Pascual J
Department of Nephrology, Hospital Ramón y Cajal, Madrid, Spain.
Nephrol Ther. 2008 Jun;4 Suppl 1:S29-S35. doi: 10.1016/S1769-7255(08)73649-6.
Immunosuppression with calcineurin inhibitors (CNI) is a major factor of chronic allograft nephropathy (CAN). When used in good conditions, proliferation signal inhibitors (PSI) could minimize CNI toxicity and improve long-term graft survival. They must not be used without CNI de novo, taking into account the high rejection rates observed for a similar or even worse renal function than with CNI. On the contrary, protocols associating CNI and PSI with subsequent withdrawal of the CNI improve renal function and decrease CAN and long-term cancer rates if the initial concentration of PSI is low. CNI/PSI associations also give good results with lower rejection rates and a better renal function, provided that low doses of CNI compared to standards are administered (i.e. 3-7 ng/m vs 8-11 ng/ml of tacrolimus) and non-nephrotoxic low circulating doses of mTORi are maintained (9 ng/ml for sirolimus and 6 ng/ml for everolimus). Finally, an alternative consisting in early substituting a CNI by a PSI is given promising results in some controlled clinical trials under way.
使用钙调神经磷酸酶抑制剂（CNI）进行免疫抑制是慢性移植肾肾病（CAN）的主要因素。在良好条件下使用时，增殖信号抑制剂（PSI）可将CNI毒性降至最低并提高移植肾长期存活率。考虑到在肾功能与使用CNI时相似甚至更差的情况下观察到的高排斥率，不能在未使用CNI起始治疗的情况下单独使用PSI。相反，如果PSI初始浓度较低，将CNI与PSI联合使用并随后停用CNI的方案可改善肾功能，降低CAN发生率和长期癌症发生率。如果给予低于标准剂量的CNI（即他克莫司3-7 ng/ml 对比8-11 ng/ml）并维持低循环剂量的非肾毒性的哺乳动物雷帕霉素靶蛋白抑制剂（mTORi）（西罗莫司9 ng/ml，依维莫司6 ng/ml），CNI/PSI联合使用也可获得良好效果，排斥率更低且肾功能更好。最后，在一些正在进行的对照临床试验中，早期用PSI替代CNI的替代方案取得了有前景的结果。
