肝移植术后应用无激素免疫抑制方案的探讨

目的 探讨肝移植术后联合应用他克莫司(FK506)、霉酚酸酯(MMF)和达利珠单抗的无激素免疫抑制方案的效果.方法 根据双盲和随机原则,将60例因良性终末期肝病而进行肝移植的受者分为研究组与对照组,每组各30例.研究组采用的免疫抑制方案为:FK506+MMF+达利珠单抗;对照组为:FK506+MMF+激素.术后对受者进行长期随访,比较两组存活率及并发症等方面的差异.结果 研究组受者术后1、2年存活率分别为89.3%和90.2%,对照组为70.2%和73.3%;研究组移植物1、2年存活率分别为92.4%和91.1%,对照组为75.1%和73.2%;研究组和对照组术后3个月内急性排斥反应发生率分别为20.0%和28.5%;两组的差异均无统计学意义(P＞0.05).研究组受者伤口愈合不良、感染、高血压病、糖尿病、高胆固醇血症以及乙型肝炎复发的发生率明显低于对照组(P＜0.05).结论 肝移植术后联合应用FK506、MMF和达利珠单抗的无激素免疫抑制方案效果良好,并发症的发生率较少.     

肝移植术后激素24小时撤离的安全性

目的探讨肝移植术后激素24小时撤离的安全性及可行性.方法 76例成人肝移植患者随机分为激素3个月（3 m）撤离组（40例）和24 h撤离组（36例）,所有患者随访至2009年12月,前瞻性比较两组患者术后生存、感染、急性排斥反应、切口愈合不良、肝炎和肝癌复发、新发糖尿病、高脂血症及高血压的发生情况.结果两组间患者术后生存、急性排斥反应、高脂血症、乙肝复发及肝癌复发无明显区别,24 h撤离组的术后切口愈合不良、高血压、感染及新发糖尿病发生率明显低于3 m撤离组.结论肝移植术后采用IL-2单克隆抗体诱导下的以FK506为基础的免疫抑制方案时,激素24 h撤离是安全的,而且可以明显减少激素相关的副作用.     

肝癌患者肝移植术后早期激素撤离对肿瘤复发的影响

目的 探讨肝癌患者肝移植术后激素撤离对肿瘤复发的影响。方法 对54例中、晚期原发性肝癌患者施行了肝移植，术后根据3个月内是否撤离激素分为激素撤离组（28例）和激素维持组（26例）。比较两组间排斥反应发生率、半年及1年的肿瘤复发率、1年存活率、血他克莫司（FK506）浓度及生化指标的平均值，运用统计学方法分析两组间差异。结果 激素撤离组和激素维持组排斥反应发生率、半年肿瘤复发率、1年存活率相比，差异无统计学意义；激素维持组1年肿瘤复发率明显高于激素撤离组，差异有统计学意义（P〈0．05）。术后半年，两组FK506浓度的差异无统计学意义。术后1周及术后半年，两组丙氨酸转氨酶、胆红素总量及肌酐分别相比，差异均无统计学意义。术后半年，两组胆固醇总量、中餐前血糖水平相比，差异均有统计学意义（P〈0．05）。结论 肝癌患者肝移植术后3个月内撤离激素是安全的，并不增加排斥反应的发生率，也不需要增加其它免疫抑制剂的用量，可明显降低肿瘤复发率，提高患者的长期存活率。     

激素最小化免疫抑制方案在肝移植术后的应用

目的 探讨肝移植术后激素最小化免疫抑制方案的安全性及可行性.方法 2005年1月至2008年6月共收治经手术治疗并符合入选条件的成人肝移植患者116例,根据术后免疫抑制方案中激素使用的不同分为三组:3个月撤离组(n=40),7 d撤离组(n=40)及24 h撤离组(n=36),比较各组患者术后生存、感染、急性排斥反应包括耐激素治疗的排斥反应、切口愈合不良、肝炎和肝癌复发、新发糖尿病、高脂血症及高血压的发生情况.结果 各组间患者术后生存、急性排斥反应、高脂血症、乙型肝炎复发及肝癌复发无明显区别(P>0.05);24 h撤离组的术后切口愈合不良及发生高血压的例数明显低于7 d撤离组及3个月撤离组(P<0.05),术后感染及新发糖尿病例数明显少于3个月撤离组(P<0.05),但与7 d撤离组无明显差异(P>0.05).结论 激素最小化的免疫抑制方案(激素7 d撤离,甚至24 h撤离)在肝移植术后的应用是安全的,在不影响患者及移植物预后的同时可以明显减少激素相关的不良反应.     

异体手移植的免疫抑制治疗

目的 探讨异体手移植免疫抑制治疗的效果。方法 术前2d受者开始服用免疫抑制剂霉酚酸酯(MMF)、他克莫司(FK506)、泼尼松(Pred),术中甲泼尼龙(MP)1.5g冲击,术后第1天甲泼尼龙1.0g冲击,并开始应用抗胸腺细胞球蛋白(ATG)100mg/d×10d,术后2h口服FK506、MMF、Pred,观察移植肢体血液循环温度、排斥情况,同时监测FK506血浓度及免疫学指标。结果 术前、术中及术后应用免疫抑制剂后未见异体手排斥现象。2例移植手血循环良好,皮肤切口顺利愈合,术后10d拆线。Tinel征检查显示神经生长速度较快,术后半年移植手功能良好,感觉已恢复至手指末节,可以持物,肌电图显示鱼际肌已见动作电位。1例应用FK506后出现血糖升高,应用胰岛素治疗后血糖降至正常。结论 良好的组织配型、免疫抑制剂的合理应用可以预防异体手移植的超急性、加速及急性排斥反应的发生。     

两剂激素联合两剂达利珠单抗及他克莫司的免疫抑制方案在肝移植中的应用

目的 探讨两剂激素联合两剂达利珠单抗及他克莫司(FK506)的免疫抑制方案在肝移植中应用的安全性及有效性.方法 中山大学附属第一医院器官移植中心2006年9月至2008年3月共实施成人肝移植74例,排除3例血型不合、4例围手术期死亡外,余67例纳人本研究,其中男性54例,女性13例,年龄28～66岁,平均(46.9±8.7)岁.将67例成人肝移植患者随机分为两组:传统免疫抑制方案(激素3个月撤离)组(n=35)和两剂激素免疫抑制方案组(n=32),比较两组术后代谢并发症、感染(含细菌、真菌及巨细胞病毒感染)及排斥反应的发生率的差异.结果 两组患者的术后早期高血糖发生率,高血糖患者使用胰岛素的平均剂量,随访期内糖尿病、高血压及感染的发生率的差异有统计学意义(P<0.05);术后早期高血压发生率及随访期内排斥反应的发生率和高脂血症发生率无明显差异(P0.05).结论 两剂激素的免疫抑制方案是安全有效的,其不增加急性排斥反应的发生率,并可显著减少长期使用激素引起的各种不良反应及并发症的发生.     

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.     

肝移植术后移植物动脉曲霉菌感染一例

患者男，49岁，因原发性肝癌行S4、S5段切除术后复发3个月入院。2005年10月于我院接受同种异体原位肝移植术，供受体血型均为B型，HLA—Ⅰ、Ⅱ类抗体及群体反应抗体（PRA）均为阴性，手术过程顺利，未输血，无肝期36min。术后给予甲泼尼龙（MP）、他克莫司（FK506）免疫抑制治疗方案，伊曲康唑预防真菌感染2周，特治星预防细菌感染，5d后无细菌感染证据停用抗生素。MP逐渐减量，FK506血药浓度维持在10—12ng／L。     

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。     

肝移植后应用巴利昔单抗同时撤减激素的免疫抑制治疗方案

目的 探讨肝移植后加用巴利昔单抗的情况下采用撤减激素的免疫抑制方案的临床效果.方法 首次肝移植患者60例,术后采用他克莫司和霉酚酸酯预防排斥反应,并分别于术中和术后第4天各给予1剂巴利昔单抗,其中20例不用激素,40例仅术中开放血流前使用甲泼尼龙1次,术后不再使用激素,此60例为撤减激素组.以同期完成的、术后采用含甲泼尼龙的免疫抑制方案的60例肝移植患者为对照组.观察两组患者及移植物的存活情况以及急性排斥反应、巨细胞病毒磷蛋白(CMV pp65)阳性及术后新发糖尿病的发生情况.结果 术后随访12个月,不用激素者、单次使用激素者及对照组的患者存活率分别为95.0%、92.5%和91.7%,移植肝存活率分别为95%、90%和90%,急性排斥反应发生率分别为10.0%、12.5%及11.7%,三者间两两比较,患者存活率、移植肝存活率和急性排斥反应发生率的差异均无统计学意义.不用激素者、单次使用激素者及对照组的CMV pp65阳性率分别为15.0%、20.0%和43.3%,新发糖尿病发生率分别为5.0%、7.5%和30.0%,撤减激素组明显低于对照组(P<0.05).结论 肝移植后,在加用巴利昔单抗的情况下采用撤减激素的免疫抑制方案,并不增加排斥反应的发生率,并能降低CMV pp65阳性率和新发糖尿病发生率.     

Prospective randomized trial of steroid withdrawal in liver transplant patients: preliminary report

Abstract Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients, no controlled studies of SW have been carried out in liver transplant patients. To evaluate this possibility a prospective controlled study was carried out in 46 liver transplant recipients operated on after may 1991. They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins (RATG) for the first 5 postoperative days, cyclosporin A (starting from day 3–5 and maintaining parenteral whole-blood trough levels at 200–300 ng/ml during the first month and at 150–250 thereafter), azathioprine (1 mg/kg per day for the first month) and steroids. Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week; this dose was maintained until day 90 when the patients were randomly allocated either to long-term steroid therapy (0.1 mg/kg per day) or to steroid withdrawal. Minimum follow-up after randomization was 6 months (6–27 months). Liver biochemistry was checked at regular intervals throughout the follow-up period. Liver biopsies were performed whenever clinically indicated and also in the first 19 patients during readmission for annual review. The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5% in patients maintained on long-term therapy. No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far. Steroid-related complications did not differ significantly between the two groups. The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients arid may be successfully accomplished in almost all patients.     

Steroid withdrawal at day 14 after liver transplantation: a double-blind, placebo-controlled study.

Some clinical studies in liver transplantation have recently reported safety advantages and similar acute rejection rates with early steroid withdrawal. The aim of this study was to evaluate the efficacy and safety of an immunosuppressive regimen with steroid withdrawal at day 14. A multicenter, 1-year, comparative, double blind, placebo-controlled study was performed. Patients undergoing a first cadaveric liver transplantation were recruited and all received basiliximab + cyclosporine + intravenous methylprednisolone. Patients without severe postoperative complications were randomized at day 7 to receive a maintenance regimen with Neoral (cyclosporine) + prednisolone (group 1) or without steroids (Neoral + placebo; group 2), after a 7-day blinded oral steroid tapering period. A total of 174 patients were randomized at day 7 (group 1: n = 90; group 2: n = 84). The incidence of biopsy-confirmed and treated acute rejection at 6 months was 38.1% in group 2 vs. 24.4% in group 1 (P = .03) with a trend for a higher incidence of Grade II / III acute rejection (28.6% vs. 18.9%; P = .12). Changes from baseline were similar with regard to metabolic parameters (glycemia, total cholesterol, and triglycerides). A trend toward a better glucose tolerance was observed, as fewer patients received an antidiabetic treatment in the placebo group (2 vs. 10). In conclusion, this first double-blind, placebo-controlled study of steroid withdrawal at day 14 showed a higher incidence of acute rejection, only balanced by a trend of a lower need of antidiabetic treatment.     

Comparative study of clinical outcome in kidney transplantation between early steroid withdrawal protocol using basiliximab, calcineurin inhibitor, and mycophenolate mofetil and triple regimen consisting of calcineurin inhibitor, mycophenolate mofetil, and steroid

AIMS: Effect of early steroid withdrawal protocol using basiliximab in kidney transplantation (KTx) on the clinical outcomes was investigated as compared with triple regimen. METHODS: Kidney transplant patients in group 1 (n = 62) were treated with 8 mg/kg of cyclosporine (CsA), 2000 mg of MMF, two bolus IV injections of 20 mg of basiliximab and 500 mg of methylprednisolone (MP) rapidly tapered and withdrawn at 14 postoperative days (POD). Group 2 (n = 56) was treated with same dose of CsA and MMF, and 250 mg of MP tapered and continued. Acute rejection (AR) episodes were treated with MP pulse therapy followed by muromonab CD3 (OKT3) in case of steroid-resistant rejection. RESULTS: In 46 of 62 cases (74.2%) in group 1, steroid was successfully withdrawn at 13.7 +/- 1.7 POD. Graft survival at 3, 6, and 12 months in group 1 was 100%, 100%, and 98.4% (one death with functioning graft), and 100%, 98.2%, and 96.4% in group 2, respectively. The incidence of AR was 12.9% for group 1 and 42.9% for group 2, among which 21 cases in group 2 were treated with ALG or OKT3; no patient needed ALG or OKT3 in group 1. Fifteen cases in group 1 and 13 cases in group 2 developed CMV antigenemia, among which febrile episode was exhibited in 3 cases (4.8%) in group 1 and 5 cases (8.9%) in group 2. CONCLUSIONS: Early steroid withdrawal protocol using basiliximab is promising for reducing the incidence of AR (especially steroid-resistant rejection), CMV diseases, and steroid-related complications.     

IL-2 receptor blockers in liver transplantation: initial experience with daclizumab in Chile

Monoclonal antibodies against the interleukin 2 receptor have been developed in an effort to decrease rejection rates and spare calcineurin inhibitors when renal dysfunction occurs after transplant. While success has been reported in kidney transplantation, its effectiveness in liver transplantation is less clear. METHODS: This prospective nonrandomized study including adult patients was performed between October 2000 and April 2003. Two groups of immunosuppressive regimens were compared: group A received 2 g of methylprednisolone intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Cellcept was also given for 2 months in the absence or for up to 4 months in the presence of rejection. Group B received the same immunosuppressive regimen but, in addition, daclizumab 1 to 1.5 mg/kg on day 1 and day 5 posttransplant. Rejection diagnosis is made on histology basis. Protocol biopsies were performed in all the patients on day 7 and if indicated by biochemistry thereafter. RESULTS: Both groups were similar in terms of preoperative CHILD score, serum creatinine, incidence of status I, donor and recipient age and ischemia times. The mean follow-up time was 20 months for Group B (n = 24) and 7 months for Group A (n = 10). The 1-month and 1-year rejection rates are 29.1% and 41% in Group A versus 20% and 30% in group B. Rejection severity was similar between both groups. One-year patient and graft survival rates were 96% and 92% in group A and 100% for both in Group B. CONCLUSIONS: In this series, daclizumab induction therapy seems to display a trend toward a lower rejection rate without increasing infectious complications nor affecting graft survival rates.     

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens

The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.     

Rapid steroid taper and neoral monotherapy in liver transplantation in Chile: a step in the right direction?

Diabetes, hypercholesterolemia, hypertension, obesity, osteopenia, and increased risk of viral recurrence are among the complications associated with posttransplant steroid use. Steroid withdrawal or rapid taper has been reported to be safe. The aim of this study was to compare the rejection incidence and severity among patients treated with two different steroid taper strategies. METHODS: This retrospective study included all the adult liver transplant recipients since the program's inception from 1993 to January 2002. The minimum follow-up was 1 year. Exclusions included patients receiving an immunosupressive regimen other than mycophenolate mofetil, steroids, and Neoral, or suffering an autoimmune etiology, or displaying patient or graft survival less than 1 year. The incidence and severity of rejection episodes were compared between the two groups of steroid taper protocols: group A received methylprednisolone (1 g) intraoperatively with a slow taper to 10 mg prednisone per day at 1 year. Group B received methylprednisolone (2 g) intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Rejection diagnosis was made on histological bases. RESULTS: One-month and 1-year rejection rates were 47% and 53%, respectively, among the rapid taper group with Neoral monotherapy, which was similar to 60% and 64%, respectively, in the slow taper group. Rejection severity was also comparable between the two groups. CONCLUSIONS: Patients treated with a rapid steroid taper protocol followed by Neoral monotherapy or a slow taper protocol showed similar acute rejection incidences and severities. Their survival rates were also comparable. Further study is necessary to evaluate the impact of rapid steroid taper to prevent the complications of steroid use.     

Low-dose maintenance prednisone and antilymphoblast globulin for the treatment of acute rejection. A steroid-sparing approach to immunosuppressive therapy

The purpose of this prospective randomized trial was to evaluate an immunosuppressive protocol involving reduced maintenance and antirejection steroid dosages in cadaver renal transplantation. The study comprises 23 first cadaver graft recipients who experienced an acute rejection episode. All patients received an initial 14-day course of antilymphocyte globulin (ALG) and azathioprine 1.5 to 2.0 mg/kg/day. In 11 patients (group 1), a low maintenance dose of prednisone (30 mg/day) was administered and first rejection episodes were treated with a second 10-day course of ALG. The remaining 12 patients (group 2) received high maintenance doses of prednisone (2 mg/kg/day with tapering) and intravenous methylprednisolone (IVMP) for first rejection episodes. Subsequent rejections in both groups were treated with high doses of steroids. In group 1, all first rejection episodes were reversed with ALG alone, 6 patients experienced no subsequent rejection, and 10 patients currently have a functioning graft. In Group 2, the first rejection episode was reversed with IMVP alone in 10 patients; in two patients in whom IVMP therapy was unsuccessful, ALG was then administered, and subsequent rejection reversal was effected. In group 2, 4 patients experienced no subsequent rejection, and 9 patients currently have a functioning graft. Patients in group 1 received significantly lower (P less than .01) cumulative steroid doses in the first six months following transplantation, which resulted in a reduced number of major infections, as compared with patients in group 2. We conclude that the steroid-sparing regimen of low maintenance prednisone and ALG for first rejection is as effective immunologically as the established high steroid protocol.     

Tacrolimus Monotherapy Without Steroids After Liver Transplantation – A Prospective Randomized Double-Blinded Placebo-Controlled Trial

Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the first year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid) (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.     

A Randomized Double-Blind, Placebo Controlled Trial of Steroid Withdrawal after Pediatric Renal Transplantation

In an effort to reduce rejection, extend allograft survival and minimize complications, we hypothesized that robust immunosuppression during the first 6 months after transplantation would allow for the safe withdrawal of steroids. A total of 274 pediatric subjects were enrolled and received an anti-CD25 antibody, sirolimus, calcineurin inhibitor and steroids. At 6 months after transplantation, subjects were randomized to steroid withdrawal (n = 73) versus continued low-dose steroids (n = 59). This study was stopped prior to target enrollment because of the incidence of post-transplant lymphoproliferative disorder. At the time of study termination, 132 subjects had been randomized and were available for analysis. At 18 months after transplantation, there was no difference in the standardized height z score; however, the standardized height velocity was greater in the steroid withdrawal group compared to the control group (p = 0.033). There were no differences in acute rejection episodes between treatment groups. The 3-year allograft survival rate was 84.5% in the control group and 98.6% in the steroid withdrawal group (p = 0.002). The immunosuppressive protocol utilized in this study allowed for the withdrawal of steroids without an increased risk of rejection or allograft loss. However, the complications associated with the use of this immunosuppressive protocol were too high to recommend its routine use in pediatric patients.     

Randomized trial of tacrolimus versus cyclosporine in steroid withdrawal in living donor renal transplant recipients

The introduction of new immunosuppressants has prompted trials of steroid withdrawal. However, several groups have reported a higher incidence of rejection. We conducted a randomized two-arm, parallel-group, open-label, prospective study to compare steroid withdrawal (at 6 months posttransplant) from the regimens of tacrolimus + mycophenolate mofetil (MMF) (FK group) versus cyclosporine + MMF (CSA group). The entry criteria were recipients of first living donor transplants with no diabetes mellitus (DM), congestive heart failure, chronic liver disease, or acute rejection within 6 months posttransplant. The primary endpoint was a biopsy-proven acute rejection episode or treatment failure within 1 year posttransplant. While 87 recipients were assigned to FK (n = 43) and CSA groups (n = 44) before transplantation, 76 recipients (FK 39, CSA 37) could be tapered off steroids at 6 months posttransplant, since 11 were excluded due to acute rejection within 6 months posttransplant (FK two, CSA three) or protocol violations (FK two, CSA four). After steroid withdrawal, the incidence of acute rejection episodes was 0% in the FK group and 13.5% in the CSA group (P < .05). Other results at 12 months posttransplantation were comparable: the incidences of DM 7.8% versus 0% (FK group vs CSA group), hypercholesterolemia 41.0% versus 59.5%, hypertensives 48.7% versus 59.6% as well as the levels of plasma creatinine 1.21 +/- 0.24 versus 1.31 +/- 0.50 mg/dL (P > .05 in every variable). These data suggest that steroid withdrawal is successful in first living donor renal transplant recipients. Tacrolimus may be significantly more effective than cyclosporine to prevent acute rejection after steroid withdrawal.