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器官移植中的免疫抑制剂

Immunosuppressants in Organ Transplantation.

作者信息

Tönshoff Burkhard

机构信息

Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.

出版信息

Handb Exp Pharmacol. 2020;261:441-469. doi: 10.1007/164_2019_331.

Abstract

The goal of immunosuppressive therapy post-transplantation in pediatric renal transplant recipients is to prevent acute and chronic rejection while minimizing drug side effects. Most therapies alter immune response mechanisms but are not immunologically specific, and a careful balance is required to find the dose that prevents rejection of the graft while minimizing the risks of overimmunosuppression leading to infection and cancer. While this chapter because of space constraints focuses on immunosuppressive therapy in pediatric renal transplant recipients, many aspects can be applied on pediatric recipients of other solid organ transplants such as the liver and heart. The major maintenance immunosuppressive agents currently used in various combination regimens are tacrolimus, cyclosporine, mycophenolate mofetil, azathioprine, everolimus, sirolimus, and glucocorticoids (steroids). Although data from adult renal transplantation trials are used to help guide management decisions in pediatric patients, immunosuppressive therapy in pediatric renal transplant recipients often must be modified because of the unique dosage requirements and clinical effects of these agents in children, including their impact on growth and development. The optimal immunosuppressive therapy post-transplant is not established. The goal remains to find the best combination of immunosuppressive agents that optimizes allograft survival by preventing acute rejection while limiting drug toxicities.

摘要

小儿肾移植受者移植后免疫抑制治疗的目标是预防急性和慢性排斥反应,同时将药物副作用降至最低。大多数治疗方法会改变免疫反应机制,但并非具有免疫学特异性,需要仔细权衡以找到既能预防移植物排斥又能将过度免疫抑制导致感染和癌症的风险降至最低的剂量。由于篇幅限制,本章重点关注小儿肾移植受者的免疫抑制治疗,但许多方面也可应用于其他实体器官移植的小儿受者,如肝移植和心脏移植受者。目前在各种联合治疗方案中使用的主要维持免疫抑制药物有他克莫司、环孢素、霉酚酸酯、硫唑嘌呤、依维莫司、西罗莫司和糖皮质激素(类固醇)。虽然成人肾移植试验的数据有助于指导小儿患者的管理决策,但小儿肾移植受者的免疫抑制治疗通常必须进行调整,因为这些药物在儿童中的独特剂量要求和临床效果,包括它们对生长发育的影响。移植后的最佳免疫抑制治疗方案尚未确定。目标仍然是找到免疫抑制药物的最佳组合,通过预防急性排斥反应同时限制药物毒性来优化同种异体移植物的存活。

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