Yatim Karim, Al Jurdi Ayman, El Mouhayyar Christopher, Morena Leela, Hullekes Frank E, Verhoeff Ruchama, Ribas Guilherme T, Pearson Daniel S, V Riella Leonardo
Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA.
Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
Transplant Direct. 2024 Aug 29;10(9):e1697. doi: 10.1097/TXD.0000000000001697. eCollection 2024 Sep.
There are no high-quality data to guide long-term mycophenolate mofetil (MMF) dosing in kidney transplant recipients (KTRs) to balance the long-term risks of allograft rejection with that of infections and malignancy. At our center, KTRs are managed with either a "preemptive" dose reduction strategy, where the MMF dose is reduced after the first year before the development of adverse events, or with a "reactive" dosing strategy, where they are maintained on the same MMF dose and only reduced if they develop an adverse event. We hypothesized that a preemptive MMF dosing strategy after the first year of transplantation is associated with decreased infections without increasing alloimmune complications.
We conducted a retrospective cohort study of all KTRs receiving MMF from January 1, 2015, to December 31, 2020. The primary outcome was the incidence of infections requiring hospitalization.
One hundred forty-two KTRs met the inclusion criteria, of whom 44 (31%) were in the preemptive group and 98 (69%) were in the reactive group. The median follow-up was 4 y (interquartile range, 3.8-4.0). Multivariable analysis showed that a preemptive MMF dose reduction strategy was associated with a lower risk of infections requiring hospitalization (adjusted hazard ratio = 0.39; 95% confidence interval, 0.16-0.92). There was no difference in graft loss, rejection, or estimated glomerular filtration rate slope.
Preemptive MMF dose reduction in KTRs may be an effective strategy to prevent infections without increasing the risk of allograft rejection. Randomized clinical trials are needed to confirm these findings.
目前尚无高质量数据可指导肾移植受者(KTR)长期使用霉酚酸酯(MMF)的剂量,以平衡同种异体移植排斥反应与感染和恶性肿瘤的长期风险。在我们中心,KTR采用“先发制人”的剂量减少策略进行管理,即MMF剂量在第一年且在不良事件发生前降低,或采用“反应性”给药策略,即他们维持相同的MMF剂量,仅在发生不良事件时降低剂量。我们假设移植后第一年采用先发制人的MMF给药策略与感染减少相关,且不增加同种免疫并发症的风险。
我们对2015年1月1日至2020年12月31日期间接受MMF的所有KTR进行了一项回顾性队列研究。主要结局是需要住院治疗的感染发生率。
142名KTR符合纳入标准,其中44名(31%)在先发制人组,98名(69%)在反应性组。中位随访时间为4年(四分位间距,3.8 - 4.0)。多变量分析显示,先发制人的MMF剂量减少策略与需要住院治疗的感染风险较低相关(调整后的风险比 = 0.39;95%置信区间,0.16 - 0.92)。在移植物丢失、排斥反应或估计肾小球滤过率斜率方面没有差异。
KTR中先发制人的MMF剂量减少可能是预防感染而不增加同种异体移植排斥风险的有效策略。需要进行随机临床试验来证实这些发现。