肾移植术后减量他克莫司联合加量吗替麦考酚酯的疗效和安全性

Clinical efficacy and safety of reduced-dose tacrolimus combined with increased-dose mycophenolate mofetil after renal transplantation

目的评价肾移植术后予以减量他克莫司（FK506）联合加量吗替麦考酚酯（MMF）方案的疗效及安全性评价。方法本前瞻性研究中收集2011年1月至2013年1月期间在安徽省立医院器官移植科接受肾移植手术超过12个月的受者52例,随机分为干预组和对照组各26例。干预组在入组后15 d内将FK506血药谷浓度调整为2.0~4.5 ng/ml,MMF的口服剂量调整为1.5 g/d;对照组入组后FK506血药谷浓度保持不变,维持在5.5~10.0 ng/ml,MMF的口服剂量仍保持1.0 g/d。比较两组治疗0、15 d,2、4、6、8、10、12个月的肾小球滤过率（GFR）、血清肌酐（Scr）的变化;比较两组治疗1年的甘油三酯、总胆固醇、24 h尿蛋白定量的变化;比较两组治疗后相关不良反应发生率。结果治疗0 d至12个月,对照组的GFR波动不大（P〉0.05）,而干预组GFR明显升高（P〈0.05）,且治疗8、10、12个月时两组的GFR变化值比较差异均有统计学意义（均为P〈0.05）。治疗0 d至12个月,干预组和对照组的Scr水平均下降,其中前者下降幅度更明显（P〈0.05）,且治疗10、12个月时两组的Scr变化值比较差异均有统计学意义（均为P〈0.05）。治疗12个月,干预组和对照组的总胆固醇、甘油三酯、平均24 h尿蛋白定量比较,差异均无统计学意义（均为P〉0.05）。干预组和对照组均未发生急性排斥反应和移植肾失功。两组的不良反应发生率比较差异无统计学意义（P〉0.05）。结论减量FK506联合加量MMF是安全有效的免疫抑制方案。

Objective To evaluate the clinical efficacy and safety of reduced-dose tacrolimus（ FK506） in combination with increased-dose mycophenolate mofetil（ MMF） after renal transplantation. Methods In this prospective study,52 patients undergoing renal transplantation for over 12 months in the Department of Organ Transplantation,Anhui Provincial Hospital from January 2011 to January 2013 were recruited. All participants were randomly divided into the intervention group and control group（ n = 26 in each group）. In the intervention group,blood trough concentration of FK506 was adjusted to 2. 0-4. 5 ng / ml and oral dose of MMF was adjusted to 1. 5 g / d during 15 d after study. And in control group,blood trough concentration of FK506 was kept in 5. 5-10. 0 ng / ml and oral dose of MMF was 1. 0 g / d constantly. The changes of the glomerular filtration rate（ GFR） and serum creatinine（ Scr） at 0 d,15 d,and 2-,4-,6-,8-,10-,12-month after corresponding treatment were statistically compared between two groups. At 1 year after therapy,triglyceride,total cholesterol and 24 h urinary protein levels were measured and compared between two groups. Moreover,the incidence of adverse reactions was also statistically compared. Results During the period from 0 d to 12 months after treatment,GFR did not significantly change in the control group（ P〉0. 05）,whereas the value in the intervention group was considerably elevated（ P〈0. 05）. The changes in terms of the GFR at 8-,10- and 12-month after treatment significantly differed betweentwo groups（ all in P〈0. 05）. From 0 d to 12 months after therapy,the levels of Scr were significantly decreased in two groups（ both in P〈0. 05）,and more apparent decline was noted in the intervention group. The changes in the Scr levels at10 and 12 months after corresponding treatment significantly differed between two groups（ both in P〈0. 05）. At 12 months after therapy,there was no significant difference in the levels of total cholesterol,triglyceride and mean 24 h urinary protein between the control and intervention groups（ all in P〉0. 05）. No acute rejection or renal allograft dysfunction occurred in two groups. And there was no significant difference in the incidence of adverse reactions between the intervention and control groups（ P〈0. 05）. Conclusions Combined therapy of reduced-dose FK506 and increased-dose MMF is an efficacious and safe immunosuppressive therapy.