High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study

In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.     

成人肝移植术后抗体介导排斥反应的治疗

目的探讨合理有效的肝移植术后抗体介导排斥反应(AMR)治疗方案。 方法回顾性分析2015年3月至2018年12月天津市第一中心医院成人肝移植术后发生AMR受者和同期肝移植术后发生急性细胞性排斥反应(ACR)受者的临床资料。收集两组受者围手术期资料、糖皮质激素使用剂量及维持时间、干预治疗以及病情转归等数据,比较常规抗排斥反应治疗方案对肝移植术后AMR与ACR的疗效差异。采用成组t检验比较两组供者年龄、受者年龄、术前终末期肝病模型(model for end-stage liver disease,MELD)评分以及肝移植至诊断ACR或AMR的时间间隔等指标。计数资料以百分比表示,采用Fisher确切概率法比较两组受者原发病、抗排斥反应治疗及联合干预情况。P<0.05为差异有统计学意义。 结果AMR发生时间晚于ACR,AMR组和ACR组确诊时间分别为肝移植术后(413±97)d和(12±5)d (t＝30.430,P<0.05)。AMR组糖皮质激素治疗时间长于ACR组,分别为(29±15)d和(11±6)d (t＝6.122,P<0.05)。在接受标准免疫抑制方案的情况下,与ACR组相比,AMR组需要糖皮质激素冲击治疗的受者比例高于ACR组(8/8和21/50, P<0.05),需要给予联合干预治疗的受者比例也高于ACR组(3/8和0,P<0.05)。 结论与ACR相比,AMR通常需要延长糖皮质激素使用疗程,并联合丙种球蛋白、血浆置换及其他方法进行联合干预。     

Borderline rejection after renal transplantation – to treat or not to treat

Abstract:  According to the Banff classification of renal allograft pathology, the category borderline changes defines changes insufficient for a diagnosis of acute rejection. The relationship between borderline changes and acute renal allograft rejection still remains unclear. The appropriate clinical management for patients showing such changes is controversial. One possible interpretation of the high incidence of subacute tubulitis is that these changes in the absence of graft dysfunction are of no consequence and that treatment with intensified immunosuppression is unnecessary and perhaps harmful. Another view, consistent with the high incidence of CAN in late protocol biopsy studies, is that immunosuppression has become so powerful, that rejection may not even be manifested by a rising serum creatinine. Borderline changes should be used as part of an algorithm, but not as the only criterion, for therapeutic decision making. Based on the weak evidence of existing studies, in our patients with clinical borderline rejection, we have to weigh the individual immunological risk against the potential side effects of increased immunosuppression. Even in the knowledge that a majority of patients with borderline infiltrates will not progress into rejection, in many transplant centers, borderline rejection is treated with additional steroids or augmentation of maintenance immunosuppression.     

儿童肾移植术后急性排斥反应的特点及思考

得益于\"儿童供肾优先分配给儿童受者\"的现行国家器官分配政策,我国儿童肾移植得到了快速的发展,但儿童肾移植的效果还有待进一步系统总结。本文通过总结儿童免疫系统的特点及相关研究进展、儿童肾移植术后急性排斥反应的发生率及影响因素,比较兔抗人胸腺细胞免疫球蛋白及抗CD25单抗诱导治疗对儿童肾移植术后急性排斥反应的预防效果,并对其未来的应用提出建议。     

抗体诱导治疗在肝移植中的应用进展

应用生物蛋白制剂——抗体作为器官移植早期实施免疫抑制覆盖治疗的方法,可显著减少器官移植术后早期急性排斥反应的发生,且未显著增加移植后感染发生率,同时可延迟或减少CNI的应用,有利于保护肾功能、促进移植物功能恢复及受者长期存活。本文通过总结常见抗体免疫诱导剂的特点及作用机制,分析不同抗体诱导治疗应用于肝移植的临床获益与风险,为肝移植抗体诱导剂的合理使用提供参考。     

儿童肾移植术后急性排斥反应相关影响因素的单中心队列研究

目的 总结单中心儿童肾移植后急性排斥反应(acute rejection,AR)发生情况和对移植物及受者存活的影响及AR发生的相关因素。 方法 回顾性分析华中科技大学同济医学院附属同济医院器官移植研究所2014年5月1日至2022年5月20日行儿童肾移植155例的临床资料,排除12例术后1周内发生移植肾血栓受者后,最终纳入143例。根据是否发生AR分为AR组(29例)和无AR组(114例),比较两组供受者的基本资料和移植肾/受者存活率,采用逻辑回归分析AR的相关影响因素。 结果 143例儿童肾移植中,130例(90.9%)来自尸体供肾,其中儿童供肾120例(83.9%)。27例(18.9%)为婴幼儿受者(年龄<3岁)。中位随访时间为33.0(14.0,58.6)个月,29例(20.3%)出现34次AR。AR组的再次移植、儿童供肾和兔抗人胸腺细胞免疫球蛋白(rabbit anti-human thymocyte globulin,rATG)诱导比率分别为27.6%(8/29)、96.5%(28/29)和79.3%(23/29),均显著高于无AR组的7.9%(9/114)、80.7%(92/114)和36.0%(41/114),组间比较,差异均有统计学意义(P＝0.007,P＝0.046,P<0.001)。多因素回归分析显示,巴利昔单抗诱导比rATG诱导显著降低AR风险(比值比为0.13,95%CI：0.04~0.43,P<0.001)。AR事件发生的中位时间为术后1.3个月,23次(67.6%)为穿刺活检证实。抗AR治疗后52.9%(18/34)获得治愈,38.3%(13/34)移植肾功能好转,8.8%(3/34)因AR不可逆导致移植肾功能丧失。AR组1年、3年的移植肾存活率分别为75.3%和68.4%,显著低于无AR组的95.2%和90.4%,组间比较,差异均有统计学意义(P＝0.01),而两组间受者的1年、3年存活率差异无统计学意义。 结论 儿童肾移植术后AR发生率较高且对移植肾存活有一定影响,巴利昔单抗诱导可有效降低AR风险。     

Prompt treatment of initial acute rejection episodes may improve long-term graft outcome

Abstract Acute rejection episodes have been cited as a major immunological risk factor for the development of chronic rejection. To examine the influence of a single rejection event on ultimate graft outcome, acutely rejection rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time. Early structural changes (days 3 and 4) were completely reversible, while signs of chronic rejection did become obvious during the long-term follow up. More advanced deteriorated grafts (days 5 and 7) were irreversibly damaged and the rats died shortly after retransplantation. Those results indicate the critical impact of acute rejection episodes on chronic graft rejection. Immediate and aggressive treatment of acute rejection episodes may remove this event as a risk factor for late deteriorating changes.     

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5–8 years. Post-transplant sodium iothalamate clearances (IoCl) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 % (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed. Received: 9 March 1999/Revised: 28 December 2000/Accepted: 11 April 2000     

Human Leukocyte Antigen Antibodies for Monitoring Transplant Patients

Human leukocyte antigen (HLA) antibody-mediated hyperacute rejection has dramatically decreased since the clinical introduction of crossmatch technology. However, the role of HLA antibody in acute and chronic rejection remains unclear. In this article, we cite publications to show the correlation between HLA antibody and allograft rejection. Potential pathological mechanisms of antibody-mediated rejection are also proposed and the rationale of commonly used HLA antibody detection techniques are introduced. The advantages and disadvantages of these technologies are further discussed in detail. We conclude that owing to the recent availability of improved antibody detection methods, a causal relationship between HLA antibodies and allograft rejection is now considered to exist.     

肾移植术后中远期急性排斥反应临床研究

目的探讨肾移植术后中远期移植肾急性排斥反应(AR)发生影响因素及移植肾生存情况。 方法回顾性分析浙江大学医学院附属第一医院肾脏病中心2018年1月至2019年12月因血清肌酐水平升高而接受移植肾病理活检并确诊移植肾AR受者临床资料,共纳入43例受者,其中急性抗体排斥反应组17例,急性T细胞排斥反应组26例;同时纳入同期(2周内)肾移植且移植肾功能正常的39例受者为对照组。正态分布计量资料比较采用配对t检验或单因素方差分析。计数资料比较采用χ²检验或Fisher确切概率法。采用Kaplan-Meier进行生存分析,并采用log-rank进行比较。P<0.05为差异有统计学意义。 结果急性抗体排斥反应组HLA-A错配2个比例(4/17)高于对照组(1/39),差异有统计学意义(P＝0.026)。急性抗体排斥反应组和急性T细胞排斥反应组AR发生时和末次血清肌酐和估算肾小球滤过率(eGFR)均高于AR发生前(P均<0.05);急性抗体排斥反应组和急性T细胞排斥反应组AR发生时和末次血清肌酐和eGFR均高于对照组(P均<0.05);急性抗体排斥反应组进入慢性肾脏病(CKD)-4期受者比例低于急性T细胞排斥反应组(χ²＝5.73,P<0.05);急性T细胞排斥反应组进入CKD-4期受者比例以及急性抗体排斥反应组移植肾失功比例均高于对照组(χ²＝17.727和9.882,P均<0.05)。AR发生时急性抗体排斥反应组和急性T细胞排斥反应组受者均接受PRA检测,前者PRA-Ⅰ和PRA-Ⅱ阳性比例分别为41.2%(7/17)和88.2%(15/17),均高于后者[11.5%(3/26)和26.9%(7/26)],差异均有统计学意义(P＝0.042,P<0.001)。急性抗体排斥反应组、急性T细胞排斥反应组及对照组术后分别有13、24和38例受者应用他克莫司。发生AR时,急性抗体排斥反应组他克莫司血药浓度[(3.72±0.76)ng/mL]与急性T细胞排斥反应组[(3.37±0.86)ng/mL]均低于对照组[(5.73±1.25)ng/mL],差异均有统计学意义(P均<0.05);急性抗体排斥反应组与急性T细胞排斥反应组他克莫司血药浓度均低于发生AR前[(6.27±1.18)和(6.33±1.63)ng/mL],差异均有统计学意义(t＝7.120和6.216,P均<0.05)。急性抗体排斥反应组4例受者应用以环孢素为基础的免疫抑制方案,其中3例术后33、36和55个月环孢素血浓度分别为112.4、138.3和7.0 ng/mL,均低于要求血药浓度。急性T细胞排斥反应组2例应用环孢素受者术后16和177个月环孢素血药浓度分别为43.2和24.6 ng/mL,均低于要求血药浓度。随访至2021年6月30日,急性抗体排斥反应组移植肾生存率低于对照组(χ²＝8.738,P<0.05)。 结论HLA-A位点错配及他克莫司低血药浓度是肾移植术后中远期诱发AR的重要原因。急性抗体介导排斥反应是移植肾生存重要影响因素。     

肝移植急性排斥反应的诊断和治疗体会(附3例改良背驼式肝移植报告)

目的探讨肝移植术后急性排斥反应的诊断和治疗。方法2001年9月至2003年6月成功进行了3例同种异体原位肝移植术。术前诊断：1．乙肝后肝硬化．2．肝移植术后感染丙型肝炎导致移植肝无功能,3．硬化性胆管炎、肝功能衰竭。术后均采用环孢素A和甲基泼尼松龙两联免疫抑制疗法。结果3例肝移植术后共出现3次急性排斥反应。排斥反应时血清谷丙转氨酶及胆红素急剧升高。肝穿刺活检明确诊断。经过冲击治疗后．3次急性排斥反应均被控制。结论合理应用免疫抑制剂是控制急性排斥反应的关键．应用环孢素A可适当延长术后早期静脉应用时间。     

Immunosuppression: Evolution in Practice and Trends, 1994–2004

Over the last 10 years, there have been important changes in immunosuppression management and strategies for solid-organ transplantation, characterized by the use of new immunosuppressive agents and regimens. An organ-by-organ review of OPTN/SRTR data showed several important trends in immunosuppression practice. There is an increasing trend toward the use of induction therapy with antibodies, which was used for most kidney, pancreas after kidney (PAK), simultaneous pancreas-kidney (SPK) and pancreas transplant alone (PTA) recipients in 2004 (72–81%) and for approximately half of all intestine, heart and lung recipients. The highest usage of the tacrolimus/mycophenolate mofetil combination as discharge regimen was reported for SPK (72%) and PAK (64%) recipients. Maintenance of the original discharge regimen through the first 3 years following transplantation varied significantly by organ and drug. The usage of calcineurin inhibitors for maintenance therapy was characterized by a clear transition from cyclosporine to tacrolimus. Corticosteroids were administered to the majority of patients; however, steroid-avoidance and steroid-withdrawal protocols have become increasingly common. The percentage of patients treated for acute rejection during the first year following transplantation has continued to decline, reaching 13% for those who received a kidney in 2003, 48% of which cases were treated with antibodies.     

移植心脏电生理改变与移植物排斥反应关系的研究

目的　探讨非创伤性监测及诊断心脏移植后急性移植物排斥反应(GR)方法。方法通过大鼠颈部心脏移植模型观察急性GR过程中移植心脏电生理改变,即房室传导有效不应期(ERP-AVCS)改变与移植心脏形态学改变的关系。结果　同系移植及异系移植免疫抑制剂投用组ERP-AVCS无延长;异系移植组移植后第3天,其ERP-AVCS出现明显延长［(96.88±6.77)ms,P＜0.05］,第5天为(114.62±7.46)ms(P＜0.01),第7天为(121.67±9.73)ms(P＜0.01)。同系移植及异系移植＋免疫抑制剂投用组形态学结构未见异常;异系移植组在移植后第3天开始出现急性GR,如心肌纤维间质明显增宽、排列紊乱,血管旁及间质内出现单核细胞等且第5天及第7天急性GR渐加重。异系移植心脏ERP-AVC与排斥反应形态学改变呈明显正相关(P＜0.01)。结论　检测移植心脏ERP-AVC是简便、可靠、低费用、非创伤性诊断移植心脏急性排斥反应手段。