Campistol J M
Nephrology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Transplant Proc. 2010 Nov;42(9 Suppl):S21-4. doi: 10.1016/j.transproceed.2010.09.015.
Combination therapy with mammalian target of rapamycin (mTOR)-inhibitors and calcineurin inhibitors (CNIs) provides significant immunosuppressive efficacy. If the combination of these agents is not properly optimized, however, important risks for synergistic toxicity and long-term complications may result. The combination of a CNI and an mTOR-inhibitor is a potent immunosuppressive therapy that effectively prevents the incidence of acute rejection, although the potential nephrotoxic impact must be considered in the longer term. The trend has therefore been to use a low-dose CNI in combination with the mTOR-inhibitor sirolimus in order to reduce the risk of nephrotoxicity. Recent studies show that an mTOR-inhibitor/low-dose CNI combination is effective in the short term following transplantation, and over time, consideration should be given to the elimination of the CNI in order to preserve renal function. In the medium to long term, it is also possible to consider the elimination of steroids from such a protocol. Considering CNI dose minimization or elimination is an essential component of this approach, as is the optimal dose and level of both drugs when used in combination.
雷帕霉素哺乳动物靶点（mTOR）抑制剂与钙调神经磷酸酶抑制剂（CNIs）联合治疗具有显著的免疫抑制效果。然而，如果这些药物的联合使用未得到适当优化，可能会导致协同毒性和长期并发症的重大风险。尽管从长远来看必须考虑潜在的肾毒性影响，但CNI与mTOR抑制剂的联合是一种有效的免疫抑制疗法，可有效预防急性排斥反应的发生。因此，趋势是使用低剂量CNI与mTOR抑制剂西罗莫司联合，以降低肾毒性风险。最近的研究表明，mTOR抑制剂/低剂量CNI联合在移植后的短期内有效，随着时间的推移，应考虑停用CNI以保护肾功能。从中长期来看，也可以考虑从该方案中停用类固醇。考虑将CNI剂量最小化或停用是这种方法的重要组成部分，联合使用时两种药物的最佳剂量和水平也是如此。
