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器官移植受者的未来趋势——皮肤科医生面临的重要问题。

Future trends in organ transplant recipients--important issues for dermatologists.

作者信息

Zecher Daniel, Steiger Jürg

机构信息

Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Petersgraben 4, Basel, Switzerland.

出版信息

Curr Probl Dermatol. 2012;43:71-80. doi: 10.1159/000335153. Epub 2012 Feb 17.

Abstract

It is on the tip of everyone's tongue in the transplant community that recent improvements in short-term survival of solid organ allografts have not translated into the expected increase in long-term survival. Besides chronic immune-mediated damage to the transplanted organ, the poor long-term survival of allografts has been attributed to the nephrotoxic effects of the calcineurin inhibitors. Moreover, the immunosuppressive burden and metabolic side effects of the current anti-rejection drugs are clearly related to increased rates of malignancies, infections and accelerated atherosclerosis, all of which make up for the premature death of a considerable proportion of transplant recipients with a functioning allograft. Therefore, attempts have been made over the last decade to either reduce or withdraw both steroids and calcineurin inhibitors from maintenance regimens. Furthermore, there is an ongoing intensive search for new less toxic and more specific drugs which would ideally selectively impair the alloimmune response while preserving the immune system's capacity to fight infection and malignancy (i.e. induce tolerance). Moreover, new concepts have emerged to individualize a patient's immunosuppressive therapy based on an improved pretransplant risk assessment. With the causes of chronic allograft damage being increasingly well defined, better and more personalized long-term follow-up strategies are being developed to ultimately prevent late allograft loss. These aspects will be reviewed here with a focus on kidney transplantation and the possible impact of these new approaches on the incidence of skin cancer.

摘要

在移植领域,每个人都在谈论一个事实,即实体器官同种异体移植短期存活率的近期改善并未转化为预期的长期存活率提高。除了对移植器官的慢性免疫介导损伤外,同种异体移植长期存活率低还归因于钙调神经磷酸酶抑制剂的肾毒性作用。此外,当前抗排斥药物的免疫抑制负担和代谢副作用显然与恶性肿瘤、感染发生率增加以及动脉粥样硬化加速有关,所有这些都导致相当一部分具有功能正常同种异体移植的移植受者过早死亡。因此,在过去十年中,人们尝试从维持治疗方案中减少或停用类固醇和钙调神经磷酸酶抑制剂。此外,人们一直在积极寻找毒性更低、特异性更强的新药,理想情况下,这些新药能选择性地损害同种免疫反应,同时保留免疫系统对抗感染和恶性肿瘤的能力(即诱导耐受)。此外,基于改进的移植前风险评估,出现了新的概念来使患者的免疫抑制治疗个体化。随着慢性同种异体移植损伤的原因越来越明确,正在制定更好、更个性化的长期随访策略,以最终预防晚期同种异体移植丢失。本文将对这些方面进行综述,重点关注肾移植以及这些新方法对皮肤癌发病率的可能影响。

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