Schweiger Martin, Wasler Andre, Prenner Guenther, Stiegler Philipp, Stadlbauer Vanessa, Schwarz Michaela, Tscheliessnigg Karlheinz
Department of Surgery, Division of Transplantation Surgery, Medical University Graz, Austria.
Transpl Immunol. 2006 Jun;16(1):46-51. doi: 10.1016/j.trim.2006.02.001. Epub 2006 Mar 24.
Long-term survival of patients after oHTX significantly increased over the last years, but CAV and chronic renal failure due to nephrotoxic side-effects of CNIs still remain unsolved problems. Everolimus has shown to reduce acute cellular rejection and may allow CsA dosage reduction. In this study the effectiveness of Everolimus in combination with CsA dosage reduction in maintenance oHTX immunosuppression and the influence on renal function was tested.
37 patients (30 male, 7 female) after oHTX were divided into group A (n = 20) receiving Everolimus in combination with CsA and prednisolone and group B (n = 17) under standard immunosuppression with CsA, MMF and prednisolone. Patients received 1.0 mg to 1.5 mg Everolimus per day and target Everolimus trough levels were between 3 and 8 ng/ml. Death, safety, side effects, BPAR, trough levels, and routine laboratory values especially creatinine levels were monitored over a follow-up period of 8 months retrospectively and statistically evaluated.
A significant reduction of CsA dosage (p < 0.001) and a significant CsA trough level reduction (p < 0.001) to a median CsA trough level of 68.5 ng/ml were achieved in group A. Mean Everolimus trough levels were reached within 1 week and 2 months. Renal function was stable in both groups. No statistical differences in BPAR, hospitalization rates or triglyceride levels were observed. Cholesterol levels significantly increased in group B (p = 0.024).
CsA trough levels and dosage can be significantly reduced in combination with Everolimus without higher rejection rates and with stable kidney function in oHTX patients.
在过去几年中，接受原位心脏移植（oHTX）患者的长期生存率显著提高，但由钙调神经磷酸酶抑制剂（CNIs）的肾毒性副作用导致的慢性移植物血管病（CAV）和慢性肾衰竭仍然是尚未解决的问题。依维莫司已显示可减少急性细胞排斥反应，并可能允许减少环孢素A（CsA）的剂量。在本研究中，测试了依维莫司联合降低CsA剂量在维持oHTX免疫抑制中的有效性及其对肾功能的影响。
37例oHTX术后患者（30例男性，7例女性）被分为A组（n = 20），接受依维莫司联合CsA和泼尼松龙治疗；B组（n = 17）接受CsA、霉酚酸酯（MMF）和泼尼松龙的标准免疫抑制治疗。患者每天接受1.0 mg至1.5 mg依维莫司治疗，依维莫司谷浓度目标值在3至8 ng/ml之间。回顾性监测8个月随访期内的死亡、安全性、副作用、活检证实的急性排斥反应（BPAR）、谷浓度以及常规实验室值，尤其是肌酐水平，并进行统计学评估。
A组CsA剂量显著降低（p < 0.001），CsA谷浓度显著降低（p < 0.001），CsA谷浓度中位数降至68.5 ng/ml。依维莫司平均谷浓度在1周内和2个月时达到目标值。两组肾功能均稳定。BPAR、住院率或甘油三酯水平无统计学差异。B组胆固醇水平显著升高（p = 0.024）。
oHTX患者联合使用依维莫司可显著降低CsA谷浓度和剂量，且排斥率不升高，肾功能稳定。
