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利妥昔单抗治疗难治性晚期急性抗体介导的排斥反应:我们的初步经验。

Rituximab in the treatment of refractory late acute antibody-mediated rejection: Our initial experience.

作者信息

Surendra M, Raju S B, Raju N, Chandragiri S, Mukku K K, Uppin M S

机构信息

Department of Nephrology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India.

Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India.

出版信息

Indian J Nephrol. 2016 Sep;26(5):317-321. doi: 10.4103/0971-4065.177207.

Abstract

Antibody-mediated rejection (AMR) is not uncommon after renal transplantation and is harder to handle compared to cell-mediated rejection. When refractory to conventional therapies, rituximab is an attractive option. This study aims to examine the effectiveness of rituximab in refractory late acute AMR. This is a retrospective study involving nine renal transplant recipients. Four doses of rituximab were administered at weekly interval for 4 weeks, at a dose of 375 mg/m. The mean age of patients was 35.3 ± 7.38 years. The median period between transplantation and graft dysfunction was 30 ± 20 months. Mean serum creatinine at the time of discharge after transplantation and at the time of acute AMR diagnosis was 1.14 ± 0.19 mg/dl and 2.26 ± 0.57 mg/dl, respectively. After standard therapy, it was 2.68 ± 0.62 mg/dl. One patient died of Pseudomonas sepsis and three patients progressed to end-stage renal disease (ESRD). Four biopsies showed significant plasma cell infiltrations. Mean serum creatinine among non-ESRD patients at the end of 1 year progressed from 2.3 ± 0.4 to 3.8 ± 1.2 mg/dl ( value 0.04). eGFR prior to therapy and at the end of 1 year were 34.4 ± 6.18 and 20.8 ± 7.69 ml/min ( value 0.04), respectively. Only one patient showed improvement in graft function in whom donor-specific antibody (DSA) titers showed significant improvement. Rituximab may not be effective in late acute AMR unlike in early acute AMR. Monitoring of DSA has a prognostic role in these patients and plasma cell rich rejection is associated with poor prognosis.

摘要

抗体介导的排斥反应(AMR)在肾移植后并不少见,与细胞介导的排斥反应相比更难处理。当对传统疗法无效时,利妥昔单抗是一个有吸引力的选择。本研究旨在探讨利妥昔单抗在难治性晚期急性AMR中的有效性。这是一项回顾性研究,涉及9名肾移植受者。利妥昔单抗以375mg/m²的剂量,每周给药1次,共4周,给予4剂。患者的平均年龄为35.3±7.38岁。移植与移植物功能障碍之间的中位时间为30±20个月。移植后出院时和急性AMR诊断时的平均血清肌酐分别为1.14±0.19mg/dl和2.26±0.57mg/dl。标准治疗后为2.68±0.62mg/dl。1例患者死于铜绿假单胞菌败血症,3例患者进展为终末期肾病(ESRD)。4次活检显示有明显的浆细胞浸润。1年末非ESRD患者的平均血清肌酐从2.3±0.4mg/dl升至3.8±1.2mg/dl(P值0.04)。治疗前和1年末的估算肾小球滤过率(eGFR)分别为34.4±6.18和20.8±7.69ml/min(P值0.04)。只有1例患者的移植物功能有改善,其供者特异性抗体(DSA)滴度有显著改善。与早期急性AMR不同,利妥昔单抗在晚期急性AMR中可能无效。DSA监测对这些患者有预后作用,富含浆细胞的排斥反应与预后不良有关。

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