不同免疫抑制方案对移植肾早期功能的影响

目的探讨不同免疫抑制方案对移植肾术后早期功能的影响及安全性比较。方法将3种不同的免疫抑制方案分别用于肾移植患者。A组：CsA＋Aza＋Pred。B组：CSA＋MMF＋Pred、C组：FK506＋MMF＋Pred。根移植肾早期功能状态，统计A、B、C3组患者1年移植肾存活率，急性排斥发生率及移植肾功能恢复情况，药物副作用等。结果在3组患者中比较，B组和C组移植肾1年存活率高于A组；C组的急性排斥发生率均低于A组、B组（P〈0．05）。同时，C组的肝功能损害，肾毒性发生率明显低于A组、B组（P〈0．05）。结论通过临床不同免疫抑制方案的比较，认为应用MMF和FKS06组成的免疫抑制方案，具有更高的安全性，可减少急性排斥反应，药物毒副作用的发生率，提高肾移植的存活率，有利于移植肾早期功能的恢复。     

The importance of PRA detection and PRA clearance in cadaveric renal transplantation

Though complement-dependent cytototicity (CDC)asSay is widely adopted as a standald histocompatibilitytest before haplantalon in most of the transplantationcenters in our countw, it yields unacceptably high ~ ofhypemeute rejechon (HR) Of the allograft because of itslow sensihvity[']. In some cases, even the new powerful~nosuPPressants fail to suPPress the disastIDus edejection (GR). In this stUdy, we examined the validity.Of Panel reactive antibodies (PRA) measmnt as a pretranSPlant h…     

流式细胞仪交叉配型对移植肾1年存活率的影响

目的：探讨流式细胞仪交叉配型（flow cytometry crossmatch, FCXM）对移植肾一年存活率的影响。方法:应用χ2检验比较FCXM阳性与阴性组间1年移植肾死亡有无差异。以“移植后1年肾脏的存活状况(是/否)”为应变量，以移植后早期排斥反应（移植后1月内发生）、血管性排斥反应、移植肾功能延迟（移植后1周内需做血液透析）、FCXM、群体抗原反应抗体(PRA)、 HLA A,B配型、HLA DR配型、供者类型（尸肾/活体供肾）、既往移植次数、免疫抑制药物的使用、血清巨细胞病毒状态、冷缺血时间、供者和受者年龄等可疑影响因素为自变量建立Logistic回归模型，探讨流式细胞仪交叉配型对移植肾1年存活有无影响。结果:258例患者平均随访时间为25个月（12～60个月），期间30例移植肾死亡，其中23例发生在移植后1年内。 χ2检验显示，FCXM阳性与阴性组间1年移植肾死亡无统计学差异（P=0.157?0）。 Logistic 回归显示，对移植肾1年死亡有影响的因素包括移植肾功能延迟（OR=8.00, P=0.001?4），供者类型为尸肾（OR=9.30, P=0.001?7）和血管排斥反应（OR=5.05, P=0.021?9）。FCXM的结果不会影响移植肾一年存活率（OR=1.60, P=0.534?6）。结论: FCXM对移植肾1年后存活尚无肯定的影响。     

Cadaveric renal transplantation: Our experience at a tertiary care centre in India

BackgroundRenal transplantation in developing countries like India is largely live donor transplantation. Cadaveric transplantation comprises <2% of all transplants in India.MethodsNinety-two cadaveric renal transplantations were included. Various donor and recipient characteristics were analysed along with graft and patient survival, using Kaplan–Meier method.ResultsThe mean age of the recipients was 35.5 ± 10.9 years while that of cadaver was 43.9 ± 17.0 years. Proportion of females among recipients was 47.8% while that of donors was 34.8%. The most common underlying pathology was chronic glomerulonephritis (44.6%). Antithymocyte globulin was used as induction in 84.8% of cases. Tacrolimus-based triple-drug regimen was most commonly used as maintenance (80.4%). The mean follow-up time was 39.02 ± 28.24 months. The most common cause of death was sepsis (47%). More than 50% deaths (9/17) occurred within first 3 years, while 61.5% of graft loss occurred 5 years after transplantation. The mean graft survival time was 81.6 months (95% confidence interval [CI]: 72.8–90.4). Cumulative proportion of graft survival was 91.6% at 3 years and 77.1% at 5 years. Although females have better mean graft survival time (91.6 vs 73.5 months), it was not a significant difference as shown by log-rank test (p value = 0.062). Pretransplant haemodialysis has no significant effect on graft loss, but patients on peritoneal dialysis have significantly higher odds of graft loss (odds: 4.86, p value < 0.05 [0.018]). The mean patient survival time was 99.5 months (95% CI: 84.0–114.9). Cumulative proportion of patient survival was 83.3% at 3 years and 70.8% at 5 years.ConclusionGraft and patient survival rate of cadaveric transplant at our centre was satisfactory. There is need to sensitise and augment the rate of cadaveric transplantation to increase the donor pool.     

儿童肾移植六例报告

目的：总结儿童肾移植的效果及经验。方法：回顾性分析6例16岁以下儿童肾移植的临床资料。结果：血肌酐恢复正常时间为术后1-6d，平均3d。术后30d内发生急性排斥反应（AR）3例。抗排斥治疗后均逆转，移植肾均存活2年以上，最长1例已存活13年，肾移植后身高未出现明显的加速生长现象。结论：儿童肾移植的手术方式，补液及免疫抑制方法的需注意儿童的特殊性，AR在儿童肾移植中发生率相当高，如何预防及逆转AR是提高移植肾存活率的关键。生长障碍仍是影响移植效果的重要因素。     

Superiority of B locus matching over other HLA matching in renal graft survival

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.     

Renal Transplantation - An Experience of 500 Patients

Background

Renal transplantation is the treatment modality of choice for patients with end stage kidney failure. We present our experience of graft and patient survival of initial 500 renal transplants performed between May 1991 and July 2006, at Army Hospital (R&R).

Material and Methods

All patients received triple drug immunosuppression with cyclosporine/tacrolimus, azathioprine/ mycophenolate mofetil and steroids. Patients in high risk group received induction therapy with IL-2 receptor blockers/anti-thymocyte globulin.

Results

Majority of the recipients (79%) were males, whereas majority of the donors (59.4%) were females. In the donor profile, 385 (77%) transplants were live related, 108 (21.6 %) were spousal and 7 (1.4%) were cadaveric transplants. Mean age of the donors and recipients was 42.11 ± 11.53 years (range 19–72 years) and 33 ± 9.39 years (range 5–60 years) respectively. Eighty two patients (16.4%) were lost to follow up and the present data on rejections, patients and graft survival pertains to 418 patients. These patients have been followed up for a mean period of 2.63 years (SE, 0.122; median 1.8 years; range 0–13.36 years). Acute rejection episodes occurred in 115 (27.3%) patients and 95% of these could be reversed with steroids/ATG. Sixty eight patients (16%) have died on follow-up. Our one-year, 5 year and 10 year estimated graft survival is 95.4% (SE, 0.01), 80.5% (SE, 0.03) and 53.1% (SE, 0.09) respectively and patient survival at one year is 93.2% (SE, 0.01). The estimated graft and patient survival in our series is 9.83 (95% CI, 8.92–10.73) and 9.80 (8.93–10.67) years respectively.

Conclusion

This centre''s short-term graft survival of 95.4% is comparable to the best centres of the world.Key Words: Kidney transplant, Graft survival, Patient survival     

High versus "low" dose corticosteroids in recipients of cadaveric kidneys: prospective controlled trial

Corticosteroids have the major role in the immunosuppressive treatment of patients who have received renal transplants. Despite their extensive use there is still debate about the appropriate dose that will prevent rejection of the renal allograft with the least morbidity. From March 1979 to November 1981 a randomised controlled trial of high (33 patients) v low oral dose (34 patients) of prednisolone along with azathioprine was conducted in recipients of first cadaveric transplants who had received a blood transfusion within six months of transplantation. The main difference in outcome between the two groups was a high incidence of some infections in the high dose group. Patient mortality, graft survival, transplant function, and number of rejection episodes were indistinguishable in the two groups, but rejection episodes tended to occur later in the high dose group. These findings suggest that the use of lower doses of corticosteroids soon after cadaveric renal transplantation does not jeopardise graft survival and results in lower patient morbidity.     

改良肝肾联合切取法和整块尸肾摘取法对供肾质量的影响

目的比较改良肝肾联合切取法和整块尸肾摘取法对供肾质量的影响。方法收集本中心近年来有完整资料尸体供肾肾脏移植手术272例,其中整块法尸肾摘取供肾198个,改良肝肾联合切取法所获供肾74个。随访满12个月者共220例,其中整块法尸肾摘取供肾174个,改良肝肾联合切取获得供肾46个。结果整块法尸肾摘取组的平均取肾时间和肾静脉损伤发生率,优于改良肝肾联合切取组。而两者的1年人存活率,术后24 h、1周以及1年的肾功能无明显差异;改良肝肾联合切取法的1年肾存活率、1年排斥发生率及平均热缺血时间,均优于整块法尸肾摘取法。结论改良肝肾联合切取法的移植肾1年肾存活率和排斥发生率优于整块尸肾摘取法,但两种术式的1年人存活率和术后肾功能恢复无明显差别。     

Canadian clinical trial of antilymphocyte globulin in human cadaver renal transplantation.

A multicentre, randomized clinical trial of antilymphocyte globulin (ALG) was conducted among patients who had undergone cadaver kidney transplantation; follow-up was continued for a minimum of 1 year. Of the 179 patients 92 were given conventional treatment only, while 87 were given in addition ALG (from a standardized, highly immunosuppressive, common pool of equine ALG), 20 mg/kg-d intravenously for 10 days after transplantation. The ALG-treated group had better accumulated graft survival, fewer nephrectomies, better graft function, less than half the number of acute rejection episodes and less prednisone use. There was a beneficial drug (ALG)-related effect in both the graft and the host during the first 3 months after transplantation.     

Renal Transplantation: Experience at a Single Centre

Background

Renal transplantation program in the Armed Forces commenced in Feb 1991 and till date 245 patients have undergone renal transplantation at INHS Asvini. We describe our protocols for donor and recipient evaluation and immunosuppression. Methods: 245 patients received renal transplants during this period, 243 (99.2%) being from live donors. Most of them were started on triple immunosuppression comprising of cyclosporine, azathioprine and prednisolone. Newer drugs like mycophenolate, tacrolimus and sirolimus were administered in a select population.

Result

69 (28.1%) of them had at least one episode of acute rejection, most of which were steroid responsive and 13 (18.8%) of them required either anti CD3 monoclonal or anti-thymocyte globulin (ATG). Complete recovery with normal renal function occurred in 54 (78.2%) cases and 15 (21.7%) recovered with residual dysfunction with maximum serum creatinine being 2.1mg/dl. There were three (1.2%) cases of accelerated rejection during the first week of transplantation and one had graft rupture. All three lost their grafts. There were eight (3.2%) cases of acute tubular necrosis, who recovered completely within 8–14 days. Immediate infections included wound sepsis, lower respiratory tract infection, disseminated candidiasis and disseminated aspergillosis. Late infections included pulmonary tuberculosis, disseminated tuberculosis, cytomegalovirus infection and recurrent urinary tract infection. 28 (11.4%) patients developed post transplant diabetes mellitus. At the end of one year and five years, graft and patient survival were 97.2%, 93%, 80.9% and 85.7% respectively.

Conclusion

Our outcomes show that the transplantation is a viable mode of renal replacement therapy in patients of end stage kidney disease with a near normal rehabilitation.Key Words: Kidney, Transplantation, Immunosuppression, Complications     

心脏死亡供者肾移植48例临床分析

目的:探讨终末期肾病患者接受心脏死亡无偿器官捐献(DCD)供者移植后的恢复情况及此类供体对受者及移植物术后的影响。方法:对48例终末期肾病患者接受DCD捐献的肾脏后行同种异体肾移植术,并对其术前和术后的诊疗及随访血肌酐、移植物及受者存活情况进行回顾性分析。结果:48例受者中无1例出现移植肾原发性无功能(PNF),18例受者术后出现肾功能延迟恢复(DGF),其发生率为37.5%,DGF组与无DGF组受者及移植肾生存率比较,差异无统计学意义(分别P=0.098,P=0.447)。48例受者中有7例(14.6%)受者移植肾丢失,其他41例受者随访时间为0.5~23(中位数8)个月,39例(95.1%)受者移植肾功能恢复正常。在1,3,6,12个月移植物的存活率分别为95.7%,93.0%,90.0%,87.5%,患者的存活率分别为100%,94.9%,90.0%,87.5%。结论:在我国尚无脑死亡法的环境下,DCD是解决我国器官移植界瓶颈的重要手段,是器官来源的重要部分,并且有着较好的短中期预后。     

树突状细胞在大鼠穿透性角膜移植排斥反应中的作用

目的 观察大鼠角膜组织中树突状细胞的分布,以了解树突状细胞在穿透性角膜移植排斥反应中的作用.方法 制作大鼠穿透性角膜移植模型,观察角膜透明度、新生血管.采用免疫组织化学方法检测OX-62 树突状细胞在角膜的分布.结果 术后角膜植片均出现不同程度的新生血管、角膜水肿、混浊、基质增厚.排斥反应发生率100%.正常角膜组织中未见OX-62 树突状细胞分布,在发生急性排斥反应的角膜上皮层中有阳性细胞表达.脾脏阳性细胞表达与文献报道一致.结论 OX-62 树突状细胞出现在移植后发生排斥的角膜组织中,角膜组织中的树突状细胞可能参与角膜移植后的免疫反应.     

PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg· d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg· kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.     

活体亲属肾移植临床分析

目的:探讨活体亲属肾移植的临床效果.方法:回顾性分析5例活体亲属供肾移植的临床资料.结果:5例供者术后无并发症,术后3个月随访无肾功能异常等情况.5例受者术后3 d～7 d血肌酐降至正常水平.1例受者出现急性排斥反应(术后4个月),用甲基泼尼松冲击治疗逆转.1例开放手术取肾的患者于术后6个月合并移植肾积水、输尿管膀胱吻合口狭窄及下段输尿管坏死而行输尿管膀胱再植术.术后1 a复查血常规、尿常规、肝功能、肾功能、移植肾彩色多普勒均正常.结论:活体亲属肾移植是安全、有效的,效果明显优于尸体肾移植.     

供肾质量和移植肾急慢性排斥反应关系分析

目的探讨影响供肾质量的因素与术后移植肾发生急、慢性排斥反应的相关性。方法观察87例移植供肾缺血时间、活检组织的光镜表现结合移植后发生急、慢性排斥反应的情况进行分析。结果移植术后跟踪3年．发生移植肾急性排斥反应28例，其中5例(17．8％)有供肾组织有不良改变；慢性排斥反应13例，其中6例(46．1％)有供肾组织有不良改变。采用Logistic回归分析，结果示冷缺血时间、肾小管损伤是急性排斥反应的危险因素；冷缺血时间、肾小球硬化是慢性排斥反应的危险因素，与慢性移植病的发生可能相关。结论提高供肾质量和减少上述的危险因素．对减少肾移植术后急慢性排斥反应的发生是有意义的。     

Clinical experience with kidney transplantation in patients older than 65 years

Objective: To explore the peculiarities of kidney transplantation in elderly patients and define the perioperative managements. Methods: The clinical data of kidney transplantation in 29 patients older than 65 years were reviewed, the eldest being 84 years old and the mean age 68.1 years. Results : Four episodes of a-cute rejection (13.80%) were encountered. FK506 toxicity occurred in one case (3. 40%) and lung infection in another (3.40%), who (along with the former 4 patients) all were cured subsequently. In one case, the kidney graft was removed for thrombogenesis of the renal artery. The 1- and 3-year patients/grafts survival of 100% and 96. 5% respectively was achieved, with the longest survival exceeding 5 years. Conclusions: Old age was not the absolute contraindication for kidney transplantation. Strict observance of the indications of kidney transplantation and donor selection with well-matched tissue-typing are crucial in elderly patients. Adequate application of immunosuppressants and effective long-term follow-up are also major factors for long-term allograft survival.     

Low-dose steroid therapy in cyclosporine-treated renal transplant recipients with well-functioning grafts. The Canadian Multicentre Transplant Study Group.

OBJECTIVE: Low-dose prednisone given on alternate days as a steroid adjunct to cyclosporine therapy was investigated primarily for its influence on kidney graft and patient survival and, secondarily, on renal function and complications. DESIGN: Multicentre randomized double-blind clinical trial. SETTING: Fourteen Canadian transplant centres. PATIENTS: A total of 523 patients with well-functioning renal transplants (cadaveric grafts or grafts from living related donors) and without active graft rejection reactions who were entered into the trial from 1982 to 1985. INTERVENTION: Patients were randomly assigned 90 days after transplantation to receive either placebo (260 patients) or low-dose prednisone (263 patients). MAIN OUTCOME MEASURES: Graft and patient survival. MAIN RESULTS: After at least 5 years of follow-up 50 patients assigned placebo had lost their graft and 17 had died; the corresponding figures for those assigned prednisone were 38 and 16. After an average interval of 1.4 years 143 patients in the placebo group and 123 patients in the prednisone group had stopped therapy with the test drug or had had their treatment group decoded or both. Patients were withdrawn from the study 2 years after stopping the test therapy. The actuarial 5-year graft survival rates were 73% and 85% in the placebo and prednisone groups respectively (p = 0.03), and the actuarial 5-year patient survival rates were 92% and 94% respectively (p = 0.6). This analysis included 43 and 29 graft losses and 14 and 12 deaths in the placebo and prednisone groups respectively. Weibull parametric modelling of graft survival identified the following variables as risk factors for graft loss: histocompatibility leukocyte antigen B (HLA-B) mismatching (p = 0.007), donor death from cerebrovascular accident (p = 0.01), increased donor age (p = 0.02) and being a male recipient (p = 0.05). When these factors were included in the Cox proportional hazards model, the influence of assigned treatment on graft survival was reduced to p = 0.1. Donor death from cerebrovascular accident (p = 0.002), diabetes mellitus in the recipient (p = 0.02) and increased recipient age (p = 0.05) were risk factors for patient death. Renal function and incidence of complications were similar in the treatment groups. CONCLUSIONS: Continued administration of low-dose prednisone on alternate days is advisable, particularly in patients with cadaveric grafts and those with previously failed transplants.     

Combined pancreas--kidney transplantation in Nebraska.

In the last 2 years, we have performed combined pancreas-kidney transplantation in 38 Type I diabetics with nephropathy. The mean age of the recipient group was 35 years (range 24-51) with a mean duration of diabetes of 22 years (range 13-41). All patients received quadruple immunosuppression with OKT3 induction. All patients are normoglycemic and insulin independent with a mean glycosylated hemoglobin level of 5.2 +/- 1.1% and a mean serum creatinine of 1.9 +/- 0.5 mg/dl. Metabolic effects of pancreas transplantation included fasting hyperinsulinemia and hyperglucagonemia with exaggerated insulin and glucagon responses to glucose and arginine, respectively, that improved slightly with time. Patient and kidney graft survival are 100% and pancreas graft survival is 94.7% after a mean follow-up interval of 15 months. Conclusion: Combined pancreas-kidney transplantation is the treatment of choice for selected Type I diabetics with nephropathy and results in euglycemia despite immunosuppression.     

Risk factors for graft survival in sensitized recipients of kidney transplantation.

OBJECTIVE: To investigate the independent prognostic factors for graft survival in sensitized recipients undergoing kidney transplantation, so as to identify the individuals at high risk of graft loss before transplantation. METHODS: A retrospective investigation was conducted in 102 sensitized kidney transplant recipients and 31 relative variables were analyzed with SPSS10.0 software. Using log-rank method, the influence of these variables on short- and long-term graft survivals was evaluated, and Kaplan-Meier analysis was performed to estimate the 1-, 3- and 5-year graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess the relative risks of the potential variables. RESULTS: In the recipients with a mean half-life of 8.9 years, the 1-, 3- and 5-year graft survival rates were 90%, 85%, and 75%, respectively. By log-rank analysis, the factors affecting short- and long-term graft survivals were identified, namely the recipient age, times of transplantation, levels of panel reactive antibody and the post-operative anti-HLA-IgG antibody, HLA mismatch, renal function, time needing for graft function recovery, presence of acute rejection, delay of graft function recovery and infection, which affected the graft survival demonstrated by Cox model multivariate analysis. CONCLUSION: High-quality donor kidney and minimization of the risk factors for graft survival may insure successful kidney transplantation in sensitized recipients.