Remuzzi Giuseppe, Cravedi Paolo, Costantini Marco, Lesti Mariadomenica, Ganeva Maria, Gherardi Giulia, Ene-Iordache Bogdan, Gotti Eliana, Donati Donato, Salvadori Maurizio, Sandrini Silvio, Segoloni Giuseppe, Federico Stefano, Rigotti Paolo, Sparacino Vito, Ruggenenti Piero
Department of Renal Medicine, Mario Negri Institute for Pharmacological Research, Negri Bergamo Laboratories, Via Gavazzeni 11, 24125 Bergamo, Italy.
J Am Soc Nephrol. 2007 Jun;18(6):1973-85. doi: 10.1681/ASN.2006101153. Epub 2007 Apr 25.
The Mycophenolate Steroids Sparing (MYSS) study found that in renal transplant recipients who were on immunosuppressive therapy with the cyclosporine microemulsion Neoral, mycophenolate mofetil (MMF) was not better than azathioprine in preventing acute rejection at 21 mo after transplantation and was 15 times more expensive. The MYSS Follow-up Study, an extension of MYSS, was aimed at comparing long-term outcome of 248 MYSS patients according to their original randomization to MMF (1 g twice daily) or azathioprine (75 to 100 mg/d). Primary outcome was estimated GFR at 5 yr after transplantation. Mean 5-yr GFR difference between azathioprine and mycophenolate was 4.67 ml/min per 1.73 m(2) (95% confidence interval [CI] -0.43 to 9.77 ml/min per 1.73 m(2); P = 0.07). GFR from month 6 (mean +/- SEM: 54.3 +/- 1.6 versus 53.9 +/- 1.5 ml/min per 1.73 m(2); P = 0.83) to month 72 after transplantation (49.5 +/- 2.2 versus 47.3 +/- 2.4 ml/min per 1.73 m(2); P = 0.50); GFR slopes (mean +/- SEM: -1.10 +/- 0.56 versus -1.23 +/- 0.31 ml/min per 1.73 m(2) per year; P = 0.83); and 72-mo patient mortality (4.0 versus 4.0% [P = 0.95]; HR 0.96; 95% CI 0.28 to 3.31; P = 0.95), graft loss (6.8 versus 6.1% [P = 0.82]; HR 0.89; 95% CI 0.32 to 2.46; P = 0.83), incidence of persistent proteinuria (25.0 versus 27.4%; P = 0.72), late (>6 mo after transplantation) rejections (25.3 versus 21.2%; P = 0.53), and adverse events were similar on azathioprine (n = 124) and MMF (n = 124), respectively. Outcomes in the two groups were comparable also among patients with or without steroid therapy, considered separately. In kidney transplantation, the long-term risk/benefit profile of MMF and azathioprine therapy in combination with cyclosporine Neoral is similar. In view of the cost, standard immunosuppression regimens for kidney transplantation should perhaps include azathioprine rather than MMF.
霉酚酸酯减用类固醇（MYSS）研究发现，对于接受环孢素微乳剂新山地明免疫抑制治疗的肾移植受者，在移植后21个月预防急性排斥反应方面，霉酚酸酯（MMF）并不比硫唑嘌呤更好，且费用贵15倍。MYSS随访研究是MYSS的一项扩展研究，旨在根据最初随机分组情况，比较248例MYSS患者接受MMF（每日2次，每次1g）或硫唑嘌呤（75至100mg/d）治疗的长期结局。主要结局指标是移植后5年的估计肾小球滤过率（GFR）。硫唑嘌呤组和霉酚酸酯组之间的平均5年GFR差异为每1.73m² 4.67ml/min（95%置信区间[CI]为每1.73m² -0.43至9.77ml/min；P = 0.07）。移植后第6个月（平均±标准误：每1.73m² 54.3±1.6与53.9±1.5ml/min；P = 0.83）至第72个月（每1.73m² 49.5±2.2与47.3±2.4ml/min；P = 0.50）的GFR；GFR斜率（平均±标准误：每年每1.73m² -1.10±0.56与-1.23±0.31ml/min；P = 0.83）；以及72个月时的患者死亡率（4.0%对4.0%[P = 0.95]；风险比0.96；95%CI为0.28至3.31；P = 0.95）、移植物丢失率（6.8%对6.1%[P = 0.82]；风险比0.89；95%CI为0.32至2.46；P = 0.83）、持续性蛋白尿发生率（25.0%对27.4%；P = 0.72）、晚期（移植后>6个月）排斥反应发生率（25.3%对21.2%；P = 0.53）以及不良事件，硫唑嘌呤组（n = 124）和MMF组（n = 124）分别相似。两组患者的结局在接受或未接受类固醇治疗的患者中单独考虑时也具有可比性。在肾移植中，MMF和硫唑嘌呤联合新山地明治疗的长期风险/获益情况相似。鉴于成本因素，肾移植的标准免疫抑制方案或许应包括硫唑嘌呤而非MMF。
