Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Müller-Str. 47, 72076, Tübingen, Germany.
BMC Nephrol. 2020 May 13;21(1):178. doi: 10.1186/s12882-020-01767-z.
Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound immunosuppression and an associated risk of serious infections. Current concepts aim to optimize dosing strategies to reduce side effects. Here we present data from an ongoing centre protocol consisting of low-dose alemtuzumab induction and tailored immunosuppression in sensitized patients undergoing kidney transplantation.
10-year results of the protocol were analysed. Low-dose alemtuzumab induction consisted of a single dose of 20 mg intraoperatively, followed by tacrolimus and corticosteroids for initial immunosuppression, with mycophenolate mofetil suspended until a total lymphocyte count (TLC) >5% or 200/μl was reached.
Between 01/2007 and 04/2017, 46 patients were treated in accordance with the protocol in 48 kidney transplantations. Median PRA was 43 [22-76; IQR] %; all patients had negative CDC-crossmatch prior to transplantation. Low-dose alemtuzumab was well tolerated. Median time to TLC recovery was 77 [62-127; IQR] d. Within a median follow-up of 3.3 [1.5-5.6; IQR] years, 12 (25%) patients developed BPAR, 10 of which were antibody-mediated (3 acute, 7 chronic ABMR). Death-censored 5-year allograft survival was 79.2%, with an excellent allograft function at the end of follow-up. There was no increased rate of infections, in particular viral infections.
Our protocol, comprising low-dose alemtuzumab induction, initial suspension of mycophenolate mofetil and triple maintenance immunosuppression, provides excellent patient and allograft outcome in sensitized renal allograft recipients.
诱导治疗在肾移植中至关重要，是长期移植物存活的重要基石。阿仑单抗是一种耗竭 CD52 特异性抗体，具有 T 细胞和 B 细胞活性，导致长达 12 个月的淋巴细胞耗竭，从而产生强烈的免疫抑制作用，并伴有严重感染的风险。目前的概念旨在优化剂量策略以减少副作用。在这里，我们介绍了一项正在进行的中心方案的数据，该方案包括在致敏患者进行肾移植时使用低剂量阿仑单抗诱导和量身定制的免疫抑制。
分析了该方案的 10 年结果。低剂量阿仑单抗诱导包括术中单次 20mg 剂量，然后使用他克莫司和皮质类固醇进行初始免疫抑制，在总淋巴细胞计数 (TLC) >5%或 200/μl 之前暂停使用霉酚酸酯。
在 2007 年 1 月至 2017 年 4 月期间，根据该方案在 48 例肾移植中治疗了 46 例患者。中位 PRA 为 43 [22-76; IQR] %；所有患者在移植前均进行了阴性 CDC 交叉配型。低剂量阿仑单抗耐受性良好。TLC 恢复的中位时间为 77 [62-127; IQR] d。在中位随访 3.3 [1.5-5.6; IQR] 年后，12 例（25%）患者发生 BPAR，其中 10 例为抗体介导（3 例急性，7 例慢性 ABMR）。死亡风险校正的 5 年移植物存活率为 79.2%，随访结束时移植物功能良好。感染率，特别是病毒感染率没有增加。
我们的方案包括低剂量阿仑单抗诱导、初始霉酚酸酯停药和三联维持免疫抑制，为致敏肾移植受者提供了优异的患者和移植物结局。
