Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse.
J Nephrol. 2010 Mar-Apr;23(2):133-42.
The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy and stress, and has pleiotropic effects. Its blockade, by mTOR inhibitors (mTOR-Is), such as sirolimus or everolimus, leads to antiproliferative effects.
We have reviewed the major studies that deal with the utilization of mTOR-Is after kidney transplant and the outcomes.
Calcineurin-inhibitor (CNI) avoidance, under the umbrella of sirolimus-based immunosuppression in de novo kidney-transplant (KT) patients, is associated with worse results compared with those observed in patients receiving CNI-based immunosuppression. Conversely, using mTOR-Is in the context of CNI minimization and CNI-free protocols is safe and efficient when used after 3 months post-transplant. If cyclosporin A (CsA) is used in combination with mTOR-I, considerable dose reduction of both drugs is required. A better choice may be withdrawal of CsA from this combination after 3-12 months. Later withdrawal or conversion to an mTOR-I may not be beneficial. Kidney transplant recipients given mTOR-Is have reduced incidence of de novo posttransplant malignancies. Posttransplant Kaposi's sarcoma and nonmelanotic skin malignancies frequently undergo remission/regression after conversion to mTOR-I immunosuppression. The associated side effects of mTOR-Is are numerous and may lead to significant drug cessation.
mTOR-Is could be more widely used in kidney transplant patients due to reduced nephrotoxicity and de novo cancer compared with CNIs.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种高度保守的丝氨酸/苏氨酸激酶，可响应营养物质、生长因子、细胞能量和应激来控制细胞生长和代谢，具有多种作用。其通过 mTOR 抑制剂（mTOR-Is）如西罗莫司或依维莫司的阻断作用，可导致抗增殖作用。
我们回顾了主要研究，这些研究涉及肾移植后 mTOR-Is 的应用及其结果。
在新诊断的肾移植（KT）患者中，与使用钙调磷酸酶抑制剂（CNI）的患者相比，在西罗莫司为基础的免疫抑制下避免 CNI，其结果更差。相反，在 CNI 最小化和无 CNI 方案中使用 mTOR-Is 在移植后 3 个月后是安全有效的。如果环孢素 A（CsA）与 mTOR-I 联合使用，则需要减少两种药物的剂量。更好的选择可能是在 3-12 个月后从该联合方案中撤出 CsA。之后的停药或转换为 mTOR-I 可能无益。接受 mTOR-Is 的肾移植受者新发移植后恶性肿瘤的发生率降低。在转换为 mTOR-I 免疫抑制后，移植后卡波西肉瘤和非黑色素瘤皮肤恶性肿瘤经常缓解/消退。mTOR-Is 的相关副作用很多，可能导致药物大量停用。
与 CNI 相比，mTOR-Is 具有较低的肾毒性和新发癌症风险，因此可更广泛地用于肾移植患者。
