一项针对中国活体供肾移植受者的单中心、开放标签、前瞻性研究，该研究采用了一种初始短期强化给药方案，即肠溶包衣的麦考酚钠，同时降低环孢素A的暴露量。

A single-centre, open-label, prospective study of an initially short-term intensified dosing regimen of enteric-coated mycophenolate sodium with reduced cyclosporine A exposure in Chinese live-donor kidney transplant recipients.

作者信息

Cai L, Zeng F, Liu B, Wei L, Chen Z, Jiang J

机构信息

The Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Ministry of Health and Key Laboratory of Ministry of Education, Wuhan, China; Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Int J Clin Pract Suppl. 2014 Apr(181):23-30. doi: 10.1111/ijcp.12403.

DOI:10.1111/ijcp.12403

PMID:24673716

Abstract

AIMS

The nephrotoxicity of cyclosporine A (CsA) accounts for dysfunction of kidney allografts in the clinic. Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) may facilitate CsA sparing after kidney transplantation without compromising safety.

METHODS

In a 12-month, single-centre open-label prospective trial, 180 de novo live-donor kidney transplant recipients at low-immunological risk were randomised to a low-dose cyclosporine group which received a low dose of cyclosporine, short-term intensified EC-MPS dosing (2160 mg/day to week 6, 1440 mg/day thereafter) and corticosteroids or a standard-dose cyclosporine group which received a standard dose of cyclosporine, standard EC-MPS dosing (1440 mg/day) and corticosteroids. The primary end-point [treatment failure including biopsy-proven acute rejection (BPAR), graft loss, death], secondary end-point and adverse events were monitored.

RESULTS

The primary end-point (treatment failure) occurred in 13.3% (12/90) of the low-dose cyclosporine group and 16.7% (15/90) of the standard-dose cyclosporine group (p = 0.53) (difference -3.4%, 95% confidence interval -11.7% to 7.5%, based on a noninferiority margin of 20%). BPAR occurred in 11.1% and 13.3% of patients in the low-dose cyclosporine group and standard-dose cyclosporine group, respectively (p = 0.65). The estimated glomerular filtration rate, as calculated by the Cockcroft-Gault formula, was similar at 12 months after transplantation (low-dose cyclosporine group 63 ± 19 ml/min/1.73 m(2) and standard-dose cyclosporine group 59 ± 15 ml/min/1.73 m(2) ; p = 0.43). The levels of serum creatinine and occurrence of adverse events between the two groups were not statistically different.

CONCLUSIONS

A regimen of early intensified EC-MPS dosing permits low-dose cyclosporine in live-donor kidney transplant patients at low-immunological risk without compromising efficacy at 12 months' follow-up.

摘要

目的

环孢素A（CsA）的肾毒性是临床肾移植受者移植肾功能障碍的原因之一。肾移植后短期强化使用肠溶型霉酚酸钠（EC-MPS）可能有助于减少CsA用量，且不影响安全性。

方法

在一项为期12个月的单中心开放标签前瞻性试验中，180例低免疫风险的初次活体供肾移植受者被随机分为低剂量环孢素组和标准剂量环孢素组。低剂量环孢素组接受低剂量环孢素、短期强化EC-MPS给药（第6周前2160毫克/天，之后1440毫克/天）和皮质类固醇；标准剂量环孢素组接受标准剂量环孢素、标准EC-MPS给药（1440毫克/天）和皮质类固醇。监测主要终点[治疗失败，包括活检证实的急性排斥反应（BPAR）、移植肾失功、死亡]、次要终点和不良事件。

结果

低剂量环孢素组主要终点（治疗失败）发生率为13.3%（12/90），标准剂量环孢素组为16.7%（15/90）（p = 0.53）（差异-3.4%，95%置信区间-11.7%至7.5%，非劣效界值为20%）。低剂量环孢素组和标准剂量环孢素组BPAR发生率分别为11.1%和13.3%（p = 0.65）。根据Cockcroft-Gault公式计算的估计肾小球滤过率在移植后12个月时相似（低剂量环孢素组63±19毫升/分钟/1.73平方米，标准剂量环孢素组59±15毫升/分钟/1.73平方米；p = 0.43）。两组血清肌酐水平和不良事件发生率无统计学差异。