Pascual J, Marcén R, Burgos F J, Villafruela J J, Teruel J L, Mampaso F, Quereda C, Ortuño J
Servicios de Nefrología, Urología y Anatomía Patológica, Hospital Ramón y Cajal, Madrid, Spain.
Transplant Proc. 2004 Mar;36(2 Suppl):117S-119S. doi: 10.1016/j.transproceed.2003.12.031.
Our experience with cyclosporine (CsA) in de novo renal transplantation (RT) may be systematized in four consecutive periods. From February 1986 to December 1989, patient survival was higher among 128 consecutive CsA-prednisone-treated cadaver allograft recipients than in previous patients on azathioprine. One-year graft survival was significantly higher in CsA patients, a difference that was thereafter progressively reduced: at 10 years graft survivals were 50% versus 45%, and at 15 years 37% versus 35%, respectively. The most frequent cause of graft loss was death with a functioning graft. Acute rejection caused more graft losses among Aza-treated patients than CsA-treated ones. However, chronic allograft nephropathy produced more graft losses in CsA patients. After this initial experience with CsA-based immunosuppression we developed a second phase in which better results were obtained in 209 first cadaveric RT recipients. The use of lower initial CsA doses, more rapid steroid tapering, and a better approach to CsA nephrotoxicity or chronic nephropathy by substantial reductions in CsA exposure and delayed azathioprine addition, lead to these improvements. From March 1995 through 2000, we used the new microemulsion CsA formulation (Neoral) with steroids or azathioprine in 110 first de novo RT recipients. Mean donor and recipient ages were significantly higher in this phase than in previous ones; consequently, survival and function results were slightly worse. Blood CsA concentrations measured 2 hours after administration represent a more precise predictor of exposure than trough concentrations. The last step in optimizing Neoral use in RT on our service was application of reduced-dosage with C2 monitoring instead of classical C0 testing. Acute rejection and treatment failure rates were low and renal allograft function improved with respect to previous full-dose C0 experiences. CsA use has evolved in these two decades in four consecutive phases. Short-term results have improved or been maintained from phase to phase, even with expanded-criteria donors until excellent features during last years with C2 monitoring and combination with potent drugs such as MMF or everolimus. During the coming years, new drugs and protocols will allow even more optimized use.
我们在初次肾移植（RT）中使用环孢素（CsA）的经验可分为连续四个阶段。从1986年2月至1989年12月，128例连续接受CsA - 泼尼松治疗的尸体同种异体移植受者的患者生存率高于先前接受硫唑嘌呤治疗的患者。CsA患者的1年移植肾生存率显著更高，此后这种差异逐渐缩小：10年时移植肾生存率分别为50%对45%，15年时为37%对35%。移植肾丢失的最常见原因是移植肾功能正常时的死亡。急性排斥反应导致硫唑嘌呤治疗组的移植肾丢失比CsA治疗组更多。然而，慢性移植肾肾病在CsA患者中导致更多的移植肾丢失。在基于CsA的免疫抑制的初步经验之后，我们进入了第二阶段，在209例初次尸体肾移植受者中取得了更好的结果。使用较低的初始CsA剂量、更快地减少类固醇用量，以及通过大幅减少CsA暴露和延迟添加硫唑嘌呤来更好地处理CsA肾毒性或慢性肾病，带来了这些改善。从1995年3月到2000年，我们在110例初次肾移植受者中使用了新的微乳剂CsA制剂（新山地明）联合类固醇或硫唑嘌呤。此阶段供体和受体的平均年龄显著高于先前阶段；因此，生存和功能结果略差。给药后2小时测得的血液CsA浓度比谷浓度更能精确预测暴露情况。我们科室在肾移植中优化新山地明使用的最后一步是采用减量并进行C2监测而非传统的C0检测。急性排斥反应和治疗失败率较低，与先前全剂量C0经验相比，肾移植功能有所改善。在这二十年中，CsA的使用连续经历了四个阶段。短期结果逐阶段得到改善或维持，即使使用扩大标准供体也是如此，直到近年来采用C2监测并与霉酚酸酯或依维莫司等强效药物联合使用时取得了优异的效果。在未来几年，新的药物和方案将使使用更加优化。
