HLA配型在致敏受者肾移植中的应用研究

目的 探讨人类白细胞抗原（ＨＬＡ）配型在致敏受者肾移植中的临床意义。方法 应用莱姆德细胞板通过补体领事微量细胞毒性试验检测受者的群体反应性抗体（ＰＲＡ）;应用单抗湿板进行供受者ＨＡＬ－Ⅰ类抗原分型;应用微量序列特异性引物（Ｍｉｃｒｏ－ＳＳＰ）进行ＨＡＬ－Ⅱ类基因分型。结果 １７例受者ＰＲＡ阳性率为５．１％￣８０％,平均３７．８９％;按交叉反应组（ＣＲＥＧｓ）配型原则,供受者ＨＬＡＣＲＡＥｓ０．１和     

浅谈改善肾移植疗效的几个问题

影响肾移植疗效的因素很多,本期收录的临床肾移植研究论著有１１篇,它们从ＨＬＡ配型与急性排斥反应的关系、乙型或丙型肝炎病毒和巨细胞病毒感染对移植效果的影响、１０年来施行肾移植１５０１例的总结、霉酚酸酯（ＭＭＦ）和国产抗ＣＤ３、ＣＤ４单克隆抗体的临床应用、老年人施行肾移植的高危因素以及活体亲属供肾移植等几个方面进行了探讨,以期改善移植效果。笔者拟讨论其中几个问题。一、ＨＬＡ抗原对急性排斥反应和短期存活率的影响国外大宗的肾移植病例统计提示,供、受者间的ＨＬＡ配型结果对肾移植后受者的长期存活肯定有明显影…     

高度致敏受者的肾移植术

目的 探讨高度致敏肾移植受者的组织配型和抗排斥治疗方案。方法 回顾性分析45例高度致敏肾移植受者的HLA抗体、HLA配型和肾移植后抗排斥反应治疗效果。结果 肾移植术后发生超急性排斥反应2例(4．4％)，急性排斥反应9例(20.9％)，经激素、抗胸腺细胞球蛋白、血浆置换等治疗后均逆转。人／肾1年存活率分别为95．6%／91．1％。结论 避开相应抗体的良好HLA配型，是高度致敏受者肾移植成功的关键。术后采用抗胸腺细胞球蛋白短程诱导、并用他克莫司、霉酚酸酯治疗，能减少急性排斥的发生率，提高移植物的存活率。     

HLA-DR基因相容对肾移植长期存活的影响

目的 研究人类白细胞Ⅱ类抗原（ＨＬＡ－ＤＲ）基因相容对肾移植长期存活的影响。方法 采用基因分型技术,回顾性分析５１８例首次肾移植ＨＬＡ－ＤＲ基因相容性情况。结果 单个移植中心达到基因水平ＤＲ相配的受者超过１０Ａ％,半数以上可达１个ＤＲ相配。ＨＬＡ－ＤＲ相容的受者急性排斥反应显著减少,早期肾功能恢复顺利,１－５年人存活率提高１０％－２１．７％,肾存活率提高１７％－３７．７％,差异有显著性。     

骁悉和环孢素-A预防肾移植术后早期急性排斥反应

目的 探讨骁悉和环孢素－Ａ预防肾移植术后早期急性排斥反应的效果。方法 回顾性分析１９９７年１２月￣１９９９年１月临床资料完整肾移植患者１４６例,随访时间６￣１６个月。根据应用免疫抑制剂方案的不同分为硫唑嘌呤（Ａｚａ）组（环孢素－Ａ、泼尼松龙、Ａｚａ）和骁悉（ＭＭＦ）组（环孢素－Ａ、泼尼松、ＭＭＦ）。其中Ａｚａ组７８例,ＭＭＦ组６８例。所有受者术前行人类白细胞抗原（ＨＬＡ）配型,ＨＬＡ错配≤３个位点     

PRA、HLA配型技术在肾移植中的应用

目的 探讨群体反应性抗体（ＰＲＡ）、ＨＬＡ配型技术对肾移植近远期效果的影响。方法对等待肾移植的１０２０例患者采用ＰＲＡ测定、ＨＬＡ组织配型,ＰＲＡ阴性或阳性者均经血浆置换,ＨＬＡ抗原３～６个位点相合为第一组;未采用ＰＲＡ、ＨＬＡ组织配型的４２３例患者为第二组。观察两组肾移植术后免疫指标的变化,近期急性排斥反应发生率以及ＨＬＡ－Ａ、Ｂ、ＤＲ位点对长期存活的影响。结果 第一组肾移植术后环孢素Ａ（ＣｓＡ     

再次尸体肾移植40例临床分析

对环孢素时代再次尸体肾移植４０例作回顾性分析及文献复习，结果再次尸体肾移植１年人／肾存活率为８０．０％／６７．５％，较同期首次肾移植约低１５％。认为环孢素时代影响再次尸体肾移植的主要危险因素为首次移植肾存活时间≤６个月、个体高免疫状态及ＨＬＡ错配。移植肾超急排斥反应、加速排斥反应并发的感染及心衰是再次肾移植失败的主要原因。高效状态患者的检测、预防性应用单克隆及多克隆抗体介导、流式细胞交叉配型及降低     

肾移植受者血清可溶性HLA-I类抗原的动态监测

目的　了解血清可溶性ＨＬＡＩ类抗原（ｓＨＬＡＩ） 与肾移植受者发生急性排斥反应及感染的关系。　方法　应用酶联免疫法动态监测３６ 例肾移植受者ｓＨＬＡＩ水平。　结果　尿毒症组ｓＨＬＡＩ水平为（２－９４±０－３４）μｇ／Ｌ,显著高于正常对照组（０－７６±０－３３）μｇ／Ｌ（Ｐ＜ ０－０５） 。移植后功能稳定组ｓＨＬＡ降至（０－６３±０－３１ ）μｇ／Ｌ,显著低于尿毒症组（ Ｐ＜０－０５）。ｓＨＬＡＩ在发生排斥反应前３ 天及感染后５～７ 天显著升高。　结论　ｓＨＬＡＩ可作为监测肾移植受者急性排斥反应和感染的参数。     

群体反应性抗体在肾移植中的意义

目的 研究群体反应性抗体（ＰＲＡ０在肾移植中的意义。方法 对１７８例肾移植患者进行了术前、术后ＰＲＡ检测。结果 肾移植术前ＰＲＡ阳性患者有２３例,肾移植术后发生急性排斥反应的为２０例。术后ＰＲＡ阳性受者５８例,发生排斥反应的有３４例。移植前后ＰＲＡ阴性患者有１０８例,有８例发生排斥。在肾移植患者中所产生的抗ＨＬＡ抗体的频率和ＨＬＡ抗原的分布不同。结论 ＰＲＡ检测对预测移植肾排斥有重要意义。     

HLA致敏原性错配对肾移植受者急性排斥反应发生率的影响

目的：探讨供受者HLA致敏原性错配(IM)对肾移植受者急性排斥反应发生率的影响。方法：回顾性分析196例首次肾移植受者IM对肾移植术后肾功能的恢复时间及1年内排斥反应发生率情况。结果：IM对肾移植术后肾功能恢复时间无明显影响；IM患者1年内急性排斥率明显增加；各类位点IM对肾移植术后急性排斥反应的影响进行比较，A位点影响不大，B位点与急性排斥反应有关，DR位点IM可致急性排斥反应明显增加。结论：在临床采用氨基酸残基配型标准判断组织配型的同时，IM不容忽视，HLA-B位点IM与肾移植术后急性排斥反应相关，HLA-DR位点IM明显影响肾移植术后排斥反应发生率。     

Risk factors for acute rejection in living donor liver transplantation

The influence of human leukocyte antigen (HLA) compatibility and lymphocytotoxic crossmatch on acute rejection in living donor liver transplantation (LDLT) has not been well examined. We analyzed 100 consecutive adult LDLT cases. The patient and graft survival rates and post-operative complications were assessed. The relation between the incidence of acute rejection and some clinical factors including HLA and lymphocytotoxic matching was also examined. Patients with HLA DR zero mismatching (p = 0.02) or negative T-lymphocytotoxic crossmatch (p = 0.04) had a significantly lower chance of rejection within 6 wk after LDLT. However the results had no influence on the patient survival. Our results demonstrate that in LDLT, a graft from an HLA-DR zero mismatching or negative T-lymphocytotoxic crossmatch might be advantageous because of the decreased probability of early acute rejection.     

Immune Regulation and Graft Survival in Kidney Transplant Recipients Are Both Enhanced by Human Leukocyte Antigen Matching

We hypothesized that donor/recipient sharing of the human leukocyte antigen (HLA) involved in allopeptide presentation to the T regulatory cell increases the incidence of immune regulation, thus contributing to long-term graft survival. Peripheral blood mononuclear cells (PBMC) were obtained from 40 living related donor (LRD) and 31 cadaver renal transplant recipients. The trans vivo delayed type hypersensitivity (DTH) assay was used to assign patients to regulator, nonregulator, and sensitized categories. In a large cohort (n=1934 patients), primary graft survival and rejection episodes were analyzed using a log rank test for comparison with the DTH results. The highest incidence of regulated anti-donor DTH was observed in the LRD HLA-identical group (6/6; 100%) followed by the LRD HLA 1 haplotype matched group (18/27; 67%). Within the cadaver population, two DR-matched recipients had a higher frequency of regulated anti-donor DTH (6/11; 55%) than 1 & 0 DR-matched recipients (3/18; 17%). In a multivariate model, matching for HLA-DR alone, or for DR plus DQ was significantly (p=0.045, p=0.041) correlated with DTH regulation. The better HLA-matched groups showed the highest incidence of DTH regulation and, in a larger retrospective analysis, displayed better graft survival and freedom from acute rejection (p<0.0001). HLA matching, and HLA-DR matching in particular, correlates with the incidence of immune regulation after kidney transplantation.     

供者特异性抗体监测在肾移植中的应用

目的 研究肾移植术后受者血清中供者特异性抗体（DSA）与发生急性排斥反应的关系,为临床早期诊断、合理制定个体化治疗方案、评估疗效提供客观的参考依据.方法 选取2012年1月至2013年8月西安交通大学医学院第一附属医院肾病医院肾移植科285例首次肾移植受者,术后动态监测DSA水平,检测时间点为术后3,5,7,14,21,30,60,90 d.观察受者肾功能和急性排斥反应发生情况.使用卡方检验或Fisher精确概率法比较不同HLA抗体类型的受者急性排斥反应发生率.结果 285例肾移植受者术后初筛人类白细胞抗原（HLA）抗体阳性率为22.11％ （63/285）,其中DSA阳性4例.急性排斥反应发生率6.67％ （19/285）.HLA抗体阴性受者和HLA抗体阳性且DSA阴性受者急性排斥反应发生率分别为3.15％ （7/222）和16.95％ （10/59）,二者相比差异有统计学意义（x2=12.891,P＜0.05）;4例DSA阳性受者有3例发生急性排斥反应,与HLA抗体阴性、HLA抗体阳性且DSA阴性受者急性排斥反应发生率相比,差异均有统计学意义（P=0.000和P=0.016）.19例发生急性排斥反应受者经甲泼尼龙、兔抗人胸腺细胞免疫球蛋白冲击治疗或血浆置换等治疗后,15例受者成功逆转,1例死于并发症.结论 动态监测肾移植术后受者DSA水平,可预测移植肾功能状态,对急性排斥反应的发生有重要预警作用,有利于及时清除或降低DSA水平,对有效预防和及时诊治排斥反应具有重要作用。     

Association of HLA class I antigen matching and early graft outcome in living donor kidney transplantation

INTRODUCTION: HLA antigen matching often plays an important role in organ transplantation. As for HLA class I antigen matching, there are differences of opinion regarding its influence on the outcome of renal transplantations. The aim of this study was to evaluate the association of HLA class I antigen matching with early graft outcomes in living donor kidney transplantation. PATIENTS AND METHODS: We evaluated graft outcomes in the first month of transplantation. Major events were slow graft function (serum creatinine > 250 micromol/L at the end of first week), delayed graft function (patients requiring dialysis in first week), and acute rejection episode. Graft outcomes were compared for normal renal function (NRF, serum creatinine < or = 175 micromol/L) impaired renal function (IRF, serum creatinine > 175 micromol/L) or impaired graft function due to an acute rejection episode (IGF). RESULTS: The 115 subjects had a mean age of 29 +/- 8 years and their donors 38 +/- 11 years (P < .01). Immunosuppression included prednisolone, azathioprine, and cyclosporine. Parents, siblings, and others were kidney donors in 46%, 33%, and 21%, respectively. Comparisons between NRF/IRF (serum creatinine 133 +/- 24 vs 201 +/- 36 micromol/L, P < .01) and NGF/IGF (serum creatinine 146 +/- 44 vs 161 +/- 39 micromol/L, P < .05) showed no difference in number or pattern of HLA matching. CONCLUSION: HLA class I antigen matching may not produce an added influence on early graft outcome among living donor kidney transplantations.     

HLA Mismatching Increases the Risk of BK Virus Nephropathy in Renal Transplant Recipients

BK virus (BKV) nephropathy is a serious complication in kidney transplant recipients that may lead to irreversible graft failure. We have analyzed the degree of donor/recipient HLA compatibility and HLA antigen association in 40 kidney transplant patients with BKV nephropathy in comparison with a control group of 404 unaffected transplant recipients who were on tacrolimus-based immunosuppression with no induction. HLA compatibility was assessed by determining the number of HLA-A, -B, -DR-mismatched antigens. BK virus nephropathy was diagnosed histologically and confirmed by immunochemistry. Univariate and multiple logistic regression statistical analyses have shown a significant association between BKV nephropathy and HLA mismatching. This analysis showed also that BKV nephritis is associated with a greater number of rejection episodes and a higher incidence of steroid-resistant rejection requiring antilymphocyte treatment. There was no association between BKV nephropathy and any specific HLA allele. We propose that HLA mismatching promotes the development of BKV nephropathy through rejection-related inflammatory processes and heavy immunosuppression which cause virus reactivation and injury of the tubular epithelium.     

Pretransplant identification of acute rejection risk following kidney transplantation

Lack of an accepted definition for ‘high immunological risk’ hampers individualization of immunosuppressive therapy after kidney transplantation. For recipient‐related risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor. Conventional immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant anti‐HLA alloantibodies, and panel reactive antibodies) are being reassessed in light of growing understanding about the role of donor‐specific antibodies (DSA). At the time of transplant, delayed graft function is one of the most clear‐cut risk factors for acute rejection. Extended cold ischemia time (≥24 h) may also play a contributory role. While it is not yet possible to establish conclusively the relative contribution of different risk factors for acute rejection after kidney transplantation, the available data point to variables that should be taken into account at the time of transplant. Together, these offer a realistic basis for planning an appropriate immunosuppression regimen in individual patients.     

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

BACKGROUND: Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. METHODS: We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. RESULTS: Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. CONCLUSION: Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.     

Long term results of living donor kidney transplantation: graft and patient survival

Donor kidney transplantation's graft and patient survivals are better than cadaver donor's. In Spain, living donor kidney transplantation hardly accounts for 1% of transplant activity in comparison to 60% in United States. Accordingly to bibliography, the experience of the Renal Transplant Unit of the Hospital Clinic de Barcelona has demonstrated better graft and receptor survival for living donor recipients. The analysis of 184 living donor kidney transplants and 1678 cadaver donor transplants performed between 1978 and 2002 showed that graft survival was higher in the group of living donors (p < 0.01). At the same time, graft survival was clearly better in receptors of HLA haploidentical grafts (n=142) (p < 0.05). The introduction of new and better immunosuppressive drugs, as well as better diagnostic and therapeutic management of acute rejection, prophylaxis for infections, and control of complications have contributed to better results. The absence of acute rejection between 1978 and 1983 was 45.1%, between 1984 and 1998 was 57.3% and 84.7% between 1999 and 2003. In conclusion, these results demonstrate better graft and patient survival for living donor kidney transplants in comparison with cadaver donor receptors. Altogether with the low risk involved for donors should incentivate authorities, professionals, and patients to promote these therapeutic option by means of adequate information and wider diffusion. Living donor kidney transplantation should contribute together with cadaver kidney transplantation to lessen our long waiting lists, because they are not excluding options.