肾移植后应用雷帕霉素低目标浓度突然转换方案的临床观察  

Clinical investigation on abrupt conversion of low-dose sirolimus after kidney transplantation

作　　者：邱甬鄞[1] 邱月[1] 王宣传[1] 赵天[1] 许明[1] 戎瑞明[1] 

机构地区：[1]复旦大学附属中山医院泌尿外科上海市器官移植重点实验室,上海200032

出　　处：《中华移植杂志（电子版）》2010年第3期20-23,共4页Chinese Journal of Transplantation(Electronic Edition)

基　　金：国家自然科学基金面上项目(81070595)

摘　　要：目的探讨肾移植术后3年以上患者应用雷帕霉素低目标浓度突然转换方案的有效性及安全性。方法选取复旦大学附属中山医院泌尿外科24例肾移植术后因各种原因转换使用雷帕霉素免疫抑制方案的患者。所有患者均以环孢素或他克莫司联合吗替麦考酚酯和泼尼松为初始免疫抑制方案。转换当天停用钙调磷酸酶抑制剂(CNI),以4mg/d雷帕霉素为起始负荷剂量,第2天起改为2mg/d,后根据药物浓度调整用药剂量。因慢性移植肾肾病而转换的患者目标浓度为4～6ng/mL,因肿瘤而转换的患者目标浓度控制在6～8ng/mL。分析患者的转换动机、转换前后血肌酐、蛋白尿、血脂、血糖和血常规指标;观察转换前后感染发生率和肿瘤患者及增生性疾病患者的转归。结果转换后慢性移植肾肾病患者血肌酐浓度明显下降(P=0.002),而因其他原因转换的患者中血肌酐变化无统计学意义(P=0.41)。转换后患者蛋白尿水平呈双向变化,总胆固醇和低密度脂蛋白胆固醇水平呈先上升后下降趋势,与转换前差异无统计学意义(P=0.80和0.51)。使用他汀类药物后,血总胆固醇及低密度脂蛋白胆固醇水平明显下降(均P=0.02)。转换前后血糖水平无显著变化(P=0.211)。转换前后外周血红细胞、白细胞、淋巴细胞、血小板计数差异无统计学意义(P=0.37、0.50、0.94、0.31)。转换前后各1年感染发生率差异无统计学意义(P=0.418)。肿瘤患者随访期间均无临床复发。1例尿路上皮癌患者肿瘤消退,1例因输尿管瘢痕增生的患者转换后未再发狭窄。结论肾移植后3年以上的患者,低目标浓度的雷帕霉素突然转换方案安全有效。对于肿瘤及增生性疾病患者,雷帕霉素可能有特殊的治疗作用。Objective To evaluate the efficacy and safety of low-dose sirolimus abrupt conversion therapy in renal allograft recipients over 3 years posttransplantation. Methods A total of 24 patients who convened from calcineurin inhibitor （CNI）-based therapy to sirolimus-based regimen because of various causes were enrolled in this study. All patients received cyclosporin or tacrolimus combined with adjunctive mycophenolate mofetil and steroids before conversion. CNI was withdrawn abmpdy and replaced by 4 nag loading-dose sirolimus on the day of conversion. The dose was cut by half thereafter and was adjusted according to therapeutic drug monitoring. The targeted trough level of sirolimus was 4-6 ng/mL in patients with chronic allogr＇aft nephropathy（CAN） and 6-8 ng/mL in other subjects. We analyzed motives invoked for conversion, serum creatinine, proteinuria, lipidemia, fasting blood glucose, and blood routine before and after conversion. We also reviewed the infection rates and the prognosis of the patients who suffered from tumor and proliferative disease. Results The serum creatinine level in CAN patients remarkably decreased compared with that before conversion （P =0. 002）, whereas no significant change was seen in other subjects （P = 0.41 ）. A two-way fluctuation in proteinuria was observed. Serum levels of total cholesterol and low- density lipoprotein cholesterol exhibited a peak at 6 month posttransplantation compared with baseline with-out statistical significances （P = 0.80 and 0.51 ） and could be well controlled by statins （P = 0. 02 ）, while the fasting blood glucose leveled off （P =0.211 ）. The blood routine remained stable after conversion. The infection rates due to immunosuppression 1 year before and after conversion were similar （ P = 0.418）. For conversion because of tumor, no clinical recurrence was observed during follow-up. One patient with urothelial carcinoma enjoyed tumor regression after conversion. No recurrent ureterostenosis was seen in 1 patient with prolifera

关 键 词：肾移植 钙调磷酸酶抑制剂 雷帕霉素 突然转换 低剂量 

分 类 号：R699[医药卫生—泌尿科学]