肾移植术后急性抗体介导排斥诊断与治疗

目的 研究探讨肾移植术后急性抗体介导排斥反应(Antibody-mediated rejection,AMR)患者的诊断与治疗,为术后出现排斥反应的患者的治疗提供宝贵的临床经验.方法 回顾性分析2000年1月至2010年1月于华山医院进行肾移植的392例患者,平均随访时间为24个月.其中共有24例患者于术后病理确诊为AMR,其中男性患者15例,平均年龄为(42.21±4.51)岁,女性患者9例,平均年龄为(40.29±4.23)岁.结果 19例患者通过积极的综合治疗,肾功能在3周内逐渐恢复正常,平均恢复时间为17.31±3.28d.治疗后肌酐为104.00±17.58umol/L.明显低于治疗前肌酐463.84±83.18umol/L.结论 通过早期诊断与积极治疗,绝大多数AMR患者能够及时挽回移植肾功能.19例患者至随访终点肾功能恢复良好,说明积极的综合治疗辅以密切的术后护理能够有效治疗AMR.     

PRA、HLA配型技术在肾移植中的应用

目的 探讨群体反应性抗体（ＰＲＡ）、ＨＬＡ配型技术对肾移植近远期效果的影响。方法对等待肾移植的１０２０例患者采用ＰＲＡ测定、ＨＬＡ组织配型,ＰＲＡ阴性或阳性者均经血浆置换,ＨＬＡ抗原３～６个位点相合为第一组;未采用ＰＲＡ、ＨＬＡ组织配型的４２３例患者为第二组。观察两组肾移植术后免疫指标的变化,近期急性排斥反应发生率以及ＨＬＡ－Ａ、Ｂ、ＤＲ位点对长期存活的影响。结果 第一组肾移植术后环孢素Ａ（ＣｓＡ     

“二袖套法”大鼠原位肝移植的技术改进

目的 探讨大鼠原位肝移植(OLT)模型的技术改进方法,并观察移植后的排斥反应。方法 将“二袖套法”大鼠肝移植技术进行了改进;并行SD→SD,SD→Wistar大鼠肝移植各30例,观察术后排斥情况。结果 全组肝移植手术无肝期约为15min。大鼠无手术死亡。SD-SD大鼠肝移植后3周内存活率为97％;SD→Wistar大鼠肝移植后8～15d死亡,组织病理学证实存在不同程度的排斥反应。结论 采用该改良大鼠肝移植方法可明显缩短手术时间,降低术后并发症,提高移植大鼠的术后生存率。SD-Wistar大鼠的肝移植可作为较理想的研究肝移植排斥反应的动物模型。     

肝移植术后抗体介导的排斥反应与胆道狭窄的关系及诊疗策略分析

背景与目的：肝移植术后抗体介导的排斥反应（AMR）相对少见,但AMR是移植后移植物失功能的重要危险因素。本研究探讨肝脏移植术后AMR的发生情况,以及AMR与胆道狭窄的关系及诊疗策略。方法：回顾性分析2016年1月—2023年10月在昆明市第一人民医院接受脑死亡捐献肝移植的203例患者的临床资料。结果：203例肝移植患者中,发生肝移植术后急性排斥反应20例,其中AMR 7例、T细胞介导的急性排斥反应（TCMR） 13例;发生胆道狭窄18例。发生急性排斥的患者中,6例（30.0%）发生胆道狭窄,未发生急性排斥患者中,12例（6.6%）发生胆道狭窄,前者胆道狭窄的发生率明显高于后者（P=0.002）。AMR患者中5例（71.4%）发生胆道狭窄,其中诊断急性AMR时3例患者合并胆道狭窄并处理,2例患者在AMR治疗好转后1年随访过程中出现胆道狭窄;TCMR患者中仅1例（7.7%）于术后3年发生胆道狭窄,AMR患者胆道狭窄的发生率明显高于TCMR患者（P=0.007）。7例AMR患者中,1例在移植术后2个月出现肝功能异常,在1周内快速出现肝功能恶化,经激素冲击治疗无效后因肝功能衰竭并颅内出血死亡;...     

Center volume effects in pediatric renal transplantation

 An inverse relationship between mortality and center volume has been established for several surgical procedures. Given the distinctiveness of pediatric renal transplantation and the large variation in center volume, investigation for relationships between center volume and graft outcome was pursued using the North American Pediatric Transplant Cooperative Study database. Center volume groups were based on the total number of pediatric transplants reported from 1987 to 1995. Centers reporting >100, 51–100, or ≤50 transplants were grouped as high- (n=11), moderate- (n=28), or low-volume (n=65), respectively. Differences between groups included increasing rates of cadaver donor graft thrombosis (2.4%, 4.3%, and 5.7%, P<0.01) and acute tubular necrosis (ATN) (10.2%, 11.5%, and 14.0%, P<0.01) with decreasing center volume. Treatment differences included a higher rate of induction with an anti-T-cell antibody preparation in the larger-volume groups, 60.2%, 51.8%, and 39.2% (P<0.001). Decreasing graft survival for decreasing center size groups was noted at 3 months post transplant, 90.4%, 90.2%, and 88.4%. These differences were significant only with the exclusion of anti-T-cell induction from the proportional hazards model (relative risk=0.81 and =0.70 for the moderate- and high-volume groups, P<0.02). Superior graft survival in the high-volume centers noted at 3 months post transplant appears predominantly the result of lower rates of cadaver donor graft thrombosis and ATN. Analysis points to the need for low-volume centers to identify risk factors influencing these outcomes. Received: 13 May 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

多普勒能量图监测移植肾急性排斥

为探讨彩色多普勒能量图（ＣＤＥ）在监测移植肾急性排斥中的应用价值，对７１例移植肾作ＣＤＥ及常规彩色多普勒血流成像（ＣＤＦＩ）等检查，其中２２例经临床及病理证实发生了急性排斥（ＡＲ）。结果表明：根据ＣＤＥ可以诊断急性排斥，其灵敏度比ＣＤＦＩ高。若ＣＤＥ与ＣＤＦＩ结合，则诊断ＡＲ的准确性更进一步提高。多次ＣＤＥ检查动态观察移植肾可预测ＡＲ的转归和监测抗排斥的效果。认为ＣＤＥ检查是目前肾移植术后较实用的一种监测手段。     

ATG-F与OKT3在肾移植术后急性排斥反应中的应用研究

目的 探讨应用注射用兔抗人T淋巴细胞多克隆抗体(ATG-F)及注射用抗人T细胞CD3鼠单克隆抗体(OKT3)治疗肾移植术后急性排斥反应的效果、安全性和副反应等.方法 本中心施行同种异体肾移植术后对于激素冲击治疗不敏感的急性排斥患者51例,分为两组,分别给予多克隆抗体ATG-F和单克隆抗体OKT3治疗,并对治疗效果、安全性和药物的副反应等进行统计学分析.结果 ATG-F治疗28例,排斥逆转26例,治愈率89.3％;OKT3抗组23例,排斥逆转16例,治愈率69.6％.两组结果间有显著性差异(P＜0.05).结论 OKT3和ATG-F同为抗淋巴细胞的抗体,但其针对难治性急性排斥反应的治疗效果,存在明显差异.ATG-F临床效果肯定,并且用量灵活,副作用小.OKT3治疗效果一般,则具有术后感染发生率增加、白细胞减少等并发症.     

抗白介素2受体单克隆抗体治疗移植肾难治性排斥反应

为了提高抗移植肾难治性排斥反应的效果，对肾移植术后急性难治性排斥反应１１例（其中２例为急性加速性排斥反应），应用抗白介素２受体单克隆抗体（抗Ｔａｃ）治疗，９例（包括１例急性加速性排斥反应）完全逆转，逆转率８１．８％。结果显示：抗Ｔａｃ特异性强、反应灵敏、安全有效、副作用小，就抗Ｔａｃ治疗急性排斥反应（ＡＲ）的机理及治疗难治性ＡＲ的应用价值进行讨论。     

儿童肾移植的临床研究

目的 总结儿童肾移植的临床经验.方法 回顾性分析1980年6月至2008年12月41例儿童肾移植的临床资料,其中1980-1993年(G1)有8例患儿,均未进行免疫诱导,术后采用以环孢素A+硫唑嘌呤+泼尼松为基础的免疫抑制方案;1994-2001年(G2)有18例患儿,均应用抗淋巴细胞球蛋白免疫诱导,术后采用他克莫司(或环孢素A)+吗替麦考酚酯(或硫唑嘌呤)+泼尼松的方案;2002年后(G3)有15例患儿,均应用抗白细胞介素-2受体单克隆抗体(IL-2RA)免疫诱导,术后采用他克莫司(或环孢素A)+吗替麦考酚酯+小剂量泼尼松(或无泼尼松)的方案.分别对三个阶段患儿术后急性排斥反应(AR)和移植肾功能恢复延迟(DGF)等并发症发生率、存活率及生长发育情况等进行比较.结果 41例患儿术后1、3、5年人/肾存活率分别为97.6%/90.2%、95.1%/82.9%和90.2%/75.6%,其中G1为87.5%/75.0%、75.0%/50.0 %和75.0%/50.0%、G2为100.0%/94.4 %、100.0%/83.3%和94.4%/72.2%以及G3为100.0%/100.0%、100.0%/100.0%和100.0%/93.3%,G3明显高于G1(P<0.05),但与G2无明显差异.41例中共有13例发生AR,发生率为31.7%,其中G3的AR发生率分别为13.3%,明显低于G1和G2的50.0%和38.9%(P<0.01).G1、G2和G3患儿的身高分别增长了(2.9±0.6)、(3.2±0.6)和(3.8±0.9)cm,G3患儿身高的增长幅度最为明显(P<0.05).G1、G2和G3患儿间DGF发生率无明显差异,高血压和感染是最为多见的并发症.结论 良好的组织配型、适宜的手术方法、恰当的免疫抑制剂血药浓度及AR早期诊断是保证儿童肾移植成功的关键.IL-2RA免疫诱导能够有效地降低AR发生率,而小剂量激素或无激素方案最大程度的改善了影响患儿骨骼发育的限制因素,促进患儿生长.     

甘露聚糖结合凝集素在肾移植中的研究进展

肾移植后感染和排斥反应是影响受者和移植肾长期存活的主要危险因素。血浆甘露聚糖结合凝集素水平及其基因多态性与感染和排斥反应的发生密切相关。本文综述了血浆甘露聚糖结合凝集素与肾移植后移植肾缺血再灌注损伤、感染、排斥反应以及长期存活的相关文献。     

小肠移植后排斥反应的监测

检测猪同种异体小肠移植后受体的血浆Ｎ－乙酰氨基已糖酶，外周血单个核细胞前凝血质活性，血清肿瘤坏死因子，血清白细胞介素２和白细胞介素６，并与同期的粘膜活检结果对照，发现它们在排斥早期即有显著升高，其是单个核细胞前凝血活性和白细胞介素２的变化早于反排斥反应的病理变化，提示术后检测这些指标将有助于排斥反应的早期诊断。     

Study of the effect of renal transplantation on methacholine challenge test in patients with end-stage renal failure in Shahid Doctor Labafinejad Hospital in Tehran, Iran

Pulmonary complications are common in patients with chronic renal failure (CRF). The objective of this study was determine the effect of renal transplantation on pulmonary function, using a methacholine challenge test. This interventional study included 14 CRF patients on maintenance dialysis who underwent serial spirometry and astography before and after renal transplantation. None of them was known to have clinically important pulmonary or heart disease. The results of spirometry, astography, echocardiography, and chest X-ray were normal. Five patients were men and all others were women. The overall age range was 15 to 45 years (mean age = 28.6 +/- 10.9). For every patient four times astography was done. The mean values of spirometric and astography indices before and after renal transplantation were within normal limit. But by repeated measure analysis of variance, the results actually showed improved airway responsiveness (although within normal limits). The most common pathological lung condition in CRF is pulmonary edema, usually due to a combination of fluid overload and abnormal permeability of the pulmonary microcirculation. However, our patients had no symptomatic pulmonary edema, but minor degrees of fluid retention are virtually impossible to detect clinically and could not be excluded. Therefore, it seems that disappearance of subclinical pulmonary edema was the likeliest cause of an increase in minimum dose of methacholine, and therefore improvement in airway responsiveness after renal transplantation.     

Pediatric renal transplantation without steroids

Pediatric renal transplant patients present a number of challenges and problems, especially the inhibited post-transplant growth seen in children receiving standard immunosuppressive triple therapy that includes steroids. We report the successful use of steroid-free immunosuppression since 1990 in 14 pediatric renal allograft recipients who received a 10-day initial course of antilymphocyte globulin and surface area-adjusted doses of cyclosporine, 7 of whom also received mycophenolate mofetil (MMF) as maintenance immunosuppression. Only 1 patient died (3 months after transplantation as a result of a primary Epstein-Barr virus infection-induced lymphoproliferative disorder), 1 patient’s graft never functioned, and another patient lost his graft after 3 years because of chronic rejection. Three patients experienced early acute cellular rejection, which resolved in 2 cases with OKT3, and in the 3rd with MMF. There were no late acute rejections. All patients evidenced growth and a growth spurt under this regimen. We conclude that all the pediatric patients benefited from our steroid-free protocol and that this protocol is superior to conventional triple therapies, which entail the eventual reduction and discontinuation of steroids, a procedure that not only inhibits growth but also carries an additional risk of acute rejection due to a steroid-adapted immune response. Received April 16, 1997; received in revised form September 8, 1997; accepted September 10, 1997     

Prior dialysis does not affect the outcome of pediatric renal transplantation

The effect of pretransplantation dialysis treatment was examined retrospectively in 70 children less than 6 years old receiving a primary renal transplant at the University of Minnesota. Patient and graft survivals were compared at 1, 2 and 3 years and there were no significant differences between patients who received only hemodialysis (group 1), only peritoneal dialysis (group 2), or no prior dialysis (group 3). All patients received deliberate blood transfusions before transplantation and children at risk for recurrent diseases were excluded from the analyses. No grafts were lost due to perioperative thrombosis. Also, treatment with cyclosporine A did not significantly influence the outcomes. In this series, the choice to proceed directly to renal transplantation without an interposed interval of dialysis imposes no penalty in terms of patient or graft survival. Likewise, when dialysis was required, the dialysis mode selected exerted no clear effect on the outcome of transplantation.     

Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n=13) or a mean dosage of 0.07 mg/kg per day (n=4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient,P<0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in preadolescents receiving FK-506 but no prednisone (P<0.02 andP<0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.     

移植肾急性排斥反应的免疫表型

目的阐明移植肾急性排斥反应的发生机制。方法发生严重急性排斥反应的１６例移植肾行免疫组化染色,其中６例行免疫胶体金电镜观察。结果移植肾组织中主要免疫活性细胞为Ｔ细胞,动脉壁及肾小管细胞间的Ｔ细胞均为ＣＤ８细胞。结论移植肾急性排斥反应主要是由Ｔ淋巴细胞尤其是ＣＤ８细胞介导的一种免疫损伤。     

肾移植术后存活影响因素分析

目的分析影响肾移植存活的因素,以提高肾移植术后长期存活率. 方法采用SAS软件,统计2 016例(2 105次)肾移植受者群体中的33个相关变量.用Kaplan-Meier曲线计算1、3、5、10年移植肾存活率及移植肾半生存期,用Log-rank方法进行单变量分析,采用COX模型多元回归计算相对危险度. 结果移植肾1、3、5、10年存活率分别为83%(1 543/1 859)、75%(1 125/1 500)、66%(800/1 212)、48%(291/607),剔除有移植肾功能死亡的病例后,存活率则为89%(1 655/1 859)、82%(1 230/1 500)、75%(909/1 212)、69%(419/607),两者的移植肾半生存期分别为(8.78±0.14)年和(14.09±0.20)年.与肾移植长期存活关系密切的单变量有供肾缺血时间,移植次数,免疫抑制药(ISA)种类和组合,排斥,移植肾功能恢复正常时间及术后肌酐水平,急性肾小管坏死(ATN),移植肾功能延迟恢复(DGF),急性排斥的治疗方法,感染并发症等因素. 结论免疫抑制剂的改进提高了肾移植短期存活率,也显示出长期存活的趋势.提高供肾质量,降低带有移植肾功能的患者的死亡率是现阶段提高移植肾长期存活率的一个最有可能实现的途径.     

Anti-lymphocyte antibodies late in the course of pediatric renal transplantation

 Beyond the immediate post-transplant period, physicians are often reluctant to use anti-lymphocyte preparations to treat episodes of acute renal functional deterioration attributable to acute rejection. This is due to the perception that such episodes are less likely to be reversible, and to concern regarding the potential adverse effects of anti-lymphocyte antibodies, including opportunistic infections, lymphoproliferative disorders, and the development of human anti-mouse antibodies. Records were reviewed for all 365 renal transplants performed in 267 patients at our center from 1971 to 1996. Anti-lymphocyte antibodies were used in an attempt to reverse 6 episodes of corticosteroid-resistant acute rejection in 5 children at a mean interval of 24.5 months following transplantation. The mean serum creatinine at initiation of therapy with the anti-lymphocyte agents was 2.9 mg/dl. Following treatment, the mean serum creatinine decreased to 1.3 mg/dl (P=0.03, Student’s t-test). Two patients developed uncomplicated opportunistic infections after completion of anti-lymphocyte therapy; none have developed lymphoproliferative disorders or antibodies to OKT3. We conclude that in the correct clinical setting with corticosteroid-resistant acute rejection, the use of anti-lymphocyte antibodies should not be withheld solely on the basis of length of time since transplantation. Received: 27 January 1998 / Revised: 19 May 1998 / Accepted: 6 July 1998     

肾移植术后应用FK506抗排斥治疗的临床研究

目的　观察ＦＫ５０６ 在肾移植术后抗排斥治疗的效果及副作用。　方法　对肾移植术后单独应用环孢素Ａ（ＣｓＡ）５０ 例和术后应用ＦＫ５０６ ５０ 例（ 术后２４ 小时应用ＦＫ５０６ ４０ 例,ＣｓＡ 中毒后改ＦＫ５０６ １０ 例）患者进行比较。　结果　ＣｓＡ 组发生急性排斥反应（ＡＲ）９ 例,发生率为１８ ％ ,逆转８ 例（８８ ％） ,肾功能在２ ～２６ 天恢复正常３８ 例（７６ ％） ,肺部感染２ 例,泌尿系感染１ 例,肾中毒２例,肝中毒３ 例,高血糖２ 例,腹泻１ 例,摘肾１ 例。ＦＫ５０６ 组ＡＲ４ 例均逆转,肾功能２～１３ 天恢复正常４０ 例（８０％ ）,高血糖１４ 例（２８％ ）,肾中毒２ 例,肝中毒１ 例,腹泻２２ 例（４４％ ）,１ 例因肺部感染、高血糖难以控制仍改用ＣｓＡ。应用ＣｓＡ 肝中毒的１０ 例患者改用ＦＫ５０６ 后肝功能７ ～１６ 天全部恢复正常。　结论　肾移植术后应用ＦＫ５０６ 安全有效,排斥率明显降低,副作用小,但对长期存活的影响及并发症还需进一步观察。     

移植肾慢性排斥组织中血小板源性生长因子受体表达研究

目的探讨生长因子在同种异体肾移植慢性排斥反应肾组织中的表达、分布及临床意义。方法采用免疫组化ＳＰ法研究１２例正常肾、１４例肾癌旁及２３例慢性排斥肾组织中血小板源性生长因子受体（ＰＤＧＦＲ）表达。结果排斥肾组织ＰＤＧＦＲ表达阳性率为９１％，明显高于正常组织及癌旁组织（２５％，２８％），差异有显著性，ＰＤＧＦＲ主要表达于血管平滑肌、肾小球膜、肾小管等细胞的胞浆、胞膜及核膜。结论ＰＤＧＦＲ表达可调控正常肾组织，高表达与慢性排斥密切相关；未发现ＰＤＧＦＲ表达与临床症状相关。