Department of Pharmacy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7574, USA.
Am J Health Syst Pharm. 2012 Nov 15;69(22):1961-75. doi: 10.2146/ajhp110624.
Current trends in immunosuppressive therapies for renal transplant recipients are reviewed.
The common premise for immunosuppressive therapies in renal transplantation is to use multiple agents to work on different immunologic targets. The use of a multidrug regimen allows for pharmacologic activity at several key steps in the T-cell replication process and lower dosages of each individual agent, thereby producing fewer drug-related toxicities. In general, there are three stages of clinical immunosuppression: induction therapy, maintenance therapy, and treatment of an established acute rejection episode. Only immunosuppressive therapies used for maintenance therapy are discussed in detail in this review. The most common maintenance immunosuppressive agents can be divided into five classes: (1) the calcineurin inhibitors (CNIs) (cyclosporine and tacrolimus), (2) costimulation blockers (belatacept), (3) mammalian target of rapamycin inhibitors (sirolimus and everolimus), (4) antiproliferatives (azathioprine and mycophenolic acid derivatives), and (5) corticosteroids. Immunosuppressive regimens vary among transplantation centers but most often include a CNI and an adjuvant agent, with or without corticosteroids. Selection of appropriate immunosuppressive regimens should be patient specific, taking into account the medications' pharmacologic properties, adverse-event profile, and potential drug-drug interactions, as well as the patient's preexisting diseases, risk of rejection, and medication regimen.
Advancements in transplant immunosuppression have resulted in a significant reduction in acute cellular rejection and a modest increase in long-term patient and graft survival. Because the optimal immunosuppression regimen is still unknown, immunosuppressant use should be influenced by institutional preference and tailored to the immunologic risk of the patient and adverse-effect profile of the drug.
综述肾移植受者免疫抑制治疗的当前趋势。
肾移植免疫抑制治疗的共同前提是使用多种药物作用于不同的免疫靶点。多药物方案的应用可使 T 细胞复制过程中的多个关键步骤具有药理活性，并降低每个药物的剂量，从而减少与药物相关的毒性。一般来说，临床免疫抑制有三个阶段：诱导治疗、维持治疗和已确立的急性排斥反应发作的治疗。本综述仅详细讨论用于维持治疗的免疫抑制治疗。最常见的维持免疫抑制药物可分为五类：（1）钙调磷酸酶抑制剂（CNI）（环孢素和他克莫司），（2）共刺激阻滞剂（巴利昔单抗），（3）雷帕霉素靶蛋白抑制剂（西罗莫司和依维莫司），（4）抗增殖剂（硫唑嘌呤和霉酚酸衍生物）和（5）皮质类固醇。移植中心的免疫抑制方案不同，但大多数方案包括 CNI 和辅助药物，有或没有皮质类固醇。选择合适的免疫抑制方案应根据患者的具体情况，考虑药物的药理特性、不良事件谱和潜在的药物相互作用，以及患者的既往疾病、排斥风险和药物治疗方案。
移植免疫抑制的进步显著降低了急性细胞排斥反应的发生率，并适度提高了长期患者和移植物的存活率。由于最佳免疫抑制方案仍不明确，免疫抑制剂的使用应受机构偏好的影响，并根据患者的免疫风险和药物的不良事件谱进行调整。
