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首页> 外文期刊>Therapeutic advances in endocrinology and metabolism. >Metabolic consequences of modern immunosuppressive agents in solid organ transplantation
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Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

机译：现代免疫抑制剂在实体器官移植中的代谢影响

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Among other factors, sophistication of immunosuppressive (IS) regimen accounts for the remarkable success attained in the short- and medium-term solid organ transplant (SOT) survival. The use of steroids, mycophenolate mofetil and calcineurin inhibitors (CNI) have led to annual renal graft survival rates exceeding 90% in the last six decades. On the other hand, attrition rates of the allograft beyond the first year have remained unchanged. In addition, there is a persistent high cardiovascular (CV) mortality rate among transplant recipients with functioning grafts. These shortcomings are in part due to the metabolic effects of steroids, CNI and sirolimus (SRL), all of which are implicated in hypertension, new onset diabetes after transplant (NODAT), and dyslipidemia. In a bid to reduce the required amount of harmful maintenance agents, T-cell-depleting antibodies are increasingly used for induction therapy. The downsides to their use are greater incidence of opportunistic viral infections and malignancy. On the other hand, inadequate immunosuppression causes recurrent rejection episodes and therefore early-onset chronic allograft dysfunction. In addition to the adverse metabolic effects of the steroid rescue needed in these settings, the generated proinflammatory milieu may promote accelerated atherosclerotic disorders, thus setting up a vicious cycle. The recent availability of newer agent, belatacept holds a promise in reducing the incidence of metabolic disorders and hopefully its long-term CV consequences. Although therapeutic drug monitoring as applied to CNI may be helpful, pharmacodynamic tools are needed to promote a customized selection of IS agents that offer the most benefit to an individual without jeopardizing the allograft survival.
机译：除其他因素外，复杂的免疫抑制（IS）方案在短期和中期实体器官移植（SOT）生存中获得了显著成功。在过去的六十年中，使用类固醇，霉酚酸酯和钙调神经磷酸酶（CNI）导致肾移植的年生存率超过90％。另一方面，同种异体移植超过第一年的流失率保持不变。此外，在具有功能性移植物的移植接受者中，心血管（CV）死亡率持续升高。这些缺点部分归因于类固醇，CNI和西罗莫司（SRL）的代谢作用，它们均与高血压，移植后新发糖尿病（NODAT）和血脂异常有关。为了减少有害维持剂的所需量，消耗T细胞的抗体越来越多地用于诱导疗法。使用它们的缺点是机会性病毒感染和恶性肿瘤的发生率更高。另一方面，免疫抑制不足会导致排斥反应反复发作，因此会导致早发的慢性同种异体移植功能障碍。除了在这些情况下需要进行类固醇抢救的不良代谢作用外，所产生的促炎环境还可能促进动脉粥样硬化疾病的加速发展，从而形成恶性循环。最近可使用更新的药物贝拉西普有望降低代谢紊乱的发生率，并有望降低其长期的心血管后果。尽管应用于CNI的治疗药物监测可能会有所帮助，但仍需要使用药效学工具来促进对IS试剂的定制选择，这些试剂可在不损害同种异体移植存活率的情况下为个体提供最大益处。

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