肾移植术后供者特异性抗体对移植肾近期效果的影响

目的 评价肾移植术后供者特异性抗体(Ds-Ab)对移植肾近期效果的影响。方法 对2001年1月至2002年7月间进行尸肾移植的92例受者，使用酶联免疫吸附(ELISA)法，检测受者血清中HLA抗体水平，随访1年。结果 16例(17．4％)受者术后出现供者特异性抗体。抗体阳性组急性排斥发生率(56．3％)高于抗体阴性组(11．9％)，P=0．000；移植肾功能延迟恢复的发生率(12．5％)与抗体阴性组(9．2％)比较，差异无显著性，P=0．102；供者特异性抗体阳性组受者发生急性排斥后，移植肾肌酐水平高于抗体阴性组或无急性排斥组。结论 供者特异性抗体与肾移植术后急性排斥有关，可能影响近期移植肾功能。     

达昔单抗预防肾移植术后急性排斥反应的效果

目的　探讨达昔单抗 (Dac ,赛尼哌 )在预防肾移植术后急性排斥反应中的作用。　方法　 2 92例肾移植患者随机分为达昔单抗治疗组 (94例 )与对照组 (198)例 ,分析 2组移植肾功能、急性排斥反应发生情况以及外周血T细胞亚群的变化。　结果　术后 1、6及 12个月时达昔单抗组移植肾功能优于对照组 ,术后 12个月时 2组SCr浓度分别为 (133.2± 4 6 .8)和 (16 5 .7± 5 5 .2 ) μmol/L ,差异有统计学意义 (P <0 .0 5 )。术后 6个月时达昔单抗组急性排斥反应发生率为 2 3.4 % ,对照组为38.4 % ,差异有统计学意义 (P <0 .0 5 ) ;术后 2组CD+ 3 与CD+ 4 表达均下降 ,但差异无统计学意义 (P>0 .0 5 )。　结论　达昔单抗可以降低急性排斥反应发生率 ,改善移植肾功能 ,对T细胞亚群无明显影响。     

移植肾切除对特异性抗HLA抗体水平的影响

目的 探讨移植肾切除对患者血中抗HLA抗体的影响。方法 采用LAT抗原板、微量酶联免疫吸附法测定血中特异性抗HLA-Ⅰ类、Ⅱ类IgG抗体水平，比较分析37例致敏患者移植肾切除前后抗HLA抗体水平。结果 37例患者中，术前抗HLA-Ⅰ类抗体升高9例（24．3％），Ⅱ类抗体升高12例（32．4％），两类抗体均升高者16例（43．2％）。移植肾切除后3、6、12个月时的抗体总水平与术前相比差异无统计学意义。25例术前Ⅰ类抗体升高的患者，术后6个月内抗体降至正常或下降〉30％者9例（36．0％），术后12个月时降至正常或下降〉30％者8例（32．0％）。术后Ⅰ类抗体下降至正常或〈20％者，术前均〈30％。28例术前Ⅱ类抗体升高患者中，术后6个月内降至正常或下降〉30％者7例（25．0％），术后6个月内抗体水平未下降者，此后下降的可能性更小。结论 对等待再次移植的PRA升高患者不应一律行移植肾切除，轻度致敏（PRA〈30％）患者宜尽早切除移植肾。     

HLA配型与肾移植术后早期急性排斥反应的关系

目的 研究ＨＬＡ配型与尸体肾移植术后早期急性排斥反应的关系。方法 将２６２例尸体肾移植受者按ＨＬＡ配型的误配率（ＭＭ）进行分组,统计各组术后１～２个月内急性排斥反应的发生次数。结果 当ＭＭ〉３时,若接受的器官ＨＬＡ抗原／基因为可接受性,术后急性排斥反应的发生率为１６．４％;若供体器官ＨＬＡ抗原／基因具免疫原性,则急性排斥反应的发生率为３３．１％,两者比较,Ｐ〈０．０５。结论 供受者间ＨＬＡ配型越好     

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-…     

肾移植术后抗HLA抗体的检测

肾移植术后抗HLA抗体的产生与急、慢性排斥反应都有直接或间接的关系。及时检测并去除抗HLA抗体可显著提高移植物存活率。本文综述了近年有关抗HLA抗体的研究及进行移植术后常规检测的意义。     

儿童肾移植术后供者特异性抗体的产生及其影响

近年来,我国儿童肾移植发展迅速,但仍缺乏足够的有关移植肾长期存活方面的临床数据。成人肾移植术后新生供者特异性抗体（dnDSA）的产生及其介导的慢性排斥反应是影响移植肾长期存活的重要危险因素,但儿童的免疫系统发育尚未完全,其术后dnDSA的产生及其对移植肾和受者的影响可能与成人有所不同。因此,本文就儿童免疫系统的特点、儿童肾移植术后供者特异性抗体（DSA）的产生及影响、儿童肾移植术后DSA产生的危险因素进行总结,并对预防策略提出建议,旨在为提高儿童肾移植术后移植肾的长期存活提供参考,促进我国儿童肾移植的发展。     

趋化因子RANTES在肾移植术后急性排斥反应中的表达及意义

为了探讨趋化因子家族之一的RANTES在肾移植术后急性排斥反应中的意义，我们采用RT—PCR等方法对57例移植肾穿刺组织RANTES表达进行检测，现报告如下。     

HLA致敏原性错配对肾移植受者急性排斥反应发生率的影响

目的：探讨供受者HLA致敏原性错配(IM)对肾移植受者急性排斥反应发生率的影响。方法：回顾性分析196例首次肾移植受者IM对肾移植术后肾功能的恢复时间及1年内排斥反应发生率情况。结果：IM对肾移植术后肾功能恢复时间无明显影响；IM患者1年内急性排斥率明显增加；各类位点IM对肾移植术后急性排斥反应的影响进行比较，A位点影响不大，B位点与急性排斥反应有关，DR位点IM可致急性排斥反应明显增加。结论：在临床采用氨基酸残基配型标准判断组织配型的同时，IM不容忽视，HLA-B位点IM与肾移植术后急性排斥反应相关，HLA-DR位点IM明显影响肾移植术后排斥反应发生率。     

肾移植后急性排斥反应发生相关术前因素分析

目的探讨影响肾移植术后发生急性排斥反应的相关术前因素,为预防移植肾急性排斥反应的发生提供临床依据。方法回顾性分析2002年1月～2008年12月在浙江大学医学院附属第一医院肾脏病中心首次接受同种异体尸体肾移植受者1316例资料,记录基线资料及术后急性排斥反应发生情况;按群体反应性抗体(PRA)水平10%和≥10%将受者分为PRA阴性组和致敏组;以2005年10月1日为界分为回顾性HLA配型组和前瞻性HLA配型组。统计分析各基线资料对术后急性排斥反应发生的影响以及不同组间急性排斥反应发生率的差异。结果手术时受者年龄、术前PRA水平、热缺血时间、HLA错配数对术后急性排斥反应的发生有显著影响。致敏组术后6个月内急性排斥反应发生率(58.8%比17.9%,P0.001)以及6个月内组织病理学检查证实急性排斥反应发生率(29.4%比11.9%,P=0.028)均显著高于PRA阴性组。采用前瞻性HLA配型后受者HLA错配数减少,且术后6个月内急性排斥反应发生率也降低(20.9%比15.5%,P=0.012)。结论术前检测受者的PRA水平从而准确评估其致敏状态,尽可能选择良好的HLA配型谱可减少移植肾术后急性排斥反应的发生。     

Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction

BACKGROUND: The goal of this study was to determine whether the production of posttransplant antibodies directed against donor HLA mismatches (donor specific antibody; DSA) is associated with renal allograft rejection and early graft dysfunction. METHODS: Forty-nine adult renal allograft recipients with increased risk of rejection were enrolled during the period of October 2001 through May 2003 and were prospectively monitored for the development of anti-HLA antibodies. RESULTS: Of 49 patients, eight (16.3 %) patients were diagnosed with acute humoral rejection (AHR) and 11/49 (22.4%) patients were diagnosed with acute cellular rejection (ACR). A strong association between pretransplant HLA sensitization and AHR was found (P=0.005). Of the eight patients diagnosed with AHR, the majority developed DSA before or concomitant with episodes of rejection (P<0.001). Only 3 of 41 patients (7.3%) without AHR developed DSA. The pathogenic role of alloantibodies was further substantiated by analyzing their association with graft function as measured by serum creatinine levels. The average serum creatinine after the third month posttransplantation in DSA producers was 2.24+/-1.01 mg/dL, while in non-DSA patients the average serum creatinine was 1.41+/-0.37 mg/dL (P<0.01). CONCLUSION: This study reveals a strong association between the production of DSA, AHR, and early graft dysfunction. Our findings indicate that prospective monitoring for anti-HLA antibodies following transplantation is a useful test for the diagnosis and classification of AHR for identifying patients at risk of early graft dysfunction.     

肾移植患者急性排斥反应与sCD30的相关性

目的 研究检测肾移植患者手术前后血清溶解性CD30（sCD30）水平的临床意义。方法 采用酶联免疫吸附剂测定法（ELISA）检测69例肾移植患者术前及术后sCD30的水平，并分析sCD30与肾移植受者术后急性排斥发生的关系。结果 术前sCD30阳性患者11例，其中有6例发生急性排斥，sCD30阴性患者58例，发生急性排斥5例。两组相比排斥反应发生率差异有统计学意义（P〈0．01）。术后5dsCD30在发生排斥患者组中的水平与对照组间差异有统计学意义（P〈0．05），而术后1、3d水平两组间差异无统计学意义（P〉0．05）。结论 肾移植手术前后监测sCD30水平，特别是术前及术后第5天左右时的检测水平，对于评估和预测急性排斥反应发生的可能性，具有重要的参考价值。     

Effect of acute rejection episode on occurrence of chronic rejection after kidney transplantation

Chronic rejection is the most prevalent cause of renal transplant failure in the late post-transplant period. The clinical significance of acute rejection episodes on occurrence of chronic rejection is controversial. We analyzed 503 cases of the first renal transplantation maintained by calcinurine inhibitor for the correlation of acute rejection and clinical chronic rejection. The later the first episode of acute rejection occurred, the shorter was the half-life of graft. The acute rejection occurring within 3 post-transplant months worsens long-term graft survival if the peak creatinine level exceeds 2 mg/dl. Multivariate analysis by the Cox proportional hazard model for factors affecting cadaver graft loss by chronic rejection, revealed that the risk factor of acute early rejection was lower than those of donor age and post-transplant hypertension.     

The early posttransplant prognosis of acute renal allograft rejection as determined by detection of cytotoxic antibodies to lymphoid B cell lines

We have studied serial samples of pretransplant and posttransplant sera for cytotoxic antibodies to lymphoid B cell lines (LCL) in 45 renal allograft recipients. A total of 48 rejection reactions occurred in 31 patients. A comparison of each patient's most reactive posttransplant serum showed a significantly higher reactivity in the ten patients with early allograft failure when compared with the 21 patients with reversible rejections and the 14 patients who had no rejections. Rejection reactions were easily differentiated by comparing the change in cytotoxic reactivity to LCL of recipients' sera drawn at the time of a rejection episode with the reactivity of their pretransplant sera. In 32 rejections considered non-antibody-associated cytotoxic reactivity of recipients' sera to LCL either decreased or remained essentially unchanged during the rejection. In 16 rejections considered antibody-associated the recipients' sera drawn during the rejection episode showed an increase in cytotoxic reactivity ranging from 40% to 100%. Response to antirejection therapy and three month graft survival had a significant correlation with changes in LCL antibody reactivity during a rejection. Only two of the 32 rejections considered non-antibody-associated failed to reverse compared with eight of the 16 antibody-associated rejections (P less than .001). Graft survival at three months in patients with non-antibody-associated rejections was 90% compared with 27% in the 11 patients who had antibody-associated rejections (P less than .001) Other parameters possibly related to the severity of a rejection reaction or to early allograft prognosis did not differ appreciably between the two types of rejections. This included the time posttransplant to the first rejection episode, the number of patients with multiple rejections in the first three months, and rejections requiring dialysis therapy. Determination of a change in cytotoxic reactivity to LCL during a rejection reaction enables one to predict the response to antirejection therapy and early allograft prognosis. This may ultimately be useful in selecting different types of antirejection therapy for individual patients.     

急性体液性排斥反应对移植肾预后的影响

Objective To explore the effect of acute humoral rejection on kidney graft survival.Methods 1098 patients received cadaveric renal transplant from January 2002 to December 2008 in our center. All patients were given triple immunosuppressants including tacrolimus or cyclosporine.According to patients who experienced biopsy-proved humoral rejection and cellular rejection within one year post-transplant, there were 53 cases in humoral rejection group, 109 in cellular rejection group (including 63 patients with borderline change), and 936 in normal group. Patients who experienced acute rejection received mythyl-prednisolone pulse, or received anti-CD3 antibody/plasma exchange/globulin. Clinical characteristics before operation including sex, age, HLA mismatch, panel reactive antibody, cold/warm ischemic time, graft loss rate and graft survival were compared among three groups. The effect of completely reversed cellular rejection and humoral rejection on graft survival was analyzed. Results There was no significant difference in sex, age and cold ischemic time among three groups, but there was significant difference in warm ischemic time, level of PRA and HLA mismatch between cellular rejection group or humor rejection group and normal group (P＜0. 05). During a follow-up period, the incidence of graft loss in humoral rejection group was 27.4 %, significantly higher than 7.3 % in cellular rejection group and 2.2 % in normal group, P＜0. 001. Kaplan-Meier analysis revealed the survival rate of grafts in humoral rejection group was significantly lower than in cellular rejection group and normal group (P＜0.001 ). After patients with irreversible rejection were excluded,there was no significant difference in the survival rate of grafts among the three groups.Conclusion Patients with acute humoral rejection survived with inferior graft outcome,but completely reversible rejection showed no effect on the graft survival.     

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.     

急性体液性排斥反应对移植肾预后的影响

Objective To explore the effect of acute humoral rejection on kidney graft survival.Methods 1098 patients received cadaveric renal transplant from January 2002 to December 2008 in our center. All patients were given triple immunosuppressants including tacrolimus or cyclosporine.According to patients who experienced biopsy-proved humoral rejection and cellular rejection within one year post-transplant, there were 53 cases in humoral rejection group, 109 in cellular rejection group (including 63 patients with borderline change), and 936 in normal group. Patients who experienced acute rejection received mythyl-prednisolone pulse, or received anti-CD3 antibody/plasma exchange/globulin. Clinical characteristics before operation including sex, age, HLA mismatch, panel reactive antibody, cold/warm ischemic time, graft loss rate and graft survival were compared among three groups. The effect of completely reversed cellular rejection and humoral rejection on graft survival was analyzed. Results There was no significant difference in sex, age and cold ischemic time among three groups, but there was significant difference in warm ischemic time, level of PRA and HLA mismatch between cellular rejection group or humor rejection group and normal group (P＜0. 05). During a follow-up period, the incidence of graft loss in humoral rejection group was 27.4 %, significantly higher than 7.3 % in cellular rejection group and 2.2 % in normal group, P＜0. 001. Kaplan-Meier analysis revealed the survival rate of grafts in humoral rejection group was significantly lower than in cellular rejection group and normal group (P＜0.001 ). After patients with irreversible rejection were excluded,there was no significant difference in the survival rate of grafts among the three groups.Conclusion Patients with acute humoral rejection survived with inferior graft outcome,but completely reversible rejection showed no effect on the graft survival.     

肾移植术后抗HLA抗体升高对移植肾功能的慢性损害作用

目的 探讨肾移植术后抗HLA抗体升高对移植肾功能的慢性损害作用.方法 采用免疫荧光液相芯片技术检测57例肾移植术后半年以上受者的抗HLA抗体水平,根据抗HLA抗体水平的不同,将受者分为抗HIA抗体(≥10%)阳性组和抗HLA抗体(＜10%)阴性组.再根据阳性组中抗HLA抗体类别的不同,将受者分为抗HLA-Ⅰ类抗体阳性、Ⅱ类抗体阴性(Ⅰ+Ⅱ+)组,抗HLA-Ⅰ类、Ⅱ类抗体均阳性(Ⅰ+Ⅱ+)组和抗HLA-Ⅰ类抗体阴性、Ⅱ类抗体阳性(Ⅰ-Ⅱ+)组.观察和比较各组受者的临床资料和血肌酐(Cr)水平,并进行统计学分析.结果 57例受者中,抗HLA抗体阴性组41例(71.9%),阳性组16例(28.1%);阳性组中,Ⅰ+Ⅱ-组和Ⅰ+Ⅱ+组受者各3例,I-II'组10例.抗HLA抗体阴性组和阳性组受者的肾移植术后时间分别为(4.55±3.16)年和(6.64±3.66)年(P＜0.5),随着术后时间的延长,抗HLA抗体阳性者呈上升趋势.抗HLA抗体阴性组有13例(31.7%)血Cr异常,平均血Cr水平为(92.12±27.52)μmol/L;阳性组有13例(81.3%)血Cr异常,平均血Cr水平为(191.1±119.95)μmaol/L,其中又以Ⅰ+Ⅱ+组的受者血Cr水平最高,为(213.00±165.38)μmol/L,与抗HLA抗体阴性组比较,差异有统计学意义(P＜0.05).结论 抗HLA抗体升高是影响肾移植预后的重要标志物;尤其是抗HLA-Ⅱ类抗体升高对移植肾功能有慢性损害作用.     

HLA mismatches remain risk factors for acute kidney allograft rejection in patients receiving quadruple immunosuppression with anti-interleukin-2 receptor antibodies

BACKGROUND: New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned. METHODS: We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling. RESULTS: Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation. CONCLUSIONS: Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.     

HLA compatibility and different features of liver allograft rejection

The influence of human leukocyte antigen (HLA) on acute liver allograft rejection was investigated in 48 adult patients. The diagnosis of rejection was always based on the full triad of histological findings, clinical signs, and the required antirejection treatment. Sixty-two percent of the patients closely observed for 6 months postoperatively revealed acute rejection within the first 3 weeks, mostly on days 7–11. HLA compatibility was not observed to have any significant influence on the incidence of acute rejection. However, different histological and clinical features were revealed in conjunction with DR compatibility. Patients without DR compatibility showed a type of rejection with fever and increase of bilirubin, frequently associated with cholestasis and cholangitis, which sometimes persisted for weeks. Patients with 1 DR compatibility showed a predominant increase of transaminases, which was never associated with cholangitis. The conjunction of different DR compatibilities and various clinical signs may indicate possible pathways from immunological assault to the clinical appearance of acute rejection. A knowledge of a patient's individual compatibility and an expectation of certain rejection patterns may lead to earlier and more reliable diagnosis and treatment.