Gupta Gaurav, Abu Jawdeh Bassam G, Racusen Lorraine C, Bhasin Bhavna, Arend Lois J, Trollinger Brandon, Kraus Edward, Rabb Hamid, Zachary Andrea A, Montgomery Robert A, Alachkar Nada
1 Department of Medicine, Virginia Commonwealth University, Richmond, VA. 2 Department of Medicine, University of Cincinnati, Cincinnati, OH. 3 Department of Pathology, Johns Hopkins University, Baltimore, MD. 4 Department of Medicine, Johns Hopkins University, Baltimore, MD. 5 Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD. 6 Department of Surgery, Johns Hopkins University, Baltimore, MD. 7 Address correspondence to: Nada Alachkar, MD, Johns Hopkins University School of Medicine, 600 Wolfe Street, Brady 502, Baltimore, MD 21287.
Transplantation. 2014 Jun 27;97(12):1240-6. doi: 10.1097/01.TP.0000442503.85766.91.
Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR.
Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength.
Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06).
A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.
尽管已经对肾移植中早期抗体介导的排斥反应（AMR）的几种治疗策略进行了研究，但关于6个月后出现的晚期AMR治疗的证据却很少。在这个单中心系列研究中，我们展示了连续23例接受晚期AMR治疗患者的数据。
根据2007年班夫标准以及供体特异性抗体（DSA）的存在和血清肌酐（SCr）的急性升高来诊断晚期AMR。通过SCr的改善、组织学改善以及DSA强度的下降来评估治疗反应。
总体而言，17%（4/23）的患者有记录显示不依从，而69%（16/23）的患者在AMR之前有医生建议减少免疫抑制。18例患者（78%）接受了血浆置换或低剂量静脉注射免疫球蛋白联合利妥昔单抗治疗；11例（49%）难治性AMR患者还接受了1至3个疗程的硼替佐米治疗。与诊断时的SCr（2.9mg/dL）相比，治疗结束时平均SCr（2.4mg/dL）有改善（P=0.02），但在最近的随访中这种改善未持续。11例（48%）患者在随访活检时组织学未缓解。组织学无反应与老年患者相关（优势比[OR]=3.17；P=0.04），诊断时存在细胞毒性DSA（OR=200；P=0.04），以及初次活检时严重慢性血管病变（cv≥2）相关（OR=50；P=0.06）。
我们队列中晚期AMR发生的一个主要情况是免疫抑制的减少或改变。我们的数据表明晚期AMR对当前和新型（硼替佐米）治疗反应不足。治疗的益处需要与潜在的不良反应相权衡，尤其是在老年患者、大量抗体负荷和慢性移植血管病变的情况下。
