骁悉和环孢素-A预防肾移植术后早期急性排斥反应

目的 探讨骁悉和环孢素－Ａ预防肾移植术后早期急性排斥反应的效果。方法 回顾性分析１９９７年１２月￣１９９９年１月临床资料完整肾移植患者１４６例,随访时间６￣１６个月。根据应用免疫抑制剂方案的不同分为硫唑嘌呤（Ａｚａ）组（环孢素－Ａ、泼尼松龙、Ａｚａ）和骁悉（ＭＭＦ）组（环孢素－Ａ、泼尼松、ＭＭＦ）。其中Ａｚａ组７８例,ＭＭＦ组６８例。所有受者术前行人类白细胞抗原（ＨＬＡ）配型,ＨＬＡ错配≤３个位点     

达利珠预防肾移植术后急性排斥反应临床观察

目的探讨达利珠（赛尼哌Zenapax）单剂给药在肾移植受者预防急性排斥反应（AR）的有效性及安全性。方法2003年1月至2005年5月,同期首次肾移植受者90例,随机分为3组：Zenapax单剂组（n=25）,男性15例,女性10例,Zenapax单剂量,术前1h给药;Zenapax双剂组（n=25）,男性15例,女性10例,Zenapax双倍剂量术前1h及术后14d给药;对照组（n=40）,男性24例,女性16例。所有病例均采用环孢素（CsA）加霉酚酸酯（MMF）加皮质类固醇三联免疫抑制方案,观察术后6个月内AR发生情况、肾功能恢复情况、不良反应及感染发生情况。结果单剂及双剂治疗组各有1例患者出现AR,对照组6例出现AR,单剂及双剂组AR的发生率无差异,与对照组比较差异具有统计学意义;两组均未发生细胞因子释放综合征。结论肾移植受者应用Zenapax单剂诱导治疗可降低术后AR发生率,无明显副作用。     

肾移植术后早期排斥反应的处理

目的：探讨。肾移植术后早期排斥反应(AR)的处理方法。方法：对14例。肾移植术后3周内发生AR的患者,应用甲基泼尼松龙(MP)治疗7例,改硫唑嘌呤(Aza)为霉酚酸脂(MMF?)治疗5例,抗CD3治疗6例。结果：应用MP治疗的7例中5例AR逆转,2例无效;改Aza为MMF治疗的5例3例逆转,2例无效(其中包括MP无效的2例改Aza为MMF治疗后1例逆转1例无效)。抗CD3治疗6例4例逆转,2例无效(其中MP治疗无效改Aza为MMF治疗后仍无效的1例逆转,MP治疗无效的基础免疫为CsA加MMF?加Pred的1例无效)。结论：MP可使大部分术后早期AR逆转。应用Aza的患者改用MMP后可使早期AR逆转,MP不能完全逆转的AR改用MMF后也有良好的效果。及时应用抗CD3几乎可使术后早期AR全部逆转。     

骁悉对肾移植术后感染的影响

目的观察骁悉(MMF)对肾移植术后感染的影响。方法将90例肾移植术后患者分为两组．1997年以前手术的56例为硫唑嘌呤(Aza)组,免疫抑制剂为环孢素A(CsA)加Aza加泼尼松;1998～1999年1月手术的34例为MMF组,免疫抑制剂为CsA加MMF加泼尼松。Aza组CsA起始用量为6mg/(kg·d-1),MMF组为5mg/(kg·d-1),以后根据血药浓度进行调整。结果90例肾移植患者术后总的感染率为17.8％,其中Aza组为21.4％(12/56),2例死亡;MMF组为11.8％(4/34),无死亡病例。两者之间感染率差异有显著性意义(P＜0.05)。结论用MMF代替Aza可以减少肾移植术后的感染率,并提高移植肾成活率。     

血浆置换治疗肾移植术后急性排斥反应

肾移植术后的急性排斥反应,常规治疗几乎都是增加糖皮质激素用量,仍有一部分病例排斥反应不能逆转。我们应用血浆置换治疗肾移植术后急性排斥反应,现将结果报告如下。一、资料与方法对11例同种异体肾移植术后出现急性排斥反应、经用糖皮质激素冲击治疗无效的患者行血浆置换治疗,其中男8例,女3例,年龄26～52岁,平均45岁。肾移植术后免疫抑制剂的用法为:环孢素Ａ10ｍｇ·ｋｇ-1·ｄ-1,分次口服;甲泼尼龙于术日至术后2ｄ500ｍｇ/ｄ静脉滴注,以后改为泼尼松2ｍｇ·ｋｇ-1·ｄ-1,开始每日递减5～10ｍｇ,至30ｍｇ/ｄ口服维持;硫唑嘌呤2ｍｇ·ｋｇ-…     

肾移植术后急性排斥反应的相关分子标记物

急性排斥反应(AR)是肾移植术后的重要并发症, 有必要寻找能早期诊断和预测AR的非侵入性标记物, 并针对不同的分子标记物为患者提供个性化治疗。本文对肾移植术后AR相关标记物趋化因子家族及其受体、信使核糖核酸、白细胞分化抗原、小分子蛋白、白细胞介素等的研究进行回顾及展望。     

应用抗CD3单克隆抗体预防肾移植术后急性排斥反应的体会

目的 观察国产抗CD3单克隆抗体在预防肾移植术后急性排斥反应中的作用。方法 将60例患者随机分为3组，每组20例，3个组移植术后均给以环孢素A、硫唑嘌呤和皮质激素组成的三联免疫抑制方案；全量组加用抗CD3单克隆抗体5mg/d，半量组加用抗CD3单克隆抗体2.5mg/d，对照组不用。观察术后肾功能的恢复情况及急性排斥反应发生率。结果 术后1周使用抗CD3单克隆抗体者的血肌酐低于对照组（P＜0．05），10d后二者的差异无显著性；在术后头3个月，使用抗CD3单克隆抗体治疗组与对照组在急性排斥反应发生率方面的差异有显著性（P＜0．05）；使用抗CD单克隆抗体全量组与半量组在术后肾功能恢复及急性排斥反应发生率方面的差异无显著性。结论 术后早期预防性使用抗CD3单克隆抗体对移植肾功能的恢复和降低急性排斥反应发生率有较好的作用；给予半量的抗CD3单克隆抗体能取得与全量同样的效果，且费用较低，并发症少。     

同种肾移植后超急性排斥反应的发生机制及临床对策(附66例报道)

目的　探讨肾移植后超急性排斥反应 (HAR)的发生机制及其临床对策。方法　回顾性分析 6 6例HAR患者。将切除的移植肾标本行形态学及荧光抗体染色观察 ;并对HAR的临床表现、治疗结果及再次手术情况等进行了总结。结果　HAR早期 ,肾间质小血管及肾小球毛细血管内大量红细胞淤滞为主要改变 ,可发现淤滞的红细胞呈串珠状贴附在血管壁上 ;本组 6 6例HAR患者中 ,2 1例于手术中立即切除移植肾 ,44例分别于术后第 1～ 2 0d切肾 ,仅 1例经对症处理后 ,移植肾逐渐萎缩未予摘除。15例HAR患者经严格配型、血浆置换及抗淋巴细胞免疫球蛋白 (ATG)治疗 ,在短期内行再次移植 ,10例获得成功。11例HAR患者 ,6个月～ 2年后再行 2次移植 ,仅 4例获得成功。结论　红细胞可能参加超急性排斥反应 ;HLAⅠ、Ⅱ类抗体高敏状态 ,是导致肾移植后HAR发生的因素 ,因此强调对高敏人群做PRA配型或随机淋巴细胞毒性试验。     

霉酚酸酯预防肾移植术后近期急性排斥反应的观察

目的 :观察霉酚酸酯 (MMF)在预防肾移植术后近期 (3个月 )急性排斥反应 (AR)的情况。方法 :将 112例患者随机分成 2组 ,MMF(2 .0 g/d)组和硫唑嘌呤 (Aza)组。两组患者均同时接受相似剂量的环孢素 A和类固醇激素治疗。结果 :观察 3个月 ,MMF组 6 0例 ,AR发生率为 16 .7% (10 /6 0 ) ,Aza组 5 2例 ,AR发生率为 42 .3%(2 2 /5 2 ) ,两组差异有极显著意义 (P <0 .0 1)。 MMF组 5例出现血白细胞、血小板等不同程度下降 ,3例出现腹泻 ,在 MMF减量或停药后均恢复正常 ,未见有 MMF引起的肝、肾功能异常病例 ;Aza组有 9例出现肝功能损害。结论 :MMF具有预防和减少肾移植术后近期 AR效果 ,MMF的安全性可靠 ,副作用轻且为可逆性。     

CD44分子在肾移植患者急性排斥反应肾组织中的表达及意义

目的:探讨CD44分子与肾移植急性排斥反应的关系。方法:回顾分析2005年7月～2009年5月间肾移植术后穿刺病理活检证实为急性排斥反应患者28例的CD44在移植肾组织中的表达。结果:28例急性排斥反应肾组织中有25例CD44呈阳性表达,阳性率为89.29%;10例慢性排斥反应肾组织中有3例阳性表达,阳性率为30%;30例正常肾脏组织中5例CD44分子的阳性表达,阳性率为16.7%;两两比较,结果差异有统计学意义(P0.05)。结论:CD44与其与配体的相互作用在移植肾急性排斥反应中可能起到重要作用,CD44分子有可能成为一个特异性和敏感性都较好的早期诊断急性排斥的预测因子。     

A Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross‐validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q‐PCR analysis of a five gene‐set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training‐set (n = 47) and validated on independent test‐set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non‐AR phenotypes with 91% sensitivity and 90% specificity. The 5‐gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.     

Monocyte Infiltration and Kidney Allograft Dysfunction During Acute Rejection

Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings.     

Lack of Improvement in Renal Allograft Survival Despite a Marked Decrease in Acute Rejection Rates Over the Most Recent Era

Acute rejection is known to have a strong impact on graft survival. Many studies suggest that very low acute rejection rates can be achieved with current immunosuppressive protocols. We wanted to investigate how acute rejection rates have evolved on a national level in the U.S. and how this has impacted graft survival in the most recent era of kidney transplantation. For this purpose, we analyzed data provided by the Scientific Registry of Transplant Recipients regarding all adult first renal transplants between 1995 and 2000. We noted a significant decrease in overall acute rejection rates during the first 6 months, during the first year, and also in late rejections during the second year after transplantation. Despite this decrease in the rate of acute rejection, there was no significant improvement in overall graft survival; furthermore, we noted a statistically significant trend towards worse death-censored graft survival. There was also a trend for a greater proportion of rejection episodes to fail to recover to previous baseline function after treatment. Our data suggest that decreasing acute rejection rates between 1995 and 2000 have not led to an increase in long-term graft survival. Part of this discordance might be related to a higher proportion of acute rejections which have not resolved with full functional recovery in more recent years. However, the etiology of this concerning trend for worse death censored graft survival in recent years will warrant further investigation.     

CD20-Positive Infiltrates in Renal Allograft Biopsies with Acute Cellular Rejection Are Not Associated with Worse Graft Survival

We examined rejection outcome and graft survival in 58 adult patients with acute cellular rejection Banff type I (ARI) or II (ARII), within 1 year after transplantation, with or without CD20-positive infiltrates. Antibody-mediated rejection was not examined. Of the 74 allograft biopsies, performed from 1999 to 2001, 40 biopsies showed ARI and 34 biopsies showed ARII; 30% of all the biopsies showed CD20-positive clusters with more than 100 cells, 9% with more than 200 cells and 5% with more than 275 cells. Patients with B cell-rich (>100 or >200/HPF CD20-positive cells) and B cell-poor biopsies (<50 CD20-positive cells/HPF) were compared. Serum creatinine and eGFR of B cell-rich (CD20 > 100/HPF) and B cell-poor were not significantly different at rejection, or at 1, 3, 6 and 12 months, and during additional 3 years follow-up after rejection, although higher creatinine at 1 year was noted in the >200/HPF group. Graft survival was also not different between B cell-rich and B cell-poor groups (p = 0.8 for >100/HPF, p = 0.9 for >200/HPF CD20-positive cells). Our data do not support association of B cell-rich infiltrates in allograft biopsies and worse outcome in acute rejection type I or II, but do not exclude the possible contribution of B cells to allograft rejection.     

Preferential Depletion of Blood Myeloid Dendritic Cells During Acute Cardiac Allograft Rejection Under Controlled Immunosuppression

Allo-Ag presentation to Ag-specific T-lymphocytes by donor or recipient dendritic cells (DCs) induces acute rejection (AR) after solid organ transplantation. It is postulated that myeloid (mDC) and plasmacytoid (pDC) subsets circulate differentially between bone marrow, heart and lymphoid tissues after cardiac transplantation (HTx). We investigated peripheral blood DC subset distribution, maturation and lymphoid homing properties in relation to endomyocardial biopsy (EMB) rejection grade after clinical HTx. Twenty-one HTx recipients under standard immunosuppression were studied in a 9-month follow-up. mDC and pDC numbers were analyzed by flow cytometry in fresh venous whole blood samples collected during the EMB procedures and before histological diagnosis of AR. Subsets were further characterized for maturation marker CD83 and lymphoid homing chemokine receptor CCR7. Although numbers of both DC subsets remained low for the whole post-HTx period, we observed a negative association of mDCs with rejection grade. Repeated measurements analysis revealed that only mDCs decreased during AR episodes. Rejectors had lower mDC numbers after a 3-month follow-up compared to nonrejectors. Furthermore, patients during AR exhibited low proportions of mDCs positive for CD83 or CCR7. These findings suggest peripheral blood mDC depletion in association with selective lymphoid homing of this subset during AR after clinical HTx.