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硼替佐米作为肾移植后早期复发性膜性肾小球肾炎的一种新方法,对联合传统利妥昔单抗治疗无效。

Bortezomib as a Novel Approach to Early Recurrent Membranous Glomerulonephritis After Kidney Transplant Refractory to Combined Conventional Rituximab Therapy.

作者信息

Barbari Antoine, Chehadi Rima, Kfoury Assouf Hala, Kamel Gaby, Jaafar Mahassen, Abdallah Ayman, Rizk Sylvana, Masri Marwan

机构信息

From the Rafik Hariri University Hospital, Beirut, Lebanon.

出版信息

Exp Clin Transplant. 2017 Jun;15(3):350-354. doi: 10.6002/ect.2016.0350. Epub 2017 Apr 3.

Abstract

We report a case of early recurrent membranous glomerulonephritis after kidney transplant from a deceased donor. The patient received induction therapy and was discharged with a serum creatinine level of 0.78 mg/dL on triple maintenance immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and prednisone. At 7 months after transplant, a graft biopsy for new-onset isolated proteinuria (2.7 g/day) revealed stage 2 recurrent membranous glomerulonephritis. In the face of persistent proteinuria despite combined conservative rituximab therapy over several months and the total eradication of CD20-positive cells, bortezomib was introduced. This resulted in a substantial decline in proteinuria within 2 months and its subsequent disappearance several months later. This was paralleled by a considerable drop in plasma CD34-positive and CD138-positive cell counts. These preliminary observations indicate that recurrent posttransplant membranous glomerulonephritis is associated in part with a B-cell- mediated immunologic process that may involve both CD20-positive and plasma cells. Rituximab-resistant or partially responsive recurrent posttransplant membranous glomerulonephritis may benefit from a proteasome inhibitor-based therapy.

摘要

我们报告了一例来自已故供体肾移植后早期复发性膜性肾小球肾炎的病例。患者接受了诱导治疗,出院时血清肌酐水平为0.78mg/dL,接受包括他克莫司、霉酚酸酯和泼尼松的三联维持免疫抑制治疗。移植后7个月,因新发孤立性蛋白尿(2.7g/天)进行的移植肾活检显示为2期复发性膜性肾小球肾炎。尽管在数月内联合使用利妥昔单抗进行保守治疗且CD20阳性细胞完全清除,但蛋白尿持续存在,于是引入了硼替佐米。这导致蛋白尿在2个月内大幅下降,并在数月后消失。与此同时,血浆CD34阳性和CD138阳性细胞计数显著下降。这些初步观察结果表明,移植后复发性膜性肾小球肾炎部分与B细胞介导的免疫过程有关,该过程可能涉及CD20阳性细胞和浆细胞。对利妥昔单抗耐药或部分反应的移植后复发性膜性肾小球肾炎可能受益于基于蛋白酶体抑制剂的治疗。

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