公民逝世后器官捐献供肾移植肺部感染诊治研究

目的分析DCD供肾移植肺部感染的特点及诊治效果。方法回顾性分析2011年6月至2014年12月施行的DCD供肾移植69例,以同期的尸体供肾移植129例作为对照组。所有受者均采用抗体诱导+他克莫司(TAC)+麦考酚酯(MMF)+泼尼松(Pred)四联免疫抑制方案。分析总结DCD供肾移植术后肺部感染特征,治疗效果。结果随访6~24个月,DCD组和SCD组受者肺部感染总体发生率分别为17.4%和33.3%,移植术后半年内肺部感染发生率分别为15.9%和15.5%;DCD组肺部感染死亡3例,SCD组死亡4例。病原体的种类主要为卡氏肺囊虫、CMV;肺部感染治疗期间急性排斥反应发生各为3例和4例;肺部感染发生同受者DGF状态、感染前使用ATG相关,同供体携带病原体无显著性关联;肺部感染治疗前后受者移植肾功能无明显差异。结论 DCD供肾移植术后肺部感染发生率同尸体供肾移植相当,DGF和T细胞清除剂使用时主要诱因,经积极治疗后可以获得良好的结局。     

肺移植100例临床分析

目的 探讨肺移植术后免疫抑制方案的安全性及有效性、术后并发症、死亡原因及其危险因素等.方法 回顾性分析100例肺移植受者的临床资料.100例受者中,单肺移植72例,双肺移植28例,61例在体外循环支持下完成,其中常规体外循环(CPB)5例,体外膜肺氧合(ECMO) 56例.2007年之前53例受者使用环孢素A(CsA)+吗替麦考酚酯(MMF)+皮质激素的三联免疫抑制方案预防排斥反应(CsA组),随后47例采用他克莫司(Tac)+ MMF+皮质激素的三联免疫抑制方案(Tac组),所有受者均使用了达利珠单抗或巴利昔单抗进行免疫诱导治疗.结果 受者术后1、2、3、5年累积存活率分别为73.3％、61.6％、53.5％和40.7％,CsA组受者存活时间为(36.57±3.44)个月,Tac组受者存活时间为(35.00±2.33)个月,两组比较,差异无统计学意义(P＞0.05).术后主要死亡原因包括原发性移植物功能丧失(PGD)、急性排斥反应(AR)、闭塞性细支气管炎(BOS)、感染等.CsA组AR和BOS的发生率明显高于Tac组(P＜0.05),但Tac组术后新发糖尿病的发生率显著高于CsA组(P＜0.05).等级相关分析显示,AR与BOS的发生呈正相关(相关系数=0.340,P＜0.01).单因素和多因素COX比例风险回归模型分析结果均显示,使用循环支持,原发病为特发性肺间质纤维化,术后出现AR、BOS和感染等因素会降低受者的存活时间(P＜0.05).结论 肺移植术后以CsA或Tac为主的免疫抑制方案均是有效的免疫抑制措施.术后加强随访、及时处理出现的并发症是延长受者存活时间和改善受者生存质量的关键.     

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.     

他克莫司与环孢素A在高致敏肾移植受者中的应用比较

目的 观察和比较高致敏肾移植受者应用他克莫司(FK506)与环孢素A(CsA)的有效性和安全性.方法 根据术后免疫抑制方案的不同,将147例高致敏肾移植受者(其中术前群体反应性抗体＞50%的首次肾移植受者59例,2次肾移植受者88例)分为FK506组(53例)和CsA组(94例),两组的免疫抑制方案分别为FK506(或CsA)+霉酚酸酯+泼尼松.观察并分析两组受者术后移植肾存活率、血肌酐水平以及并发症的发生率.结果 FK506组术后1、3和5年的移植肾存活率(86.8%、82.3%和75.3%)略高于CsA组(81.9%、75.4%和66.9%),但差异无统计学意义(P＞0.05);FK506组术后1年时血肌酐水平为(100.72±15.88)μmol/L,CsA组为(117.29±11.77)μmol/L,两组比较,差异有统计学意义(P＜0.01);FK506组与CsA组相比,术后急性排斥反应、慢性排斥反应、肝功能损害、高血压和高血脂的发生率显著降低(P＜0.05),而高血糖的发生率明显升高(P＜0.01),两组移植肾功能延迟恢复和感染的发生率无明显差异(P＞0.05).结论 FK506与CsA相比,能有效降低高致敏受者肾移植术后急、慢性排斥反应的发生率,减少术后并发症的发生,提高移植肾的长期存活率,对高致敏肾移植受者是非常有效和安全的.     

供者DC介导的淋巴细胞反应在肾移植后个体化免疫抑制治疗中的作用

目的 探讨根据供者骨髓源性树突状细胞(DC)介导肾移植受者淋巴细胞反应指导肾移植术后免疫抑制剂个体化应用的价值。方法 2008年1月至2010年1月间接受亲属活体供肾移植者30例,根据药物剂量调整依据的不同分为试验组和对照组,每组各15例,免疫抑制方案同为他克莫司(Tac)+吗替麦考酚酯(MMF)+皮质激素。试验组术后根据受者淋巴细胞对供者DC的反应强度,结合血Tac、MMF浓度调整药物剂量;对照组术后仅根据血药浓度调整药物剂量。术后每月检查肝功能、肾功能、血常规、尿常规、血糖,随访时间为1年。结果 随访期内试验组急性排斥反应的发生率为13.3％,对照组为46.7％(P＜0.05);试验组和对照组的感染发生率分别为6.7％和40.0％(P＜0.05);试验组和对照组不良反应的总体发生率分别为13.3％和46.7％(P＜0.05)。两组各时间点的血清肌酐的差异无统计学意义(P＞0.05)。结论 利用供者骨髓源性DC介导肾移植受者淋巴细胞反应结合治疗药物血药浓度监测作为免疫监测指标,指导肾移植术后免疫抑制剂个体化应用,较仅利用血药浓度监测更全面、准确。     

麦考酚钠肠溶片在肾移植术后早期治疗中的有效性和安全性

目的 评估麦考酚钠肠溶片(EC-MPS)在中国肾移植术后早期免疫抑制治疗中的有效性是否与吗替麦考酚酯(MMF)相当,并对其安全性进行评价.方法 采用多中心、前瞻性、随机、双盲、双模拟和平行对照研究.在肾移植术后0～48 h内,将符合标准的受者随机分成EC-MPS组和MMF组.分别用EC-MPS和MMF治疗6个月,观察其有效性和安全性.结果 肾移植术后6个月内,EC-MPS组受者发生急性排斥反应、移植肾功能丧失和死亡的总发生率(14.3%)有低于MMF组(20.3%)的趋势,但两组比较,差异无统计学意义(P>0.05).两组不良反应总的发生率(66.7%和66.0%)也较为接近.但EC-MPS组重度感染和重度肺部感染的发生率略低于MMF组,因严重胃肠道不良反应而导致药物减量或停药的受者比例也略低于MMF组,但差异均无统计学意义(P>0.05).结论 EC～MPS在中国肾移植术后早期对受者的免疫抑制治疗中,其有效性与MMF相等.并且具有良好的安全性.     

骁悉对肾移植术后感染的影响

目的观察骁悉(MMF)对肾移植术后感染的影响。方法将90例肾移植术后患者分为两组．1997年以前手术的56例为硫唑嘌呤(Aza)组,免疫抑制剂为环孢素A(CsA)加Aza加泼尼松;1998～1999年1月手术的34例为MMF组,免疫抑制剂为CsA加MMF加泼尼松。Aza组CsA起始用量为6mg/(kg·d-1),MMF组为5mg/(kg·d-1),以后根据血药浓度进行调整。结果90例肾移植患者术后总的感染率为17.8％,其中Aza组为21.4％(12/56),2例死亡;MMF组为11.8％(4/34),无死亡病例。两者之间感染率差异有显著性意义(P＜0.05)。结论用MMF代替Aza可以减少肾移植术后的感染率,并提高移植肾成活率。     

肾移植术后应用来氟米特与霉酚酸酯两种三联免疫抑制方案的比较

来氟米特（leflunomide，LEF）是一种新型免疫抑制剂，大量动物实验证实，来氟米特可以有效地预防和治疗肾移植术后急性排斥反应。因此，我们在肾移植术后应用环孢素A（CsA）＋来氟米特（LEF）＋泼尼松（Pred）三联免疫抑制方案（LEF组）与CsA＋霉酚酸酯（MMF）＋Pred三联免疫抑制方案（MMF组）进行对比观察，评价肾移植受者使用LEF的免疫抑制效果和安全性，结果报道如下。     

肾移植后泌尿系肿瘤24例的诊治体会

肾移植受者的恶性肿瘤发生率远高于正常人,其中泌尿系肿瘤的发生率最高.1998年10月至2011年12月,我院共完成肾移植2572例,其中24例(0.93％,24/2572)术后并发泌尿系肿瘤,现报告如下. 资料与方法 一、一般资料 24例中,男性10例,女性14例.肾移植时年龄为(49.3±11.6)岁(24～68岁),术后首次诊断为肿瘤时年龄为(55.6±9.8)岁(32～70岁),肿瘤诊断距手术时间为2～180个月,中位数为54个月.尸体供肾22例,亲属活体供肾2例.术后免疫抑制方案为环孢素A(CsA)+吗替麦考酚酯(MMF)+泼尼松(Pred)者16例,他克莫司(Tac)+ MMF+Pred者4例,CsA+硫唑嘌呤(Aza)+Pred者4例.     

硫唑嘌呤或骁悉治疗的肾移植患者术后早期并发症比较

目的:比较硫唑嘌呤(azathioprine,Aza)或霉酚酸酯(mycophenolate mofetil,MMF)联合环孢素 激素两种免疫抑制方案的肾移植患者,在术后并发症方面的差异,探讨较理想的免疫抑制方案。方法:收集两组肾移植患者249例:Aza组(即应用Aza CsA 激素)、MMF组(MMF CsA 激素),统计两组患者在术后1年内各种并发症(包括排斥反应、各种感染、肝损害、白细胞减少等)的发生。结果:Aza组与MMF组术后1年急性排斥反应的发生率差异显著;两组总的感染率、肺部感染率相近,但发生急性呼吸窘迫综合征(ARDS)及肺部感染病死率后者明显高于前者。在肝损害、白细胞减少、糖尿病等方面,两组也无统计学差异。结论:MMF组在减少急性排异方面优于Aza组,但增加重症肺部感染机会,肺部感染的病死率升高,且费用贵,故临床上应根据具体情况选择。     

骁悉、环孢素A和泼尼松在肾移植受者联合应用中最适剂量探讨

目的探讨国人肾移植后骁悉(MMF)、环孢素A(CsA)和泼尼松(Pred)联合应用的最适剂量。方法比较常规剂量组(104例)和低剂量组(96例)患者肾移植术后免疫抑制剂用量和急性排斥反应、肺部感染发生率和人/移植肾生存率。结果MMF和CsA用量在术后3个月、Pred用量在术后6个月内常规剂量组明显高于低剂量组。常规剂量组在6个月内包括活检证实、临床推断和亚临床排斥,其总的急性排斥发生率为17.3%,而低剂量组为19.8%,两组间差异无显著性意义(P=0.55)。两组患者在6个月内肺部感染发生率分别为40.4%和11.5%(P<0.0001),尤其是重症肺部感染发生率常规剂量组明显要高(26.9%比5.2%,P<0.0001)。两组患者人/肾1年生存率分别为87.4%/85.5%和97.9%/96.9%(P均<0.01)。排除感染所致的带功死亡后两组患者人/肾1年生存率差异无显著性意义。结论低剂量MMF、CsA和Pred联合应用并不增加急性排斥率、亚临床排斥发生率、排斥治疗逆转率和排斥反应的严重程度,但明显降低肺部感染发生率和病死率。     

Results of kidney transplantation in patients receiving MMF- or MMF and basiliximab-containing immunosuppression

Mycophenolate mofetil (MMF) is a more potent immunosuppressive drug than azathioprine or mizoribine in combination with cyclosporine (CsA) and steroids. Recently, basiliximab (BA), an interleukin-2 receptor antagonist, has become available in Japan. The purpose of this study was to evaluate the efficacy of an extremely low CsA dose immunosuppressive protocol with MMF versus MMF plus BA after renal transplantation (RTx). PATIENTS: Between September 2001 and March 2003, we performed 79 RTx with CsA-based immunosuppression, including nine from cadavers and 70 from living donors with 15 ABO-incompatible RTx. Immunosuppression consisted of methylprednisolone (MP), CsA and MMF (group 1; n = 24) versus added BA during the induction phase (group 2; n = 55). In group 2, MP was withdrawn on postoperative day 14. Supplementary MP, muromonab-CD3, or gusperimus was administered if rejection was suspected clinically or diagnosed by biopsy. RESULTS: The incidence of biopsy-proven acute rejection (AR) was significantly higher among group 1 than group 2 patients (P < .05). CsA C2 levels in group 1 were significantly higher than group 2 at each time (P < .01). The incidence of infection was comparable. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 98% and 98%, respectively. CONCLUSION: The short-term results of RTx were favorable in both the MMF, and the MMF plus BA immunosuppression. In addition, BA significantly reduced the number of AR episodes. Early steroid withdrawal in recipients receiving BA induction was not associated with an increased risk of AR.     

The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation

PURPOSE: The present retrospective study investigated the influence of mycophenolate mofetil (MMF) instead of azathioprine (AZA) as part of tacrolimus-based immunosuppression. Mycophenolic acid (MPA) pharmacokinetic (PK) parameters were used for associations with the incidence of acute rejection (AR) episodes and infectious complications after renal transplantation. METHODS: The 66 consecutive renal transplant recipients reported herein excluded ABO-incompatible transplants or cytomegalovirus (CMV)-seronegative recipients. The immunosuppressive regimen consisted of tacrolimus, steroids, and AZA 1-2 mg/kg/d in 22 patients (between February 1998 and December 2000) or MMF 2 g/d in 44 patients (since January 2001). CMV infection was defined as positive CMV-antigenemia. MPA PK was studied on day 28 after transplantation in 21 recipients. RESULTS: AR occurred in 13.6% of patients in the MMF group compared with 18.2% in the AZA group. The viral infection (CMV, varicella zoster virus, adenovirus hemorrhagic cystitis, and malignancy related to Epstein-Barr [EB] virus) rate was 22.7% in the MMF group and 0% in the AZA group (P = .015). There were no bacterial or fungal infections observed in the 2 groups. MMF dose per body weight was significantly lower among patients with AR than those without AR (25.1 vs 35.6 mg/kg; P = .026). There were no differences in MPA PK parameters between patients with and without viral infections. CONCLUSIONS: Patients treated with MMF required less treatment for AR, however, there were no significant differences. MMF dose per body weight may play an important role in the occurrence of AR. Although virus infections occurred in recipients treated with MMF, MPA PK did not influence the infectious complications after renal transplantation.     

雷公藤多苷对移植肾长期存活率的影响

目的:探讨雷公藤多苷(TW)作为免疫抑制剂对肾移植患者长期存活率的疗效及副作用.方法:104例患者在肾移植术后采用TW 泼尼松(Pred) 环孢霉素(GsA) 硫唑嘌呤(AZa)免疫抑制剂治疗,48例患者在肾移植术后采用Pred GsA 骁悉(MMF)免疫抑制剂治疗,就以下方面对两组患者进行观察比较:(1)术后5年内发生排斥反应及临界改变情况;(2)外周血白细胞下降、肝功能异常的发生率;(3)严重感染情况;(4)出现尿蛋白情况;(5)术后5年内肾功能变化情况及移植肾5年存活率.结果:5年内AZa TW组急性排斥反应及临界改变的发生率较MMF组低,分别为11.5%、16.7%和4.8%、6.3%(P＞0.05);GPT高于正常的发生率分别为7.7%、16.6%(P＞0.05);外周血白细胞低于正常的发生率分别为0.96%、18.8%(P＜0.01);严重感染的发生率分别为1.9%、18.8%(P＜0.05),5年内出现蛋白尿的患者例数分别为17.3%、29.2%(P＞0.05),两组移植肾5年存活率相似,分别为89.6%、85.4%(P＞0.05).结论:在肾移植术后应用CsA Pred AZa TW免疫抑制方案是可行的,既可以使肾移植术后急性排斥反应减少,同时还能减少蛋白尿及慢性排斥反应的发生率下降,为国内提高移植肾长期存活率提供了一条新的途径.     

Improved clinical outcomes in Chinese renal allograft recipients receiving lower dose immunosuppressants

BACKGROUND: The application of potent immunosuppressants has decreased the incidence of acute rejection and increased short- and long-term graft survival; however, these drugs cause a variety of complications. In China, many transplant centers have adopted the immunosuppressive protocols based on the white population, neglecting the differences between the races. The purpose of this study was to explore a suitable immunosuppressive regimen for Chinese renal allograft recipients. METHODS: Two hundred cadaveric renal allograft recipients who underwent transplantation between July 1999 and October 2001 were observed. Before October 2000, 104 recipients received the conventional dose of immunosuppressants; thereafter, 96 recipients received lower dose treatment. Doses of immunosuppressive agents, the incidence of acute rejection and pulmonary infection, and patient and graft survival rates were compared between the two groups. RESULTS: Doses of mycophenolate mofetil (MMF) and cyclosporine A (CsA) administered in the conventional dose group were significantly higher than in the lower dose group at 3 months posttransplant, as was prednisone at 6 months posttransplant. The incidence of acute rejection and subclinical rejection that was biopsy-proven or diagnosed by clinical manifestations was 17.3% and 19.8%, respectively, in the conventional dose group and the lower dose group within the first 6 months, and no significant difference was noted (P=0.55). The incidence of pulmonary infection, especially severe infection, was much higher in the conventional treatment group (40.1% and 26.9%, respectively) than that in the lower dose group (11.5% and 5.2%, respectively), and the differences were statistically significant (P<0.001). The corresponding 1-year survival rate of patients was 87.4% and 97.9% (P<0.01), and that of renal grafts was 85.5% and 96.9% (P<0.01), for patients receiving conventional dose and lower dose immunosuppressive drugs, respectively. The rate of death with a functioning allograft caused by infection in the conventional dose group was significantly higher than that in the lower dose group (12.5% vs. 0%, P<0.01). CONCLUSIONS: The regimen of lower dose MMF, CsA, and prednisone in combination can significantly reduce the incidence of pulmonary infection, especially severe pulmonary infection, without increasing the incidence and severity of allograft rejection.     

个体化免疫抑制方案在心脏移植高危患者中的应用

目的 探讨个体化免疫抑制方案在心脏移植高危患者中的应用.方法 回顾分析2001年9月至2006年12月51例在围手术期合并HBV感染、糖尿病、肾功能不全或肺部感染的心脏移植病例,全组患者术前均采用达利珠单抗进行免疫诱导治疗,基础免疫抑制方案为环孢霉素A(CsA)、硫唑嘌呤(Aza)或吗替麦考酚酯(MMF)和泼尼松的三联方案.其中术前合并HBV感染10例,术后强调使用MMF,术后1个月停用泼尼松;术前合并糖尿病9例,术后并发移植后糖尿病4例,术后强调使用CsA,不用FK506,减量使用或停用泼尼松,配合胰岛素治疗;术前肾功能不全16例,术后常规使用MMF,术后第5～19天开始使用CsA;术后并发肺部感染12例,减量或暂停使用CsA、MMF和泼尼松.结果 术前合并HBV感染10例,随访1年肝功能稳定,1例于术后第13个月发生急性排斥反应.糖代谢异常13例,术后血糖控制满意,随访6个月无急性排斥反应发生.术前肾功能不全16例,随访1个月无急性排斥反应发生,肾功能恢复正常.术后并发肺部感染12例,2例死于严重的肺部感染,其他患者均存活;随访1个月,1例患者于术后第17天发生急性排斥反应.结论 免疫抑制方案的个体化能使心脏移植的高危患者平稳渡过围手术期,不会增加急性排斥反应的发生率.     

Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols.

BACKGROUND: The need for better immunosuppressive protocols after lung transplantation led us to investigate tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination with MMF and steroids in a prospective, open, randomized trial after lung transplantation. METHODS: Between September 1997 and April 1999, 50 lung transplant recipients were randomized to receive either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All patients underwent induction therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute rejection (AR), patient survival, infection episodes, and side effects were monitored. RESULTS: There was no difference in patient demographics between the two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1 year after lung transplantation was slightly higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of treated rejection episodes per 100 patient days in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had to be switched to Tac. Two patients in the CsA group had to be retransplanted. Incidence of infections was similar in both groups with a trend toward more fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have slightly higher immunosuppressive potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent is not paralleled with undue signs of overimmunosuppression.     

用于肾移植的几种免疫抑制方案的对比研究

目的 比较肾移植后几种常用免疫抑制治疗方案的疗效与副作用。方法 根据所使用的免疫抑制治疗方案将８７例肾移植患者分为４组,Ａ组的免疫抑制治疗方案为他克莫司（ＦＫ５０６）、霉酚酸酯（ＭＭＦ）和泼尼松（Ｐｒｅｄ）;Ｂ线为环孢素Ａ（ＣｓＡ）、ＭＭＦ和Ｐｒｅｄ;Ｃ组为ＣｓＡ、硫唑嘌呤（Ａｚａ）和Ｐｒｅｄ;Ｄ组为ＣｓＡ和Ｐｒｅｄ。观察术后移植肾功能的恢复情况、排斥反应发生率、并发症及免疫抑制剂用量的变化。结果     

不同剂量咪唑立宾在临床肾移植中的应用研究

目的 探讨不同剂量咪唑立宾(MZR)在临床肾移植中的应用效果及其安全性.方法 将206例首次接受肾移植的受者按手术时间排序,以奇偶数将受者列入吗替麦考酚酯(MMF)组,MZRⅠ组和MZRⅡ组.MMF组受者术后采用MMF+环孢素A(CsA)+泼尼松(Pred)的免疫抑制方案,MZRⅠ组和MZRⅡ组采用MZR+CsA+Pred的免疫抑制方案;MMF组MMF的用量为1.0g/d,MZRⅠ组和MZRⅡ组MZR的用量分别为100和200mg/d,3组间CsA和Pred的用法相同.排除失随访受者,MMF组、MZRⅠ组和MZRⅡ组分别有100、60和30例受者获得完整随访,研究终点为肾移植术后5年.比较各组受者人、肾存活率和排斥反应发生率,以及与药物相关不良反应的发生情况等.结果 MZR Ⅰ组、MZRⅡ组和MMF组受者术后总体存活率分别为88.3%(53/60)、90%(27/30)和88%(88/100),移植肾总体存活率分别为85%(51/60)、86.7%(26/30)和86%(86/100),急性排斥反应发生率分别为10%(6/60)、6.7%(2/30)和9%(9/100),3组间人、肾存活率以及急性排斥反应发生率的差异均无统计学意义(P>0.05);严重肺部感染发生率分别为3.3%(2/60)、10%(3/30)和15%(15/100),MZRⅠ组显著低于MMF组(P<0.05),而MZRⅡ组与其他两组的差异均无统计学意义(P>0.05).MZR Ⅰ组和MZRⅡ组发生严重感染者均经治疗后痊愈,而MMF组死亡11例,死亡率为73.3%(11/15).MZRⅠ组和MZRⅡ组腹泻发生率均显著低于MMF 组(P<0.05),而高尿酸血症发生率均显著高于MMF组(P<0.05).结论 咪唑立宾对预防肾移植后排斥反应是安全、有效的,受者耐受性好,对于免疫功能低下易发生感染的高危人群,以及使用MMF致顽同性腹泻者,可将含咪唑立宾的免疫抑制方案作为首选.

Abstract：

Objective To observe the efficacy and safety of different doses of mizoribine to prevent rejection after renal transplantation. Methods Sorted by time of operation and odevity, 206 primary kidney transplant recipients were divided into 3 groups, including MMF group, MZR Ⅰ group and MZR Ⅱ group. All recipients in 3 groups were administrated CsA and Pred, combined with mycophenolate mofitile (MMF) in MMF group and mizoribine (MMF) in MZR Ⅰ and Ⅱ groups.The dosage of MMF was 1. 0 g/day, while dosage of MZR in MZR Ⅰ and Ⅱ groups was 100 and 200 mg/day, respectively. There was no difference in usage of cyclosporine (CsA) and prednisone (Pred) among 3 groups. 100, 60 and 30 recipients were followed up in MMF, MZR Ⅰ and MZR Ⅱ groups respectively in 5 years. During the follow-up period of 5 years, the incidence of acute rejection, patient/graft survival and adverse effects associated with drugs in three groups were observed. Results The patient/graft survival was 88. 3 % (53/60), 85 % (51/60) in MZR Ⅰ group, 90 % (27/30),86.7 % (26/30) in MZR Ⅱ group, and 88% (88/100), 86% (86/100) in MMF group, respectively (P>0. 05). There was no significant difference in incidence of acute rejection among MZR Ⅰ (10 %, 6/60), MZR Ⅱ (6. 7 %, 2/30) and MMF groups (9 %, 9/100). The incidence of severe pulmonary infection in MZR Ⅰ group was 3. 3 % (2/60), and 10 % (3/30) in MZR Ⅱ , and the former was lower than MMF group (15 %, 15/100) significantly. There was significant difference in mortality of severe pulmonary infection between MZR Ⅰ group (0, 0/2) and MMT group (73. 3 %, 11/15). The rate of ACR in MZR Ⅱ group (10 %, 3/30) was lower significantly than MMF group (30 %, 30/100) and MZR Ⅰ group (31.7 %, 19/60). There was significant difference in the incidence of hyperuricacidemia between two MZR groups (30 %, 56. 7 %) and MMF group (10 %)(P<0. 05), while the incidence of diarrhea and myelosuppression was lower significantly in MZR Ⅰ group than in MMF group. Conclusion MZR can prevent acute rejection after kidney transplantation effectively and safely. Immunosuppressive therapy including mizoribine is the best choice especially for high risk group because of susceptibility to infection and those who suffer from tenacious diarrhea owing to the side effect.     

肾移植后不同免疫抑制方案的效果及不良反应的临床分析

目的 总结肾移植后使用不同免疫抑制方案的效果和不良反应,以提高人/肾的长期存活率.方法 对单中心3102例肾移植受者的临床资料进行回顾性分析,所采用的免疫抑制方案有环孢素A(CsA)+硫唑嘌呤(Aza)+泼尼松(Pred)、低剂量CsA+吗替麦考酚酯(MMF)+Pred、低剂量他克莫司(Tac)+MMF+Pred、低剂量CsA(或Tac)+西罗莫司(SRL)+Pred等方案,分析各方案的效果和不良反应.结果 低剂量CsA+MMF+Pred方案的人/肾1、5、10年存活率均高于CsA+Aza+Pred方案,而高血压、震颤、高尿酸、肝肾毒性、白细胞下降等的发生率显著低于CsA+Aza+Pred方案(P＜0.05),腹泻发生率显著高于CsA+Aza+Pred方案(P＜0.05).低剂量Tac+MMF+Pred方案的高血糖发生率显著高于低剂量CsA+MMF+Pred方案(P＜0.05),多毛症发生率显著低于低剂量CsA+MMF+Pred方案(P＜0.05);低剂量CsA(或Tac)+SRL+Pred方案的腹泻、高尿酸血症、肝肾毒性和多毛症等的发生率显著低于低剂量CsA(或Tac)+MMF+Pred方案(P＜0.05),但高血脂发生率显著高于后者(P＜0.05).以低剂量Tac为基础的方案者高血糖发生率显著应用低剂量CsA者.结论 低剂量CsA(或Tac)+MMF+Pred方案改善了肾移植受者和移植肾的存活,降低了不良反应发生率,尤以低剂量Tac+MMF+Pred方案为优;调整免疫抑制方案或剂量,改善饮食习惯,加强锻炼,优化降血压、降血脂、控制血糖的治疗措施对预防和控制不良反应尤为重要.

Abstract：

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.