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兔抗胸腺细胞球蛋白对使用钙调神经磷酸酶抑制剂和霉酚酸酯为基础的免疫抑制疗法的肾移植受者急性排斥反应的疗效

The Efficacy of Rabbit Anti-Thymocyte Globulin for Acute Kidney Transplant Rejection in Patients Using Calcineurin Inhibitor and Mycophenolate Mofetil-Based Immunosuppressive Therapy.

作者信息

van der Zwan Marieke, Clahsen-Van Groningen Marian C, Roodnat Joke I, Bouvy Anne P, Slachmuylders Casper L, Weimar Willem, Baan Carla C, Hesselink Dennis A, Kho Marcia M L

机构信息

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam Transplant Group, Rotterdam, Netherlands.

Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam Transplant Group, Rotterdam, Netherlands.

出版信息

Ann Transplant. 2018 Aug 17;23:577-590. doi: 10.12659/AOT.909646.

Abstract

BACKGROUND T cell depleting antibody therapy with rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant acute kidney allograft rejection (AR) and is used as first-line therapy in severe AR. Almost all studies investigating the effectiveness of rATG for this indication were conducted at the time when cyclosporine A and azathioprine were the standard of care. Here, the long-term outcome of rATG for AR in patients using the current standard immunosuppressive therapy (i.e., tacrolimus and mycophenolate mofetil) is described. MATERIAL AND METHODS Between 2002 to 2012, 108 patients were treated with rATG for AR. Data on kidney function in the year following rATG and long-term outcomes were collected. RESULTS Overall survival after rATG was comparable to overall survival of all kidney transplantation patients (P=0.10). Serum creatinine 1 year after rATG was 179 µmol/L (interquartile range (IQR) 136-234 µmol/L) and was comparable to baseline serum creatinine (P=0.22). Early AR showed better allograft survival than late AR (P=0.0007). In addition, 1 year after AR, serum creatinine was lower in early AR (157 mol/L; IQR 131-203) compared to late AR (216 mol/L; IQR 165-269; P<0.05). The Banff grade of rejection, kidney function at the moment of rejection, and reason for rATG (severe or glucocorticoid resistant AR) did not influence the allograft survival. CONCLUSIONS Treatment of AR with rATG is effective in patients using current standard immunosuppressive therapy, even in patients with poor allograft function. Early identification of AR followed by T cell depleting treatment leads to better allograft outcomes.

摘要

背景 用兔抗胸腺细胞球蛋白(rATG)进行的T细胞清除抗体疗法是糖皮质激素抵抗性急性肾移植排斥反应(AR)的首选治疗方法,并被用作严重AR的一线治疗。几乎所有研究rATG用于该适应症有效性的研究都是在环孢素A和硫唑嘌呤作为标准治疗手段时进行的。在此,描述了rATG用于采用当前标准免疫抑制疗法(即他克莫司和霉酚酸酯)的患者AR治疗的长期结果。

材料与方法 2002年至2012年期间,108例患者接受了rATG治疗AR。收集了rATG治疗后一年的肾功能数据和长期结果。

结果 rATG治疗后的总体生存率与所有肾移植患者的总体生存率相当(P = 0.10)。rATG治疗后1年血清肌酐为179μmol/L(四分位间距(IQR)136 - 234μmol/L),与基线血清肌酐相当(P = 0.22)。早期AR显示出比晚期AR更好的移植肾存活率(P = 0.0007)。此外,AR发生后1年,早期AR的血清肌酐(157μmol/L;IQR 131 - 203)低于晚期AR(216μmol/L;IQR 165 - 269;P < 0.05)。排斥反应的Banff分级、排斥发生时的肾功能以及使用rATG的原因(严重或糖皮质激素抵抗性AR)均不影响移植肾存活率。

结论 对于采用当前标准免疫抑制疗法的患者,用rATG治疗AR是有效的,即使是移植肾功能较差的患者。早期识别AR并进行T细胞清除治疗可带来更好的移植肾结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b79/6248318/4bc55969c7ee/anntransplant-23-577-g001.jpg

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