Liefeldt Lutz, Waiser Johannes, Bachmann Friederike, Budde Klemens, Friedersdorff Frank, Halleck Fabian, Lachmann Nils, Peters Robert, Rudolph Birgit, Ünlü Sinem, Wu Kaiyin, Glander Petra
Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany.
Department of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
J Clin Med. 2024 Jul 23;13(15):4305. doi: 10.3390/jcm13154305.
The use of mammalian target of rapamycin inhibitors (mTORis) in kidney transplantation increases the risk of donor-specific human leukocyte antigen (HLA) antibody formation and rejection. Here, we investigated the long-term consequences of early mTORi treatment compared to calcineurin inhibitor (CNI) treatment. In this retrospective single-center analysis, key outcome parameters were compared between patients participating in randomized controlled immunosuppression trials between 1998 and 2011, with complete follow-up until 2018. The outcomes of eligible patients on a CNI-based regimen (n = 384) were compared with those of patients randomized to a CNI-free mTORi-based regimen (n = 81) and 76 patients randomized to a combination of CNI and mTORi treatments. All data were analyzed according to the intention-to-treat (ITT) principle. Deviation from randomized immunosuppression for clinical reasons occurred significantly more often and much earlier in both mTORi-containing regimens than in the CNI treatment. Overall patient survival, graft survival, and death-censored graft survival did not differ between the treatment groups. Donor-specific HLA antibody formation and BPARs were significantly more common in both mTORi regimens than in the CNI-based immunosuppression. The tolerability and efficacy of the mTORi treatment in kidney graft recipients are inferior to those of CNI-based immunosuppression, while the long-term patient and graft survival rates were similar.
在肾移植中使用雷帕霉素哺乳动物靶点抑制剂（mTORi）会增加供体特异性人类白细胞抗原（HLA）抗体形成和排斥反应的风险。在此，我们研究了与钙调神经磷酸酶抑制剂（CNI）治疗相比，早期mTORi治疗的长期后果。在这项回顾性单中心分析中，对1998年至2011年间参与随机对照免疫抑制试验且随访至2018年的患者的关键结局参数进行了比较。将接受基于CNI方案治疗的符合条件患者（n = 384）的结局与随机接受无CNI的基于mTORi方案治疗的患者（n = 81）以及76例随机接受CNI和mTORi联合治疗的患者的结局进行了比较。所有数据均根据意向性分析（ITT）原则进行分析。与CNI治疗相比，在两种含mTORi的方案中，因临床原因偏离随机免疫抑制的情况出现得更频繁且更早。各治疗组之间的总体患者生存率、移植物生存率和死亡删失移植物生存率无差异。在两种mTORi方案中，供体特异性HLA抗体形成和BPARs均比基于CNI的免疫抑制更为常见。肾移植受者中mTORi治疗的耐受性和疗效低于基于CNI的免疫抑制，而长期患者和移植物生存率相似。
