIONS: We conclude that post-transplant glucose intolerance could be due to a dose-dependent, direct effect of FK506 on the pancreatic beta cell function, which can be controlled by dose reduction.     

采用程序化肾活检评估肾移植后低水平和标准水平他克莫司的疗效

目的以程序化肾活检评估低水平与标准水平他克莫司(FK506)的免疫抑制方案的疗效及其安全性。方法采用前瞻性、开放、随机对照研究,将48例首次接受尸体肾移植受者按随机数字分为两组:低水平FK506组(低FK506组,24例)和标准水平FK506组(标准FK506组,24例)。两组患者均采用麦考酚吗乙酯(MMF)+FK506+肾上腺皮质激素(激素)的三联免疫抑制方案,两组的MMF与激素用法相同。标准FK506组的FK506血药谷浓度:在入组后前3个月维持在10～12 ng/ml,3个月后维持在8～10 ng/ml。低FK506组的FK506血药谷浓度:入组后头2个月为8～10 ng/ml,第3个月为3～7 ng/ml,3个月后为3～5 ng/ml。术后定期随访1年,内容包括测定FK506血药谷浓度,检测肾功能[血清肌酐(Scr)、内生肌酐清除率(endogenous creatinine clearancerate,Ccr)]、空腹血糖、糖化血红蛋白、血清白蛋白、血脂。同时于术后3个月和12个月予以程序化移植肾活组织检查(活检),了解急性排斥反应(AR)发生情况、病理损伤指标评分及慢性移植物损伤指数(chronic allograft damage index,CADI)变化。观察术后1年的人、肾存活率及不良事件发生情况。结果移植术后1年,与标准FK506组比较,低FK506组:(1)FK506血药谷浓度较低(P<0.01),且达到目标水平的患者所占比例较高;(2)Ccr水平较高,(83±14)ml/min比(62±16)ml/min,P<0.05;(3)血糖水平较低(P<0.05);(4)根据程序化肾活检的结果,间质纤维化、肾小管萎缩和肾小球硬化评分较低(均为P<0.05);(5)AR发生率及其严重程度相似,术后1年人、肾存活率相近,均为100%(均为P>0.05)(6)术后1年的肺部感染与新发糖尿病的发生率较低(分别为P<0.05和P<0.01)。结论采用程序化肾活检评估疗效结果可靠,并有助于发现移植肾的慢性化改变,移植术后早期适度降低FK506血药谷浓度对于移植肾和患者均有较大益处,且不增加发生排斥反应的风险。     

他克莫司抗同种肾移植排斥反应的临床研究(附136例报道)

目的 研究他克莫司（ＦＫ５０６）在同种肾移植术后抗排斥反应的效果及毒副作用。方法 １３６例肾移植患者在术后２４ｈ开始服用ＦＫ５０６,起始量０．１５ｍｇ．ｋｇ＾－１,ｄ＾－１,同时口服霉酚酸酯（ＭＭＦ）１．０ｇ／ｄ、泼尼松（Ｐｒｅｄ）３０ｍｇ／ｄ。观察ＦＫ５０６的治疗效果、理想的治疗窗及毒副反应。结果 肾移植术后１３６例应用ＦＫ５０６的患者中,肾功能２～７ｄ恢复正常为９６例,８～１５ｄ恢复正常为２３     

Liver, kidney, and thoracic organ transplantation under FK 506.

The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93.3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cyclosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index.