Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA.
Transpl Int. 2010 May 1;23(5):447-60. doi: 10.1111/j.1432-2277.2010.01051.x. Epub 2010 Feb 3.
All immunosuppressive medications require a learning curve that enables clinicians to improve the therapeutic index of agents. Mammalian target of rapamycin (mTOR) inhibitors are potentially a less nephrotoxic form of immunosuppression than calcineurin inhibitors (CNIs) that has been used in kidney transplant recipients for more than two decades. This drug class has a novel immunosuppressive action, probably mediated in part through inhibition of growth receptor signaling mechanisms. In addition, it has a unique drug toxicity, which is partially dose-related. This medication class also possesses antiproliferative activity, which may be useful in-post-transplant patients with increased atherosclerotic and malignancy risks. mTOR inhibitors have been utilized for de novo immunosuppression with CNIs, corticosteroids, and antimetabolites. mTOR inhibitors also have been used as CNI-sparing agents both early and late post-transplant. Much debate remains over how to best utilize mTOR inhibition in kidney transplantation.
所有免疫抑制药物都需要一个学习曲线，使临床医生能够提高药物的治疗指数。雷帕霉素（mTOR）抑制剂是一种潜在的、比钙调磷酸酶抑制剂（CNI）毒性更小的免疫抑制剂，CNI 已在肾移植受者中使用了二十多年。这类药物具有新颖的免疫抑制作用，可能部分通过抑制生长受体信号机制介导。此外，它具有独特的药物毒性，部分与剂量有关。这类药物还具有抗增殖活性，这在移植后动脉粥样硬化和恶性肿瘤风险增加的患者中可能有用。mTOR 抑制剂已被用于与 CNI、皮质类固醇和抗代谢物联合用于新的免疫抑制治疗。mTOR 抑制剂也被用作 CNI 节约剂，无论是在移植后早期还是晚期。关于如何在肾移植中最好地利用 mTOR 抑制仍存在许多争议。
