HLA抗体筛选技术的最新进展及其在器官移植中的应用

人类白细胞抗原(HLA)是介导器官移植排斥反应的主要因素,良好的组织配型是肾移植患者长期存活和术后移植肾功能恢复的重要条件之一。在多次输血、生育史、再次移植的受者受到同种HLA免疫致敏可产生群体反应性抗体(panelreactive antibody,PRA)。PRA是一组特定的人类白细胞抗原(HLA)抗体,有多种类型,包括HLA-A、B、C、DR、DQ等抗体[1],是造成超急性和加速性排斥反应和移植物丢失的危险因素之一。PRA水平的高低更直接地影响移植肾的近期存活率。因此,将抗体筛选技术应用于器官移植实践,对减少移植后排斥反应,提高移植成功率和移植…     

再次免疫应答导致肾移植后早期严重急性体液排斥反应

背景：国内外有关预防高致敏受者肾移植后发生超急性、急性排斥反应提高人肾存活率取得满意效果,然而临床对群体反应性抗体检测阴性既往致敏受者肾移植后发生再次免疫应答研究则罕见报道。 目的：探讨群体反应性抗体阴性的既往致敏受者肾移植后早期发生严重急性体液性排斥反应机制,为其早期诊断和治疗既提供参考依据。 方法：选择21例群体反应性抗体阴性术后早期发生严重急性体液性排斥的首次肾移植患者,动态分析移植后14 d内反映急性体液性排斥的相关指标,包括IgG型抗HLA抗体,病理苏木精-伊红染色、C4d及细胞表面分子原位检测。 结果与结论：21例患者既往均有输血或妊娠史;18例患者移植后第7天抗HLAⅠ类IgG抗体阳性率>80%,11例于移植后第7天抗HLA Ⅱ类IgG抗体> 80%;5例女性患者于移植后第5~8天发生移植肾破裂,抗HLAⅠ类和Ⅱ类IgG抗体均>96%;21例受者均检出抗供者特异性抗体(DSA),13例(61.90%)供、受者存在HLA-A2和HLA-A11的错配并产生对应DSA,包括5例移植肾破裂受者;病理组织形态学均有不同程度急性损伤,免疫组化可见管周毛细血管区(PTC)C4d沉积,原位染色CD34(+)、CD68(+)、CD4(+)。提示移植前群体反应性抗体监测不能完全反映受者的预致敏状态;移植后早期监测群体反应性抗体可预测和诊断既往致敏受者急性体液性排斥的发生;C4d、CD68(+)作为其的辅助诊断指标,可提高诊出率;HLA-A2和HLA-A11在既往致敏受者是高危致敏基因。     

非HLA 抗体在肾脏移植中作用的研究进展

肾移植术后产生的抗体与移植肾排斥反应密切相关,并影响移植肾长期存活。近年来非HLA 抗体在肾移植 领域越来越受到关注。尽管对非HLA 抗体的研究并不全面,然而实验及临床研究均发现针对某些非HLA 抗原诸如血管紧张 素1 类受体、基底膜聚糖、自身抗原等产生的抗体能够影响移植肾急性及慢性排斥反应的进程。非HLA 抗体影响移植肾排斥 反应及存活的潜在机制是目前研究的重要领域之一。本文针对肾移植领域主要的非HLA 抗体做一综述,并阐述其对移植物 的致病机制。鉴别出非HLA 介导的移植肾抗体性排斥反应的免疫表型,有利于为治疗移植肾抗体性排斥反应提供新的靶点, 并为提高移植物的长期存活提供有效策略。     

活体亲属肾移植患者HLA配型配合率的分析

HLA配型在肾移植的应用对提高肾移植的长期存活率及对抗HLA抗体高敏感患者的肾移植具有重要意义.良好的HLA配型是维持移植器官长期存活的必备因素之一,对预测移植肾的长期存活具有一定的临床意义.本研究对亲属肾移植供受者HLA配型的配合率进行了调查.     

群体反应性抗体（PRA）检测—附180例报告

本文研究了群体反应性抗体(PRA)对肾移植的影响,发现PRA 是免疫应答抗体,高PRA 与严重排斥反应强关联,亦是丧失移植肾的重要指征,并讨论了PRA 和CDC 作为HLA 组织配型对肾移植中提高人/肾双存活率的应用意义,证实PRA 比CDC 敏感性高。     

初次等待肾移植患者产生群体反应性抗体的因素分析

背景：移植前后群体反应性抗体的存在与否是影响移植肾存活率及肾功能的重要因素之一。 目的：分析研究初次等待肾移植手术的患者产生群体反应性抗体的因素。 方法：检测1 674例初次等待肾移植患者群体反应性抗体。根据患者肾移植前的输血史和妊娠史,将患者分单纯输血组(n=509)：输血均为全血,输血量为200 mL以上;单纯妊娠组(n=397);输血+妊娠组(n=235);未输血未妊娠组(n=533)。 结果与结论：初次等待肾移植的患者中,群体反应性抗体阳性患者单纯输血组88例,阳性率为17.29%(88/509);单纯妊娠组33例,阳性率8.31%(33/397);输血+妊娠组64例,阳性率27.23%(64/235)。结果提示,单纯妊娠导致群体反应性抗体产生的概率较低,其阳性率并不随着妊娠次数的增加而增加;其次是输血的的影响,女性患者移植前输血产生群体反应性抗体的概率高于男性;既输血又妊娠的患者群体反应性抗体产生概率大于单纯输血或单纯妊娠患者;既未输血又未妊娠的患者一般不会产生群体反应性抗体。     

亲属肾移植后群体反应性抗体的调查

背景:亲属肾移植后产生群体反应性抗体的频率如何,对术后移植肾功能和长期存活是否有影响,目前国内尚无相关报道。目的:调查亲属肾移植后群体反应性抗体产生的频率,为预测亲属肾移植长期存活提供参考资料。方法:纳入2005-03/2007-10收治的亲属肾移植患者54例,分别于移植后一两年内再次检测群体反应性抗体及血肌酐、尿素氮浓度。群体反应性抗体检测采用美国Onelanmbda公司提供的酶联免疫吸附法筛选HLA-Ⅰ类、Ⅱ类混合抗原板。血肌酐和尿素氮检测数据由检验科提供。结果及结论:54例亲属肾移植患者中有7例移植后产生了抗体,占12.96%。其中6例产生了抗HLA-Ⅱ类抗体,仅1例产生了抗HLA-Ⅰ,Ⅱ类抗体。在此7例患者中6例为初次肾移植,且肾移植前群体反应性抗体均阴性;1例为再次肾移植,移植前抗HLA-Ⅱ抗体阳性。1例具有抗HLA-Ⅰ+Ⅱ类抗体和2例高强度抗HLA-Ⅱ类抗体的患者血肌酐和尿素氮浓度均超过正常水平,而另外4例出现低水平抗HLA-Ⅱ类抗体的患者血肌酐和尿素氮浓度则在正常水平。结果提示,具有抗HLA-Ⅰ+Ⅱ类抗体和高效价抗HLA-Ⅱ类抗体影响亲属肾移植患者的肾功能,而低效价的抗HLA-Ⅱ类抗体并不影响亲属移植肾功能。     

HLA配型和DSA对移植肾功能的影响研究

器官移植中良好的供受者间HLA配型对预防移植肾早期排斥和移植肾的长期存活具有重要意义.肾移植术后发生排斥的重要因素之一是群体反应性抗体(PRA)的参与,特别是肾移植术后产生抗供者特异性抗体(DSA).因此本文对肾移植供受者HLA分型和DSA对移植肾急性排斥反应和近期肾功能进行研究.现报道如下. 材料和方法 一般资料:选择了2007年10月至2009年12月间在我院接受肾移植的128例患者,男性88例,女性40例;最大年龄63岁,最小年龄20岁.     

高PRA介导肾移植后延迟性超急排斥反应

目的：了解HLA-A、B、DR、DQ表现型为纯合子的终末期肾脏疾病患者的PRA水平,并研究其与肾移植预后的关系。方法：对2006年8月至2007年8月间在我院登记等待首次肾移植的438例终末期肾脏疾病患者HLA、PRA情况以及其中1例PRA65的HLA纯合子患者肾移植效果进行分析。HLA基因分型采用PCR-SSP技术,PRA、抗体强度及抗体特异性分析采用ELISA技术,数据统计采用SPSS11.5统计软件。结果：438例患者中有HLA纯合子12例,杂合子426例;12例纯合子中PRA阳性者6例,阳性率50,平均HLA抗体强度为55,广泛致敏率达100;426例杂合子中PRA阳性者65例,阳性率15.26,平均HLA抗体强度为28,广泛致敏率为40;纯合子与杂合子之间的PRA阳性率、平均HLA抗体强度和广泛致敏率相比差异均有统计学意义（P〈0.05）,纯合子高PRA的风险大（OR=5.29,95CI：1.67～16.70）;1例PRA65的纯合子患者术前经血浆置换、蛋白免疫吸附、静滴丙种球蛋白治疗使PRA降低至阴性,在舒莱免疫诱导下行尸体肾移植术,供受者HLA抗原2个错配,术后移植肾功能逐渐恢复,第3天开始PRA呈阳性并逐渐升高,伴随临床逐渐出现尿少、血压升高、移植肾区疼痛等排斥反应征象,血清肌酐逐渐升高,移植肾B超见动脉阻力指数逐渐升高,提示急性排斥反应,采用术前有效清除HLA抗体的所有方法再次治疗无效,于术后第36天因移植物失功行移植肾切除。结论：HLA纯合子产生高PRA的风险大;文中1例PRA阳性的HLA纯合子早期移植肾功能恢复随后出现不可逆排斥反应致移植肾失功的情况,提示近年来随着各种有效清除HLA抗体的治疗方法不断用于临床导致了抗体介导的延迟性超急排斥反应（AMDR）的出现从而使移植肾失功;高PRA患者行肾移植术需高度慎重,应尽可能避开受者PRA峰值时的全部抗体谱来选择供体。     

无血缘夫妻活体供肾7例肾移植

背景：通过诱导移植受体产生供-受体嵌合体或免疫耐受以利于受体长期存活,一直是器官移植的研究热点,并且在实验动物模型中获得了大量成功的经验和知识。在临床实践中也观察到结婚多年的夫妻,丈夫-妻子器官移植后排斥反应小,具有比其他的亲属器官移植有更多的优点。 目的：回顾性分析无血缘关系的活体供肾移植—丈夫对妻子供肾移植的临床效果。 方法：选择7例夫供妻活体肾移植,供者年龄 32~58岁,受者年龄 31~56岁,双方婚龄在5~36年。供、受者 ABO血型完全相同者 4例,O-B 1例,O-A 1例,A-AB型 1例。淋巴细胞毒交叉配合试验阴性。HLA配型情况：1个抗原错配 1例,2个抗原错配 2例,3个抗原错配3例,4抗原错配 1例。开放手术取肾,6例左肾,1例右肾。术后采用三联免疫抑制方案：环孢素A/他克莫司+麦考酚酸吗乙酯+泼尼松预防排斥反应,7对供受者随访3~70个月。 结果与结论：手术成功率100%,供受者均未发生手术相关并发症,所有供者血压、尿常规及肾功正常,受者及移植肾全部存活。验证了虽然移植前组织配型结果较差,但由于夫妻间长期生活在一起产生的免疫耐受,使夫供妻肾移植后排斥反应小、移植效果理想,具有比其他的亲属肾移植有更多的优点。     

B-Cell crossmatching and kidney allograft outcome in 9031 United States transplant recipients

The predictive power of a positive B-cell crossmatch remains controversial due to the presence of cofactors, such as sensitization and human leukocyte antigen (HLA) mismatch levels. UNOS OPTN/Scientific Registry data were analyzed on 9031 cadaveric kidney graft recipients who were B-cell crossmatched during 1994 and 1995 for graft outcome. This 2-year time period was chosen so that most US transplant recipients in this study would have had a similar regimen of immunosuppression consisting of prednisone, Sandimmune, and azathioprine The two patient groups that were analyzed were B-pos (n = 336) and B-neg (n = 8,695). All T-cell crossmatches were negative. Data analyzed included donor-recipient demographics, sensitization levels, B-cell crossmatch techniques, histocompatibility mismatching, graft rejection incidence, early graft loss, cause of graft failure, and statistical analyses (univariate and multivariate) in primary and repeat graft recipients. Significant factors in both crossmatch groups included pretransplant transfusions, peak and most recent class I PRA levels, a previous kidney graft, histocompatibility mismatching at HLA-A plus -B, urine in first 24 h, and rejection incidence between discharge and 6 months post-transplantation. Class II antibody specificities and panel reactive antibody (PRA) levels were not available from the UNOS database. Fifty-seven percent of 15,896 (1994-1995) transplant recipients (n 9031) were B-cell crossmatched, and 336 of 9031 recipients (3.7%) were transplanted with a B-pos crossmatch. Sixteen percent of B-pos recipients experienced early graft loss (< 6 months) compared with 11% of B-neg recipients (p < 0.001). Both primary and repeat grafts with B-pos crossmatches experienced an increase in rejection incidence (p = 0.023) and early graft loss (p < 0.001). In the sensitized (PRA > 10%) recipient subset (n = 2,789), both primary (n = 93) and regraft (n = 52) recipients with B-pos crossmatches had a higher incidence of early graft loss at 3 months, p < 0.001 and p = 0.016, respectively. HLA-DR mismatch levels in both patient groups were not different (p = 0.109). There was a 68% increase in the odds of 3-month graft loss in B-pos versus B-neg recipients (multivariate logistic regression analysis p = 0.054, 95% confidence interval 0.99-2.85). In conclusion, a B-pos crossmatch in primary and regraft recipients, including a sensitized subset, is predictive of inferior kidney graft outcome.     

The role of HLA matching in renal transplantation: experience from one center

The influence of serology-based HLA matching on the risk of acute rejection episodes and of graft loss was analyzed in a material of 678 living donor (LD) and 997 cadaveric donor (CD) renal transplantations performed in our center in the period 1989-97. In LD transplantation, recipients of HLA-identical sibling grafts had the lowest rejection risk and the best graft survival, with a half-life estimate of 30 years. One-HLA-haplotype mismatched grafts did better than two-haplotype mismatched related or unrelated donor grafts. Matching for HLA-DR significantly reduced the rejection risk of one-haplotype mismatched grafts. In CD first transplants, HLA-DR matched grafts had a lower incidence of rejection and better survival than HLA-DR mismatched grafts. Expected half-life for HLA-DR matched grafts was 12 years compared to less than 7 years for HLA-DR mismatched grafts. The effects of matching for HLA-A and -B did not reach statistical significance. In CD regrafts, a two-antigen mismatch for HLA-A or -DR led to a significantly poorer graft survival, but the panel-reactive antibody (PRA) status of the recipient was the most influential factor. In CD renal transplantation, we conclude that organ allocation based on matching for HLA-DR 1-14 is effective and not too difficult to obtain even in centers with a short patient waiting list.     

Does cyclosporine influence the results of cadaver retransplantation?

The results of cadaveric retransplantation in 55 recipients immunosuppressed with cyclosporine and prednisone were compared to 156 recipients of primary renal allografts. By 3 yr posttransplant, there is no significant difference in patient survival, but the yearly graft survival for primary (79%, 72%, 72%) as compared to retransplant (69%, 58%, 58%) recipients was significantly (p less than 0.05) better. There was no significant difference in rejection episodes or mean +/- SD serum creatinine (mg/dl) at 2 yr between primary (32%, 2.14 +/- 1.1) and retransplant (33%, 2.08 +/- 1.4) patients, respectively. Donor source, third kidneys, human leukocyte antigen AB and Dr matching, percent reactive antibody levels, and cause of first graft loss do not have significant impact on cyclosporine-treated retransplant outcome. However, retransplant patients who have lost a previous graft in less than 3 months continue to be at high risk for subsequent early graft loss. These results suggest that the combination of cyclosporine and prednisone is the preferred regimen for cadaveric retransplantation.     

Platelet-specific alloantigens in cadaveric renal transplantation. A prospective study. Effect of HPA-5b mismatch in acute vascular rejection of renal allografts

This prospective study comprised 166 renal allograft-recipient pairs that were studied for human platelet alloantigens (HPA) 1-3 and 5, which have been shown to be expressed by adhesion molecules of the vascular endothelium. Four of the five (80%) HPA-5a5a regraft recipients developing acute vascular rejection (AVR) had received an HPA-5b-incompatible graft in contrast to one of the 32 (3%) regraft recipients without rejection. The occurrence of AVR was not explained by the degree of HLA mismatches. All four regraft recipients of an HPA-5b-mismatched graft with AVR were HLA-A3,B7, and the combination of HLA-A3 and/or B7 match and an HPA-5b-mismatched graft was associated with AVR. No antibodies against HPA-5b were detected in the patients with AVR of an HPA-5b-mismatched graft. These preliminary findings suggest that HPA-5b is a minor histocompatibility antigen involved in the development of AVR.     

CPRA for allocation of kidneys in the US: More candidates ≥98% CPRA,lower positive crossmatch rates and improved transplant rates for sensitized patients

In 2009 calculated panel reactive antibody (CPRA) replaced PRA as the metric for HLA sensitization in the US kidney allocation system. During the next four years, registrants with at least one unacceptable antigen increased (34–40%) and registrants with ≥98% PRA/CPRA increased from 7% to 9% of the waitlist. These changes were accompanied by a reduction in kidney offers refused for positive crossmatch: 14,137 (1.7%) in 2009 and 3,310 in 2013 (0.4%). Registrants with ≥98% PRA/CPRA had highest rates of refusal but also showed substantial improvement (20% in 2009 vs 8% in 2013). For registrants with ≥98% PRA/CPRA, 45% of accepted offers in 2009 were not transplanted into the intended recipient compared to 11% in 2013. Transplant rates remained low for these patients (∼50/1000 active patient-years), but rates improved for patients with 80–97% PRA/CPRA (223/1000 active patient-years in 2009 vs 354/1000 in 2013). In 2013, 40% regraft candidates had CPRA ≥98% compared to 4% of primary graft candidates. More females than males were ≥98% CPRA (14% vs 7%) and more females had CPRA above 0 (50% vs 28%). In the CPRA era, listing of unacceptable antigens increased, positive crossmatches were diminished and transplant rates for sensitized patients improved.     

Survival in end-stage diabetic renal disease. A prospective study of 100 kidney transplant patients

The results of renal transplantation in patients with diabetes mellitus were studied in 100 consecutive patients transplanted between Dec. 1972 and June 1982. The study period was divided into two parts, 1972-76 (era I, 21 patients, 18 with juvenile onset diabetes) and 1977-82 (era II, 79 patients, 72 with juvenile onset diabetes). A group of 168 non-diabetic patients, aged 20-54 years, receiving primary grafts during the same period served as controls to the 72 juvenile onset diabetics from era II. The three-year actuarial patient survival of transplanted diabetics improved from 48% during era I to 76% during era II and was then not significantly inferior to that of the non-diabetic controls. The three-year actuarial graft survival rate was significantly higher for recipients of kidneys from living related donors than for those who had received kidneys from cadaveric donors (CD) among both diabetic and non-diabetic patients. However, the three-year graft survival rate was significantly higher (56%) for non-diabetic than diabetic CD recipients (37%). The overall survival in diabetes mellitus was strongly influenced by the outcome of retransplantation during era II (12 patients). Thus, 69 patients were alive, 64 with a functioning graft, at the end of the observation period.     

The modern potential of histocompatibility in clinical kidney transplantation

To many clinicians, the improvement of cadaveric kidney graft survival, achieved in the last decade, has become a reason to reconsider the importance of HLA matching in renal transplantation under modem conditions. Nevertheless, there still are arguments to continue selecting donors on the basis of HLA compatibility. Single-center cadaveric renal transplantation data were used to calculate graft survival rates by Kaplan-Meyer analysis and to create the Cox model of the probability of seven-year transplanted kidney survival. One-year and seven-year survival rates for 362 cadaveric kidneys transplanted in 1996-2004 were 83.1% and 60.7%, respectively. One-factor analysis found five factors--HLA-DR compatibility, common HLA epitope compatibility, HLA-DQl compatibility, the replacement of Azathyoprine with Cellsept, and donor's age--to have significant effect on transplant survival rate. All these factors were used as variables in a highly significant (p < 0.00001) multifactor Cox model of graft survival. The summary influence of histocompatibility factors on renal graft survival was found to be as high as 86% compared to 6% related to Cellsept and 8% related to donor's age. These results show that histocompatibility is still the main factor favoring the survival of cadaveric renal allograft.     

前群体反应性抗体对肾移植长期存活的影响

目的：分析术前PRA水平与肾移植长期存活之间的关系 。方法：收集我中心2001年1月至2014年6月间,接受首次肾移植术的1 162例受者临床资料,根据受者术前PRA水平分组,将PRA≤10%分为阴性组,PRA>10%为阳性组,并对其进行回顾性分析。结果：术前PRA阴性者1、5、10年人存活率为96.8%、89.4%、78.6%,阳性者为93.5%、81.6%、65.4%,而术前PRA阴性者1、5、10年肾存活率为95.9%、84.8%、63.1%,阳性者为92.3%、74.1%、51.9%,两组移植人/肾间生存曲线均有统计学差异（人/肾log-rank检验χ²=9.623/11.019,P=0.002/0.001）。Cox多因素回归分析显示PRA水平是影响人/肾存活的重要因素（P<0.001）,PRA与术后急性排斥反应发生相关（OR=8.25,95% CI=2.86-5.72, P）。术前PRA阴性受者术后5年、10年血肌酐均较术前PRA阳性者低,具有统计学差异（P<0.05）,而两者术后1年血肌酐无统计学差异。此外,PRA与术后抗供体特异性抗体（DSA）出现相关（OR=6.89,95% CI=4.52-9.17, P）。结论：PRA是肾脏移植术前筛选致敏受者的重要指标,术后更应注重PRA阳性受者急性排斥反应及DSA的监测和诊断。<0.05<0.001     

Post transplant development of MICA and anti-HLA antibodies is associated with acute rejection episodes and renal allograft loss

This study was undertaken with the primary aim of analyzing the clinical relevance of posttransplant appearance of anti-human leukocyte antigen (HLA) and major histocompatibility (MHC) class I related chain A (MICA) antibodies in response to live related donor (LRD) renal transplantation. A total of 185 consecutive post renal transplant recipient serum samples were analyzed for the detection of anti-HLA by enzyme-linked immunoabsorbent assay (ELISA) and MICA antibodies using Luminex techniques. Patients with IgG HLA class I antibodies had more acute rejection episodes compared to the negative group (67% vs. 20%, chi(2) = 7.95, p = 0.005) and also had poor graft survival (44% vs 86%, chi(2) = 6.67, p = 0.01). Similarly, patients with anti-HLA class II antibodies also had significantly lower graft survival and a higher number of rejection episodes as compared to the antibody negative group (p = 0.002 and p = 0.000, respectively). Following transplantation, 30 patients (16%) developed antibodies against any of the MICA alleles (MICA*001, MICA*002, MICA*004, MICA*008, or MIC*009). The graft survival was significantly compromised in these patients as compared to the negative group (60% vs 86%, chi(2) = 10.26, p = 0.001). Further, patients carrying both antibodies (MICA+/HLA+) were the worst affected and showed significantly poor graft survival as compared to the MICA-/HLA- group (17% vs 89%, chi(2) = 19.63, p = 0.000). Similarly, patients with only MICA antibodies or those with only HLA antibodies also had significantly lower graft survival and a higher number of acute rejection episodes (p = 0.035 and p = 0.001, respectively) as compared to the nonsensitized group. The study illustrates that posttransplant monitoring of antibodies to both MICA as well as HLA could be an important prognostic marker in renal transplant subjects.     

Pediatric Liver Transplantation Outcomes in Korea

Pediatric liver transplantation is the standard of care for treatment of liver failure in children. The aim of this study was to identify the characteristics of pediatric liver transplantation in centers located in Korea and determine factors that influence outcomes. This retrospective study was performed using data from between 1988 and 2010 and included all recipients 18 yr old and younger who underwent pediatric liver transplantation in Korea during that period. Our data sources were hospital medical records and the outcome measure was overall patient survival. Univariate and multivariate statistical analyses were undertaken using the Cox proportional hazards model. Five hundred and thirty-four pediatric liver transplantations were performed in 502 children. Median age and average pediatric end-stage liver disease (PELD) score were 20 months and 18 point, respectively. Biliary atresia (57.7%, 308/534) was the most common cause of liver disease. Eighty-two (15.3%) were deceased donor liver transplantations and 454 (84.7%) were living donor liver transplantations. Retransplantation was performed in 32 cases (6%). Overall, 1-, 5-, and 10-yr patient survival rates were 87.8%, 82.2%, and 78.1%, respectively. In multivariate analysis, independent significant predictors of poor patient survival were chronic rejection and retransplantation. This study presents the epidemiologic data for nearly all pediatric liver transplantation in Korea and shows that the independent prognostic factors in patient survival are chronic rejection and retransplantation.