Partial therapeutic response to Rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts
Partial therapeutic response to Rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts
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DOI：
10.1016/j.trim.2012.08.005
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发表时间：
2012-10-01
影响因子：
1.5
通讯作者：
Wong, Waichi
中科院分区：
文献类型：
--
作者：
Smith, R. Neal;Malik, Fahim;Wong, Waichi
背景和目的：慢性排斥反应导致肾移植衰竭，并在许多肾移植受者中发展。慢性排斥反应的原因之一，慢性抗体介导的排斥反应（CAMR），归因于同种异体抗体。包括强的松、霉酚酸酯（MMF）和钙调磷酸酶抑制剂在内的维护性免疫抑制可能限制某些患者的同种抗体产生，但许多患者维持或发展同种抗体产生，导致CAMR。因此，目前还没有有效的治疗CAMR的方法来防止CAMR发展为同种异体肾移植衰竭。设计、环境、参与者和测量：我们对31例CAMR患者进行了回顾性研究，其中14例接受了利妥昔单抗治疗，17例未接受治疗。对利妥昔单抗的反应定义为血清肌酐下降或稳定至少一年。回顾的数据包括人口统计学、临床、同种异体移植、移植后和病理变量。根据Banff标准对异体移植物活检诊断的病理变量进行评分。结果：同种异体移植物对照组的中位生存时间（MST）为439天，利妥昔单抗治疗组的中位生存时间为685天。利妥昔单抗组分为两组，8例患者的中期生存时间为1180天，6例患者的中位生存时间为431天。反应者的MST与无反应者和对照组相比具有统计学意义。没有病理参数区分受试者的任何子集。结论：这些数据表明，利妥昔单抗后标准维持免疫抑制在治疗CAMR中显示出治疗效果，但仅限于治疗对象的一部分，无法先验识别。(C) 2012 Elsevier B.V.版权所有
Background and Objectives: Chronic rejection leads to kidney allograft failure and develops in many kidney transplant recipients. One cause of chronic rejection, chronic antibody mediated rejection (CAMR), is attributed to alloantibodies. Maintenance immunosuppression including prednisone, mycophenolate mofetil (MMF) and calcineurin inhibitors may limit alloantibody production in some patients, but many maintain or develop alloantibody production, leading to CAMR. Therefore, no efficacious therapy to treat CAMR is presently available to prevent the progression of CAMR to kidney allograft failure.Design, Setting, Participants, and Measurements: We performed a retrospective review of 31 subjects with CAMR, of which 14 received Rituximab and 17 subjects did not. Response to Rituximab was defined as decline or stabilization of serum creatinine for at least one year. Data reviewed included demographic, clinical, allograft, post-transplant, and pathological variables. Pathological variables in the diagnostic allograft biopsy were scored according to Banff criteria.Results: The median survival time (MST) for allografts in the control group was 439 days, and for the Rituximab treated group was 685 days. The Rituximab group was dichotomous with 8 subjects showing a medial survival time of 1180 days, and 6 subjects having a median survival time of 431 days. The MST for the responders was statistically significant from the non-responders and controls. No pathological parameter distinguished any subset of subjects.Conclusions: These data show that Rituximab followed by standard maintenance immunosuppression shows a therapeutic effect in the treatment of CAMR, which is confined to a subset of treated subjects, not identifiable a priori. (C) 2012 Elsevier B.V. All rights reserved.