CD20阳性细胞和HLA-DR表达对移植肾急性排斥反应预后判断的价值

目的：探讨CD20阳性细胞在移植肾细胞性排斥反应中浸润程度与预后的关系及其在移植物中的作用。方法：2001年至2002年共29例经移植肾活检诊断为细胞性和混合性移植肾急性排斥患者,肾活检组织标本行CD20、人白细胞DR抗原（HLA-DR）免疫组化染色,C4d免疫荧光染色。并对病理结果行半定量分析,根据CD20细胞在肾组织内浸润程度,分为重度浸润组（H组,〉50%小管间质面积）,中度浸润组（M组,10%～50%）,阴性组（N组,〈10%）,C4d染色按照Banff标准分为阳性组和阴性组,HLA-DR染色分为阳性（〉50%）和阴性（〈50%）组。分别分析CD20和排斥反应分型、HLA-DR、C4d之间的相关性。所有病例均随访42月,随访内容包括患者急性排斥反应临床资料和治疗反应情况,随访期间肌酐变化和移植肾的预后。结果：29例患者中H组有6例,M组7例,N组16例。H组耐激素发生率高于另外两组（4/6vs2/7vs2/16,P=0.05）。42月时H组移植肾生存率明显低于另外两组（4/6vs1/7vs1/16,P〈0.05）,M组平均血肌酐高于N组（208.6μmol/Lvs112.3μmol/L,P〈0.01）。CD20阳性（H＋M组）和C4d染色阳性之间没有一致性（P〉0.05）。而H＋M组HLA-DR表达明显高于N组（59.5%vs16.3%,P〈0.01）;HLA-DR阳性与CD20阳性具有很好的一致性（P〈0.01）。结论：CD20阳性细胞在肾移植急性排斥反应内浸润的程度与移植肾短期和长期预后有明显相关性。CD20细胞的浸润与体液性排斥反应无明显相关性,但是和肾组织中HLA-DR有一定的相关性,提示CD20细胞在移植物内不产生抗体,推测可能与抗原呈递有关,有待进一步研究。     

移植肾超急性排斥反应

１病例报告患者男性，５０岁，因高血压３年半，肾功能不全２年余，行血液透析治疗１７个月，１９９８０８１９入院。缘于１９９５年３月因双眼视物模糊，至当地医院检查，测血压３２／１６ｋＰａ（２４０／１２０ｍｍＨｇ），面色苍白，无恶心、呕吐，无冷汗，无心前...     

CD4+CD25+调节性T细胞回输对大鼠肝移植急性排斥反应的影响

目的:探讨回输CD4 CD25 调节性T细胞对大鼠肝移植急性排斥反应的影响．方法:免疫磁珠阴性加阳性分选Lewis大鼠脾脏、外周淋巴结内的CD4 CD25 调节性T细胞,分离后的细胞与丝裂霉素C处理过的DA 大鼠脾细胞混合培养3 d．淋巴细胞增殖实验评价新鲜分离和体外培养后的CD4 CD25 调节性T细胞对CD4 CD25-T细胞增殖的抑制作用．以DA大鼠为供体,Lewis大鼠为受体,建立4组原位肝移植模型,每组12例,共48例．A 组术后不进行任何干预;B组术后0-6 d FK506 0．2 mg/(kg·d)灌胃;C组、D组术前1 d经阴茎背静脉分别向受体回输新鲜分离、体外培养后的1×106的CD4 CD25 T细胞．术后7 d每组随机处死6只,收集血标本作血清天冬氨酸氨基转移酶(asparate transaminase,AST)、总胆红素(bilirubin,BIL)检测,取肝脏标本作病理学检查,每组各留6只观察生存期．结果:分选后的CD4 CD25 T细胞纯度为 90．2％±1．8％(86％-93％,n=10),淋巴细胞混合培养实验中新鲜分离和体外培养后的 CD4 CD25 T细胞均可抑制CD4 CD25-T细胞的增殖(7 681．7±1 004．9,6 573．3±1 722．7 cpm vs 24 918．7±2 276．3 cpm;P=0．000,P =0．000)．术后7 d,新鲜细胞回输组以及体外培养细胞回输组AST低于对照组(8．1±2．0 μkat/L vs 17．9±3．8 μkat/L,P=0．000;8．4±1．4 μkat/L vs 17．9±3．8 μkat/L,P=0．000),BIL亦低于对照组(45．8±9．0 μmol/L vs 98．4±21．2 μmol/L,P=0．000;44．7±12．0 μmol/L vs 98．4 ±21．2 μmol/L,P=0．000)．四组的Banff评分比较,两组细胞回输组与对照组比较有统计学差异(P<0．05)．两组细胞回输组生存时间均大于对照组(21．7±1．7 d vs 12．8±0．5 d,P=0．0001; 30．3±1．7 vs 12．8±0．5 d,P=0．000 4),体外培养细胞回输组生存时间大于新鲜细胞回输组 (30．3±1．7 d vs 21．7±1．7 d,P=0．0017)．结论:回输新鲜分离/经供体抗原体外激活的受体CD4 CD25 调节性T细胞,可以明显减轻大鼠肝脏移植的急性排斥反应,延长生存期; 其中经供体抗原体外激活的CD4 CD25 调节性T细胞的作用更持久．     

移植肾后期急性排斥反应的临床研究

目的 :探讨肾移植一年后急性排斥反应 (晚期急性排斥 )的临床、病理、抗排斥治疗效果及其预后。　 方法 :将肾移植一年后发生急性排斥反应 (AR)的 83例患者列入本研究对象 ,应用甲基强的松龙 (MP) 0 5g/d冲击治疗 ,连续 3天。然后以环孢素A(CsA)切换成普乐可复 (FK5 0 6 )或霉酚酸酯 (MMF)替代硫唑嘌呤 (Aza)。根据抗排斥治疗效果 ,判断疗效和预后。　 结果 :平均随访时间 4 3 6 (13～ 6 4 )个月 ,晚期AR发生率为 18 9%。移植后一年 1、2、3次发生AR者分别占 6 5 1%、2 5 3%和 9 6 %。其中有症状性排斥和无症状性排斥反应各占 5 6 6 %和4 3 4 %。有症状性AR患者中以高血压最为常见 (6 1 7% )。 7 6 %的患者于移植后一年擅自减用或停用免疫抑制药物 ,导致免疫抑制不足发生排斥反应。 83例晚期AR经抗排斥治疗 ,87 9%获得缓解 (2 7 7%完全缓解 ,6 0 2 %部分缓解 ,12 1%治疗无反应 )。首次发生AR者经冲击治疗 ,35 2 %完全缓解 ,6 4 8%部分缓解 ;2次排斥反应治疗缓解率为 81 0 % (完全缓解 19 1% ,部分缓解 6 1 9% ) ;3次AR抗排斥治疗效果极差 (无反应者高达 75 % )。晚期急性细胞性排斥反应 (ACR)组抗排斥治疗后 ,5 4 8%完全逆转 ,4 5 2 %部分缓解 ;ACR 慢性排斥反应 (CR)组 14 2 %抗排斥逆转 (     

两剂量赛尼哌预防移植肾急性排斥反应的临床观察

赛尼哌 (Ｚｅｎａｐａｘ)是一种通过基因合成的人 /小鼠嵌合体型单克隆抗体 ,由小鼠抗ＩＬ 2受体单克隆抗体的高变区取代人ＩｇＧ的高变区构建而成[1,2 ] 。我院从 2 0 0 0年 9月至 2 0 0 1年 3月选择 2 0例肾移植受者 ,用两剂量Ｚｅｎａｐａｘ预防肾移植术后急性排斥反应 ,取得了较满意的临床效果 ,现总结报告如下。1　对象和方法1.1　病例选择　选择同期首次肾移植受者 4 0例 ,随机分为 2组。即Ｚｅｎａｐａｘ治疗组 (简称Ｚｅｎａｐａｘ组 ,ｎ =2 0 )和常规治疗组 (简称对照组 ,ｎ =2 0 )。两组之间的性别、年龄、冷热缺血时间、淋巴细胞…     

血小板T细胞活化抗原1与移植肾急性排斥反应的相关性

目的 :观察肾移植术后血清可溶性血小板T细胞活化抗原 1 (sPTA1 )水平及细胞膜性血小板T细胞活化抗原 1 (mPTA1 )的表达与排斥反应 (AR)的相关性。　 方法 :选取 1 7例围手术期同种尸体肾移植患者以及 2例术后超过 1年的AR的患者 ,根据患者的不同病况每周采取血样 ,采用夹心ELISA法测定血清sPTA1水平 ,流式细胞术检测淋巴细胞mPTA1表达 ,对明确有排斥反应、可疑有排斥反应以及不能区分排斥反应的患者在B超引导下行移植肾活检穿刺病理检查。　 结果 :术前sPTA1水平及mPTA1表达与对照无显著差异 (P >0 0 5)。术后第 1天sPTA1即有高水平的表达 ,与对照组差异显著 (P <0 0 5)。 1 9例尸体肾移植患者中经病理证实的 5例排斥反应患者sPTA1显著升高 ,mPTA1表达增强 ,与对照组差异非常显著 (P <0 0 1 )。经激素冲击治疗后 ,血清sPTA1下降 ,mPTA1表达下降。而且sPTA1水平变化早于AR的临床表现 ,持续时间较长。　 结论 :PTA1可以作为移植物AR的预警和监测指标 ,与病理检查的结果有较好的一致性 ;PTA1水平变化早于临床表现和病理学变化     

同种异体移植肾急性细胞性排异反应的免疫病理诊断

探讨标记蛋白质在肾移植急性细胞性排异时的作用及其临床诊断意义。选择一组具有重要生物学功能的蛋白质，如ＰＣＮＡ，Ｂｃｌ－２，ＩＬ－２Ｒ，ＩＣＡＭ－１，ＨＬＡＤＲ等作为标记蛋白。着重观察移植肾发生ＡＣＲ时，肾小管和间质浸润细胞中上述记蛋白的变化，及其与间质浸润ＣＤ４或ＣＤ８细胞的关系，并与未发生排异反应者作对照。无ＡＣＲ的肾组织中，ＰＣＮＡ和ＤＲ蛋白仅轻度增加，Ｂｃｌ－２，ＩＬ－２Ｒ和ＩＣＡＭ－１的增     

移植肾慢性排斥反应的某些进展

随着配型技术的不断发展及新型免疫抑制剂应用于临床,早期急性排斥发生率明显下降,移植肾短期存活率得到显著提高。但是,慢性排斥反应仍然是移植肾功能减退和最终移植肾丧失最主要的原因[1]。本文就移植肾慢性排斥反应的临床和病理诊断、免疫和非免疫性因素方面的最新研究进展作一综述。旨在深入研究慢性排斥反应的原因,提供有效的防治措施。1　慢性排斥的临床和病理研究慢性排斥的发病机制尚不十分清楚,通常发生在肾移植3个月后,肾功能呈缓慢减退,血肌酐(ＳＣｒ)进行性升高。在排除其它原因引起的肾功能异常,最终通过肾活检才能明确诊断[1]…     

肾移植急性体液性排斥反应的诊断及治疗

同种异体肾移植术后早期发生急性排斥反应时 ,如果受者体内出现新的针对供者特异性的ＨＬＡ抗体 ,通常称为急性体液性排斥反应 (ａｃｕｔｅｈｕｍｏｒａｌｒｅｊｅｃｔｉｏｎ ,ＡＨＲ) ,其发病率为 4 6%～ 6 8%。ＡＨＲ临床表现为移植术后早期急性难治性排斥反应或加速性排斥反应 ,并具有独特的病理学特点和血清学特点 ,从发病机制上讲 ,被认为是一种独立类型的排斥反应。ＡＨＲ预后较差 ,常导致移植物丧失功能。近年来 ,由于抗ＨＬＡ抗体检测技术的进展 ,以及血浆置换 /免疫吸附联合ＦＫ50 6、霉酚酸酯、γ 球蛋白或15 脱氧腈胍素等新型免…     

趋化因子与移植排斥反应

趋化因子 (ｃｈｅｍｏｋｉｎｅｓ) ,又称趋化蛋白或趋化性细胞因子 ,属于细胞因子超家族 ,是具有内源性白细胞趋化性和活性化作用的低分子量蛋白。趋化因子不仅对白细胞具有趋化效应 ,还具有一系列调节免疫细胞生物学活性的功能 ,参与调节机体的免疫应答。趋化因子及其受体超家族是目前研究进展迅猛的领域 ,近来不断有新的成员被发现 ,其免疫学特性也不断受到重视。本文概述了与移植排斥反应密切相关的趋化因子及其受体 ,展望了在临床监测和治疗中的意义。1　趋化因子及其受体趋化因子目前已发现 50余种 ,含有保守的半胱氨酸 (Ｃｙｓ)结构 ,…     

同种异体移植肾组织中CD40/CD40L的表达及其意义

目的：探讨移植肾急性排斥（AR）时CD40及其配体（CD40L）表达的作用及临床意义。方法：采用SP免疫组织化学染色法对10例正常肾，12例无急性排斥（N-AR）及24例AR移植肾组织中CD40，CD40L表达进行观察，并结合肾间质中CD3，CD68细胞数进行分析，结果：AR组肾间质CD3，CD68细胞数较N-AR组和正常肾明显增高，与此相一致的是间质CD40^ ,CD40L^ 细胞数也较N-AR组明显增高，AR肾组织中CD40/CD40L表达分布不同，间质淋巴细胞以表达CD40为主，CD40L表达以肾实质细胞表达为主，结论：CD40/CD40L在AR移植肾组织中的原位表达及其分布特点可能与其参与AR的病理损伤机制有关。     

Acute allograft rejection: cellular and humoral processes

Acute cellular rejection affects greater than one-third of lung transplant recipients. Alloreactive T-lymphocytes constitute the basis of lung allograft rejection. Recent evidence supports a more complex immune response to the allograft. Interaction between recipient genetics, immunosuppression therapies, and allograft environmental exposures likely contribute to high rejection rates after lung transplantation. A greater understanding of the heterogeneous mechanisms of lung rejection is critical to developing effective therapies that target the precise pathophysiology of the disease and ultimately improve long-term lung transplant outcomes.     

注射用霉酚酸酯预防移植肾急性排斥反应的多中心临床观察

目的：观察霉酚酸酯(MMF)注射剂与环孢素(CsA)和类固醇激素联合应用预防同种异体肾移植急性排斥反应的有效性和安全性。方法：免疫抑制方案为MMF(注射剂及口服剂)联合应用CsA和类固醇激素。观察肾移植术后3个月内急性排斥反应的发生率、程度、人／肾存活率、临床不良反应及感染发生情况。结果：所有受试者、移植肾均存活，82例受试者除1例为移植肾功能延迟恢复外，其余在移植术后3个月的血肌酐和尿量均满意，生命体征、症状和生活质量显著改善。有6例出现急性排斥反应，排斥率为7．32％，经相应治疗后均缓解。有15例受试者16次肝功能异常，经保肝治疗后均转为正常。1例血白细胞下降，经对症处理后缓解。药物相关不良反应发生率为20．73％。7例受试者出现机会感染，发生率为8.53％，经抗生素和抗病毒治疗后均痊愈。未见胃肠道副作用。结论：MMF注射剂有效，可预防肾移植术后急性排斥反应，特别适用于术后早期不能口服药物的肾移植患者。     

CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection

Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen “indirectly,” as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are “unlinked” on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the “semidirect” pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell–mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation.Cytotoxic CD8 T-cell responses directed against MHC class I alloantigens are one of the principal mediators of acute allograft rejection (1, 2). Exceptionally, at very high precursor frequency, cytotoxic CD8 T cells can effect graft rejection autonomously (3), but generally, differentiation of naïve CD8 T cells to fully functional cytotoxic effector cells capable of mediating acute allograft rejection requires help from activated CD4 T cells. How such help is delivered remains unclear. Studies of conventional CD8 T-cell responses against nontransplant antigens have demonstrated that CD4 T-cell help does not involve cognate cell-surface interaction between the helper CD4 T cell and cytotoxic CD8 T cell, but that instead, help is delivered to an intermediary antigen presenting cell (APC), which is then licensed to prime CD8 T cells (4–6). A critical requirement for such help is the expression of both the CD4 and CD8 T-cell epitopes on the same APC, and an analogous three-cell cluster model (Fig. 1A) in transplantation is only possible if help for CD8 T cells is provided by CD4 T cells that recognize intact MHC class II alloantigen on the surface of donor APCs, via the so-called “direct pathway” (7). Murine studies have confirmed that restricting CD4 T-cell help to the direct pathway generates strong cytotoxic CD8 T-cell alloresponses that effect rapid allograft rejection (8).Open in a separate windowFig. 1.Possible mechanisms for provision of CD4 T-cell help to alloreactive CD8 T cells. Analogous to provision of CD4 T-cell help for cytotoxic CD8 T-cell responses against nominal protein antigen, simultaneous linked direct-pathway allorecognition of MHC class I and class II alloantigen on donor antigen presenting cells (APCs) by cytotoxic CD8 and helper CD4 T cells, respectively, is considered the dominant helper mechanism (A). Nevertheless, indirect-pathway CD4 T cells that recognize self-restricted alloantigen following internalization and processing by recipient APCs can also provide help; an unlinked four-cell cluster model has been proposed (B). Provision of linked help by indirect pathway CD4 T cells may be achieved by a three-cell cluster model in which the recipient APC simultaneously presents intact and processed MHC class I alloantigen to, respectively, the cytotoxic CD8 T-cell and helper CD4 T-cell (C).The indirect pathway of allorecognition, whereby CD4 T cells recognize processed alloantigen as self-restricted allopeptide (7, 9), is now viewed as being at least as important as the direct pathway for initiating and mediating allograft rejection. This importance partly reflects the unique ability of indirect-pathway CD4 T cells to act as helper T cells for generating sophisticated alloantibody responses (10), but it is now also clear that effective cytotoxic CD8 T-cell responses can be generated when CD4 T-cell help is restricted exclusively to the indirect pathway (11). This observation is surprising, because the delivery of indirect-pathway T-cell help is only readily explained by postulating the unlikely formation of a cumbersome four-cell cluster, comprising CD4 and CD8 T lymphocytes and both recipient and donor APC (Fig. 1B), a cluster in which there are no apparent cell surface ligands to enable physical linkage between the donor APC/recipient CD8 T-cell couplet and the recipient APC/CD4 T-cell couplet. This scenario raises concerns of potentially uncontrolled CD8 T-cell alloimmunity, because such “unlinked” help could in principle be provided by concurrent exposure to any unrelated antigen.The appreciation that many types of cells, but particularly dendritic cells (DCs), can capture (“trogocytose”) membrane fragments from other cells (12, 13) has prompted the proposal that cytotoxic CD8 T-cell alloimmunity may be initiated by a “semidirect” pathway, whereby intact donor MHC class I alloantigen is recognized after its acquisition onto the surface of recipient DCs. In support, murine studies have detailed in vivo capture of membrane alloantigen by host cells (14, 15). This phenomenon provides a possible mechanism by which the same recipient APC as represents intact MHC class I alloantigen could simultaneously present processed allopeptide for recognition by indirect-pathway CD4 T cells. This scenario would enable formation of a linked three-cell cluster (Fig. 1C) that obviates many of the concerns associated with the above four-cell cluster model. However, although we have recently demonstrated simultaneous presentation of intact and processed alloantigen by recipient DCs following heart transplantation (16), the contribution of trogocytosis of alloantigen to graft rejection has yet to be clarified. To have functional relevance, presentation of intact donor alloantigen by recipient APCs must, at least in certain circumstances, be more effective for triggering cytotoxic alloimmunity than conventional encounter on donor APCs, and this has not been shown. Addressing this key concern is challenging, because it requires development of an experimental model in which CD8 T-cell allorecognition of target MHC class I alloantigen is limited to the surface of recipient, but not donor APCs. One way this scenario could perhaps be achieved is by resolving the paradox created by the seminal observations that CD8 T cells can still effect allograft rejection when target MHC class I alloantigen is expressed by graft parenchyma only (17), but that rejection of vascularized allografts does not occur in the absence of secondary lymphoid tissue (SLT) (18). Why SLT is necessary for CD8 T-cell allorecognition of graft parenchymal cells has not been explained, but one elegant and compelling solution is that alloreactive CD8 T-cell activation occurs in lymphoid tissue because shed, intact MHC class I alloantigen is only presented by recipient APCs at these sites.Here, we show that rejection of heart allografts in mice lacking hematopoietic APCs is mediated by alloreactive CD8 T cells, and that the participation of CD8 T-cells is dependent upon the acquisition and presentation of intact MHC class I alloantigen by recipient DCs within host SLT. We further demonstrate that representation of intact alloantigen enables the delivery of essential help from indirect-pathway CD4 T cells. These findings provide strong functional support for the provision of indirect-pathway CD4 T-cell help to alloreactive CD8 T cells via a “linked” three-cell cluster model.     

Association of renal allograft rejection with virus infections

Sixty-one immunosuppressed renal transplant recipients were systematically screened for virus infections and the findings correlated with their clinical course. Only herpesvirus (cytomegalovirus, herpes simplex and herpes zoster) were consistently isolated. The onset of virus infections could usually be associated with clinical syndromes. Patients without virus infections were usually asymptomatic. The clinical syndrome associated with virus infection consisted of fever, leukopenia and renal allograft rejection. Renal biopsy, performed at the time serum creatinine levels were elevated, revealed classic rejection; most rejections were reversed by increasing the dose of steroids. Patients continued to excrete virus even after antibody response and clinical recovery. Virus infections do not appear to be incidental findings in transplant patients except after recovery when the virus persists in the immune patient. The clear-cut association between virus infection and rejection episodes suggests a pathogenic relationship. The two mechanisms which seem to best explain the relationship are (1) the virus infection acting as an adjuvant and triggering the rejection of the allograft or (2) the allograft rejection activating a latent virus infection.     

Prevention of early acute rejection with daclizumab and triple immunosuppression in cadaveric renal allograft recipients

We carried out a prospective study of the safety and efficacy of daclizumab combined with triple immunosuppression in adult recipients of at least one HLA-mismatched cadaveric renal allograft. All studied patients received the same immunosuppression: a daclizumab infusion of 1 mg/kg immediately before transplantation, and at 2, 4, 6, and 8 weeks following the transplantation. Infusion of cyclosporine (CsA) (0.08 mg/kg/h) was started at the time of the operation and continued by CsA microemulsion (CsA-Neoral), 3 mg/kg twice daily on day 2, methylprednisolone, 0.4 mg/kg intravenously at operation, and mycophenolate mofetil started on day 1. The dose of CsA-Neoral was adjusted to maintain target blood trough levels. Oral methylprednisolone was tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg/day. Fifty-five patients, with a mean age of 48 +/- 11 years, were studied. Six of them received a second renal allograft. The mean donor age was 38 +/- 14 years. Mean cold ischemia time was 19.5 +/- 6.5 h, mean value of HLA-antigen mismatches was 2.7 +/- 0.9, mean latest PRA value was 3 +/- 7%. Fifteen patients experienced delayed graft function. During a follow-up period of 3 months three acute rejection episodes occurred. One patient died because of systemic aspergillosis. After 3 months mean serum creatinine was 104 +/- 38 micromol/L. Five renal allografts failed, one of them due to rejection. Patient and graft survival was 98.2% and 90.9%, respectively. Daclizumab with this triple therapy represents safe and efficient immunosuppression strategy, demonstrated with low incidence of early acute rejection episodes and an acceptable adverse event profile in cadaveric renal allograft recipients.     

他克莫司作为急性加速性排斥反应补救治疗的临床观察--附5例报道

目的：探讨他克莫司(FK506)治疗急性加速性排斥反应(AAR)的疗效及副作用。方法：5例患者在肾移植术后5天内经移植肾活检发现均存在血管内膜炎、小管炎及小球炎。将患者环孢素A(CsA)切换为FK506，并给予行连续性静脉．静脉血液滤过(CVVH)。结果：FK506起始剂量为1．5mg/(kg．d)，调整剂量，使FK506谷值浓度维持在5～15ng／ml之间。在给予：FK506治疗10～19天后患者血肌酐(SCr)开始下降，治疗20～39天后SCr降至正常或稳定在134～157μmol／L之间。患者少尿过程中均给予CBP治疗，无一例出现心衰、肺水肿及电解质紊乱。3例患者分别在间隔6、6、2个月后行重复活检术，组织学结果提示肾小球炎、间质小管炎及血管内膜炎较前有明显好转。结论：FK506联合CVVH治疗能有效逆转移植肾AAR。