Maes B D, Vanrenterghem Y F Ch
Department of Medicine, Division of Nephrology, University Hospital Gasthuisberg, Leuven, Belgium.
Transplant Proc. 2004 Mar;36(2 Suppl):40S-49S. doi: 10.1016/j.transproceed.2004.01.038.
Despite a different molecular structure and biochemical properties, cyclosporine and tacrolimus--by inhibiting calcineurin activity--have been shown in the previous two decades of solid organ transplantation to be well tolerated and effective immunosuppressants. Initial randomized clinical trials showed a lower incidence of acute rejection in tacrolimus than in cyclosporine-treated patients, in combination with steroids and azathioprine. But in conjunction with mycophenolate mofetil, the difference in the incidence of acute rejection episodes is less clear. In general, short- and medium-term outcome variables (1-year serum creatinine, graft and patient survival) with cyclosporine and tacrolimus are excellent, and (almost) identical, with both substances having the same intrinsic nephrotoxic potential. On the other hand, cyclosporine and tacrolimus have a different impact on cardiovascular risk factors with tacrolimus having a better profile on arterial tension and lipid metabolism and cyclosporine on glucose metabolism. However, at present no data are available to discern that these differences in risk profile alter patient or graft survival or long-term cardiovascular morbidity/mortality. Therefore, prospective long-term trials are needed to study the quantitative impact of different immunosuppressive agents and concomitant cardiovascular risk factors on long-term patient and graft survival, before evidence-based (patient, graft, or cardiovascular) risk reduction can be firmly claimed by tailoring calcineurin inhibitors.
尽管环孢素和他克莫司的分子结构和生化特性不同，但在过去二十年的实体器官移植中，通过抑制钙调神经磷酸酶活性，它们已被证明是耐受性良好且有效的免疫抑制剂。最初的随机临床试验表明，与使用环孢素治疗并联合使用类固醇和硫唑嘌呤的患者相比，使用他克莫司的患者急性排斥反应的发生率更低。但与霉酚酸酯联合使用时，急性排斥反应发生率之间的差异不太明显。总体而言，环孢素和他克莫司的短期和中期结局变量（1年血清肌酐、移植物和患者生存率）都非常好，而且（几乎）相同，两种药物具有相同的内在肾毒性潜力。另一方面，环孢素和他克莫司对心血管危险因素的影响不同，他克莫司在动脉血压和脂质代谢方面表现较好，而环孢素在葡萄糖代谢方面表现较好。然而，目前尚无数据能够确定这些风险特征的差异是否会改变患者或移植物的生存率或长期心血管疾病的发病率/死亡率。因此，在能够通过调整钙调神经磷酸酶抑制剂明确声称实现基于证据的（患者、移植物或心血管）风险降低之前，需要进行前瞻性长期试验来研究不同免疫抑制剂和伴随的心血管危险因素对患者和移植物长期生存率的定量影响。
