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高敏患者:迈阿密移植研究所的经验

Highly Sensitized Patients: Miami Transplant Institute Experience.

作者信息

Mattiazzi Adela D, Centeno Alexandra, Amador Alexandra, Fernandez-Bango Casiana, Scowby Catherine Dillard, O'Rourke Marian, Hill-Matthie Tamieka, Patel Ronak, Barrios Frances, Ruiz Phillip, Chen Linda, Saghesima Junichiro, Ciancio Gaetano, Burke George W, Goldstein Michael, Chandar Jayanthi, Contreras Gabriel, Roth David, Kupin Warren, Guerra Giselle, Vianna Rodrigo

出版信息

Clin Transpl. 2014:171-8.

Abstract

BACKGROUND

Transplantation continues to be challenging in highly sensitized patients. Herein, we compared induction immunosuppression (IS) based on immunologic risk stratification and desensitization with intravenous immunoglobulin (IVIG).

METHODS

Of the 42 highly sensitized kidney and 3 kidney-pancreas transplant recipients who underwent IVIG for desensitization from 2008-2014, 10 (Control group) received standard induction IS with antithymocyte globulin, basiliximab, and methylprednisolone, and 35 (Rituximab group) received standard IS with rituximab ± IVIG ± plasmapheresis. Immunologic risk stratification was based on donor specific antibodies (DSA), flow crossmatch ratio, and calculated panel reactive antibody. All patients received tacrolimus, mycophenolate, and steroids for maintenance IS. Unacceptable antigen cut-offs for class I and II DSA were 6000 and 9000 mean fluorescence intensity and 2.0 and 4.4 channel shift ratios for T and B cell flow cytometry crossmatch, respectively. All complement dependent cytotoxicity T cell crossmatch negative patients were transplanted.

RESULTS

Characteristics between groups, including high risk level, previous transplantation rate, number of human leukocyte antigen mismatches, delayed graft function rate, rejection rate, serum creatinine, and estimated glomerular filtration rate at 1 year (1.48 ± 0.6 and 50 ± 17 versus 1.1 ± 0.4 mg/dl and 66 25 ml/min) were not statistically significant between the Control and the Rituximab groups, respectively. Waiting time for the Control group was 6.4 years versus 4.1 years for the Rituximab group (p = 0.009). The cumulative proportion of patients who remain free of death or allograft failure was significantly higher in the Rituximab (87%) versus the Control group (60%) (p = 0.047).

CONCLUSIONS

In highly sensitized patients who received desensitization with IVIG, the addition of Rituximab to our standard IS (and/or IVIG and plasmapheresis as per the immunologic risk stratification model) resulted in higher cumulative patient and graft survival.

摘要

背景

在高敏患者中,移植仍然具有挑战性。在此,我们比较了基于免疫风险分层的诱导免疫抑制(IS)以及静脉注射免疫球蛋白(IVIG)脱敏疗法。

方法

在2008年至2014年间接受IVIG脱敏治疗的42例高敏肾移植受者和3例肾胰联合移植受者中,10例(对照组)接受了抗胸腺细胞球蛋白、巴利昔单抗和甲泼尼龙的标准诱导IS,35例(利妥昔单抗组)接受了利妥昔单抗±IVIG±血浆置换的标准IS。免疫风险分层基于供者特异性抗体(DSA)、流式交叉配型比率和计算的群体反应性抗体。所有患者均接受他克莫司、霉酚酸酯和类固醇进行维持IS。I类和II类DSA的不可接受抗原临界值分别为平均荧光强度6000和9000,T细胞和B细胞流式细胞术交叉配型的通道偏移率分别为2.0和4.4。所有补体依赖细胞毒性T细胞交叉配型阴性的患者均接受了移植。

结果

两组之间的特征,包括高风险水平、既往移植率、人类白细胞抗原错配数、移植肾功能延迟恢复率、排斥反应率、血清肌酐以及1年时的估计肾小球滤过率(分别为1.48±0.6和50±17与1.1±0.4mg/dl和66±25ml/min)在对照组和利妥昔单抗组之间无统计学显著差异。对照组的等待时间为6.4年,而利妥昔单抗组为4.1年(p = 0.009)。利妥昔单抗组(87%)无死亡或移植失败的患者累积比例显著高于对照组(60%)(p = 0.047)。

结论

在接受IVIG脱敏治疗的高敏患者中,在我们的标准IS中添加利妥昔单抗(和/或根据免疫风险分层模型进行IVIG和血浆置换)可提高患者和移植肾的累积生存率。

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