高龄患者肾移植126例临床分析

目的：探讨高龄患肾移植的临床特点及四联免疫抑制疗法对临床治疗效果的影响。方法：分析1990年1月至2000年12月l25l例肾移植中126例高龄患临床资料，将术后使用免疫抑制剂为三联疗法(CsA Aza 激素)的55例作组I；而使用四联疗法(CsA MMF 激素 抗T细胞单抗)的7l例作为组Ⅱ，组Ⅱ中47例患术后使用2周Wu—T3抗排斥治疗，另24例应用抗IL—2R抗体预防急性排斥反应。将两组的术后并发症、急性排斥率及1年人／肾存活率相比较，并与本院同期非高龄患相同指标比较。结果：高龄患肾移植后心脑血管并发症以及感染发生率均明显高于非高龄患。组I和组Ⅱ患的术后并发症发生率分别为74．55％和38．03％；急性排斥发生率分别为12．73％和4．23％；1年人／肾存活率分别为81．82％/78．18％和97．18％／95．77％。结论：高龄患肾移植术后较容易发生心脑血管并发症及感染，使用新的四联免疫抑制疗法能有效地降低心脑血管并发症、感染和急性排斥反应的发生率，1年人／肾存活率亦明显提高。     

肾移植术后早期应用雷帕霉素的疗效和并发症观察

目的:评价肾移植术后早期应用雷帕霉素(RPM)的疗效和安全性。方法:58例同种尸体供肾移植患者分为试验组(28例)与对照组(30例),免疫抑制方案分别为环孢素A(CsA)+RPM+强的松(Pred)、CsA+霉酚酸酯(MMF)+Pred。观察2组在移植术后6月内的疗效、并发症及药品不良反应情况,同时监测血脂水平、肝肾功能等生化指标,分析2种免疫抑制方案对移植肾急性排斥反应、人/肾存活率的影响。结果:2组患者观察期内均移植肾带功存活。试验组急性排斥反应发生率(4/28,14.3%)稍低于对照组(5/30,16.7%),差异无统计学意义。试验组发生血脂异常11例(39.3%),切口感染4例(14.3%),腹泻3例(10.7%),白细胞减少1例(3.6%);对照组中血脂异常3例(10.0%),切口感染2例(6.7%),腹泻8例(26.7%),白细胞减少5例(16.7%)。结论:肾移植术后早期应用CsA+RPM+Pred三联免疫抑制治疗方案,会产生更强的免疫抑制效果,术后急性排斥反应发生率稍低于对照组。其主要副作用是血脂升高和切口感染,但腹泻和白细胞减少的发生率明显低于对照组。     

肾移植术后应用2种不同剂量环孢素A的临床对照研究

目的:探讨肾移植术后应用环孢素A(CsA)、强的松(Pred)和吗替麦考酚酯(MMF)后是否允许CsA减量而不增加排斥反应发生率,是否可以减少CsA相关副作用以提高疗效。方法:将使用常规剂量CsA的肾移植患者(213例)与使用低剂量CsA患者(176例)进行对照研究。结果:2组肾功能水平、排斥反应发生率及人/肾存活率均无显著性差异,但低剂量CsA组总体疗效稍好,而且不良反应发生率明显减少。结论:肾移植术后患者CsA+MMF+Pred三联用药,在使用足够剂量MMF的情况下,可以允许CsA减量而不增加急性排斥反应的风险。     

咪唑立宾防治肾移植急性排斥疗效观察

目的　观察咪唑立宾(mizoribine,MZR)在肾移植术后排斥反应的效果及不良反应。方法　56例肾移植受者术后服用MZR作为观察组。56例肾移植受者术后服用霉酚酸酯 (MMF)作为对照组。两组同时合用环孢素(CsA)和强的松(Pred),组成三联免疫抑制方案,术后随访观察 12个月。结果　观察组肾移植术后 6个月急性排斥发生率 20%, 1年内人 /肾存活率 93%。发生肝不良反应 2例 ( 3. 57% ),肾不良反应 1例(1. 78% ),消化道症状 11例(20% ),骨髓抑制 5例 (8. 92% )。对照组排斥发生率 24%,人 /肾存活率 91%。结论　咪唑立宾近期疗效稳定,确切可靠,且不良反应小,具有重大临床应用价值及社会经济效益。     

肾移植患者应用咪唑立宾与麦考酚酸酯2种三联免疫抑制方案的疗效比较

目的:观察咪唑立宾(MZR)的免疫抑制效果及安全性,采用MZR替代麦考酚酸酯(MMF),比较环孢素A(CsA)+MZR/MMF+泼尼松龙(Pre)两种三联免疫抑制治疗的疗效。方法:尸体肾移植患者70例,按手术顺序交替登记MZR组和MMF组。移植后采用CsA+MZR/MMF+Pre三联免疫抑制疗法,MZR组剂量为200mg.d-1(体重>60kg)或150mg.d-1(体重<60kg);MMF组剂量为1500mg.d-1(体重>60kg)或1000mg.d-1(体重<60kg)。观察肾移植术后1年的人/肾存活率、急性排斥反应发生率及治疗逆转率、感染发生情况及药物毒副作用。结果:全部病例术后随访至少1年,MZR组和MMF组的急性排斥反应发生率分别为17.1%和11.4%,两组之间无显著性差异。MZR组和MMF组肺部感染的发生率分别为8.6%和48.6%,MMF组的发生率显著升高。血尿酸升高的发生率两组之间比较未见显著性差异,MZR组在术后24,36,48周时血尿酸的水平要高于MMF组。MZR组的持续用药率显著高于MMF组。结论:MZR可以与钙调神经素阻滞剂、激素联合应用于肾移植患者,具有一定的安全性和有效性,不良...     

肾移植受者血药浓度监测与最佳浓度选择

目的:寻找环孢素A(CsA)在肾移植受者三联免疫抑制用药方案中的最佳浓度.方法:用特异荧光偏振免疫法测定82例患者全血环孢素A的浓度,比较不同剂量组(各41例)患者肾移植术后CsA浓度高低、急性排斥反应和毒性反应发生率以及移植患者的人/肾生存率.结果:高浓度组在1年内总的急性排斥反应发生率为16.8%,低浓度组为18.2%,两组间差异无显著性(P＞0.05),高低浓度组患者1年内毒性反应发生率分别为32.1%和16.4%(P＜0.01),人/肾生存率分别为85.2%/82.8%和92.1%/90.9%(P＜0.05).结论:实验结果表明,低浓度组并不增加急性排斥反应的发生率,但明显降低毒性反应发生率以及移植患者的人/肾死亡率.     

雷帕霉素联合环孢素预防肾移植急性排斥反应的随机对照前瞻性研究

目的:评价雷帕霉素(RPM)口服液联合环孢素(CsA)预防肾移植术后早期急性排斥反应的疗效。方法:首次肾移植患者20例,随机分成RPM试验组和硫唑嘌呤(Aza)对照组,每组各10例,分别接受以CsA和类固醇激素为基础的免疫抑制治疗方案6mo,比较2组人/肾存活率、急性排斥反应发生、不良事件发生等指标的差异。结果:17例完成治疗者人/肾均存活;仅Aza组1例发生2次急性排斥反应;2组各发生2例严重不良事件。结论:RPM联合CsA可有效预防移植肾急性排斥反应,并维持肾功能于良好水平,但是也可能增强CsA的肝毒性。     

他可莫司与环孢素A用于肾移植的对比观察

为了观察他可莫司(FK506)对肾移植患者免疫抑制作用的疗效和安全性，将79例首次肾移植患者分为FK506与环孢素A(CsA)两组，进行对比观察。FK506组(n=23)：FK506+霉酚酸酯(MMF)+泼尼松(Pred)；CsA组(n=56)：CsA+MMF+Pred。结果表明，FK506组和CsA组急性排斥反应的发生率分别为4．4％和14．3％，差异有显著意义(P&;lt;0．05)。1年人、肾存活率分别为100％／100％和100％／96．4％。FK506组高血压、高血脂及肝功能异常的发生率低于CsA组，而糖尿病发生率高于CsA组。结论：FK506能有效地预防肾移植术后急性排斥反应，且不良反应较少。     

赛尼哌预防肾移植术后急性排斥反应的临床观察

目的　 观察人源化的抗IL 2R单克隆抗体赛尼哌预防肾移植术后急性排斥反应的疗效。 方法 　6 5例肾移植受者分为两组 ,赛尼哌组 2 2例 ,对照组 4 3例。两组均采用环孢素A +骁悉 +肾上腺皮质激素的三联免疫抑制方案。赛尼哌组在此基础上在术前 1h和术后 15d分别给赛尼哌 5 0mg。观察术后 3个月内急性排斥反应发生情况、肾功能恢复情况、不良反应及感染发生情况。 结果 　赛尼哌组急性排斥反应发生率为 4 5 % ,对照组为 16 2 %。两组比较有显著性差异 (P <0 0 5 )。在不良反应和感染方面 ,两组无显著差异。 结论 　赛尼哌可以显著减少肾移植后急性排斥反应发生率 ,同时并不增加感染和其他不良反应     

肝移植术后他克莫司加泼尼松免疫抑制治疗的临床疗效

目的 :探讨肝移植术后他克莫司 (FK5 0 6 ) +泼尼松 (Pred)二联免疫抑制治疗方案的临床疗效及药物不良反应。方法 :对肝移植术后应用FK5 0 6 +Pred二联免疫抑制方案治疗的 2 5例患者 (A组 ,术后 2 4h即应用FK5 0 6 +Pred方案的 15例 ,以及因出现排斥反应或严重药物不良反应由CsA +MMF +Pred改为FK5 0 6 +Pred方案的 10例 )和应用环孢素 (CsA) +霉酚酸酯(MMF) +Pred三联免疫抑制方案治疗的 2 0例患者 (B组 )进行比较 ,临床观察 12mo。结果 :2组移植前后血Cr均无明显变化 ,但A组移植术后排斥反应及药物不良反应发生率显著低于B组 (P <0 0 1) ;由CsA +MMF +Pred改为FK5 0 6 +Pred方案的 10例患者 ,排斥反应和药物不良反应均得到有效控制。A组的主要药物不良反应有腹泻和神经系统毒性 ,仅有 2例分别于术后mo 1,2发生血糖升高。结论 :肝移植术后FK5 0 6 +Pred二联免疫抑制治疗方案是有效的     

Early steroid withdrawal protocol with basiliximab, cyclosporine and mycophenolate mofetil in renal-transplant recipients

OBJECTIVE: Adverse effects of steroids have led to efforts to minimize their use in recipients of organ transplants. This study evaluated an early steroid withdrawal protocol including basiliximab, cyclosporine (CsA) and mycophenolate mofetil (MMF) in renal-transplant recipients. METHODS: Between January 2001 and April 2005, our early steroid withdrawal protocol was used in 130 patients who underwent renal transplantation. Immunosuppression consisted of CsA (6-8 mg/kg), MMF (2 g/kg) and methylprednisolone (MP); basiliximab was given as induction therapy (steroid withdrawal group). MP was administered in a dose of 500 mg or 250 mg at renal transplantation; thereafter, the dose was rapidly tapered and MP was withdrawn on day 14 post-transplant. RESULTS: The incidence of acute rejection in the steroid withdrawal group was similar to that in the conventional steroid treatment group (without basiliximab) (18% vs. 21%). The severity of rejection episodes was similar in the two groups. Patient and graft survivals were 100% and 97% in the steroid withdrawal group. In 80 of the 130 patients (62%) in the steroid withdrawal group, MP was successfully withdrawn, with good allograft function during follow-up. In the other 50 patients (38%), MP was reinitiated because of acute rejection or other reasons. The success rate of steroid withdrawal 12 months after transplantation in recipients of ABO-compatible grafts was significantly higher than that in recipients of ABO-incompatible grafts (66% vs. 44%). The dose of MMF during the 12 months after renal transplantation was significantly lower in steroid reinitiated group than in the successful withdrawn group (p<0.05). Patients in the successful withdrawn group showed metabolic benefits such as lower cholesterol levels as compared with the steroid reinitiated group. CONCLUSION: Although further follow-up is necessary to confirm our results, our protocol successfully permitted the early withdrawal of steroids in 62% of renal-transplant recipients, with no resumption of steroid treatment during 3 years of follow-up.     

Calcineurin inhibitor-free immunosuppression in pediatric renal transplantation: a viable option?

The introduction, in the mid-1980s, of calcineurin inhibitors - namely ciclosporin (cyclosporine) and later tacrolimus - has significantly improved short-term renal graft survival by lowering acute rejection rates in both adult and pediatric kidney transplantation. Nonetheless, long-term transplant survival is still not satisfactory, with calcineurin inhibitor-induced chronic nephrotoxicity being one of the main causes of progressive nephron loss and declining renal transplant function. Hence, different immunosuppressant regimens have been proposed to avoid or ameliorate calcineurin inhibitor-induced nephrotoxicity. These comprise the use of non-depleting or depleting antibodies for calcineurin inhibitor minimization, calcineurin inhibitor avoidance, or calcineurin inhibitor withdrawal from mycophenolate mofetil-based immunosuppressant protocols. De novo use of a mammalian target of rapamycin (mTOR) inhibitor (sirolimus or everolimus) or conversion from a calcineurin inhibitor to an mTOR inhibitor may constitute another therapeutic option to avoid or reduce calcineurin inhibitor-induced nephrotoxicity. To date, complete calcineurin inhibitor avoidance seems to be inappropriate because other relatively potent immunosuppressant agents such as lymphocyte-depleting antibodies are needed for rejection prophylaxis, which are frequently accompanied by a higher incidence of infections and an unacceptably high acute rejection rate under calcineurin inhibitor avoidance. In some studies, calcineurin inhibitor withdrawal in adult and pediatric kidney allograft recipients with stable or declining transplant function has been associated with an amelioration of renal function; however, this is attained at the cost of a higher acute rejection rate in 10-20% of patients. It has been frequently stressed that conversion from a calcineurin inhibitor-based regimen to an mTOR inhibitor-based immunosuppressant regimen should be performed early (e.g. 3 or 6 months post-transplant) in patients with well-preserved renal transplant function without significant proteinuria in order to prevent, or at least limit, calcineurin inhibitor-induced tissue damage and provide long-term benefit. It should be borne in mind though that the use of an mTOR inhibitor carries the risk of potential adverse events such as aggravation of proteinuria, hyperlipidemia, myelosuppression, and hypergonadotropic hypogonadism. Even though everolimus may be better tolerated than sirolimus, studies on everolimus for calcineurin inhibitor-free immunosuppression in the pediatric kidney transplant patient population are lacking. At present, the safest therapeutic strategy for pediatric renal allograft recipients with chronic calcineurin inhibitor-induced nephrotoxicity appears to be a mycophenolate mofetil-based regimen with low-dose calcineurin inhibitor therapy and corticosteroids; available published data show that dual immunosuppression with mycophenolate mofetil and corticosteroids, as well as an mTOR inhibitor plus mycophenolate mofetil plus corticosteroid-based regimens, are associated with an increased risk of acute rejection episodes. In individual patients with evidenced chronic allograft dysfunction and over-immunosuppression leading to recurrent infections, dual maintenance immunosuppression with mycophenolate mofetil and corticosteroids may be appropriate. As stated in the annual report issued by the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry, currently the most popular immunosuppressant protocol consists of a calcineurin inhibitor combined with mycophenolate mofetil and corticosteroids: 59.1% and 53.2% of patients with a functioning graft receive a calcineurin inhibitor plus mycophenolate mofetil plus corticosteroid-based immunosuppression at 1 and 5 years post-transplant, respectively. 91.4% and 87.8% of patients are administered a calcineurin inhibitor-containing regimen 1 and/or 5 years after transplantation, respectively. Undoubtedly, the use of calcineurin inhibitor-free immunosuppressant regimens with or without antibody induction, plus an mTOR inhibitor and mycophenolate mofetil, requires more comprehensive long-term investigations to determine whether acceptable rejection rates and conservation of renal function can be achieved.     

他克莫司应用于初次肾移植三年临床观察

目的总结他克莫司在初次肾移植患者中的临床效果。方法总结2002年1月至2004年12月初次尸体肾移植的患者共207例,比较同期接受他克莫司治疗与环孢素治疗患者的体重、血压、血常规、血清电解质、血糖、血脂、血尿酸、肾功能及肝功能、病毒血清学检测、血药浓度,同时监测急性排斥反应和不良事件的发生,观察时间0·5～3·5年。结果他克莫司组40例,1年、3年人/肾存活率为97·5%/95·0%,95·0%/92·5%;环孢素组167例,1年、3年人/肾存活率为95·8%/94·0%,94·6%/92·8%。他克莫司组与环孢素组急性排斥反应发生率分别为15·0%和25·2%(P>0·05),肺部感染发生率分别为4·8%,20·4%(P<0·05),糖尿病发生率分别为12·5%,9·6%(P>0·05),肝损害、肾损害、高血压两组差异无统计学意义,血脂变化,颤抖,口舌、手脚麻木在环孢素组较明显,体重增加、多毛、牙龈增生在他克莫司组不明显。结论他克莫司用于首次尸体肾移植后免疫抑制作用显著,急性排斥反应发生率低,肺部感染发生率降低,生活质量好。起始剂量0·15mg·kg-1·d-1,患者耐受性较好,长期使用安全,肾功能稳定。     

The role of tacrolimus in renal transplantation

Tacrolimus gained FDA approval for use in liver transplantation in 1994 and, approximately 3 years later, was approved for the prevention of acute rejection in kidney transplantation. Over the last decade tacrolimus has become the calcineurin inhibitor of choice for the prevention of rejection in renal transplantation. The objective of this study was to provide a review and update of the literature on the use of tacrolimus in renal transplantation. Numerous clinical trials have shown tacrolimus to be superior to cyclosporine in the prevention of acute rejection and recent trials have demonstrated superiority of tacrolimus over cyclosporine in terms of allograft survival. Post-transplant diabetes remains more common with tacrolimus than cyclosporine, despite lower doses of both tacrolimus and corticosteroids. A novel once-daily dosage form of tacrolimus has recently been developed and is approved for use in Europe. Tacrolimus remains an important immunosuppressant for the prevention of acute rejection. The prolonged-release formulation may improve compliance and possibly long-term outcomes.     

Review of the proliferation inhibitor everolimus

Everolimus (Certican) is being developed for prevention of acute and chronic rejection of solid organ transplants. A novel proliferation inhibitor, everolimus synergies with cyclosporine to prevent and reverse acute rejection in preclinical models of kidney, heart or lung transplantation. The manifestations of chronic rejection that may contribute to graft loss are also inhibited by everolimus in preclinical models. Although everolimus is metabolised by the cytochrome P450 CYP3A isoenzyme, coadministration with cyclosporine does not alter the pharmacokinetics of cyclosporine, but cyclosporine coadministration increases exposure to everolimus. Everolimus interacts with inhibitors and inducers of this system; its clearance is reduced in patients with hepatic impairment. In an immunosuppressive regimen with cyclosporine microemulsion formulation and corticosteroids, transplant recipients treated with everolimus show low rates of acute rejection and, in one heart and one renal trial, lower rates of cytomegalovirus infection. Acute rejection rates are lower than those seen with azathioprine in cardiac transplant recipients and similar to those seen with mycophenolate mofetil in renal transplant recipients. Low rates of acute rejection are maintained when everolimus is given as part of a quadruple immunosuppressive regimen with low-dose cyclosporine in renal transplant recipients, with the added benefit of better renal function compared with full-dose cyclosporine. Use of C(2) monitoring to optimise cyclosporine exposure and enhance efficacy and safety of everolimus is planned in future studies. Hypertriglyceridaemia and hypercholesterolaemia have been associated with everolimus, but these effects are not dose-limiting. There is no clear upper therapeutic limit of everolimus. However, thrombocytopenia occurs at a rate of 17% at everolimus trough serum concentrations above 7.8 ng/ml in renal transplant recipients. There are limited safety data available in patients with trough concentrations > 12 ng/ml. Studies suggest everolimus targets primary causes of chronic rejection by reducing acute rejection, allowing for cyclosporine dose reduction (which may lead to improved renal function relative to full-dose cyclosporine) and by reducing cytomegalovirus infection and inhibiting vascular remodelling.     

肾移植患者低浓度环孢素A应用研究

目的 研究低浓度环孢素A免疫抑制剂方案在肾移植患者中的应用效果.方法 对133例接受肾移植手术的患者进行回顾性分析,根据应用的骁悉剂量和环孢素血药浓度不同,将其分为三组:高环孢素浓度一高骁悉剂量组、高环孢素浓度-低骁悉剂量组和低环孢素浓度-高骁悉剂量组.监测全血环孢素浓度、血肌酐、尿素氮浓度、血脂以及其他并发症的发生情况.并对各组间的差异进行对比分析.结果 应用低环孢素浓度-高骁悉剂量免疫抑制剂方案的患者与应用其他方案的患者相比排斥反应的发生率无明显差异,术后感染、代谢异常、药物不良反应的发生明显低于其他方案组.结论 应用低环孢素浓度-高骁悉剂量免疫抑制剂方案可以有效的预防排斥反应的发生,同时降低了不良反应的发生.     

The use of mycophenolate mofetil in transplant recipients

With the development of new immunosuppressive agents, the focus of anti-rejection therapy has shifted from prevention of acute allograft rejection to an emphasis on sufficient immunosuppression with minimal toxicity. Mycophenolate mofetil (MMF) is a recently developed immunosuppressive drug, which acts to inhibit T and B cell proliferation by blocking the production of guanosine nucleotides required for DNA synthesis. It also prevents the glycosylation of adhesion molecules that are involved in attachment of lymphocytes to endothelium and potentially in leukocyte infiltration of an allograft during an immune response. High-quality randomized clinical trials have demonstrated that MMF, when used with cyclosporine (CsA) and steroids, reduces the frequency and severity of acute rejection episodes in kidney and heart transplants, improves patient and graft survival in heart allograft recipients and increases renal allograft survival at 3 years. It has also been effective in reversing acute and resistant rejection episodes in heart, kidney and liver recipients. The ability of MMF to facilitate sparing of other immunosuppressive agents, particularly in CsA-related nephrotoxicity, is also promising. By permitting reduction in CsA doses, MMF may stabilize or improve renal graft function in patients with CsA-related nephrotoxicity or chronic allograft nephropathy. Early results of phase I and II trials evaluating MMF therapy in liver and combined pancreas/kidney transplant recipients are encouraging. The main adverse effects associated with oral or intravenous MMF are gastrointestinal and hematologic in nature. Although the direct costs of using MMF vs. azathioprine (AZA) are higher, the decreased incidence and treatment of acute rejection in patients treated with MMF supports its use as a cost-effective option during the first year following transplantation.Thus, MMF has become an important therapeutic tool in the transplant clinician's armamentarium. Ongoing issues to be resolved in clinical trials include the role of MMF in the absence of other potent agents, e.g., as monotherapy or with a steroid but without calcineurin inhibitor; whether MMF will have an impact on chronic allograft dysfunction; and the cost-effectiveness of treatment following the first year of transplantation.