McCune T R, Thacker LR I I, Peters T G, Mulloy L, Rohr M S, Adams P A, Yium J, Light J A, Pruett T, Gaber A O, Selman S H, Jonsson J, Hayes J M, Wright F H, Armata T, Blanton J, Burdick J F
Nephrology Associates of Tidewater Sentara Norfolk General Hospital, Virginia, USA.
Transplantation. 1998 Jan 15;65(1):87-92. doi: 10.1097/00007890-199801150-00017.
Tacrolimus has been shown to have a less adverse effect on the lipid profiles of transplant patients when the drug is started as induction therapy. In order to determine the effect tacrolimus has on lipid profiles in stable cyclosporine-treated renal transplant patients with established hyperlipidemia, a randomized prospective study was undertaken by the Southeastern Organ Procurement Foundation.
Patients of the 13 transplant centers, with cholesterol of 240 mg/dl or greater, who were at least 1 year posttransplant with stable renal function, were randomly assigned to remain on cyclosporine (control) or converted to tacrolimus. Patients converted to tacrolimus were maintained at a level of 5-15 ng/ml, and control patients remained at their previous levels of cyclosporine. Concurrent immunosuppressants were not changed. Levels of total cholesterol, triglycerides, total high-density lipoprotein, low-density lipoprotein (LDL), very-low-density lipoprotein, and apoproteins A and B were monitored before conversion and at months 1, 3, and 6. Renal function and glucose control were evaluated at the beginning and end of the study (month 6).
A total of 65 patients were enrolled; 12 patients failed to complete the study. None were removed as a result of acute rejection or graft failure. Fifty-three patients were available for analysis (27 in the tacrolimus group and 26 controls). Demographics were not different between groups. In patients converted to tacrolimus treatment, there was a -55 mg/dl (-16%) (P=0.0031) change in cholesterol, a -48 mg/dl (-25%) (P=0.0014) change in LDL cholesterol, and a -36 mg/dl (-23%) (P=0.034) change in apolipoprotein B. There was no change in renal function, glycemic control, or incidence of new onset diabetes mellitus in the tacrolimus group.
Conversion from cyclosporine to tacrolimus can be safely done after successful transplantation. Introduction of tacrolimus to a stable renal patient does not effect renal function or glycemic control. Tacrolimus can lower cholesterol, LDL, and apolipoprotein B. Conversion to tacrolimus from cyclosporine should be considered in the treatment of posttransplant hyperlipidemia.
已表明，他克莫司作为诱导疗法开始使用时，对移植患者的血脂状况副作用较小。为确定他克莫司对已确诊高脂血症且接受环孢素治疗的稳定肾移植患者血脂状况的影响，东南器官采购基金会开展了一项随机前瞻性研究。
13个移植中心中，胆固醇水平在240mg/dl及以上、移植后至少1年且肾功能稳定的患者，被随机分配继续使用环孢素（对照组）或改用他克莫司。改用他克莫司的患者维持在5 - 15ng/ml的水平，对照组患者维持在先前的环孢素水平。同时使用的免疫抑制剂不变。在转换前以及第1、3和6个月监测总胆固醇、甘油三酯、总高密度脂蛋白、低密度脂蛋白（LDL）、极低密度脂蛋白以及载脂蛋白A和B的水平。在研究开始和结束时（第6个月）评估肾功能和血糖控制情况。
共纳入65例患者；12例患者未完成研究。均未因急性排斥反应或移植失败而被剔除。53例患者可供分析（他克莫司组27例，对照组26例）。两组患者的人口统计学特征无差异。改用他克莫司治疗的患者，胆固醇变化为 - 55mg/dl（-16%）（P = 0.0031），LDL胆固醇变化为 - 48mg/dl（-25%）（P = 0.0014），载脂蛋白B变化为 - 36mg/dl（-23%）（P = 0.034）。他克莫司组的肾功能、血糖控制或新发糖尿病的发生率无变化。
成功移植后可安全地从环孢素转换为他克莫司。将他克莫司应用于稳定的肾移植患者不会影响肾功能或血糖控制。他克莫司可降低胆固醇、LDL和载脂蛋白B。在治疗移植后高脂血症时应考虑从环孢素转换为他克莫司。
