单中心成人原发性肾移植受者中他克莫司/依维莫司与他克莫司/肠溶包衣麦考酚酸钠对比的前瞻性随机试验

Pilot Randomized Trial of Tacrolimus/Everolimus vs Tacrolimus/Enteric-Coated Mycophenolate Sodium in Adult, Primary Kidney Transplant Recipients at a Single Center.

作者信息

Ciancio G, Tryphonopoulos P, Gaynor J J, Guerra G, Sageshima J, Roth D, Chen L, Kupin W, Mattiazzi A, Tueros L, Flores S, Hanson L, Powell R H, Ruiz P, Vianna R, Burke G W

机构信息

Department of Surgery, Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL.

出版信息

Transplant Proc. 2016 Jul-Aug;48(6):2006-10. doi: 10.1016/j.transproceed.2016.03.048.

DOI:10.1016/j.transproceed.2016.03.048

PMID:27569936

Abstract

BACKGROUND

Recent studies suggest that the combination of tacrolimus (TAC) and everolimus (EVL) could become a viable option for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients.

METHODS

We conducted a single-center, open-label, randomized pilot trial comparing two maintenance immunosuppression regimens in non-highly sensitized, adult, primary kidney transplant recipients: (TAC/EVL, Group A) vs our standard maintenance regimen of TAC plus enteric-coated mycophenolate mofetil (TAC/EC-MPS, Group B). In both treatment arms, dual induction therapy consisting of anti-thymocyte globulin (Thymoglobulin) and basiliximab was given. Early corticosteroid withdrawal (by 7-10 days posttransplantation) was also planned in both arms. There were 30 study participants, 15 per treatment arm. Results during the first 12 months posttransplantation are reported here.

RESULTS

Between 1 month and 12 months posttransplantation, mean TAC trough levels ranged between 5 and 8 ng/mL in both arms. Mean trough EVL level in Group A ranged between 4 and 6 ng/mL, and mean EC-MPS dose in Group B ranged from 1440 mg at 1 month to 945 mg at 12 months. One patient in Group A vs three patients in Group B experienced a first biopsy-proven acute rejection during the first 12 months posttransplantation (P = .32). Four patients in each group experienced biopsy-proven chronic allograft injury (interstitial fibrosis/tubular atrophy) (P = .99). There was a slight trend toward more favorable renal function in Group A at months 1-3 posttransplantation (P = .06, .10, and .18 for estimated glomerular filtration rate, respectively). No graft failures or deaths were observed in either group during the first 12 months posttransplantation. Four patients in each group developed an infection during the first 12 months posttransplantation. Two patients in Group A developed new-onset diabetes after transplant during the 12-month follow-up period, vs no patients in Group B (P = .13).

CONCLUSION

TAC/EVL may be a viable alternative to TAC/EC-MPS for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients and should be given further consideration.

摘要

背景

近期研究表明，他克莫司（TAC）与依维莫司（EVL）联合使用可能成为非高敏肾移植受者标准维持免疫抑制治疗的一个可行选择。

方法

我们开展了一项单中心、开放标签、随机对照试验，比较非高敏成年初次肾移植受者的两种维持免疫抑制方案：（TAC/EVL，A组）与我们的TAC加肠溶霉酚酸酯标准维持方案（TAC/EC-MPS，B组）。在两个治疗组中，均给予抗胸腺细胞球蛋白（即复宁）和巴利昔单抗组成的双重诱导治疗。两组还计划在移植后7 - 10天早期停用皮质类固醇。共有30名研究参与者，每个治疗组15名。本文报告移植后前12个月的结果。

结果

移植后1个月至12个月期间，两组的TAC平均谷浓度均在5至8 ng/mL之间。A组的依维莫司平均谷浓度在4至6 ng/mL之间，B组的肠溶霉酚酸酯平均剂量从1个月时的1440 mg至12个月时的945 mg。移植后前12个月，A组有1例患者与B组有3例患者发生首次经活检证实的急性排斥反应（P = 0.32）。每组有4例患者发生经活检证实的慢性移植肾损伤（间质纤维化/肾小管萎缩）（P = 0.99）。移植后1 - 3个月时，A组的肾功能有稍好的趋势（估计肾小球滤过率分别为P = 0.06、0.10和0.18）。移植后前12个月，两组均未观察到移植肾失功或死亡。每组有4例患者在移植后前12个月发生感染。A组有2例患者在12个月随访期内移植后发生新发糖尿病，而B组无患者发生（P = 0.13）。