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Systematic Review on Role of Mammalian Target of Rapamycin Inhibitors as an Alternative to Calcineurin Inhibitors in Renal Transplant: Challenges and Window to Excel

机译:系统评价的雷帕霉素抑制剂的哺乳动物靶标在肾移植中替代钙调磷酸酶抑制剂的作用:挑战和Excel窗口

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Objectives: This review focuses on the current limited evidence of graft function and graft survival in various immunosuppressive regimens involving mammalian target of rapamycin inhibitors with or without calcineurin inhibitors. Materials and Methods: We evaluated the current literature for describing the role of mammalian target of rapamycin inhibitors as an alternative to calcineurin inhibitors by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus databases using medical subject heading terms. Results: Our detailed analyses of all relevant literature showed use of mammalian target of rapamycin inhibitor-based de novo regimens, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimens, and late conversion from a calcineurin inhibitor-based regimen to mammalian target of rapamycin inhibitor-based regimens. Notably, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimen seemed to be a more practical and realistic approach toward immuno-suppressive treatment of renal transplant recipients. However, in view of the high rejection rate observed in these studies, it is advisable not to offer these regimens to patients with moderate to high immuno-logic risk. Conclusions: The present evidences suggest that treatment with mammalian target of rapamycin inhibitors allows early and substantial calcineurin inhibitor minimization. The mammalian target of rapamycin inhibitors everolimus and sirolimus are preferred due to their complementary mechanisms of action and favorable nephrotoxicity profile, which have opened the way for calcineurin inhibitor reduction/withdrawal in the early posttransplant period.
机译:目的:本综述着眼于目前在涉及哺乳动物雷帕霉素抑制剂(有或没有钙调神经磷酸酶抑制剂)的各种免疫抑制方案中,移植物功能和移植物存活的有限证据。材料和方法:通过使用医学主题词搜索PubMed,EMBASE,Cochrane,Crossref和Scopus数据库,我们评估了描述哺乳动物靶标雷帕霉素抑制剂替代钙调神经磷酸酶作用的最新文献。结果:我们对所有相关文献的详细分析表明,使用了基于雷帕霉素抑制剂的从头治疗方案的哺乳动物靶点,提前停用钙调神经磷酸酶抑制剂,随后引入了以雷帕霉素抑制剂为基础的哺乳动物靶点以及从基于钙调神经磷酸酶抑制剂的方案中后期转化以雷帕霉素抑制剂为基础的治疗方案的哺乳动物靶点。值得注意的是,早期钙调神经磷酸酶抑制剂的退出以及随后引入基于雷帕霉素抑制剂的哺乳动物靶向治疗方案似乎是对肾脏移植受体进行免疫抑制治疗的一种更实际和现实的方法。但是,鉴于在这些研究中观察到的高排斥率,建议不要为中度至高免疫学风险的患者提供这些治疗方案。结论:目前的证据表明,以哺乳动物为目标的雷帕霉素抑制剂治疗可以使早期和大量的钙调神经磷酸酶抑制剂减至最少。雷帕霉素抑制剂依维莫司和西罗莫司的哺乳动物靶标是优选的,因为它们具有互补的作用机制和良好的肾毒性,为移植后早期钙调神经磷酸酶抑制剂的减少/撤出开辟了道路。

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