雷公藤防治异体肾移植术后急性排斥反应作用的临床研究

目的：通过观察雷公藤防治尸体肾移植术后急性排斥反应的作用，验证雷公藤免疫抑制在抗排斥反应中的疗效。方法：３９例肾移植患者接受雷公藤治疗，根据服用雷公藤剂量的不同分为双倍剂量组（ｎ＝２０，２ｍｇ／ｋｇｄ－１）和常规剂量组（ｎ＝１９，１ｍｇ／ｋｇｄ－１）。以同期未接受雷公藤治疗的肾移植患者作为对照（ｎ＝４０）。所有患者均无合并感染、环孢素肾中毒和手术并发症的情况。三组之间的性别、年龄、冷热缺血时间、淋巴细胞毒性试验、群体反应性抗体水平都非常接近。结果：双倍剂量组患者术后１个月和３个月内无一例急排的发生，其对照组急排发生率分别高达２５％～４５％。常规剂量组术后１个月和３个月内仅各有１例急排的发生。同期对照组急排发生率为１５％～３５％。术后满３年的雷公藤常规剂量组，３年移植肾存活率为８９．５％，显著高于其对照组移植肾６５．０％的３年存活率。此外，长期服用雷公藤未有严重感染等并发症的增加。结论：雷公藤的确具有减少肾移植术后发生急性排斥反应的作用，有助于提高移植肾的长期存活率。     

老年患者肾移植的围手术期治疗

目的 探讨老年患者肾移植的临床特点和围手术期治疗要点，提高老年肾移植患者人／肾存活率。方法 对27例老年肾移植患者的临床资料进行分析总结。结果 21例发生各类并发症，主要有感染和药物性肝功能损害等，治疗后19例恢复正常，治愈率90．5％。1、3年人／肾存活例数分别为25／25，23／21；存活率分别为92．6％／92．6％；85．2％／77．8％。结论 术前全身状态差，术后并发症多时老年肾移植患者的主要临床特点，也是制约其人／肾存活率的主要因素；完善围手术期治疗措施，及时准确检测，合理调整用药是提高老年肾移植患者人／肾长期存活的重要保证。     

注射用霉酚酸酯预防移植肾急性排斥反应的多中心临床观察

目的：观察霉酚酸酯(MMF)注射剂与环孢素(CsA)和类固醇激素联合应用预防同种异体肾移植急性排斥反应的有效性和安全性。方法：免疫抑制方案为MMF(注射剂及口服剂)联合应用CsA和类固醇激素。观察肾移植术后3个月内急性排斥反应的发生率、程度、人／肾存活率、临床不良反应及感染发生情况。结果：所有受试者、移植肾均存活，82例受试者除1例为移植肾功能延迟恢复外，其余在移植术后3个月的血肌酐和尿量均满意，生命体征、症状和生活质量显著改善。有6例出现急性排斥反应，排斥率为7．32％，经相应治疗后均缓解。有15例受试者16次肝功能异常，经保肝治疗后均转为正常。1例血白细胞下降，经对症处理后缓解。药物相关不良反应发生率为20．73％。7例受试者出现机会感染，发生率为8.53％，经抗生素和抗病毒治疗后均痊愈。未见胃肠道副作用。结论：MMF注射剂有效，可预防肾移植术后急性排斥反应，特别适用于术后早期不能口服药物的肾移植患者。     

活体亲属供肾肾移植25例分析

行活体亲属供肾肾移植25例。结果本组供者供肾后未出现严重的并发症，术后7—10d出院。受者首次肾移植23例，二次。肾移植2例。术后随访2-37个月，肾功能恢复良好，仅1例出现急性排斥反应，2例出现慢性排斥反应，经激素冲击治疗后逆转，人／肾存活率为100％。认为活体亲属供肾肾移植供者切除一侧肾脏恢复良好，受者人／。肾存活率高，是扩大供肾来源的较好途径。     

重复肾移植患者的临床特点及其转归

目的：提高多次肾移植的尿毒症患者移植物的存活率，探讨其术式、用药特点和人／肾存活情况。方法：回顾性分析36例二次肾移植和7例三次肾移植患者再次移植的时间，以及是否保留原移植肾，是否应用抗体诱导治疗，应用不同免疫抑制剂方案和人／肾存活率等临床资料。结果：本组患者急性排斥反应发生率为34．9％(15／43)，移植肾功能延迟恢复的发生率为率为39．5％(17／43)，1年人／肾存活率分别为88．4％(38／43)／81．4％(35／43)，3年人／肾存活率分别为78．3％(18／23)／65．2％(15/23)。结论：再次肾移植的患者宜切除原移植肾，术前最好采用抗体诱导治疗，术后宜采用肝毒性较小的免疫抑制剂。多次肾移植的患者移植肾功能延迟恢复的发生率高，人／肾存活率较初次移植的患者低。     

肾移植患者个体化免疫诱导治疗方案的临床评价

目的:评价兔抗人T淋巴细胞免疫球蛋白(ATG-F)、巴利昔单抗(Basiliximab)在肾移植个体化免疫诱导治疗中的有效性及安全性,探讨肾移植免疫抑制诱导的个体化治疗方案. 方法:回顾性分析381例肾移植受者的临床资料,其中应用ATG-F诱导179例,Basiliximab诱导124例,78例未接受免疫诱导者为对照组.所有肾移植受者术后均采用常规免疫抑制方案抗排斥治疗.对不同组受者术前的一般情况、术后肾功能恢复、移植人/肾存活率及早期并发症的发生情况等进行对比. 结果:ATG-F组与Basiliximab组急性排斥反应、早期移植肾功能恢复、12月的移植人/肾存活率差异无统计学意义(P＞0.05),均优于对照组(P＜0.05);ATG-F组与Basiliximab组感染及相关并发症发生率稍高于对照组,但三组间比较无显著的统计学差异. 结论:临床应用抗体诱导治疗是安全、有效的,但应严格遵守适应证和禁忌证的筛选原则,采取个体化的免疫诱导疗法,积极预防相关并发症,有利于减少排斥反应的发生,提高移植人/肾的存活率.     

霉酚酸酯联合低剂量环孢素A防治肾移植急性排斥反应

目的：了解肾移植术后霉酚酸酯（MMF）与低剂量环孢素A（Cs) 的疗效。方法：对54例尸体供肾移植患者术后一个月,六个月,十二个月的肝,肾功能,急性排斥发生率进行随访。结果：40例患者（74．1％）术后一年内未发生排斥;14例（25．9％）发生一次急性排斥,排斥导致移植肾失功2例（3．7％）死亡2例（3．7％）。结论：以MMF代替硫唑嘌呤应用于三联免疫疗法时,降低CsA要的剂量对部分患者不会产生免疫不足或免疫过度,近期疗法确切可靠,可安全应用于肾脏移植。     

老年患者的肾移植 (51例临床经验)

目的：探讨老年患者肾移植手术适应证及术后免疫抑制剂的应用特点,提高人／肾存活率。方法：对５１例年龄为６０～８３岁老年肾移植患者进行临床分析,研究手术成功与失败者的经验与教训,探讨供肾者的质量,ＰＲＡ、ＨＬＡ配型,术后免疫抑制应用情况。结果：５１例患者后发生并发症２０例（３９．２％）,其中,急性肾小管坏死３例,急性排斥反应６例,ＣｓＡ肝、肾中毒２例,肺部感染５例,心力衰竭３例,脑出血１例。１、３、５     

雷公藤多苷片在肾移植术后早期抗排斥中的作用

目的探讨肾移植术后围术期及术后6个月应用雷公藤(TW)多苷的临床效果。方法对80例同期肾移植受者进行对照性临床研究,随机分为TW组和未应用TW环孢素(Cs A)组各40例。患者术后给予Cs A、吗替麦考酚酯及激素三联免疫抑制疗法。观察患者围术期及术后6个月排斥反应发生情况。结果肾移植术后应用TW可以明显降低肾移植术后早期急性排斥发生率,加快患者肌酐恢复至正常的速度,同时降低术后6个月急性排斥反应发生率。结论 TW多苷片可降肾移植早期急性排斥反应发生率,加快患者恢复速度。     

老年肾脏移植的临床特点

目的探讨老年患者肾移植的风险、以及影响肾长期存活的因素。方法对54例≥60岁老年肾移植病例（老年组）进行回顾性分析,并与同期305例〈60岁肾移植病例（对照组）进行对比分析。结果老年患者在术后1年,3年的人/肾存活率分别为92.6%/88.9%、79.6%/75.9%。老年组急性排斥反应发生率为7.4%,与对照组（8.9%）无显著性差异（P〉0.05）。结论老年患者进行肾移植手术,需进行详实有效的术前检查（特别是心脑血管方面的检查）,并积极运用个体化抗排斥药物。     

他克莫司治疗移植肾慢性排斥的初步临床观察

目的：探讨他克莫司（FK506）、环孢素A（CsA)治疗移植肾慢性排斥（CR)的可行性及安全性。方法：40例同种异体肾移植患者肾功能减退经病理证实为CR，随机分为CsA切我为FK506组20例、继续使用CsA组20例。观察各组移植肾功能、肾小球滤过率、蛋白尿、血压、血脂变化及急性排斥（AR）发生率，治疗后随访12个月。结果：追踪12个月，FK506组16例移植肾功能稳定（80％）；3例行血液透析治疗，1例死亡，人存活率95％。CsA组15例移植肾功能稳定，3例行血液透析治疗，逆转成功率75％；2例死亡，人存活率90％。结论：FK506可以延缓慢性移植物失功。FK506的使用是安全和有效的。     

CsA对大鼠移植心脏细胞凋亡的影响

目的 :探讨细胞凋亡与心脏移植急、慢性排斥反应之间的关系。方法 :Wistar大鼠为供体 ,SD大鼠为受体 ,心脏移植术后给予环孢霉素A(CsA)治疗 ,在移植术后的不同时间 ,取下移植心脏 ,流式细胞术测定移植心脏组织的细胞凋亡率。结果 :CsA治疗的慢性排斥反应组 ,移植心脏的细胞凋亡率显著增高。结论 :细胞凋亡参与移植排斥反应 ,移植心脏细胞凋亡率的检测可作为诊断排斥反应和移植物能否长期存活的指标之一。     

423例尸体肾移植患者的长期随访

目的:探讨肾移植患者较理想的免疫抑制治疗方案.方法:收集我院1992年1月以前成功实施的肾移植手术共423例,按免疫抑制方案分为:环孢素(CsA)二联用药组248例、CsA三联用药组70例、硫唑嘌呤 强的松组(Aza Pred)105例.统计分析各治疗组患者及移植肾第三、五、十年的存活率,各组患者心血管疾病、肿瘤、糖尿病等严重并发症的发生率,及各组患者的急性排斥发生率、逆转率和带肾死亡率.结果:423例肾移植患者中,第三、五、十年患者的存活率分别为79.4%、70.9%、58.9%,移植肾存活率为74.0%、60.3%、45.4%.CsA二联组与CsA三联组各阶段的人、肾存活率在统计学上均无明显差异;Aza Pred治疗组在第三、五年的人、肾存活率与前两组相比明显降低(P＜0.05),但十年存活率无显著差异.各组患者在不同时期均有排斥发生,仅以急性排斥计,所有患者的排斥发生率为38.3%.CsA二联组与CsA三联组在急性排斥的发生率上无明显统计学差异;而Aza Pred组与前两组相比,急性排斥的发生率明显增加,逆转率降低.比较三组患者的并发症发生率和带肾死亡率发现,CsA三联组的感染和糖尿病的发生率较其他两组相比显著增高,带肾死亡率也明显增加;Aza组患者带肾死亡率最低.结论:CsA治疗明显提高患者及移植肾的近期存活率,可能与其明显降低急性排斥的发生率、增加急性排斥的逆转率有关.但比较患者和移植肾的长期存活率可见,CsA治疗组(二联与三联治疗)与Aza组无明显不同.     

Prevention of early acute rejection with daclizumab and triple immunosuppression in cadaveric renal allograft recipients

We carried out a prospective study of the safety and efficacy of daclizumab combined with triple immunosuppression in adult recipients of at least one HLA-mismatched cadaveric renal allograft. All studied patients received the same immunosuppression: a daclizumab infusion of 1 mg/kg immediately before transplantation, and at 2, 4, 6, and 8 weeks following the transplantation. Infusion of cyclosporine (CsA) (0.08 mg/kg/h) was started at the time of the operation and continued by CsA microemulsion (CsA-Neoral), 3 mg/kg twice daily on day 2, methylprednisolone, 0.4 mg/kg intravenously at operation, and mycophenolate mofetil started on day 1. The dose of CsA-Neoral was adjusted to maintain target blood trough levels. Oral methylprednisolone was tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg/day. Fifty-five patients, with a mean age of 48 +/- 11 years, were studied. Six of them received a second renal allograft. The mean donor age was 38 +/- 14 years. Mean cold ischemia time was 19.5 +/- 6.5 h, mean value of HLA-antigen mismatches was 2.7 +/- 0.9, mean latest PRA value was 3 +/- 7%. Fifteen patients experienced delayed graft function. During a follow-up period of 3 months three acute rejection episodes occurred. One patient died because of systemic aspergillosis. After 3 months mean serum creatinine was 104 +/- 38 micromol/L. Five renal allografts failed, one of them due to rejection. Patient and graft survival was 98.2% and 90.9%, respectively. Daclizumab with this triple therapy represents safe and efficient immunosuppression strategy, demonstrated with low incidence of early acute rejection episodes and an acceptable adverse event profile in cadaveric renal allograft recipients.     

乙型肝炎表面抗原阳性供肝在肝移植中的应用

目的 探讨HBsAg阳性供肝在成人肝移植中应用的安全性及其对患者预后的影响.方法 回顾性分析本中心2007年1月至2010年2月23例接受HBsAg阳性供肝的成人肝移植患者临床资料,患者全部为男性,中位年龄42.5岁(29 ～ 61岁),原发病均为乙型肝炎相关终末期肝病,其中13例术前HBsAg、HBeAg和抗-HBc为阳性,10例术前HBsAg、抗-HBe和抗-HBc为阳性.供体HBsAg均为阳性,术后口服恩替卡韦0.5mg,1次/d,静脉滴注乙型肝炎免疫球蛋白(HBIG),术后1周每天滴注2000 IU.术中及术后采用无激素的免疫抑制方案,术后第1、7、14、21、30天检测患者血清HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc、HBV DNA水平,并行肝脏彩色多普勒超声检查.1个月后每月检测及检查1次,并记录患者术后肝功能、肾功能、急性排斥反应、感染、血管并发症、胆道并发症、乙型肝炎复发、肿瘤复发及患者生存等数据.结果 围手术期2例患者死于严重肺部感染,其余21例患者随访至2010年12月(10 ～ 38个月),所有患者术后乙型肝炎未转阴,其中1例患者于术后5个月因胆道缺血再次行肝移植,3例肿瘤患者分别于术后9、14、18个月死于肿瘤复发,18例患者生存,肝功能良好,彩色多普勒超声监测显示肝脏形态、质地良好,HBV DNA监测显示其均为阴性.随访期内,23例患者的生存率为78.3％(18/23),移植肝生存率为73.9％(17/23),未出现乙型肝炎复发所致的肝功能异常、移植肝丢失和病死患者.结论 HBsAg阳性供肝可以安全地应用于乙型肝炎相关终末期肝病的患者.     

Pretreatment with cyclosporine and anti-interleukin 2 receptor antibody abrogates the anti-idiotype response in rat recipients of cardiac allografts.

A 10-day course with ART-18, a mouse monoclonal antibody (mAb) directed against the rat interleukin 2 receptor (IL-2R), prolongs the survival of (LEW x BN)F1 cardiac allografts in LEW recipients to approximately 3 weeks (acute rejection = 8 days, P less than 0.001). We examined host responses against ART-18 idiotype (Id) and mouse immunoglobulin in recipients immunomodulated with ART-18 mAb. Treatment with ART-18 elicited high titers of anti-Id antibodies 14 days after transplantation. However, naive rats given ART-18 before transplantation showed strong anti-Id responses as early as day 4 after engraftment, coinciding with abrogation of the treatment effect (graft survival, approximately 10 days). Preimmunization with irrelevant mouse IgG, which elicited high titers of anti-IgG, did not influence the efficacy of ART-18 upon graft survival (17 days). The use of cyclosporin A (CsA) in conjunction with ART-18 prior to transplantation suppressed the anti-Id response and led to dramatic graft prolongation (greater than 58 days), with two of five grafts surviving indefinitely. This striking effect of CsA plus ART-18 pretreatment did not depend upon CsA per se, as grafts were rejected within 12 days in animals pretreated with CsA alone; in both groups CsA trough levels were comparable. Moreover, administration of CsA before transplantation in concert with control IgG (instead of ART-18) prompted rejection within 2-4 weeks. Thus, discrete interaction(s) between anti-IL-2R mAb and CsA prior to engraftment induces partial host unresponsiveness/tolerance to anti-IL-2R mAb treatment following transplantation and suppresses the neutralizing anti-Id responses, which results in long-term/permanent graft acceptance. This study provides a strategy to overcome the anti-Id response mounted by graft recipients that otherwise limits the efficacy of anti-IL-2R mAb treatment.     

Improved outcome following renal transplantation with reduction in the immunosuppression therapy for rejection episodes

Renal transplantation is superior to hemodialysis in terms of rehabilitation and cost, but it is offered to only a minority of patients with end-stage renal failure because of complications related to immunosuppression therapy. To reduce morbidity, we modified our therapy of patients with transplant rejection from high dose intravenous methylprednisolone (group A: January 1968–September 1972) to lower dose oral prednisone (group B: September 1972–December 1977). Patient survival in group B was significantly improved over that in group A, both in recipients of cadaver transplants (91 per cent versus 81 per cent, respectively, at one year, p < 0.0009) and in recipients of transplants from living related donors (99 per cent versus 86 per cent, respectively, at one year p < 0.001). The improvement in patient survival was the result of a significant decrease in the incidence of infections. Patients with multiple rejection episodes, a very high risk group, experienced an 18 per cent increase in patient survival in group B. With reduction and rapid tapering of corticosteroids for the treatment of patients with acute rejection and curtailment of the therapy of patients with multiple rejection episodes, survival after renal transplantation becomes comparable to that following hemodialysis; in addition, graft function is not compromised.     

Immunotolerance of liver allotransplantation induced by intrathymic inoculation of donor soluble liver specific antigen

AIM: To study the effects of liver specific antigen (LSA) on the immunoreaction of liver allotransplantation and its significance.METHODS: Orthotopic liver transplantation was used in this study. Group Ⅰ: syngeneic control (Wistar-to-Wistar);Group Ⅱ: acute rejection (SD-to-Wistar). Group Ⅲ: acute rejection treated by intramuscular injection of cyclosporine A (CsA) (SD-to-Wistar+CsA). Group Ⅳ: Intrathymic inoculation of SD rat LSA one week before transplantation (LSA+SD-to-Wistar). The common situation and survival time, rejection grades, NF-κB activity of splenocytes and intragraft cytokine gene expression were observed to analyze the acute rejection severity and immune state of animals.RESULTS: The common situation of Wistar-to-Wistar group was very good after the transplantation and no signs of rejection were found. Recipients of SD-to-Wistar group lost body weight progressively. All died within 9 to 13 days after transplantation with the median survival time of 10.7±0.51days. It was an optimal control for acute rejection. The common situation of SD-to-Wistar+CsA group was bad during CsA medication but only with mild rejection. As for LSA+SD-to-Wistar group, 5 of 6 recipients survived for a long time and common situation was remarkably better than that of SD-to-Wistar group and SD-to-Wistar+CsA group.Its rejection grades were significantly lower than that of SD-to-Wistar group (P=0.026). Furthermore, no significant discrepancies of rejection were found between SD-to-Wistar group and LSA+SD-to-Wistar group at day7 and day12(P=0.067). NF-κB activity, IFN-γ and IL-2mRNA expression were significantly inhibited in LSA+SD-to-Wistar group compared with that of SD-to-Wistar group (P＜0.05).CONCLUSION: LSA is an important transplantation antigen which involves in the immunorejection of liver transplantation directly. We reported for the first time that intrathymic inoculation of LSA can induce immnotolerance of liver allotransplantation and grafts can survive for a long time thereby, thus leading to a novel way to liver transplantation immunotolerance.     

肾脏HLA-DR抗原表达在肾移植中的意义

应用免疫酶标技术对47例异体肾移植患者的95例次肾活检标本进行HLA-DR抗原的检测,并同时做光镜、电镜、免疫病理检查及淋巴细胞亚群的研究。结果显示:肾移植后近曲小管上皮细胞的DR抗原表达增加,肾小球的DR抗原表达减少;急、慢性排导反应,急性肾小管坏死时,肾小管及肾间质的DR抗原表达均明显增加;环孢素中毒时,肾单位的DR抗原表达正常,肾间质的DR抗原表达增加。肾脏HLA-DR抗原表达在肾移植后的变化,对于排异反应的诊断、鉴别诊断、判断预后及治疗决策具有重要意义。