Fairbanks Kyrsten D, Eustace Joseph A, Fine Derek, Thuluvath Paul J
Division of Gastroenterology and Hepatology, The Johns Hopkins University Hospital, Baltimore, MD 21205, USA.
Liver Transpl. 2003 Oct;9(10):1079-85. doi: 10.1053/jlts.2003.50183.
Sirolimus (Rapamune; Wyeth-Ayerst, Philadelphia, PA) is a newer immunosuppressive drug with no known acute or chronic nephrotoxic effects; however, limited data are available in liver transplant recipients. We prospectively evaluated changes in renal function in liver transplant recipients after conversion from a calcineurin inhibitor to sirolimus monotherapy. We measured serial serum creatinine levels in liver transplant recipients with chronic nephrotoxicity caused by calcineurin inhibitors before and after conversion to sirolimus therapy. Estimated glomerular filtration rate (eGFR) was calculated from the Modification of Diet in Renal Disease formula. Change in eGFR over time, incidence of acute hepatocellular rejection, and adverse events while being administered sirolimus monotherapy were recorded. Mean interval between liver transplantation and initiation of sirolimus therapy was 310 weeks (range, 9 to 780 weeks). Of 21 patients included in our study, 18 patients were converted to sirolimus monotherapy and 3 patients were switched to sirolimus and low-dose steroid therapy. Patients were followed up for a mean of 66.8 +/- 38.9 (SD) weeks after conversion. Renal function improved in 71% of patients (15 of 21 patients). Median eGFR improved significantly from 34 mL/min/1.73 m2 at the time of conversion to 43 mL/min/1.73 m2 at the last follow-up (27% increase in eGFR; P = 001). Median monthly change in eGFR was from -0.25 mL/min/1.73 m2 pre-sirolimus therapy to +1.28 mL/min/1.73 m2 post-sirolimus therapy (P =.09). Adverse events were mostly mild and self-limited. Only 1 patient developed biopsy-proven acute cellular rejection, which was treated with sirolimus and mycophenolate mofetil. Two patients discontinued sirolimus therapy because of toxicity (oral ulceration, 1 patient; interstitial pneumonitis, 1 patient). Renal function improved significantly in the majority of liver transplant recipients with renal insufficiency caused by calcineurin inhibitors when converted to sirolimus therapy. Sirolimus monotherapy provided adequate immunosuppression with a low incidence of acute cellular rejection and minimal adverse events.
西罗莫司（雷帕鸣；惠氏-艾尔斯特公司，宾夕法尼亚州费城）是一种新型免疫抑制药物，尚无已知的急性或慢性肾毒性作用；然而，肝移植受者的相关数据有限。我们前瞻性评估了肝移植受者从钙调神经磷酸酶抑制剂转换为西罗莫司单药治疗后肾功能的变化。我们测量了因钙调神经磷酸酶抑制剂导致慢性肾毒性的肝移植受者在转换为西罗莫司治疗前后的系列血清肌酐水平。根据肾病饮食改良公式计算估计肾小球滤过率（eGFR）。记录eGFR随时间的变化、急性肝细胞排斥反应的发生率以及接受西罗莫司单药治疗时的不良事件。肝移植与开始西罗莫司治疗之间的平均间隔为310周（范围9至780周）。在我们纳入研究的21例患者中，18例患者转换为西罗莫司单药治疗，3例患者转换为西罗莫司和低剂量类固醇治疗。转换后患者平均随访66.8±38.9（标准差）周。71%的患者（21例中的15例）肾功能得到改善。中位eGFR从转换时的34 mL/min/1.73 m²显著改善至最后一次随访时的43 mL/min/1.73 m²（eGFR增加27%；P = 0.01）。eGFR的中位每月变化从西罗莫司治疗前的-0.25 mL/min/1.73 m²变为西罗莫司治疗后的+1.28 mL/min/1.73 m²（P = 0.09）。不良事件大多轻微且为自限性。仅1例患者发生经活检证实的急性细胞排斥反应，采用西罗莫司和霉酚酸酯治疗。2例患者因毒性（1例口腔溃疡；1例间质性肺炎）停用西罗莫司治疗。对于大多数因钙调神经磷酸酶抑制剂导致肾功能不全并转换为西罗莫司治疗的肝移植受者，肾功能显著改善。西罗莫司单药治疗提供了充分的免疫抑制，急性细胞排斥反应发生率低且不良事件极少。
