Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Clin Transplant. 2013 Jan-Feb;27(1):15-24. doi: 10.1111/j.1399-0012.2012.01694.x. Epub 2012 Aug 2.
Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.1%) reduced tacrolimus (≤ 7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus (>7 ng/mL); enteric-coated mycophenolate sodium 589 (67.7%) and mycophenolate mofetil 281 (32.3%). During baseline to month 1, months 1-3, months 3-6, and months 6-12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535) patients, respectively, required MPA dose changes. These patients experienced an increased risk of biopsy-proven acute rejection at one yr with tacrolimus exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28-5.29, p = 0.008) or excluded (HR 2.58, 95% CI 1.28-5.23, p = 0.008). MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included (HR 2.23; 95% CI 1.01-4.89, p = 0.047) but not when tacrolimus exposure was excluded (HR 2.16; 95% CI 0.99-4.79; p = 0.054). These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels.
前瞻性数据缺乏关于减少霉酚酸（MPA）剂量对疗效的影响，以及同时使用他克莫司暴露的影响。Mycophenolic Renal Transplant（MORE）Registry 是一项前瞻性、观察性研究，纳入了接受 MPA 治疗的初诊肾移植患者，这些患者接受常规管理。在 870 例接受他克莫司治疗的患者中评估了 MPA 剂量减少、中断或停药（剂量改变）的效果：375 例（43.1%）患者减少了他克莫司（基线时≤7ng/mL），495 例（56.9%）患者使用标准他克莫司（>7ng/mL）；肠溶剂型麦考酚钠 589 例（67.7%）和麦考酚酸酯 281 例（32.3%）。在基线至 1 个月、1-3 个月、3-6 个月和 6-12 个月期间，分别有 9.3%（78/838）、16.6%（132/794）、20.7%（145/701）和 13.1%（70/535）的患者需要进行 MPA 剂量改变。这些患者在 1 年时发生经活检证实的急性排斥反应的风险增加，在模型中纳入（危险比[HR]2.60，95%置信区间[CI]1.28-5.29，p=0.008）或排除（HR2.58，95%CI1.28-5.23，p=0.008）他克莫司暴露时。当纳入他克莫司暴露时，MPA 剂量改变与 1 年时移植物失败显著相关（HR2.23；95%CI1.01-4.89，p=0.047），但当排除他克莫司暴露时（HR2.16；95%CI0.99-4.79；p=0.054）则无显著相关。这些结果表明，减少或停止 MPA 可能会对移植物结果产生不利影响，而与他克莫司谷浓度无关。
