ABO血型不相容肾移植5例临床报告并文献复习

目的:探讨ABO血型不相容肾移植临床效果并进行相关文献复习。方法:回顾性分析2017年5月～2018年12月在我院施行的5例ABO血型不相容肾移植供受者的临床资料。基于受者初始血型抗体效价水平,采用利妥昔单抗、血浆置换和免疫抑制剂相结合的个体化脱敏治疗方案。结果:经个体化脱敏治疗,5例受者在肾移植手术当天血型抗体IgM、IgG效价水平均≤1∶8,其中4例于术后2周内未出现血型抗体效价反弹,患者肾功能顺利恢复至正常,同时在围手术期未出现明显凝血功能障碍;随访至今患者移植肾功能稳定。1例于术后第3天血型抗体效价出现反弹,考虑发生血型抗体导致的急性抗体介导排斥反应,临床综合治疗后效果差,于术后第9天行二次肾移植手术(公民逝世后器官捐献供肾,血型相容),随访至今移植肾功能稳定。结论:根据血型抗体效价水平采用利妥昔单抗、血浆置换和免疫抑制剂相结合的个体化脱敏治疗进行ABO血型不相容肾移植是安全、可行的。     

ABO血型不相容亲属活体肾移植23例报告

目的 探讨ABO血型不相容（ABOi）亲属活体肾移植的临床疗效和安全性。方法 回顾性分析23例ABOi亲属活体肾移植受者的临床资料。术前根据受者的初始血型抗体滴度,采取不同的个体化预处理方案,包括口服免疫抑制药+利妥昔单抗,或口服免疫抑制药+血浆置换和（或）血浆双重滤过+利妥昔单抗等,监测预处理前、后,肾移植术前及术后的血型抗体滴度和围手术期移植肾功能、相关并发症。并随访移植肾功能及相关并发症。结果 23例ABOi亲属活体肾移植受者中,除1例术中出现超急性排斥反应,其余22例血清肌酐水平恢复良好。围手术期并发症包括4例淋巴瘘、1例尿瘘、1例肾周血肿合并T细胞介导的排斥反应、6例泌尿系统感染、1例急性肾小管坏死、1例急性胰腺炎、1例血型抗体反弹、1例原发病复发,经治疗均痊愈。截止至随访日,22例受者的移植物和受者存活率均为100%,移植肾功能良好。随访期间血型抗体滴度均≤1:8。随访期并发症包括2例严重肺部感染、1例抗体介导的排斥反应、2例原发病复发、1例淋巴囊肿、1例泌尿系统感染、1例带状疱疹、1例BK病毒尿症和2例血糖异常。结论 根据不同血型抗体水平选择个体化预处理方案,可以安全地实...     

ABO血型基因与移植肾急性排斥反应相关性的研究

目的 探讨ABO血型基因与移植肾急性排斥反应(AR)的相关性.方法 采用引物特异性聚合酶链式反应(PCR-SSP)技术检测2009年5月至2010年2月87例肾移植受者及其对应的48例供者ABO(A1、A2、B、O1、O2)血型基因,分析供受者ABO血型基因相合组与错配组受者AR发生、治疗及转归情况.结果 PCR-SSP测定ABO血型基因推定的表型和血清学方法测定ABO血型表型完全相符.供受者ABO血型基因相合组受者50例,发生AR 6例,经甲泼尼龙(MP)冲击治疗后临床逆转.ABO血型基因错配组受者37例,发生AR 11例,经MP冲击治疗后,临床逆转10例,周期性反复发生AR 1例.错配组与相合组受者AR发生率差异有统计学意义(29.7%与12.0%,P<0.05).错配组1例A2O1血型基因受者接受A1O1血型基因供肾后,受者血清检测发现抗A1抗体,抗体效价IgG 1:64,IgM 1:16,移植术后3～10个月周期性反复发生AR,且周期逐渐变短,激素疗效逐渐降低,术后1年SCr达441μmol/L.结论 检测供受者HLA时同步检测ABO血型基因具有很强的可行性.A2血型基因受者适宜选择O型供肾.供受者ABO血型基因错配是介导肾移植术后AR的危险因素,检测供受者ABO血型基因,降低ABO血型基因错配率对预防AR有一定的临床意义.     

ABO血型不相容肾移植术后并发过客淋巴细胞综合征一例并文献复习

正供肾来源短缺是目前制约肾移植发展的主要瓶颈,ABO血型不相容肾移植(ABO-incompatible kidney transplantation,ABOi-KT)是缓解供肾来源短缺的重要方式之一。已有部分终末期肾病患者接受ABOi-KT,且术后生存率逐步提高。少数行ABOi-KT的受者术后并发过客淋巴细胞综合征(passenger lymphocyte syndrome,PLS),主要表现为移植术后血红蛋白短期内迅速下降,其原因为供者来源淋巴细胞分泌的血型抗体针对受者抗原产生免疫反应,引起以     

高致敏Rh阴性受者二次接受Rh阳性供肾移植一例

正近年来,随着Rh血型不合肾移植的开展,如何确保术后移植肾长期存活已成为肾移植领域的重要课题[1]。我国Rh阴性血型较罕见,故Rh阴性肾移植受者寻找同型供肾非常困难。近年来,国内部分移植中心已有多例关于Rh阴性受者成功接受Rh阳性供肾移植的报道[1-2],但群体反应性抗体(panel reactive antibody,PRA)高敏Rh阴性受者二次接受Rh阳性供肾移植国内尚未见报道。本研究回顾性     

致敏患者经双滤过法血浆分离方案预处理后行肾移植的临床效果分析

目的 分析致敏患者经双滤过法血浆分离(DFPP)方案预处理,并联合使用抗CD25单抗诱导治疗后行肾移植的临床效果和安全性.方法 回顾性分析2000年11至2012年1月45例致敏受者在肾移植前经DFPP方案预处理,并联合使用抗CD25单抗诱导治疗后接受肾移植的临床资料.所有受者预处理前的群体反应性抗体(PRA)水平均大于20％,为(56.5±19.9)％,预处理后PRA水平降至(18.9±19.1)％.受者与供者的HLA抗原错配数为(2.1±0.7)个,术前2次供、受者淋巴细胞毒交叉配型试验均为阴性.所有受者术后至少随访1年,观察术后1年受者和移植肾存活率,以及排斥反应和肺部感染的发生情况.结果 随访期间,无受者死亡,有2例受者发生移植肾功能丧失,术后1年受者存活率为100％(45/45),移植肾存活率为95.6％ (43/45).术中肾血管开放后1例发生超急性排斥反应,发生率为2.2％,受者在切除移植肾后恢复血液透析;术后发生急性排斥反应12例,发生率为26.7％(12/45),经甲泼尼龙和(或)ATG冲击治疗后,11例完全逆转,1例出现移植肾功能丧失而恢复血液透析.术后肺部感染发生率为8.9％(4/45),经抗感染治疗后均好转,未发生重症肺部感染.结论 肾移植前采用DFPP 预处理,并联合使用抗CD25单抗诱导治疗安全有效,能使致敏受者获得良好的肾移植效果.     

肾移植术后早期移植肾失功的危险因素分析

目的探讨肾移植术后发生早期移植肾失功的危险因素。方法回顾性分析35例肾移植术后2个月内发生移植肾失功患者（失功组）和同期70例未发生移植肾失功患者（对照组）的临床资料,应用单因素分析和多因素逐步Logistic回归分析找出导致早期移植肾失功的危险因素和独立危险因素,得出回归方程,并计算该模型判断有危险因素病例的早期移植肾失功的准确率。结果单因素分析表明,两组间供肾的热缺血时间、冷缺血时间、供肾血管异常、受者术前群体反应性抗体（panel reactive antibody,PRA）水平、供受者之间人类白细胞抗原（human leucocyte antigen,HLA）位点错配数是影响肾移植术后早期移植肾失功的危险因素（P〈0.05-0.01）。多因素逐步Logistic回归结果提示供受者之间HLA位点错配数、受者术前PRA水平、供肾冷缺血时间是早期移植肾失功的独立危险因素,其优势比分别为7.823、5.389和1.259（P〈0.05-0.01）。由此得出回归方程为：Y=-8.544＋2.057X1＋1.684X2＋0.230X3,该模型对具有危险因素的病例发生早期移植肾失功的预测准确率为80%。结论供受者之间HLA位点错配数、受者术前PRA水平、供肾冷缺血时间是肾移植术后早期移植肾失功的高危因素。     

心脏死亡器官捐献供肾移植单中心60例经验总结

目的 探讨单中心DCD供肾移植的临床效果,总结DCD供肾移植的经验.方法 回顾性分析2011年12月至2013年4月间60例DCD和112例DCD供肾移植的临床资料.结果 依据《中国心脏死亡器官捐献指南》,实施DCD 60例,共捐献肾脏118个,实施肾移植112例.14例受者术后发生移植肾功能延迟恢复(DGF),发生率12.5％,其中未使用LifePort机械灌注冷保存DGF发生率23.1％ (6/26),使用LifePort移植肾DGF发生率9.3％(8/86).14例DGF受者4例切除移植肾,10例肾功能术后16～52 d恢复正常.急性排斥反应发生率6.3％(7/112),其中1例术后第12天移植肾破裂切除肾脏,其余经治疗后逆转.1例受者术后第15天因急性心肌梗死亡,1例术后第7天发生急性心功能衰竭死亡.移植肾存活的105例受者,随访1～15个月,移植肾功能正常.结论 在我国实施DCD切实可行,是符合伦理和我国国情的器官来源根本途径.DCD供肾移植临床效果良好,Lifeport具有清除肾脏残余微血栓、疏通肾脏微血管、评估肾脏功能及预防DGF的良好作用.     

致敏受者移植肾存活率和抗HLA抗体的临床观察

目的观察致敏受者与非致敏受者移植肾存活率的差别,以及移植肾功能与抗HLA抗体变化的关系。方法纳入中山大学附属第一医院器官移植中心2000年4月至2008年12月间行肾移植后资料完整受者1309例。根据受者术前ELISA检测群体反应性抗体（PRA）的结果将受者分为50%≤PRA≤100%组（n=35）、10%≤PRA〈50%组（n=47）和PRA〈10%组（n=1227）。所有供受者采用PCR序列特异性引物进行HLA分型。运用标准HLA配型和氨基酸残基配型。采用Kaplan-Meier法对3组受者术后存活率进行组间生存分析。分析肾移植后抗HLA抗体的变化及其与移植肾功能和HLA错配的关系。结果随着随访时间增加,3组移植肾累积存活率均有下降。在术后3年内3组移植肾存活率差异较小（P〉0.05）,3年后3组移植肾存活率差异有统计学意义（P〈0.05）。10%≤PRA≤100%受者移植肾累积存活率显著低于PRA〈10%受者（P〈0.05）,50%≤PRA≤100%受者移植肾累积存活率也显著低于10%≤PRA〈50%受者（P〈0.05）。12例移植肾失功的受者中7例（58.3%）出现抗体增强,62例移植肾功能正常的受者中仅8例（12.9%）出现抗体增强,两者差异有统计学意义（P〈0.05）。出现新生抗体的受者抗体谱中,大多数包含有针对错配抗原的抗HLA抗体。结论无论是供者特异性还是非供者特异性抗体,抗HLA抗体的存在及其效价都会影响移植肾的存活。术后抗HLA抗体的变化与移植肾功能有关。     

心脏死亡器官捐献供肾与传统尸体供肾肾移植的疗效比较

目的 比较心死亡器官捐赠(DCD)供肾与传统尸体供肾肾移植的疗效.方法 回顾性分析单中心2007年2月至2012年6月的69例DCD供肾肾移植受者的资料,并根据受者年龄(相差10岁以内)、移植次数和免疫抑制剂应用情况,按1∶2的比例匹配同期138例传统尸体肾移植受者,进行资料比较.结果 DCD肾移植组术后移植肾功能恢复延迟(DGF)和原发性移植肾无功能(PNF)的发生率为29.0％和2.9％,而传统尸体肾移植组为13.8％和0,差异有统计学意义(P＜0.05).Kaplar-Meier分析结果表明,DCD肾移植组术后6个月、1年和3年的移植肾存活率分别为95.7％、95.7％和93.3％;而传统尸体肾移植组分别为97.8％、97.8％和96.8％,两组的差异无统计学意义(P＞0.05).两组受者存活率的差异也无统计学意义(P＞0.05).术后7和14d,DCD肾移植组的移植肾肾小球滤过率低于传统尸体肾移植组(P＜0.05),但术后1个月至1年,两组移植肾肾小球滤过率的差异无统计学意义(P＞0.05).结论 虽然术后DGF和PNF发生率较高,但DCD肾移植的长期疗效与传统尸体肾移植相当,DCD供肾可以作为替代传统尸体供肾的良好来源.     

Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation

ABO blood group incompatible renal transplantation, using desensitization procedures, is an effective strategy. Efforts have been made to reduce desensitization: these are usually applied to all patients indiscriminately. The Guy's Hospital ABO blood group incompatible desensitization regimen uses a tiered approach, tailoring strategy according to initial antibody titres. Sixty‐two ABO blood group incompatible living donor transplant recipients were compared with 167 recipients of blood group compatible living donor renal transplants. There were no statistically significant differences in allograft survival rates at 1 or 3 years post‐transplant, rejection in the first year post‐transplant or renal function in the first 3 years post‐transplant. There was a higher rate of death in ABO blood group incompatible transplant recipients – this could be associated with differences in age and HLA mismatch between the two groups. Four ABO blood group incompatible patients experienced antibody‐mediated rejection (no episode was associated with a rise in ABO blood group antibodies). Of the patients who received no desensitization, or rituximab alone, none has experienced antibody mediated rejection or experienced allograft loss. Tailoring the use of desensitization in ABO blood group incompatible renal transplantation according to initial ABO blood group antibody titres led to comparable results to blood group compatible transplantation.     

Successful living donor renal transplantation despite ABO incompatibility and a positive crossmatch

Potential live kidney donors have been rejected when the prospective recipients are blood type or crossmatch incompatible. By utilizing plasmapheresis combined with intravenous immune globulin (PP/IVIg) prior to surgery, donor-specific antibodies against blood group or human leukocyte antigens (HLA) have been removed, thereby allowing successful renal transplantation. A 26-yr-old male with a panel reactive antibody level of 100% and repeated positive crossmatches against deceased donor kidney offers, including zero HLA mismatched donors, successfully underwent ABO-incompatible kidney transplantation from his HLA-identical but nevertheless crossmatch-incompatible sister. The initial anti-A blood group isoagglutinin titers were 128, 256, and 1024 at room temperature, 37 degrees C, and 37 degrees C anti-IgG enhanced, respectively. With an individualized PP/IVIg regimen based on donor-specific antibody titer, however, the relevant antibodies were adequately reduced and hyperacute rejection avoided. Subsequent antibody-mediated rejection, likely directed against a minor histocompatibility antigen, was diagnosed on postoperative day 7 and successfully treated. Neither ABO, or crossmatch incompatibility, or both in combination prohibit kidney transplantation.     

Equivalent Outcomes for Pediatric Heart Transplantation Recipients: ABO‐Blood Group Incompatible versus ABO‐Compatible

ABO‐blood group incompatible infant heart transplantation has had excellent short‐term outcomes. Uncertainties about long‐term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO‐incompatible recipients. ABO‐incompatible (n = 35) and ABO‐compatible (n = 45) infant heart transplantation recipients (≤14 months old, 1996–2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor‐specific antibodies against blood group antigens, in only two ABO‐incompatible patients were these antibodies implicated in antibody‐mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow‐up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO‐blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO‐compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor‐specific isohemagglutinins and the implications for graft accommodation are warranted.     

Increasing the supply of kidneys for transplantation

Kidney transplantation confers a survival advantage for patients with end-stage renal disease (ESRD) when compared to dialysis and improves the quality of life in a cost-effective manner. Currently there are more than 60,000 patients on the U.S. waiting list for kidney transplantation. In 2004, 16,879 kidney transplants, including 880 simultaneous kidney and pancreas transplants, were performed in this country. Recent strategies for increasing the supply of kidneys hold promise, such as systematic programs designed to improve consent rates for deceased donor organ procurement. Efforts to increase donation after cardiac death (DCD) have been highly successful and now account for more than 5% of all deceased organ donors. Transplantation of kidneys from DCD donors yields 1-year graft and patient survival rates equivalent to kidneys from brain-dead donors. Expanded criteria donor (ECD) kidneys from donors > or = 60 years of age (or donors age 50-59 years with certain comorbidities) confer a survival benefit for end-stage renal disease (ESRD) patients compared to remaining on dialysis on the waiting list. The number of live donor kidney transplants, both from biologically related and unrelated donors, is increasing. Paired live donor kidney transplants provide yet another transplantation opportunity for ESRD patients with willing but incompatible (by ABO or direct antibody) living donors.     

Acquired Downregulation of Donor‐Specific Antibody Production After ABO‐Incompatible Kidney Transplantation

The mechanism of long‐term B cell immunity against donor blood group antigens in recipients who undergo ABO‐incompatible (ABOi) living‐donor kidney transplantation (LKTx) is unknown. To address this question, we evaluated serial anti‐A and anti‐B antibody titers in 50 adult recipients. Donor‐specific antibody titers remained low (≤1:4) in 42 recipients (84%). However, antibodies against nondonor blood group antigens were continuously produced in recipients with blood type O. We stimulated recipients' peripheral blood mononuclear cells in vitro to investigate whether B cells produced antibodies against donor blood group antigens in the absence of graft adsorption in vivo. Antibodies in cell culture supernatant were measured using specific enzyme‐linked immunosorbent assays (ELISAs). Thirty‐five healthy volunteers and 57 recipients who underwent ABO‐compatible LKTx served as controls. Antibody production in vitro against donor blood group antigens by cells from ABOi LKTx patients was lower than in the control groups. Immunoglobulin deposits were undetectable in biopsies of grafts of eight recipients with low antibody titers (≤1:4) after ABOi LKTx. One patient with blood type A1 who received a second ABOi LKTx from a type B donor did not produce B‐specific antibodies. These findings suggest diminished donor‐specific antibody production function in the setting of adult ABOi LKTx.     

Underutilization of A2 ABO incompatible kidney transplantation

Redfield RR, Parsons RF, Rodriguez E, Mustafa M, Cassuto J, Vivek K, Noorchashm H, Naji A, Levine MH, Abt PL. Underutilization of A2 ABO incompatible kidney transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01543.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: ABO compatibility creates a disadvantage for O and B renal allograft candidates. A2 ABO incompatible transplant may decrease waiting times and generate equivalent graft survival to an ABO compatible transplant. Methods: Death‐censored graft survival was compared between A recipients and O, B, and AB recipients of an A2 allograft with multivariate Cox regression models utilizing data from the United Network of Organ Sharing (UNOS) between 1997 and 2007. Results: Eighty‐five percent of A2 kidneys were transplanted into ABO compatible recipients vs. 15% into ABO incompatible recipients. Rates of A2 incompatible kidney transplants did not increase over the study period (14.8% to 14.6%). Mean wait time for A2→O kidneys was 337 vs. 684 d for O→O and for A2→B kidneys, 542 vs. 734 d for B→B. Adjusted relative risk of graft loss at five‐yr was similar between O, B, and AB recipients compared to A recipients of an A2 allograft, corresponding to a five‐yr graft survival of 84%, 86.2%, 86.1%, and 86.1%, respectively. Conclusion: A2 incompatible kidney transplantation is underutilized. Graft outcomes are similar among A2 compatible and incompatible recipients. Shorter waiting time and improved access might be achieved if A2 kidneys are considered in all blood groups.     

幼儿心脏死亡器官捐献单侧供肾成人肾移植的临床研究

目的总结幼儿心脏死亡器官捐献(donation after cardiac death,DCD)单侧供肾成人肾移植的手术经验,探讨其临床效果及安全性。方法 1例5岁8个月幼儿DCD提供了两个供肾,分别为两例成人受者做肾移植手术。总结术中、术后管理经验,随访1年,监测移植肾功能、移植肾大小的变化及并发症的发生情况。结果供肾大小:右肾长径8.0cm、短径3.0cm、宽径4.0cm,左肾长径8.2cm、短径3.1cm、宽径4.3cm。2例受者均为50kg以下的女性。采用单肾右髂窝移植,手术方式及术后免疫抑制方案与成人供肾移植相同。受者的血清肌酐(Scr)分别于术后10d和30d降至正常水平,估算肾小球滤过率分别于术后15d和50d增加至稳定水平(>50ml/min),移植肾各径长度在2周内达到稳定水平并接近成人肾大小。随访至交稿日,两受体的肾功能、尿量均正常,无发生蛋白尿及并发症。结论 5岁左右的幼儿DCD单侧供肾用于成人肾移植,在选择合适受者的前提下具有良好的临床效果和安全性。     

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis

Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49–0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90–1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72–4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl ].     

ABO incompatible kidney transplantation

PURPOSE OF REVIEW: Although ABO incompatible kidney transplantation is increasingly recognized as effective, the procedure is still evolving. The purpose of this review is to summarize recent advances in this area. RECENT FINDINGS: Short to intermediate-term outcome appears good, although long-term results are still preliminary. Pretransplant risk stratification based on antidonor antibody titer may be of limited value. Splenectomy, previously reported to be an important component of ABO incompatible transplantation, appears to be avoidable under many circumstances. The wider implementation of A2 blood group incompatible transplantation shortens waiting time for deceased donor transplantation of blood group B recipients without significantly disadvantaging others. The diagnosis of acute humoral rejection has become clearer following the recognition that C4d deposition commonly occurs in well functioning ABO incompatible allografts. The long-term implications of acute humoral rejection appear substantial even following successful acute therapy, with a significant percentage of patients developing chronic humoral rejection manifested as transplant glomerulopathy. Finally, although ABO incompatible transplantation entails increased expense, when compared with maintenance dialysis and taking into account the health related quality of life benefits of a successful transplant, it is clearly cost effective. SUMMARY: ABO incompatible kidney transplantation is an effective therapy, and will become more widely implemented in the future.     

ABO-incompatible kidney transplantation

When a renal transplant candidate's only medically-acceptable living kidney donor is ABO incompatible, the most common practice is to place them on the deceased donor list. Over the past few years, the implementation of paired kidney donor exchange programs and the development of protocols to overcome the ABO blood group barrier have become much more successful and widespread. Here we review the therapeutic options for patients whose only living kidney donor is ABO incompatible, with a specific emphasis on the rationale for and the current outcomes of ABO incompatible living donor kidney transplantation.