Swenson J M, Fricker F J, Armitage J M
Department of Pediatric Cardiology and Cardiac Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania 15213.
J Am Coll Cardiol. 1995 Apr;25(5):1183-8. doi: 10.1016/0735-1097(94)00551-z.
We studied rejection, allograft function and side effects, such as hypertension, renal dysfunction and hypercholesterolemia, in seven patients switched from cyclosporine-based triple-drug immunosuppression to FK 506.
A subset of pediatric heart transplant recipients treated with triple-drug immunosuppression consisting of cyclosporine, azathioprine and prednisone experience either persistent rejection when attempts are made to taper corticosteroids or morbidity from cyclosporine and corticosteroids. Experience with the new immunosuppressive agent FK 506 has demonstrated its effectiveness as a single agent in heart transplant recipients, and anecdotal evidence has shown that side effects such as hypertension and hypercholesterolemia may be lower.
Seven patients whom we deemed corticosteroid dependent were switched to FK 506-based therapy. Allograft function, episodes of rejection, need for corticosteroids and incidence of side effects from FK 506 were monitored. The switch to FK 506 was performed using an established protocol. Follow-up time has ranged from 15 to 41 months. Serial right heart catheterizations and endomyocardial biopsies were performed after each reduction of corticosteroid dosing.
Catheterization data showed no significant change in pulmonary wedge pressure, mean right atrial pressure or cardiac index, indicating no decline in allograft function. Serial echocardiographic variables of allograft function were also stable. At present, all seven patients are free of the corticosteroid portion of their immune suppression. There have been only two episodes of significant acute rejection requiring treatment with intravenous corticosteroids. Antihypertensive medications have been discontinued in five of six patients previously treated with these drugs. Plasma cholesterol, low density lipoprotein and triglyceride levels were decreased, and renal function was stable.
Preliminary studies suggest that FK 506 may be an alternative immunosuppressive agent for pediatric and adolescent patients experiencing ongoing rejection or significant morbidity from cyclosporine and corticosteroids and in those patients dependent on corticosteroids for immune suppression.
我们研究了7例从基于环孢素的三联药物免疫抑制转换为使用FK506治疗的患者的排斥反应、移植物功能及副作用，如高血压、肾功能不全和高胆固醇血症。
一部分接受由环孢素、硫唑嘌呤和泼尼松组成的三联药物免疫抑制治疗的小儿心脏移植受者，在尝试减少皮质类固醇用量时会出现持续性排斥反应，或者因环孢素和皮质类固醇而出现发病情况。新型免疫抑制剂FK506在心脏移植受者中作为单一药物的有效性已得到证实，且有轶事证据表明其高血压和高胆固醇血症等副作用可能较少。
我们将7例被认为依赖皮质类固醇的患者转换为基于FK506的治疗。监测移植物功能、排斥反应发作情况、对皮质类固醇的需求以及FK506的副作用发生率。采用既定方案进行向FK506的转换。随访时间为15至41个月。每次减少皮质类固醇剂量后进行系列右心导管检查和心内膜心肌活检。
导管检查数据显示肺楔压、平均右心房压或心脏指数无显著变化，表明移植物功能未下降。移植物功能的系列超声心动图变量也保持稳定。目前，所有7例患者均无需使用免疫抑制方案中的皮质类固醇部分。仅出现过2次严重急性排斥反应发作，需要静脉注射皮质类固醇进行治疗。6例先前接受过抗高血压药物治疗的患者中有5例已停用此类药物。血浆胆固醇、低密度脂蛋白和甘油三酯水平降低，肾功能稳定。
初步研究表明，对于正在经历持续性排斥反应或因环孢素和皮质类固醇出现显著发病情况的小儿及青少年患者，以及依赖皮质类固醇进行免疫抑制的患者，FK506可能是一种替代免疫抑制剂。
