再次肾移植受者和移植肾长期预后影响因素分析

目的探究再次肾移植受者和移植肾存活情况及长期预后影响因素。 方法回顾性分析1991年1月1日至2017年12月31日于浙江大学医学院附属第一医院肾脏病中心接受肾移植受者临床资料。共纳入再次肾移植受者37例,首次肾移植受者5 374例。根据再次肾移植受者移植肾存活时间长短,将其分为长期存活组(19例,>5年)和短期存活组(18例,≤5年)。采用成组t检验比较长期和短期存活组供受者年龄、首次与再次肾移植间隔时间、HLA错配数和再次移植供肾冷/热缺血时间。采用卡方检验比较长期和短期存活组受者性别、再次移植供肾类型、再次移植前后群体反应性抗体阳性比例、首次移植失功移植肾切除比例、再次移植前免疫诱导比例及再次移植后移植肾功能延迟恢复(DGF)和急性排斥反应发生比例。采用Kaplan-Meier法分析再次和首次肾移植受者/移植肾1、5和10年存活率。采用Cox比例风险模型分析影响再次肾移植术后移植肾长期存活影响因素。P<0.05为差异有统计学意义。 结果截至2018年3月1日,37例再次肾移植受者中位随访时间为152个月(11～323个月),2例死亡,18例发生移植肾失功,17例移植肾功能稳定。5 374例首次肾移植受者中位随访时间为108.9个月(0.1～350.0个月),459例死亡,1 343例发生移植肾失功。再次移植组受者/移植肾1、5和10年存活率分别为86%/81%、86%/62%和82%/36%,首次移植组受者/移植肾1、5和10年存活率分别为99%/98%、93%/89%和88%/80%。再次移植组移植肾1、5和10年存活率均低于首次移植组(χ²＝60.816、25.110和43.900,P均<0.05);再次移植组受者1年存活率低于首次移植组,差异有统计学意义(χ²＝40.409,P<0.05)。长期和短期存活组受者再次移植后移植肾DGF和急性排斥反应发生比例差异均有统计学意义(χ²＝4.039和4.748,P均<0.05)。Cox回归分析结果示DGF和急性排斥反应是影响再次肾移植受者移植肾长期存活的独立危险因素,差异有统计学意义(RR＝4.317和4.571,P均<0.05)。 结论再次肾移植受者移植肾存活率低于首次肾移植受者,DGF和急性排斥反应是影响再次移植受者移植肾存活的独立危险因素。     

丙型肝炎病毒感染对肾移植受者排斥反应及人/肾存活率的影响

目的 研究丙型肝炎病毒(HCV)感染是否影响移植肾急性和慢性排斥反应的发生率,以及受者和移植肾的存活率.方法 对1992年6月至2004年6月所行肾移植的495例受者进行了随访,其中术前HCV抗体阳性受者27例(HCV阳性组),随机抽取HCV抗体阴性受者27例作为对照组,行组间配对研究,分析HCV感染状态对肾移植受者急性和慢性排斥反应发生率以及人/肾存活率的影响.结果 HCV阳性组受者急性排斥反应的发生率显著高于对照组(19.14%和6.38%,P<0.01),HCV阳性组慢性排斥反应的发生率也明显高于对照组(23.40%和12.76%,P<0.01),对照组肾移植后1、3、5年人/肾存活率显著高于HCV阳性组,差异有统计学意义(P<0.01).结论 HCV感染可以明显增加肾移植受者急性和慢性排斥反应的发生率,降低人/肾存活率.     

再次肾移植的临床研究

目的对再次肾移植进行临床总结。方法回顾性分析86例再次移植患者的临床资料,并与86例首次肾移植患者进行对比分析。首次肾移植失败的原因,17例为超急性排斥反应,9例为急性排斥反应,55例为慢性移植肾肾病,4例为移植肾破裂,1例为严重肾结核;再次移植前,31例群体反应性抗体(PRA)或补体依赖细胞毒(CDC)阳性;再次移植后,16例采用泼尼松(Pred)和硫唑嘌呤(Aza)预防急性排斥反应,70例采用环孢素A(或他克莫司)、Aza(或霉酚酸酯)及Pred组成的三联用药方案,32例再次移植前后接受抗体诱导治疗。结果再移植组人/肾1、3和5年存活率分别为84.8%/61.6%、79.1%/45.3%和58.1%/41.9%,对照组分别为89.5%/79.1%、81.4%/74.4%和67.4%/58.1%,两组人存活率的差异无统计学意义,而各时间段的肾存活率的差异均有统计学意义(P<0.05);术前使用抗体诱导治疗者以及术后采用环孢素A(或他克莫司)预防排斥反应者移植肾1年存活率明显优于未用抗体诱导治疗者和仅用Aza、Pred治疗者;术后排斥反应发生率,再移植组明显高于首次移植组(P<0.05);再移植组术后感染发生率明显高于首次移植者。结论再次移植的肾存活率明显低于首次移植,术后排斥反应和感染的发生率较高;采用抗体诱导治疗有利于再移植肾的存活。     

他克莫司与环孢素A在高致敏肾移植受者中的应用比较

目的 观察和比较高致敏肾移植受者应用他克莫司(FK506)与环孢素A(CsA)的有效性和安全性.方法 根据术后免疫抑制方案的不同,将147例高致敏肾移植受者(其中术前群体反应性抗体＞50%的首次肾移植受者59例,2次肾移植受者88例)分为FK506组(53例)和CsA组(94例),两组的免疫抑制方案分别为FK506(或CsA)+霉酚酸酯+泼尼松.观察并分析两组受者术后移植肾存活率、血肌酐水平以及并发症的发生率.结果 FK506组术后1、3和5年的移植肾存活率(86.8%、82.3%和75.3%)略高于CsA组(81.9%、75.4%和66.9%),但差异无统计学意义(P＞0.05);FK506组术后1年时血肌酐水平为(100.72±15.88)μmol/L,CsA组为(117.29±11.77)μmol/L,两组比较,差异有统计学意义(P＜0.01);FK506组与CsA组相比,术后急性排斥反应、慢性排斥反应、肝功能损害、高血压和高血脂的发生率显著降低(P＜0.05),而高血糖的发生率明显升高(P＜0.01),两组移植肾功能延迟恢复和感染的发生率无明显差异(P＞0.05).结论 FK506与CsA相比,能有效降低高致敏受者肾移植术后急、慢性排斥反应的发生率,减少术后并发症的发生,提高移植肾的长期存活率,对高致敏肾移植受者是非常有效和安全的.     

肾移植术后远期移植肾功能丧失的原因浅析

近年来,随着临床肾移植技术的提高和免疫抑制方案的不断改善,肾移植后急性排斥反应发生率已经显著降低,移植肾术后近期存活率也不断提高.目前,如何提高移植肾远期存活率已成为大家关注的问题.不少临床研究显示,肾移植1年后,受者的移植肾功能会出现进行性减退,一部分受者会在术后5～10年内最终发生移植肾功能丧失,需再次行血液透析或再次肾移植.本文将对肾移植术后远期移植肾功能丧失的原因进行探讨,以供参考.     

急性体液性排斥反应对移植肾预后的影响

目的 探讨急性体液性排斥反应对移植肾预后的影响.方法 共有1098例接受首次尸体肾移植的受者纳入研究.所有受者术后均采用以他克莫司或环孢素A为基础的三联免疫抑制方案,当发生排斥反应时,采用甲泼尼龙冲击治疗,疗效较差者则联合应用莫罗单抗-CD3或丙种球蛋白或行血浆置换进行治疗.术后1年内经病理检查证实,有53例受者发生急性体液性排斥反应(急性体液性排斥反应组),109例发生急性细胞性排斥反应(急性细胞性排斥反应组),其余936例受者术后1年内肾功能稳定(对照组).分析和比较3组受者性别、年龄、术前淋巴毒、HLA抗原错配数、群体反应性抗体(PRA)水平及供肾冷/热缺血时间等冈素间的差异,比较3组受者术后移植肾功能丧失情况及移植肾存活率,分析完全逆转的急性体液性排斥反应与细胞性排斥反应对移植肾预后的影响.结果 3组受者在性别、年龄、术前淋巴细胞毒性试验、供肾冷缺血时间及术后随访时间等方面比较,差异均无统计学意义(P＜0.05).急性体液性排斥反应组和急性细胞性排斥反应组受者在术前HLA抗原错配数、PRA水平及供肾热缺血时间等方面均明显高于对照组,与对照组比较,差异均有统计学意义(P＜0.05).随访期间,急性体液性排斥反应组受者移植肾功能丧失的发生率为27.4%(14/53),明显高于急性细胞性排斥反应组的7.3%(8/109)和对照组的2.2%(21/936),3组间差异均有统计学意义(P＜0.01).通过kaplan-meier生存分析发现,急性体液性排斥反应组受者的移植肾存活率明显低于急性细胞性排斥反应组和对照组(P＜0.01).剔除发生排斥反应后未逆转者,3组间移植肾存活率的比较,差异均无统计学意义(P＞0.05).结论 急性体液性排斥反应明显影响移植肾存活,但完全逆转的急性体液排斥反应并不影响移植肾的预后.     

HLA配型对肾移植长期效果的影响(2508例次总结)

目的 探讨HLA配型对肾移植受者术后近期和远期效果的影响.方法 根据肾移植术前HLA配型结果,将2508例次肾移植受者分为7组(即:0、1、2、3、4、5、6个抗原错配组).观察HLA配型对受者术后急性排斥反应发生率以及移植肾1、5、10年存活率的影响.结果 2508例次进行了HLA-A、B、DR抗原配型的肾移植中,0个抗原错配仅有7例,2～3个抗原错配占74%.0个抗原错配组急性排斥反应发生率为5%,显著低于其他各组(P＜0.01);而6个抗原全部错配组急性排斥反应发生率为23%,显著高于其他各组(P＜0.01).0个抗原错配组移植肾1、5、10年存活率分别为97%、90%和88%;1个抗原错配组分别为94%、86%和83%;2个抗原错配组为94%、84%和82%;3个抗原错配组为93%、85%和81%;4个抗原错配组为91%、82%和74%;5个抗原错配组为90%、81%和72%;6个抗原错配组为88%、80%和70%.结论 良好的HLA配型可以降低肾移植急性排斥反应发生率;HLA抗原错配越少,移植肾的长期存活率越高;移植前供、受者HLA配型以抗原错配数≤3个为宜,尽量避免6个抗原全部错配.     

儿童肾移植46例报道

目的探讨儿童肾移植的手术特点、术后并发症及免疫抑制治疗方案。方法回顾性研究1998年2月至2004年12月46例儿童肾移植患者的临床资料。观察受者及移植肾存活情况,受者生长发育情况及术后并发症。结果46例儿童肾移植后发生急性排斥反应10例,肾功能延迟恢复4例,尿漏1例,肝功能损害8例,肺部感染8例,全骨髓抑制3例,粒细胞减少2例,输尿管坏死1例,移植肾动脉狭窄1例。术后4周所有患者肾功能均恢复正常。术后1年人和移植肾存活率均为100%,3年人和移植肾存活率分别为100%和97.4%。结论肾移植是治疗儿童终末期肾病的有效手段。儿童肾移植术后急性排斥发生率高,免疫抑制治疗应根据不同个体的特点制定不同的方案。     

乙型肝炎免疫球蛋白预防肾移植后新发乙型肝炎

目的 探讨肾移植受者应用小剂量乙型肝炎免疫球蛋白(HBIG)预防术后新发乙型肝炎的安全性和有效性.方法 回顾性分析单中心2007年1月至2010年6月间肾移植受者的资料,将术前无乙型肝炎的138例受者作为试验组,术前肌肉注射小剂量HBIG,术后定期监测乙型肝炎表面抗体(HBsAb)滴度,根据其滴度调整术后应用HBIG的剂量,持续应用1年或1年以上.将2004年1月至2006年12月间术前无乙型肝炎的196例肾移植受者作为对照组,不采用乙型肝炎预防措施.观察两组移植后新发乙型肝炎的发病率,并记录急性排斥反应发生情况、受者和移植肾1年存活率.结果 随访12个月,试验组仅1例(0.7％)于术后6个月出现新发乙型肝炎,对照组11例(5.6％)出现新发乙型肝炎,其中2例因爆发性肝功能衰竭而死亡.两组新发乙型肝炎发病率的差异有统计学意义(P＜0.05).术后6个月内,试验组有19例(13.8％)发生急性排斥反应,对照组有34例(17.3％)发生急性排斥反应,两组急性排斥反应发生率的差异无统计学意义(P＞0.05).试验组受者1年存活率为97.8％(135/138),移植肾1年存活率为(96.4％,133/138);对照组受者1年存活率为(91.8％,180/196),移植肾1年存活率为(90.3％,177/196).两组受者和移植肾1年存活率的差异有统计学意义(P＜0.05.P＜0.05).结论 小剂量HBIG用于肾移植后预防新发乙型肝炎是安全、有效的.     

改善移植肾长期存活策略的探讨

强效免疫抑制剂——钙调磷酸酶抑制剂(CNI)问世前,肾移植后排斥反应的发生率非常高,而移植肾的存活率较低.环孢素A的出现显著降低了移植物排斥反应发生率,提高了移植受者的存活率.而他克莫司的出现则进一步降低了移植后排斥反应的发生率,移植肾和受者的存活率均得到了显著改善.美国器官分配网络(UNOS)的统计资料显示,目前尸体肾移植术后受者和移植肾的5年存活率分别为66.5％和81.3％.与环孢素A相比,他克莫司可以带来更好的移植肾和受者存活率,他克莫司也已成为肾移植中应用最广泛的免疫抑制剂之一.免疫抑制剂的改进,有效的控制了移植后早期排斥反应的发生,使术后早期的移植肾功能得到明显改善,本文将对提高移植肾长期存活的策略进行探讨.     

Kidney Retransplantation: Removal or Persistence of the Previous Failed Allograft?

A significant percentage of patients with failed renal graft are candidates for retransplantation. The outcomes of retransplantation are poorer than those of primary transplantation and sensitization is documented to be a major reason. The management of a failed allograft that is not immediately symptomatic is still very controversial. The aim of this study was to determine the impact of the failed allograft nephrectomy on a subsequent transplantation and its importance in the sensitization. We performed a retrospective analysis of the local prospective transplantation registry of the outcome of 126 second kidney transplantations among 2438 transplantations performed in our unit between June 1980 and March 2013, comparing those who underwent allograft nephrectomy prior to retransplantation with those who retained the failed graft. Primary endpoints were graft and patient survival. The levels of panel-reactive antibodies (PRA) and rate of acute rejections on retransplantation outcomes were also studied. Among the 126 patients who underwent a second renal transplantation, 76 (60.3%) had a prior graft nephrectomy (Group A), whereas 50 (39.7%) kept their failed graft (Group B). Group A showed significantly more positive PRA levels when compared with the other group (38% vs 10%; P < .001), as measured before the most recent transplantation, and a higher rate of acute rejection (19% vs 5.6%; P = .016). There were 28 (36%) renal allograft losses for Group A and 18 (36%) for those who had not had transplantectomy (P = not significant [NS]). One-, 3-, and 5-year graft survival rates were 96.6%, 90.7%, and 83.4%, respectively, in Group A and 95%, 82%, and 68.4%, respectively, in Group B, with no statistical differences (P = .19). Five-year actuarial patient survival rates in the 2 groups was 89.3% and 82.8%, respectively (P = .55). Multivariate analysis showed that PRA level and delayed graft function (DGF) had a statistically significant influence on graft survival (P = .028; odds ratio [OR] = 1.029; and P = .024; OR = 8.6), irrespective of whether the patient had graft nephrectomy or not. The allosensitization indicated by PRA increases after transplantectomy and leads to a higher incidence of acute rejection after retransplantation. Nephrectomy of failed allograft does not seem to significantly influence the survival of a subsequent graft. The decision to remove or retain a failed graft in the context of retransplantation should thus be based on known clinical indications for the procedure.     

Long-Term Outcome of Kidney Retransplantation in Comparison With First Transplantation: A Propensity Score Matching Analysis

BackgroundAdvances in renal transplantation have improved graft survival. However, many patients experience graft failure due to chronic renal allograft nephropathy. Although renal retransplantation is increasingly performed, its outcome is controversial. The aim of this study was to evaluate outcomes of renal retransplantation compared with those of first renal transplantation.MethodsFrom March 1969 to August 2018, there were 3000 cases of renal transplantation performed at Seoul St. Mary’s Hospital, Korea. Because the number of third renal transplantation was too small, only first and second renal transplantation groups were compared using propensity score matching. Outcomes of the third renal transplantation were then added. Graft survival rates were determined using Kaplan-Meier survival curves and assessed for significance using log-rank test.ResultsFive- and 10-year patient-graft survival rates for the first renal transplantation were 82.6% and 72.8%, respectively. Those for the second renal transplantation were 78.4% and 73.9%, respectively (P = .588). Five- and 10-year patient survival rates were 91.2% and 85.1%, respectively, for the first renal transplantation. These were 87.8% and 85.5%, respectively, for the second renal transplantation (P = .684). Five- and 10-year death-censored graft survival rates were 88.8% and 80.6%, respectively, for the first renal transplantation. These were 84.6% and 80.5%, respectively, for the second renal transplantation (P = .564).ConclusionsThis study showed that graft survival of second renal transplantation was not significantly different from that of first renal transplantation. Therefore, renal retransplantation might be a reasonable option for patients who lost the first renal graft.     

群体反应性抗体在肾移植中的意义

目的 研究群体反应性抗体（ＰＲＡ０在肾移植中的意义。方法 对１７８例肾移植患者进行了术前、术后ＰＲＡ检测。结果 肾移植术前ＰＲＡ阳性患者有２３例,肾移植术后发生急性排斥反应的为２０例。术后ＰＲＡ阳性受者５８例,发生排斥反应的有３４例。移植前后ＰＲＡ阴性患者有１０８例,有８例发生排斥。在肾移植患者中所产生的抗ＨＬＡ抗体的频率和ＨＬＡ抗原的分布不同。结论 ＰＲＡ检测对预测移植肾排斥有重要意义。     

肾移植受者致敏状态的预测及其临床意义

群体反应性抗体（ＰＲＡ）的测定对了解受者体内抗ＨＬＡ抗体的水平及致敏状态，预防超急和加速排斥反应的发生具有重要意义，其敏感性明显高于供受者交叉配型试验（ＣＤＣ），高ＰＲＡ（阳性率≥５０％）与严重排斥反应及移植物存活率下降密切相关。血浆置换（ＰＥ）能有效清除ＰＲＡ阳性受者血清中的抗体，避免超急和加速排斥反应的发生，但良好的ＨＬＡ配型对提高ＰＲＡ阳性患者的手术成功率和移植物存活率更重要。通过随机多次淋     

Are autoimmune diseases or glomerulonephritis affecting the development of panel-reactive antibodies in candidates for renal transplantation?

Panel-reactive antibodies (PRA) are a major obstacle to kidney transplantation (KTx). It is not completely clear why only some patients develop PRA, whereas others do not. We hypothesized that other factors, such as autoimmune diseases involving the kidney, might be a trigger for PRA development. We reviewed the original diseases that led to renal failure and their possible role in PRA development. Charts of 270 patients on the active waiting list for KTx were reviewed for complete demographics, presence of PRA, peak PRA level, first KTx or retransplantation, original disease, blood transfusions, pregnancy and rejection. Patients were divided into group 1 (PRA >10%) and group 2 (PRA <10%). There was a significantly higher proportion of patients in group 1 with autoimmune diseases than in group 2. The same proportion was found significant for all of the patients as well as for the patients listed for the first KTx (new patients). Previous KTx has significant impact on both class I and II peak PRA levels when compared with new patients who are already sensitized. A subanalysis of retransplantation showed patients with autoimmune disease (54%) have more graft loss due to rejection compared with nonautoimmune disease (43%). There is an association between high PRA level and autoimmune diseases causing renal failure regardless of the previous KTx status. Besides the risk of recurrence, autoimmune disease seems to affect the risk of graft loss due to rejection.     

Single‐center experience with third and fourth kidney transplants

Kidney retransplantation is often associated with a higher immunological risk than is primary renal transplantation. Faced with increasing organ shortage and growing waiting lists, results of kidney retransplantation are of particular interest. Fifty‐six third and fourth kidney transplants were analyzed retrospectively. Parameters included patient and donor demographics, operative details, incidence of surgical, immunological and infectious complications and patient and graft survival. Patients receiving third kidney grafts had 1‐ and 5‐year patient/graft survival rates of 97.4%/72.9% and 88.9%/53.6%, respectively. Episodes of acute rejection and delayed graft function were observed in 44% and 49% of these patients. Fourth kidney transplantation was associated with 1‐ and 2‐year patient/graft survival rates of 84.8%/68.5% and 63.6%/47%, respectively. Acute rejection and delayed graft function occurred in 33% and in 60% of cases. Acceptable patient and graft survival may be achieved after third and fourth kidney transplantation. Graft losses in this sensitized population are mainly because of rejection. Profound immunosuppression may lead to major infectious problems.     

肾移植受者HLA特异性抗体的监测及临床应用

目的：探讨人类白细胞抗原（HLA）群体反应性抗体（PRA）对肾脏移植效果的影响。方法：采用酶联免疫吸附法（ELISA）和微量补体依赖性细胞毒试验（CDC）对897例例次肾移植受者的PRA进行动态监测。结果856例初次肾移植受者中术前PRA阳性者121例,占11％,而33例次2次移植和8次3次移植受者术前PRA阳性分别为58％和87％,与初次肾移植受者组比较,PRA阳性受者比例均显著增高（P＜0．001）。PRA阳性组受者肾移植术后排斥发生率为40％,而阴性组受者仅17％,两组比较有显著性（P＜0．01）。PRA阳性组受者的移植物存活率则明显低于阴性组（P＜0．001）,尤其是PRA＞40％的高效敏受者的1、3、5年和7年多移植物存活率与阴性组比较分别下降了24％、38％、57％和56％,均为P＜0．001。ELISA法与CDC法的双盲试验发现,319份受者血清中CDC－PRA的假阳性和假阴性率分别为3．8％和3．1％。结论PRA是预测受者致敏状态的敏感指标,对移植后排斥反应和移植物存活率均有明显影响。     

群体反应性抗体检测在肾移植中的应用

目的 了解肾移植受者的ＨＬＡ体液致敏状态及致敏者受者的ＨＬＡ抗体特异性,筛选合适供者。方法 应用配组淋巴细胞板通过微量补体依赖淋巴细胞毒试验检测６２３例患者的群体反应性抗体（ＰＲＡ）。结果 肾移植受者中ＰＲＡ阳性受者占１１．５％,致敏受者移植后排斥反应发生率明显高于非致敏受者（Ｐ〈０．０１）,而移植物存活率则显著低于非致敏受者（Ｐ〈０．０１）。移植后ＰＲＡ水平升高级的排斥发生率和移植物丢失率殚显著     

肾移植2 123例临床总结

目的：总结肾移植的临床经验,探讨影响肾移植存活的因素,提高长期存活率。方法：回顾性总结2123例肾移植病例的临床资料,对人和（或）肾存活率,供肾的切取,灌注,热冷缺血时间对移植的影响,植肾技术,免疫抑制剂的应用,HLA配型,群体反应抗体（PRA）检测及术后并发症的发生情况等进行了分析。结果：1978－1990年423例中发生超急性排斥反应者9例（2．1％）,急性排斥反应198例（46．8％）,1,3和5年人和（或）肾存活率为86.7%/76.3%,72.5%/67.9%和69.5%/59.3%,1991-2001年,共1700例肾移植,其中未发生超急性排斥反应,急性排斥反应252例（14.8%),1,3和5年人（或）肾存活率高达98.6%/96.7%,93.1%/87.3%和88.1%／83.6%。结论：适应证的选择,高质量的供肾是保证肾移植成功的关键;PRA的检测,良好的HLA配型有利于减少移植肾的早期失功能并提高肾移植长期存活率;加强对肾移植患者的随访,指导康复治疗,对患者能否长期存活有重要意义。