PRA配型技术在肾移植中的应用研究

目的 探讨群体反应性抗体（PRA）配型新技术对肾移植近远期的效果。方法 854例患者肾移植前运用PRA新技术进行组织配型,并行血浆置换,未采用PRA组配型的423例作为对照,观察肾移植术后免疫指标变化、近期（AR）发生率以及对长期存活的影响。结果 未采用PRA组织配型组发生超急性排斥反应（HR）9例（2.1%)、急性排斥反应198例（47%）;1年人/肾存活率86.7%/76.3%、3年人/肾存活率725%/67.9%、5年人/肾存活率69.5%/d49.3%。采用PRA配型新技术共854例,肾移植术后未发生超急性排斥反应,发生急性排斥反应162例（19.0%),1年人肾存活率达97.3%/49.3% 。采用PRA配型新技术共854例,肾移植术后未发生超急性排搞清反应,发生急性排斥反应162例（19.0%),1年人肾存活率达97.3%/95.0%、3年人肾存活率92.0%/84.2%、5年人/肾存活率87.0%/81.6%。结论 PRA阴性配型可杜绝超急性排斥反应发生,降低急性排斥反应发生率,提高人/肾长期存活率。     

群体反应性抗体技术及HLA配型在1700例肾移植中的应用研究

目的探讨群体反应性抗体(panel reactive antibody,PRA)、HLA配型技术对肾移植近远期的效果。方法对拟行肾移植的患者运用PRA检测、HLA组织配型,要求HLA抗原3~6个位点相合,PRA阳性(20%以上)给予3~5次血浆置换,共1 700例作为第一组,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(cyclosporine A,CsA)用量减至5~7 mg·kg-1·d-1,移植肾功能恢复时间2~16 d,平均5 d,均未发生超急性排斥反应,发生急性排斥反应252例(14.8%),1年人/肾存活率高达98.6%/96.7%,3年人/肾存活率93.1%/87.3%,5年人/肾存活率88.1%/83.6%。第二组肾移植术后CsA用量8~12 mg·kg-1·d-1,移植肾功能恢复时间4~30 d,平均13 d,发生超急性排斥反应者9例(2.1%),急性排斥反应198例(46.8%),1年人/肾存活率86.7%/76.3%,3年人/肾存活率72.5%/67.9%,5年人/肾存活率69.5%/59.3%。结论PRA阴性加良好的HLA配型可杜绝超急性排斥反应的发生,降低急性排斥反应发生率,提高人/肾长期存活率。     

3 102例次尸体肾移植临床分析

目的 对3 102例次尸体肾移植进行临床分析.方法回顾性分析1978年1月～2007年1月3 102例次肾移植受者存活率、主要并发症以及死亡因素,并应用Cox模型对组织配型、免疫抑制剂方案、排斥,再次肾移植等影响因素进行多因素分析.结果 (1)应用钙调神经素抑制剂前、后1、3、5、10年人/肾存活率(%)为65.6/65.6 vs 95.1/94.8, 48.3/48.3 vs 88.4/85.4, 30.1/30.1 vs 78.0/73.2和11.8/11.8vs 66.0/60.6;(2)超急性排斥发生率1997年前后分别为23/1 120 vs 1/1 897;急性排斥反应19.5%,慢性移植物肾病18.9%;(3)多因素分析结果表明,肾功延迟恢复、高龄受者、配型、免疫药物方案、急性排斥、外科并发症等因素可对移植肾的长期存活产生重要影响;(4)肾移植受者死亡的主要原因依次为:心脑血管系统疾病(51.4%),肝功能衰竭(23.1%),严重感染(12.9%),消化道出血(6.9%);(5)HLA供、受者配型、淋巴细胞毒和PRA可明显减少超急性排斥反应,有利于移植肾长期存活.结论尸体肾移植是救治晚期肾功能衰竭患者的有效方法.     

肾移植326例临床分析

目的对1990～2005年间326例次肾移植情况进行临床分析。方法统计肾移植术后受者1、3、5年的人、肾存活率;肾移植主要并发症及其处理原则;影响受者再次移植存活率的因素;HLA抗原/基因配型及群体反应抗体(PRA)检测情况。结果(1)自1990年使用环孢素A(CsA)后1年人、肾存活率(人、肾均存活)为86.33%,3年为80.26%,5年为66..34%;(2)50岁以上肾移植患者102例,1年移植肾存活率83.44%,1年人存活率85.43%;(3)肾移植术后患者心脑血管系统疾病占死亡原因的50.7%,感染占病死率的13.5%;(4)恶性肿瘤的发病率为1.5%。(5)良好的HLA供受者配型可减少术后急性排斥反应的发生率,利于移植肾的长期存活。结论良好的组织配型,肾移植术后免疫抑制药物的合理应用,对移植术后并发症的预防和及时治疗是提高肾移植术后人/肾存活率的重要因素。     

PRA配型技术在致敏受者肾移植术中的应用研究

目的 探讨群体反应性抗体(PRA)配型技术在致敏受者肾移植中的临床效果.方法 应用抗原板(LAT),采用酶联免疫吸附法(ELISA)检测肾移植受者术前的PRA;采用PRA配型技术进行术前配型.结果 12例致敏受者组采用PRA配型技术,肾移植术后肾功能恢复正常,无1例发生超急性排斥反应,术后1个月内急性排斥反应的发生率为25%;同期43例非致敏受者组,术后1个月内急性排斥反应的发生率为18.6%,虽较致敏受者组低,但两组之间差异无统计学意义.结论 PRA配型技术对减少致敏受者肾移植排斥反应,提高移植物存活率具有重要意义.     

再次肾移植的临床特点及治疗体会

目的 分析影响再次移植肾存活率的各种因素,提高再次移植肾的长期存活率.方法 对39例再次肾移植进行回顾性分析.结果 再次肾移植术后1、3、5年移植肾存活率显著低于初次肾移植(分别为76.5%、64.2%、56.5%和87.1%、75.1%、68.2%, P<0.05);群体反应性抗体(PRA)阳性受者术后急性排斥反应发生率高于PRA阴性受者,使用抗体诱导治疗患者术后急性排斥反应发生率低于未用抗体诱导治疗患者.是否切除失功肾对再次移植肾存活率无明显影响.结论 再次移植肾存活率明显低于首次移植.个体高免疫状态是再次肾移植的危险因素,必须更加严格地进行组织配型,进行抗体诱导治疗有利于再次移植肾的存活.如没有排斥反应及并发症的发生,不主张切除原移植肾.     

同种异体肾脏移植20例,胰肾联合移植1例临床报告

目的对19例同种异体肾移植,1例胰肾联合移植资料进行分析、总结。方法统计肾移植术后1年人、肾存活率,人类组织相容性抗原(HLA)供受者之间配型以及群体反应抗体(PRA)检测情况。结果人肾存活率95%/95%,19例恢复工作,1例死亡,未出现外科并发症,术后4例出现加速排斥反应,2例出现急性排斥反应。结论充分的术前准备和高质量的供肾是提高手术成功率的保证;严格的HLA配型和术后合理用药是提高长期存活的关键;免疫抑制剂合理使用可降低感染的发生率。     

尸体肾移植56例临床分析

目的：对56例尸体肾移植资料进行分析、总结。方法：统计肾移植术后受者1年人、肾存活率、人类组织相容性抗原(HLA)供—受者配型及群体反应抗体(PRA)检测情况；肾移植术后主要并发症。结果：1年人、肾存活率92．9％／88．1％，加速性排斥1例，急性排斥(AR)8例(14．3％)，环孢素A(CsA)急性肾中毒1例，无1例出现急性肾小管坏死(ATN)。结论：①受者充分的术前准备和高质量的供肾是提高手术成功率的保证；②严格的HLA配型和术后合理用药是提高存活率的关键；③免疫抑制剂的合理应用使感染发生率明显降低。     

诱导治疗对肾移植急性排斥反应的预防作用

目的观察诱导治疗对肾移植术后急性排斥反应的预防作用。方法45例肾移植患者行术前诱导治疗,其中组反应性抗体(PRA)阴性患者23例,行赛尼哌诱导治疗13例,ALG诱导治疗4例,OKT3诱导治疗6例;PRA阳性患者22例,行赛尼哌诱导治疗11例,ALG诱导治疗5例,OKT3诱导治疗6例。结果45例患者均行肾移植手术。23例PRA阴性患者中,术后3个月内无急性排斥反应发生,一年内急性排斥反应发生率为22%,与同期相同条件患者(26%)比较,差异无统计学意义;22例PRA阳性患者术后无超急排斥反应发生,1例(4.5%)发生加速排斥反应。术后3、6个月内急性排斥反应发生率分别为18.2和27.2%,与同期PRA阳性患者比较,差异无统计学意义;一年内人、肾存活率分别为90.9和81.8%,与术前无诱导治疗的PRA阳性患者(87.0、72.0%)比较,差异有统计学意义(P<0.01)。结论对于PRA阴性患者,诱导治疗预防肾移植术后急性排斥反应的作用不明显,但对PRA阳性患者,诱导治疗能有效预防急性排斥反应的发生,显著提高移植肾的长期存活率。     

双膜滤过治疗降低肾移植患者群体反应性抗体水平的临床观察

目的探讨分子筛治疗对移植肾失功患者群体反应性抗体(panel reactive antibody,PRA)含量及再次肾移植排异反应的影响。方法选择2008年1-12月第三军医大学新桥医院肾内科就诊的初次肾移植后慢性移植肾功能不全合并PRA阳性的移植肾失功患者10例进行5次分子筛治疗,检测PRA、配型的变化,再次肾移植的排异反应。结果与分子筛治疗前[(40.8±6.2)%]比较,PRA水平[(18.8±3.4)%]显著下降(P<0.05)。PRA抗体阳性特异性位点和阳性频率均明显减少。Ⅰ、Ⅱ类抗原配型错配率也显著降低,10例患者接受肾移植均未发生超急性排异反应。结论分子筛治疗可有效减少再次肾移植患者PRA水平和移植肾超急性排异反应。     

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…     

群体反应性抗体技术及HLA配型在1700例肾移植中的应用研究

OBJECTIVE: To evaluate the role of panel reactive antibody (PRA) screening and human leukocyte antigen (HLA) typing in renal transplantation. METHODS: PRA screening and HLA typing were performed in 1 700 patients eligible for the first group of renal transplantation who had 3 to 6 HLA matches in HLA-A, B and DR with the donor, and in cases positive for PRA, plasma exchange was conducted. Another 423 patients who did not receive PRA screening or HLA typing constituted the second group. The changes of immune variables, incidences of acute rejection and the effect of HLA-A, B, DR matching on long-term graft survival were observed. RESULTS: In 1 700 cases of group 1, post-transplantation CsA dose was reduced to 5 to 7 mg*kg(-1)*d(-1) and the graft function recovery time ranged from 2 to 16 d, averaging 5 d. Acute graft rejection occurred in 252 (14.8%) cases, but no hyper-acute rejection was observed. The 1-, 3- and 5-year patient/graft survival rates were 98.6%/96.7%, 93.1%/87.3% and 88.1%/83.6% respectively. In group 2, CsA dose ranged from 8 to 12 mg*kg(-1)*d(-1) and the graft function recovery time was 4 to 30 d, averaging 13 d. Hyper-acute rejection occurred in 9 (2.1%) and acute rejection in 198 (46.8%) cases, and the 1-, 3- and 5-year patient/graft survival rates were 86.7%/76.3%, 72.5%/67.9% and 69.5%/59.3% respectively. CONCLUSIONS: Negative PRA and good HLA matching can eliminate the incidences of hyper-acute rejection, decrease the rate of acute rejection and improve both patient and graft survival rates.     

肾移植患者围手术期群体反应性抗体检测的临床意义

目的:研究肾移植患者围手术期群体反应性抗体(PRA)的水平与移植肾急性排斥的关系。方法:采用ELISA-PRA检测法,对34例尸体肾移植患者进行手术前、术后1周、术后2周、术后1个月血清PRA检测,并分析其结果与肾移植急性排斥的关系。结果:34例患者中,移植前PRA阳性者(PRA)>10％)9例(26.5％),有5例PRA>50％(51％～80％),术前行血浆置换。PRA阴性者25例(73.5％)。PRA阳性组中,有5例发生急性排异,其中2例切除移植肾恢复血液透析。PRA阴性组中,有4例发生急性排异,治疗后肾功能恢复正常。两组相比排异发生率有统计学差异(P<0.05)。术后PRA阳性者11例(术前PRA阴性转阳者2例),发生排异6例(1例为术前PRA阴性)。术后PRA阴性者中,有3例发生排异。两组相比排异发生率有统计学差异(P<0.05)。结论:①患者肾移植术前体内PRA水平对移植肾排异有显著影响;②患者肾移植术后体内PRA水平影响移植肾急性排异的发生和转归。     

Simulect 和 Zenapax 应用于肾移植诱导治疗的5年临床观察

目的评价2剂Simulect和5剂Zenapax在肾移植中诱导治疗预防急性排斥反应(AR)的有效性、安全性以及对近、远期人/肾存活的影响。方法选择1999年4月~2001年4月首次肾移植患者102例,分成Simulect组(54例)和Zenapax组(48例),在三联免疫抑制剂基础上(环孢素A/FK506、骁悉、皮质激素)加用Simulect(术前2h和术后第4天分别予20mg静滴)或Zenapax(1mg.kg-1.d-1,最大剂量100mg,首剂术前2h,此后每2周1剂,共5剂)。观察术后3个月内肾功、AR、移植肾功能延迟恢复(DGF)、急性肾小管坏死情况;术后5年内肾功、排斥反应、并发症及人/肾存活情况。结果术后3个月内AR发生率明显降低(Simulect组:14.8%;Zenapax组:14.6%);首次AR发生时间延迟;激素治疗对大部分AR有效;5年内再次排斥反应发生率为9.3%(Simulect组)和6.3%(Zenapax组)。术后肾功能恢复明显加快,早期及远期肾功能良好。未出现细胞因子释放综合征,仅2例DGF。5年内,感染、糖尿病、高脂血症、恶性肿瘤等未见增加。5年人/肾存活良好,均达95%以上。结论2剂Simulect和5剂Zenapax预防肾移植术后AR的效果好、安全性高,有利于早期肾功能恢复和远期人/肾存活。     

MICA抗体监测在肾移植术后急、慢性排斥反应中的意义

目的探讨肾移植受者的抗MICA抗体水平与急性和慢性排斥反应的相关性及其对移植肾功能的影响。方法采用酶联
免疫吸附方法检测接受同种异体肾移植手术的患者血清中MICA 抗体,并同步检测HLA抗体、肾功血肌酐、尿量及移植肾超声
等临床指标。本研究分两部分分别监测在肾移植术后急、慢性排斥反应中MICA抗体的变化。结果第一部分41例研究对象
中有18例发生急性排斥反应,该组中MICA抗体阳性率高于肾功能稳定组（P<0.05）;MICA抗体阳性组的急性排斥反应发生率
高于MICA抗体阴性组（P<0.05）;术后MICA抗体动态监测时发现,MICA抗体水平逐渐升高2~3 d后出现排斥反应,给予抗排
斥治疗后血肌酐水平逐渐降至正常,MICA抗体水平亦逐渐下降,但仍维持在阳性范围。第二部分40例患者中21例患者出现
慢性排斥反应,其中MICA抗体阳性率明显高于肾功稳定组患者（P<0.05）。慢排组中MICA抗体阳性患者的血肌酐与阴性组
的血肌酐水平比较有统计学差异（P<0.05）。移植肾穿刺病理结果显示MICA抗体阳性患者C4d沉积均为阳性。结论MICA
抗体可预测急性排斥反应的发生及治疗效果,对于及时诊断及治疗排斥反应提供了一个重要指标,同时也是导致慢性排斥的主
要因素之一,可影响移植肾的长期存活。
     

肾移植群体反应性抗体检测641例分析

目的探讨群体反应性抗体检测(PRA)对于肾移植的意义。方法采用ELISA方法对641例肾移植患者进行PRA检测:术前570例、术后71例。结果570例术前检测PRA,阴性490例,术后发生急性排斥反应35例;弱阳性68例,术后发生急性排斥反应36例;12例阳性术后检测仍为阳性,发生急性排斥反应10例。71例术后检测PRA,阴性59例,发生急性排斥反应3例;阳性12例,发生急性排斥反应7例。结论肾移植患者术前检测PRA有助于减少排斥反应的发生。     

Factors affecting the long-term renal allograft survival

Background  In the past decades, the one-year graft survival of cadaveric renal allografts has been markedly improved, but their long-term survival has not kept pace. The attrition rate of renal allografts surviving after one year remains almost unchanged. The causes for late graft loss are multiple. The aim of this study was to analyze the predictive factors that impact long-term survival of grafts after kidney transplantation.

Methods  We retrospectively analyzed 524 kidney transplantation patients who were treated in our hospital between January 1991 and January 2000, including 254 patients who had lived more than 10 years with normal graft function (long survival group), and 270 cases whose renal graft had survived less than 10 years (control group). Specifically, we analyzed 10 factors that may potentially affect graft survival by both univariate and Logistic model multivariate analyses to pinpoint the independent risk factors. 

Results  Univariate analyses showed that no significant differences existed in the age or gender of recipients, dialysis time, lymphotoxin levels, or cold ischemia time between the two groups. However, the ratio of delayed graft function and acute rejection, and the uric acid levels of patients in the long survival group were significantly lower than those in the control group (P <0.01). Furthermore, we found that the concentration of cyclosporin A at one year after transplantation and the histocompatibility antigen match of donor-recipients for patients within the long survival group were significantly higher than those in the control group (P <0.01). Furthermore, multivariate analyses showed that these four factors were independent risk factors that impact patient survival.

Conclusions  The ratios of delayed graft function and acute rejection, the concentration of cyclosporin A at one year after transplantation, and serum uric acid levels are very important factors that affect the long-term survival of renal grafts.

     

肾移植2 200例次临床分析

目的 总结1908例（2200例次）肾移植手术的临床经验,提高肾移植术后人、肾存活率。方法 总结1985年以后人、肾1年、3年、5年的存活率;肾移植主要并发症及其处理原则;影响患者再移植存活率的因素;HLA－抗原／基因配型及群体反应抗体（PRA）检测。结果 （1）自1985年临床使用环孢素A（CSA）后,其1年人、肾存活率为87.3％,3年人、肾存活率为80.2%,5年人、肾存活率为67.0%.(2)50岁以上肾移植患者302例,术后1年移植肾存活率8.4%(252/302),1年人存活率8534%(258/302).(3)肾移植术后患者死亡原因主要是心血管系统疾病及感染。心血管系统疾病占死亡原因的50.7%,感染占死亡率的13.5％（4）。肾移植术后恶性肿瘤 的发病率为1.5％（23／1580）。（5）肝损害患者有独特的药代动力学特点。（6）良好的HLA供－受者配型可以减少肾移植术后急性排斥反应的发生率,有利于移植肾的长期存活。在HLA抗原不配合的情况下,受者应尽量选择不具有免疫原性抗原／基因的供肾移植。（8）对于慢性排斥应应采取综合方法进行治疗。结论 良好的组织配型、肾移植术后免疫抑制药物的合理应用、对移植术后并发症的预防及及时治疗是提高肾移植术后人、肾存活率的重要因素。     

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.     

Expression characteristics of major histocompatibility complex class I-related chain A antibodies and immunoadsorption effect in sensitized recipients of kidney transplantation

Background  Sensitized recipients have a high risk of immunological graft loss due to hyperacute rejection and/or accelerated acute rejection. The presence of major histocompatibility complex class I-related chain A (MICA) antibodies has also been described associated with an increased rate of kidney-allograft rejection. The aim of this study was to describe the expression of MICA antibodies in sensitized recipients of renal transplantation and evaluate its influence on the kidney transplantation recipients.

Methods  A total of 29 sensitized recipients were included in this study. All patients received the MICA antibodies detection before and after protein A immunoadsorption. Panel reactive antibody (PRA), HLA-matches, acute rejection and postoperative one to four-week serum creatinine level were also collected and analyzed, respectively. No prisoners were used in this study.

Results  Eight patients (27.6%) in all 29 sensitized recipients expressed the MICA antibodies but did not show higher acute rejection rate than the non-expressed patients (3/8, 37.5% vs. 8/21, 38.1%; P=1.000). Recipients with PRA >40% showed higher expression levels of MICA antibodies than the recipients with PRA <40% (7/16, 43.8% vs. 1/13, 8.3%; P=0.044). HLA mismatch did not have any effect on the expression of MICA antibodies (P=1.000). MICA antibodies positive group had higher serum creatinine level than the control in postoperative one week ((135.4±21.4) µmol/L vs. (108.6±31.6) µmol/L, P=0.036), but no significant difference in postoperative four weeks ((89.0±17.1) µmol/L vs. (77.1±15.9) µmol/L, P=0.089). MICA antibodies decreased significantly after protein A immunoadsorption.

Conclusions  MICA antibodies increase in the sensitized recipients, which have significant effects on the function of allograft in early postoperative period. Protein A immunoadsorption can decrease MICA antibodies effectively in sensitized recipients.