供者特异性活化T细胞频度预测肾移植急性排斥反应

背景：提高移植后排斥反应风险预报的准确性,可为移植后个体化使用免疫抑制剂提供参考。目的：寻找一种能定量分析供受者间免疫反应强度的方法来预测急性排斥反应。方法：对同种异体尸肾移植的患者115例采用前瞻性分析,用ELISPOT法检测移植前分泌γ-干扰素的供者特异性活化T细胞的频度,观察随访期内有无急性排斥及肺部感染,并观察HLA错配与急性排斥的关系。结果与结论：115例群体反应性抗体阴性肾移植受者中有25例发生急性排斥反应,发生急性排斥反应患者的供者特异性活化T细胞频度高于未发生急性排斥反应者（P〈0.01）,而HLA-I、II及总的错配数比较,差异均无显著性意义（P〉0.05）。提示,通过移植前对产生γ-干扰素的供者特异性活化T细胞频度的检测,可预测急性排斥反应,对潜在供者进行选择。     

抗供者特异性抗体与肾移植后的急性排斥反应

目的:大部分肾移植失败的患者体内都存在抗HLA抗体.检测抗供者特异性HLA抗体在肾移植受者体内的表达,并分析其在预测排斥反应中的作用.方法:2006-10/2008-03郑州人民医院器官移植科采用酶联免疫吸附法检测179例肾移植受者血清中的抗供者特异性HLA抗体以及群体反应性抗体水平,群体反应性抗体>10%为阳性,群体反应性抗体阳性受者即致敏受者.检测移植后2个月内早期急性排斥反应的发生率,统计分析群体反应性抗体及抗供者特异性HLA抗体与移植后早期急性排斥反应的关系.结果:肾移植前血清抗供者特异性HLA抗体阳性50例受者的急性排斥反应率发生率为66%,移植前血清群体反应性抗体阳性56例受者的发生率为25%,两者比较差异具有显著性意义(P<0.01),抗供者特异性HLA抗体水平与急性排斥反应的发生具有更强的相关性.移植前血清抗供者特异性HLA抗体阳性受者的急性排斥反应发生率显著高于抗供者特异性HLA抗体阴性受者(66%,11%,P<0.01).体内含抗HLA-Ⅱ类抗体受者的急性排斥反应发生率显著高于含HLA-Ⅰ类抗体的受者(78.1%,43.8%,P<0.05).结论:抗供者特异性HLA抗体是肾移植前筛选致敏受者的重要指标,抗供者特异性HLA抗体阳性患者移植后更容易发生急性排斥反应.     

肾移植术后尿液DYZ-1检测的临床意义

背景:对移植受者尿液成分进行定期监测可以作为判断移植肾功能、状态的一种方法.目的:分析肾移植受者尿液中供者细胞出现与急性排斥反应的关系及临床意义.方法:选取60例供者为男性、受者为女性的肾移植受者,分为移植后早期检测组40例、急性排斥组10例、移植后功能稳定组10例.定期提取尿液中细胞DNA,利用PCR检测Y染色体上特异的基因片段DYZ-1.结果与结论:在手术第1日受者的尿液中可检测到供者细胞DNA,随着时间的延长,尿液中供者细胞DNA量逐渐减少,至术后1个月,有8例受者的尿液中供者细胞DNA消失,其中1例发生急性排斥反应;另外32例受者的尿液中仍有供者细胞DNA的出现,其中7例发生了急性排斥反应;存活3个月以上发生急性排斥反应10例患者,7例尿液标本中能检测到供者细胞DNA,对急性排斥者进行治疗后1个月,71.4%转为阴性;而在稳定期的10例肾功能良好受者,仅1例受者尿液中DYZ-1基因阳性.提示对肾移植受者尿中供者细胞DNA的进行定期检测,可以作为监测急性排斥反应发生及预后的一种手段.     

肾移植排斥反应的早期诊断与新疗法

进修医生肾移植后排斥反应是怎样引起的呢？教授肾移植后排斥反应是由于供、受体间的组织相容性不好引起的，受体免疫系统识别供体抗原后发生一系列的细胞免疫和体液免疫反应，该过程有局部和全身性免疫反应参与。肾移植后受者的T细胞进入移植肾内，与供者不相容的组织相容性抗原接触，T细胞被活化，释放多种细胞因子，如：白细胞介素（IL）－２，IL－４，干扰素γ（IFN－γ）等，导致T、B细胞的活化和增殖，产生大量细胞毒性T细胞和特异性抗体、巨噬细胞被活化，共同破坏移植肾。排斥反应是导致肾移植失败的原因之一。进修医生肾移植…     

肾移植后急性体液排斥反应:5年同一机构296例随访

背景:肾移植后急性体液排斥反应虽然发生率不高,但对移植物功能恢复可造成严重影响,是移植物早期丢失的主要原因.目的:分析肾移植后急性体液排斥反应早期诊断和防治的意义.方法:选择接受肾移植后规律随访的受者296例,其中移植前群体反应性抗体阳性受者26例,阴性受者270例.酶联免疫吸附试验动态监测肾移植受后外周血中的群体反应性抗体和供者特异性抗体,免疫组织化学染色观察穿刺活检组织中C4d的沉积及浸润淋巴细胞表面分子标记,按Banff 2005标准结合临床相关指标诊断急性体液排斥反应.结果与结论:26例移植前群体反应性抗体阳性受者中6例(23%)移植后发生了急性体液排斥反应,270例阴性受者中19例(7%)发生了急性体液排斥反应,差异有显著性意义(P < 0.01).发生急性体液排斥反应的患者中22例(88%)外周血清中检测到供者特异性抗体,271例无急性体液排斥反应的患者中仅1例检出供者特异性抗体,差异具有显著性意义(P < 0.01).急性体液排斥反应受者中C4d阳性率为80%,未发生急性体液排斥反应的患者C4d阳性率仅为6.7%,差异具有显著性意义(P < 0.001).肾移植后早期监测群体反应性抗体和供者特异性抗体水平,通过穿刺活检观察移植肾组织中的C4d沉积情况,可及时诊断急性体液排斥反应,有效改善移植物功能并提高移植物存活率.     

肾移植受者血清中抗供者特异性抗体检测及预测排斥反应的意义

目的 研究肾移植受者体内的HLA致敏状态以及抗供者特异性抗体在预测排斥反应中的作用。方法 提取供者的HLA特异抗原,用ELISA法检测受者血清中抗供者特异性抗体（DSA）,结合群体反应性抗体（PRA）检测结果及临床急性排斥反应的发生进行统计分析。结果 肾移植前血清DSA阳性的受者,急性排斥反应发生率（63．2％）远高于DSA阴性的受者（14．7％）（P〈0．01）;术后DSA阳性的受者排斥反应的发生率也升高;DSA随着PRA水平的升高阳性率也增加（P〈0．01）。结论 抗供者特异性抗体对临床筛选供体、预测术后排斥反应及提高移植物的存活率有重要意义。     

抗供者特异性抗体对致敏肾移植受者的临床意义

背景:应用灵敏的技术可以检测到致敏肾移植患者体内低水平抗体,但是即便如此临床上依然无法完全检测出全部抗体.目的:探讨抗供者特异性抗体对致敏肾移植受者的临床意义及其在预测排斥反应中的作用.方法:肾移植术前常规检测补体依赖淋巴细胞毒试验和群体反应性抗体,群体反应性抗体阳性者(PRA≥10%)检测抗供者特异性抗体,其术后临床结果与抗供者特异性抗体阴性患者做比较.结果与结论:在379例接受肾移植的患者中,55例患者的群体反应性抗体≥10%,这些患者中75%曾有过致敏史.其中20例检测出抗供者特异性抗体,这些阳性患者肾移植术后更易发生急性排斥反应,移植肾功能恢复延迟和移植肾存活率低下等.结果提示抗供者特异性抗体的存在与移植物失功、排斥反应有显著相关性.而体内仅存非抗供者特异性抗体的患者移植效果相对好.对于淋巴细胞毒试验阴性但体内抗供者特异性抗体阳性的肾移植患者,术后需要更积极地监测免疫功能和调整免疫抑制方案.     

肾移植患者抗人类白细胞抗体配型与术后急性排斥反应及移植肾存活的关系

背景:群体反应性抗体可介导超急性排斥反应,导致群体反应性抗体阳性致敏患者肾移植成功率和移植物存活率均低于非致敏患者.目的:根据人类白细胞抗原交叉反应组配型标准为群体反应性抗体阳性致敏肾移植患者选配合适供者,观察移植后急性排斥反?发生率及移植肾存活情况.设计:病例观察.单位:南方医科大学珠江医院.对象:选择1997-01/2003-12在南方医科大学珠江医院器官移植科施行肾移植136例群体反应性抗体阳性的致敏受者,男41例,女95例,年龄(45±9)岁.初次肾移植115例,2次移植18例,3次移植2例,4次移植1例.所有受试对象均对检测项目知情同意,实验经过医院伦理委员会批准.LAT莱姆德抗原板和LAT-Mix混合抗原板购自美国One Lambda公司.SMT72R抗人类白细胞抗原-1类单克隆抗体湿板和人类白细胞抗原-Ⅱ类DNA分型试剂购自美国One Lambda公司.方法:以酶联免疫吸附试验动态监测患者手术前后IgG型抗人类白细胞抗原抗体水平及其特异性.应用抗人类白细胞抗原-Ⅰ类单克隆抗体湿板进行供、受者人类白细胞抗原-Ⅰ类抗原分型,微量序列特异性引物法进行供、受者人类白细胞抗原-Ⅱ类基因分型,根据美国器官共享网制定的人类白细胞抗原交叉反应组配型标准和Ⅱ类抗原可接受性错配原则进行供、受者选配.评估抗原交叉反应组配型原则下患者移植术后急性排斥反应发生率及移植肾1,3,5年存活率进行评价.主要观察指标:①致敏患者手术前后抗人类白细胞抗原抗体水甲及特异性.②供受者人类白细胞抗原组织配型.③肾移植术后急性排斥反应发生率及移植肾存活率.结果:纳入136例PRA阳性致敏患者均进入结果分析,无脱落者.①致敏患者中104例存在抗人类白细胞抗原-Ⅰ类IgG抗体,76例存在抗人类白细胞抗原-Ⅱ类IgG抗体,44例同时存在抗人类白细胞抗原-Ⅰ类和Ⅱ类IgG抗体.②按照传统人类白细胞抗原配型标准供、受者人类白细胞抗原0,1,2,3,4个抗原错配者分别为7,26,47,39和17例;按照人类白细胞抗原交叉反应组配型标准供、受者人类白细胞抗原抗原0,1,2,3,4个抗原错配者分别为31,53,36,16和0例.③按人类白细胞抗原交叉反应组配型原则,人类白细胞抗原无错配者的急性排斥反应发生率明显低于2个和3个抗原错配者,差异有统计学意义(P<0.05),人类白细胞抗原无错配者移植肾1,3,5年存活率高于2个和3个抗原错配者,差异有统计学意义(P<0.05).结论:①人类白细胞抗原交叉反应组配型标准能提高肾移植供受者的相配率.②良好的人类白细胞抗原配型可降低肾移植术后急性排斥反应的发生率,提高移植肾的存活率.     

未致敏肾移植受者术前不做交叉配型的可行性分析

目的探讨未致敏肾移植受者术前不做交叉配型的可行性和安全性。方法回顾性分析了96例未致敏肾移植受者群体反应性抗体（PRA）术前淋巴细胞毒配型结果，并对75例未致敏肾移植受者PRA术前不做交叉配型，直接行肾移植术。结果96例未致敏肾移植受者术前交叉配型结果均为阴性，75例术前未做交叉配型的肾移植受者未发生超急性排斥反应或加速性排斥反应，手术同时或术后行回顾性交叉配型，结果均为阴性。结论未致敏肾移植受者PRA无针对供者错配抗原特异性HLA抗体的受者移植术前可以不做交叉配型。     

供者特异性抗体对肾移植术后患者急性排斥和肾功能的影响研究

目的研究抗供者特异性抗体(DSA)对移植肾急性排斥反应和近期肾功能的影响。方法采用MicroAMS HLA-III供者特异性抗体检测试剂盒检测96例肾移植患者术后排斥及恢复期2个时间点的DSA,同时检测移植肾功能。结果①96例肾移植患者有8例肾移植术后出现DSA,占8.33%(8/96)。②8例DSA阳性患者6例发生急性排斥反应,其中5例为抗HLA-I类抗体,1例为抗HLA-II类抗体;未发生急性排斥反应的2例为抗HLA-II类抗体。移植肾功能恢复时,仍有2例DSA-I类弱阳性。③DSA阳性对肾移植术后排斥和肾功能均有影响。结论 DSA是预测肾移植术后发生急性排斥反应的有效方法之一。     

高度致敏受者行肾移植术的临床研究

目的探讨高度致敏（下称高敏）肾移植受者的组织配型和抗排斥治疗方案。方法对81例高敏肾移植受者的人类白细胞抗原（HLA）抗体、HLA配型和肾移植结果进行回顾性分析。结果81例受者共行肾移植术85次。术后发生超急性排斥反应（HAR）6例（7．1％）；急性排斥反应（AR）17例（21．0％），其中急性体液性排斥反应（AHR）9例（11．1％）。经抗胸腺细胞球蛋白（ATG）、血浆分离（PP）和静脉注射大剂量免疫球蛋白（IVIG）等治疗后均逆转。AR组术前峰值群体反应性抗体（PRA）（58．6±12．4）％，抗原错配（2．9±1．3）个；未发生AR组术前峰值PRA（60．5±14．5）％，抗原错配（1．9±0．8）个。两组PRA值差异无统计学意义（P〉0．05），抗原错配数差异有统计学意义（P〈0．01）。结论避开相应抗体的良好HLA配型（HLA错配数小于或等于2个）是高敏受者肾移植成功的关键。高敏受者术后AHR的发生率高，采用ATG、PP、IVIG联合治疗能有效逆转AHR。     

肾移植患者群体反应性抗体水平与移植肾急性排斥的关系

背景:目前众多实例和资料证实,群体反应性抗体的存在与否及该抗体的致敏程度对于是否发生排斥反应及移植物存活率的高低、移植后器官功能的实现都有着重要意义.目的:检测肾移植受者术前、术后群体反应性抗体水平,并结合患者临床排异情况,分析肾移植患者术前、术后群体反应性抗体水平与急性排斥反应的关系.设计、时间及地点:回顾性病例分析,于1998-09/2000-05在北京首都医科大学附属北京友谊医院泌尿科肾移植研究室完成.对象:选择在北京友谊医院接受肾移植的633例患者,男348例,女285例,年龄16～67岁.方法:采用美国One Lambda 公司和德国Biotest公司淋巴细胞冷冻板,检测患者术前和术后一两个月内血清中的群体反应性抗体.主要观察指标:术前及术后患者群体反应性抗体水平、临床排斥反应发生情况.结果:移植前群体反应性抗体阴性591例,移植后群体反应性抗体阳性164例,61例术后发生急性排斥反应,占10.3%;移植前群体反应性抗体阳性42例,移植后30例发生了急性排斥反应,占71.4%,12例未发生急性排斥反应.肾移植术前群体反应性抗体阴性与阳性术后发生排斥反应比较差异有非常显著性意义(P < 0.001);肾移植前后群体反应性抗体均为阴性患者427例,术后24例发生了急性排斥反应,占5.6%;肾移植后群体反应性抗体阳性164例,70例发生了急性排斥反应,占42.7%.肾移植前群体反应性抗体阴性与术后群体反应性抗体阳性并发生排斥反应的比较差异有非常显著性意义(P < 0.001).术前群体反应性抗体阴性和阳性与术后排异与否的相关系数为0.612,术后群体反应性抗体阴性和阳性与术后排异与否的相关系数为0.685,二者在P=0.01水平有明显相关性.结论:群体反应抗体对预测移植肾的急性排斥反应具有重要的意义.术前、术后群体反应性抗体阳性患者,术后发生急性排斥的概率较高;而术前、术后群体反应抗体阴性的患者发生急性排斥的概率较低.     

异基因造血干细胞移植前巩固化疗对第一次形态学完全缓解且微小残留病阴性中/高危急性髓系白血病患者预后的影响

目的探讨异基因造血干细胞移植(allo-HSCT)前巩固化疗对第1次形态学完全缓解且微小残留病阴性(CR1/MRD-)中/高危急性髓系白血病(AML)患者预后的影响。方法对2010年1月至2019年3月在CR1/MRD-状态下接受allo-HSCT的155例中/高危AML(不含急性早幼粒细胞白血病)患者进行回顾性分析。结果全部155例患者中,102例获得CR1/MRD-后接受移植前巩固化疗(巩固组),53例获得CR1/MRD-后直接行allo-HSCT(非巩固组),两组中位年龄分别为39(18~56)岁、38(19~67)岁。巩固组、非巩固组移植后5年总生存率分别为(59.3±7.5)%、(62.2±6.9)%(P=0.919),无复发生存率分别为(53.0±8.9)%、(61.6±7.0)%(P=0.936),累积复发率分别为(21.9±5.4)%、(18.3±6.0)%(P=0.942),非复发死亡率分别为(22.4±4.3)%、(28.4±6.5)%(P=0.464)。多因素分析显示,移植前是否接受巩固化疗及其疗程(<2个/≥2个)对预后无显著影响。结论中/高危AML患者可在获得CR1/MRD-后直接进行allo-HSCT。     

Impact of alloantibody strength in crossmatch negative DSA positive kidney transplantation

Objectives

The clinical relevance of pre-transplant “low-level” donor specific anti-HLA antibodies (DSAs) in crossmatch negative kidney transplant recipients remains unclear. To determine what level of DSA associates with antibody mediated rejection (AMR) could be the way to measure the clinical relevance of pre-transplant “low-level” donor specific anti-HLA antibodies (DSAs) in crossmatch negative kidney transplant recipients.

Design and methods

A retrospective analysis of 221 patients from October 2008 to December 2009 was included in this study. Sera were obtained pre-transplant and two weeks post-transplant and tested for DSA using LABScreen single antigen beads.

Results

Among the 221 patients, 11 experienced AMR within 200 days after transplant (5%). Pre-transplant DSA was associated with AMR at multiple mean fluorescence intensity (MFI) cutoffs (500, 1000, 2000, 3000, 5000; p = 0.003, 0.001, 0.007, 0.003, and 0.003, respectively). No correlation was seen between acute T-cell mediated rejection (CMR) and pre-transplant DSA at any of the same MFI cutoffs. There was an increased risk of AMR with higher levels of pre-transplant DSA. Finally, an increase in DSA MFI from pre- to two weeks post-transplant was indicative of a higher probability of AMR.

Conclusion

Overall, this data supports using the single antigen bead to detect “low-level” DSA both pre- and post- as having a positive and persistent DSA may be predictive of higher AMR rates and poorer graft survival.     

Donor-specific ELISPOT assay for predicting acute rejection and allograft function after kidney transplantation: A systematic review and meta-analysis

Acute rejection remains an important problem after kidney transplantation. Enzyme-linked immunosorbent spot (ELISPOT) assay has been investigated extensively and has shown promising results as a predictor of allograft rejection. The objective of this study was to systematically review and analyze the predictive value of the donor-specific ELISPOT assay to identify recipients at risk for acute rejection. Electronic databases were searched for studies reporting donor-specific ELISPOT and kidney transplantation outcomes. Odds ratio (OR) for acute rejection was calculated, along with standardized mean difference (SMD) of cytokine producing-cells between recipients with and without acute rejection. Pooled estimates were calculated using random-effect models. The positive ELISPOT cutoff frequencies were extracted from each study. From 665 articles found, 32 studies were included in the meta-analysis. IFN-γ was the most investigated cytokine (30 out of 32 studies). Patients with positive pre-transplantation donor-reactive IFN-γ ELISPOT had an OR of 3.3 for acute rejection (95%-CI 2.1 to 5.1), and OR of 6.8 (95%-CI 2.5 to 18.9) for post-transplantation ELISPOT. Recipients with rejection had significantly higher frequencies of pre- and post-transplantation cytokine producing-cells (SMD 0.47, 95%-CI 0.07 to 0.87 and SMD 3.68, 95%-CI 1.04 to 6.32, respectively). Pre-transplantation ELISPOT had a positive predictive value of 43% and a negative predictive value of 81% for acute rejection. A positive ELISPOT result was associated with a lower estimated glomerular filtration rate (SMD −0.59, 95%-CI −0.83 to −0.34). In conclusion, patients with a high frequency of donor-reactive IFN-γ ELISPOT are at higher risk for acute rejection. The donor-specific IFN-γ ELISPOT assay can serve as an immune-monitoring tool in kidney transplantation.     

肾移植受者血清sCD30水平与移植后急性排斥反应发生的关系

目的探讨肾移植前后血清中sCD30水平与移植术后急性排斥反应的关系。方法利用ELISA试剂盒检测62例肾移植受者移植前、移植后3,7,21 d血清中sCD30的水平。结果肾功能衰竭患者移植前血清sCD30水平比正常人高(P<0.0001);移植后发生急性排斥的受者移植前血清sCD30水平较未发生急性排斥者高(P=0.01);术后第3,7 d sCD30的水平与急性排斥反应的发生有明显的相关性(P<0.01),而未发生排斥反应的患者sCD30则很快下降。术后第21 d肾移植受者的sCD30水平基本已降至正常水平,与正常对照组比较无统计学意义(P>0.05)。结论提示肾移植前及移植后7 d内测定sCD30水平有助于预测术后发生急性排斥的风险。     

Time to reach tacrolimus maximum blood concentration,mean residence time, and acute renal allograft rejection: an open-label, prospective, pharmacokinetic study in adult recipients

OBJECTIVES: The aims of this study were to determine whether disposition-related pharmacokinetic parameters such as T(max) and mean residence time (MRT) could be used as predictors of clinical efficacy of tacrolimus in renal transplant recipients, and to what extent these parameters would be influenced by clinical variables. METHODS: We previously demonstrated, in a prospective pharmacokinetic study in de novo renal allograft recipients, that patients who experienced early acute rejection did not differ from patients free from rejection in terms of tacrolimus pharmacokinetic exposure parameters (dose interval AUC, preadministration trough blood concentration, C(max), dose). However, recipients with acute rejection reached mean (SD) tacrolimus T(max) significantly faster than those who were free from rejection (0.96 [0.56] hour vs 1.77 [1.06] hours; P < 0.001). Taking into account that neither differences in tacrolimus steady-state clearance nor T(1/2) could explain this unusual finding, we used data from the previous study to calculate MRT from the concentration-time curves. RESULTS: As part of the previous study, 100 patients (59 male, 41 female; mean [SD] age, 51.4 [13.8] years;age range, 20-75 years) were enrolled in the study The calculated MRT was significantly shorter in recipients with acute allograft rejection (11.32 [031] hours vs 11.52 [028] hours; P = 0.02), just like T(max) was an independent risk factor for acute rejection in a multivariate logistic regression model (odds ratio, 0.092 [95% CI, 0.014-0.629]; P = 0.01). Analyzing the impact of demographic, transplantation-related, and biochemical variables on MRT, we found that increasing serum albumin and hematocrit concentrations were associated with a prolonged MRT (P < 0.05). Conversely, serum albumin and hematocrit concentrations were significantly lower in recipients with acute rejection (P < (101). CONCLUSIONS: In this selected population of de novo renal allograft recipients, a shorter tacrolimus T(max) and calculated MRT were associated with a higher incidence of early acute graft rejection. These findings suggest that a shorter transit time of tacrolimus in certain tissue compartments, rather than failure to obtain a maximum absolute tacrolimus blood concentration, might lead to inadequate immunosuppression early after transplantation.     

合并危险因素肾移植受者18例应用西罗莫司的观察

评价服用环孢素A肾移植受者合并危险因素时,应用西罗莫司为主要免疫抑制剂的临床效果及安全性.纳入应用标准的18例受者,将环孢素A转换为以西罗莫司为主要免疫抑制剂的抗排斥治疗,环孢素A在1周内迅速撤除,西罗莫司的目标血药浓度为5～8 μg/L,随访观察移植肾功能、并发症和不良反应.环孢素A转换为西罗莫司时距移植后时间为5～108个月,随访4～31个月,发生急性排斥反应1例,经甲基泼尼松龙冲击治疗后逆转;环孢素A相关肾毒性4例,转换后血清肌酐均正常;慢性移植肾肾病5例,1例发生移植肾失功,另4例肌酐转换前为(327.4±105.0)μmol/L,转换后6个月下降为(215.6±A2.3)μmol/L(P＜0.05);2例急性难治性移植肾排斥逆转;环孢素A相关肝毒性5例,其中环孢素A相关肾、肝毒性2例,肝功能恢复正常4例,改善1例;2例骨质疏松症安全撤除皮质激素;2例移植后恶性肿瘤,手术治疗后转换为西罗莫司,随访11～16个月病情稳定.西罗莫司主要不良反应为高脂血症、白细胞减少及慢性腹泻.提示以环孢素A为主要免疫抑制剂的肾移植受者合并一个或多个危险因素时,转换为西罗莫司是一种较为安全有效的选择.     

Incidence,risk factors,and outcome of BK polyomavirus infection after kidney transplantation

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.AIM To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODS This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTS BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these patients.Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.5% vs 15%, P <0.00001), and polyomavirus-related graft loss(27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity(33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50%(30% vs14.6%, P = 0.0047), human leukocyte antigen(HLA) mismatching > 4(26.7% vs13.4%, P = 0.0110), and rejection within thirty days of transplant(21.7% vs 9.5%; P= 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However,viremic recipients showed higher 5-year crude cumulative(22.5% vs 12.2%, P =0.0270) and 30-d-event-censored(22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27%(P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1%(P = 0.008) and 29.1% vs 7.2%(P <0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.CONCLUSION Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panelreactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.