Kamar Nassim, Rostaing Lionel, Cassuto Elisabeth, Villemain Florence, Moal Marie-Christine, Ladrière Marc, Barrou Benoît, Ducloux Didier, Chaouche Kamel, Quéré Stephane, Di Giambattista Fabienne, Be François
Department of Nephrology, Dialysis and Organ Transplantation, Hôpital Rangueil, Toulouse, France.
Clin Nephrol. 2012 Feb;77(2):126-36. doi: 10.5414/CN107227.
Mycophenolic acid (MPA) dose is frequently reduced in tacrolimus-treated kidney transplant patients, but alternatively the recommended MPA dose can be maintained with reduced tacrolimus exposure. In a 6-month, multicenter, randomized, openlabel study, maintenance kidney transplant patients receiving MPA (mycophenolate mofetil 1g/d or enteric-coated mycophenolate sodium (EC-MPS) 720 mg/d) and tacrolimus were randomized to convert to EC-MPS 1,440 mg/d with reduced tacrolimus (n = 46), or receive EC-MPS 720 mg/d with unchanged tacrolimus (n = 48). Mean estimated GFR (eGFR, aMDRD) at Month 6 was 49.1 ± 11.1 and 44.7 ± 11.5 ml/min/1.73 m2 in the EC-MPS 1,440 mg and 720 mg groups, respectively (p = 0.07). The primary endpoint, change in eGFR from Day 0 to Month 6, was 2.48 ± 0.95 ml/min/1.73 m2 with EC-MPS 1,440 mg and -0.48 ± 0.93 ml/min/1.73 m2 with EC-MPS 720 mg (difference 2.96 ml/min/1.73 m2; 95% CI 0.32 - 5.60; p = 0.028). There were no deaths, graft losses or acute rejections. Adverse events were more frequent with EC-MPS 1,440 mg than 720 mg (66.7% vs. 44.7%, p = 0.034). Adverse events with suspected relation to EC-MPS occurred in 26.7% and 21.3% of patients, respectively (p = 0.59). Conversion of kidney transplant patients to increased MPA dosing using EC-MPS 1,440 mg/d, with reduced tacrolimus exposure, appears an effective immunosuppression strategy and may improve renal function. Adverse events overall, but not those with a suspected relation to EC-MPS, were higher with ECMPS 1,440 mg/d.
在接受他克莫司治疗的肾移植患者中，霉酚酸（MPA）的剂量常常会降低，但也可以在减少他克莫司暴露量的情况下维持推荐的MPA剂量。在一项为期6个月的多中心、随机、开放标签研究中，接受MPA（霉酚酸酯1g/天或肠溶包衣的霉酚酸钠（EC-MPS）720mg/天）和他克莫司治疗的维持性肾移植患者被随机分为两组，一组转换为1440mg/天的EC-MPS并减少他克莫司用量（n = 46），另一组接受720mg/天的EC-MPS且他克莫司用量不变（n = 48）。在第6个月时，EC-MPS 1440mg组和720mg组的平均估计肾小球滤过率（eGFR，采用aMDRD公式计算）分别为49.1±11.1和44.7±11.5ml/min/1.73m²（p = 0.07）。主要终点指标，即从第0天到第6个月eGFR的变化，在EC-MPS 1440mg组为2.48±0.95ml/min/1.73m²，在EC-MPS 720mg组为 -0.48±0.93ml/min/1.73m²（差异为2.96ml/min/1.73m²；95%CI为0.32 - 5.60；p = 0.028）。未发生死亡、移植肾丢失或急性排斥反应。1440mg的EC-MPS组不良事件比720mg组更频繁（66.7%对44.7%，p = 0.034）。分别有26.7%和21.3%的患者发生了疑似与EC-MPS相关的不良事件（p = 0.59）。肾移植患者转换为使用1440mg/天的EC-MPS增加MPA剂量并减少他克莫司暴露量，似乎是一种有效的免疫抑制策略，且可能改善肾功能。总体不良事件在1440mg/天的EC-MPS组中更高，但疑似与EC-MPS相关的不良事件并非如此。
