Forgacs B, Merhav H J, Lappin J, Mieles L
Department of Surgery, Division of Immunology and Organ Transplantation, University of Texas, Health Science Center, Houston, Texas 77030, USA.
Transplant Proc. 2005 May;37(4):1912-4. doi: 10.1016/j.transproceed.2005.02.101.
Neurotoxicity is a well-recognized side effect of calcineurin inhibitors. Rapamycin is considered to be significantly less neurotoxic than calcineurin inhibitors (CNIs). The aim of this study was to retrospectively analyze a group of post-liver transplant patients who had been converted to rapamycin because of CNI-related neurotoxicity.
Orthotopic liver transplantation (OLT) was performed in 56 consecutive patients between April 1, 2003, and August 15, 2004. Immunosuppression was administered with tacrolimus, mycophenolic acid, and corticosteroids.
Seven patients were converted to rapamycin due to new-onset neurotoxicity or exacerbation of previous neurological symptoms secondary to CNI. None of the patients had toxic levels tacrolimus (>15 ng/mL) at the time of symptoms, which persisted despite reduction of CNI dose. The indications for conversion were: (1) peripheral neuropathy; (2) seizure; (3) metabolic encephalopathy; and (4) central pontine myelinolysis. All patients showed improvement or resolution of their neurological symptoms after conversion to rapamycin. Two patients died, the first due to a hypoxic event and the second due to central pontine myelinolysis with limited improvement and a family decision to withdraw care. There were no complications directly attributed to rapamycin. Specifically, there were no thrombotic events, wound complications, or biliary leaks. Three patients had a rejection episode that was successfully treated with pulse corticosteroids and low-dose tacrolimus (levels < 5 ng/mL).
Rapamycin can be safely used in OLT recipients with severe neurological symptoms ascribed to or exacerbated by CNIs. Rapamycin monotherapy may be inadequate to control rejection early after transplantation. Rapamycin can be combined with low doses of CNI to prevent rejection.
神经毒性是钙调神经磷酸酶抑制剂一种广为人知的副作用。雷帕霉素被认为神经毒性明显低于钙调神经磷酸酶抑制剂（CNIs）。本研究的目的是回顾性分析一组因CNI相关神经毒性而转换为使用雷帕霉素的肝移植术后患者。
2003年4月1日至2004年8月15日期间，对56例连续患者进行了原位肝移植（OLT）。免疫抑制采用他克莫司、霉酚酸和皮质类固醇。
7例患者因新发神经毒性或继发于CNI的既往神经症状加重而转换为雷帕霉素治疗。症状出现时，所有患者他克莫司水平均未达到中毒水平（>15 ng/mL），尽管降低了CNI剂量，症状仍持续存在。转换治疗的指征为：（1）周围神经病变；（2）癫痫发作；（3）代谢性脑病；（4）中枢性桥脑髓鞘溶解症。所有患者转换为雷帕霉素治疗后，神经症状均有改善或缓解。2例患者死亡，第一例死于缺氧事件，第二例死于中枢性桥脑髓鞘溶解症，改善有限，家属决定放弃治疗。没有直接归因于雷帕霉素的并发症。具体而言，没有血栓形成事件、伤口并发症或胆漏。3例患者发生排斥反应，经脉冲皮质类固醇和低剂量他克莫司（水平<5 ng/mL）成功治疗。
雷帕霉素可安全用于因CNIs引起或加重严重神经症状的OLT受者。雷帕霉素单药治疗可能不足以在移植早期控制排斥反应。雷帕霉素可与低剂量CNI联合使用以预防排斥反应。
