Russ Graeme R
Transplant Res. 2013 Nov 20;2(Suppl 1):S4. doi: 10.1186/2047-1440-2-S1-S4.
Renal transplantation is the treatment of choice for end-stage renal failure. Although advances in immunosuppression have led to improvements in short-term outcomes, graft survival beyond 5 to 10 years has not improved. One of the major causes of late renal allograft failure is chronic allograft nephropathy, a component of which is nephrotoxicity from the use of calcineurin inhibitors (CNIs). In addition, premature patient death is a major limitation of renal transplantation and the major causes are cancer, cardiovascular disease and infection. CNI-free immunosuppressive regimens based on mammalian target of rapamycin (mTOR) inhibitors have been trial led over the last few years and have defined the rational use of these agents. Conversion from a CNI-based to an mTOR-inhibitor-based regimen has been successful at improving renal function for a number of years after conversion, although long-term survival outcomes are still awaited. The studies suggest that the safest and most effective time to convert is between 1 and 6 months after transplant. In addition, mTOR-inhibitor-based regimens have been shown to be associated with lower rates of post-transplant malignancy and less cytomegalovirus infection, which may add further to the appeal of this approach.
肾移植是终末期肾衰竭的首选治疗方法。尽管免疫抑制方面的进展已使短期疗效有所改善，但超过5至10年的移植物存活率并未提高。晚期肾移植失败的主要原因之一是慢性移植肾肾病，其一部分是使用钙调神经磷酸酶抑制剂（CNIs）导致的肾毒性。此外，患者过早死亡是肾移植的一个主要限制因素，主要原因是癌症、心血管疾病和感染。在过去几年中，基于雷帕霉素哺乳动物靶点（mTOR）抑制剂的无CNI免疫抑制方案已进行了试验，并明确了这些药物的合理使用方法。从基于CNI的方案转换为基于mTOR抑制剂的方案，在转换后的数年里已成功改善了肾功能，尽管长期生存结果仍有待观察。研究表明，转换的最安全、最有效时间是在移植后1至6个月之间。此外，基于mTOR抑制剂的方案已被证明与移植后恶性肿瘤发生率较低和巨细胞病毒感染较少有关，这可能会进一步增加这种方法的吸引力。
