Arreola-Guerra José Manuel, Serrano Marcos, Morales-Buenrostro Luis E, Vilatobá Mario, Alberú Josefina
Department of Transplantation, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
Department of Nephrology-Mineral Metabolism, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
Ann Transplant. 2016 Feb 16;21:105-14. doi: 10.12659/aot.895104.
Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR).
This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed.
We included 198 patients with an average age of 32 years (±12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow-up duration.
In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events.
他克莫司（TAC）的使用对于肾移植（RT）免疫抑制维持方案至关重要。本研究的目的是评估TAC谷浓度与急性排斥反应（AR）发生之间的关系。
这是一项回顾性队列研究。我们纳入了2008年1月至2012年5月期间接受移植的受者。进行了回归分析（Cox比例风险模型）以及不同时间段内AR和TAC水平的亚组分析。
我们纳入了198例患者，平均年龄32岁（±12.1），男性占主导（54.5%）。平均随访时间为2年（最短 - 最长15天 - 5.2年）。记录了62例AR事件（抗体介导性排斥反应：31例，细胞性AR：19例，体液性AR：12例）。我们发现TAC水平（风险比0.76，0.65 - 0.88，p<0.001）、巨细胞病毒感染高风险（D+/R-）（风险比2.92，1.47 - 1.014，p = 0.002）、移植前供者特异性HLA抗体（DSA）（风险比3.04，1.29 - 7.16，p = 0.011）以及移植后DSA（风险比2.4，1.16 - 4.9，p = 0.018）与AR显著相关。TAC水平与排斥反应之间的关系独立于随访持续时间。
在本分析中，TAC谷浓度与AR事件直接相关；谷浓度>8 ng/ml在降低免疫不良事件方面最为有效。考虑到其可能与AR事件相关，在移植后的随访期间应考虑TAC水平的降低。
