Kari Jameela A, Trompeter Richard S
Pediatrics Department, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia.
Pediatr Transplant. 2004 Oct;8(5):437-44. doi: 10.1111/j.1399-3046.2004.00201.x.
Cyclosporine microemulsion (CyA) and tacrolimus (Tac) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. In the majority of patients, these calcineurin inhibitors have been used in combination with other immunosuppressive drugs, such as azathioprine or mycophenolate mofetil (MMF). In this review we will address the question of what calcineurin inhibitor we should use in an individual pediatric renal transplant patient. Well-designed randomized studies in children showed no difference in short-term patient and graft survival with cyclosporine microemulsion and tacrolimus. However Tac is significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population when used in conjunction with azathioprine and corticosteroids. This difference disappears when calcineurin inhibitors are used in combination with MMF as both Tac and CyA produce similar rejection rates and graft survival. However, Tac is associated with improved graft function at 1 and 2 yr post-transplant. Adverse events of hypomagnesaemia and diarrhea seem to be higher in Tac group whereas hypertrichosis, flu syndrome and gum hyperplasia occurs more frequently in the CyA group. The incidence of post-transplant diabetes mellitus was almost identical between Tac and CyA treated patients. The recommendation drawn from the available data is that both CyA and Tac can be used safely and effectively in children. However Tac may be preferable to CyA because of steroid sparing effect and less hirsutism. We recommend that cyclosporine should be chosen when patients experience Tac-related adverse events. Nevertheless, the best calcineurin inhibitor should be decided on individual patients according to variable risk factors, such as risk of rejection in sensitized patient or delayed graft function. The possibility of adverse events should also be considered.
环孢素微乳剂(CyA)和他克莫司(Tac)是成人及儿童肾移植中常用的主要免疫抑制剂。在大多数患者中,这些钙调神经磷酸酶抑制剂已与其他免疫抑制药物联合使用,如硫唑嘌呤或霉酚酸酯(MMF)。在本综述中,我们将探讨在个体儿童肾移植患者中应使用哪种钙调神经磷酸酶抑制剂的问题。针对儿童的精心设计的随机研究表明,环孢素微乳剂和他克莫司在短期患者和移植物存活方面没有差异。然而,在儿童人群中,当他克莫司与硫唑嘌呤和皮质类固醇联合使用时,在预防肾移植后急性排斥反应方面,他克莫司比环孢素微乳剂显著更有效。当钙调神经磷酸酶抑制剂与霉酚酸酯联合使用时,这种差异消失,因为他克莫司和环孢素产生相似的排斥率和移植物存活率。然而,他克莫司与移植后1年和2年时移植物功能的改善相关。他克莫司组低镁血症和腹泻等不良事件的发生率似乎更高,而环孢素组多毛症、流感样综合征和牙龈增生的发生频率更高。他克莫司和环孢素治疗的患者移植后糖尿病的发生率几乎相同。根据现有数据得出的建议是,环孢素和他克莫司均可安全有效地用于儿童患者。然而,由于具有激素节省作用且多毛症较少,他克莫司可能比环孢素更可取。我们建议,当患者出现与他克莫司相关的不良事件时,应选择环孢素。尽管如此,应根据个体患者的可变风险因素,如致敏患者的排斥风险或移植肾功能延迟,来决定最佳的钙调神经磷酸酶抑制剂。还应考虑不良事件的可能性。