Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients
Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients
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DOI：
10.1007/s00467-019-04377-6
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发表时间：
2020-02-01
影响因子：
3
通讯作者：
Hayde, Nicole
中科院分区：
文献类型：
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作者：
Solomon, Sonia;Colovai, Adriana;Hayde, Nicole
背景供体特异性抗体（DSA）是抗体介导的排斥反应和移植物存活缩短的危险因素。我们研究了他克莫司谷浓度的患者内变异性对移植结局的作用（即，方法本研究为单中心回顾性研究，共纳入38例小儿肾移植受者。使用移植后3个月获得的所有水平的变异系数（CV; SD/平均值x 100）定义患者内他克莫司变异性。结果两组的中位变异系数分别为43.1%（35.0%，58.6%）。在38例患者中，19例（50%）发生了新发DSA。在logistic回归模型中，校正年龄、排斥史、维持免疫抑制和CV后，他克莫司变异性每增加10%，新发DSA的几率增加53%（p = 0.048，CI 1.0005，1.11）。移植时的年龄也是发生DSA的独立风险因素;年龄每增加1岁，发生DSA的几率增加31%（p = 0.03，CI 1.03，1.67）。当CV临界值>= 30%时，他克莫司变异性越高，同种异体移植排斥反应发生率越高（分别为0% vs 42%，< 30 and >= 30%，p = 0.07）。由于在我们的研究人群中很少有移植物丢失事件（n = 4），他克莫司变异性和移植loss.Conclusion之间的关联不能确定他克莫司变异性和年龄在移植被确定为独立的危险因素从头DSA发展。他克莫司变异性与儿童肾移植受者的排斥反应之间存在相关性。将他克莫司变异性评估加入到当前的监测方法中可能是改善移植结局的重要一步。
Background Donor-specific antibody (DSA) is a risk factor for antibody-mediated rejection and shortened graft survival. We investigated the role of intrapatient variability in tacrolimus trough levels on graft outcomes (i.e., de novo DSA, rejection, graft loss) in pediatric renal transplant recipients.Methods This was a single-center retrospective study which included 38 pediatric renal transplant recipients. Intrapatient tacrolimus variability was defined using the coefficient of variation (CV; SD/Mean x 100) for all levels obtained after 3 months post-transplant. CV cut-points of 30%, 40%, and 50% were used in the analyses.Results The median CV 43.1% (35.0%, 58.6%). Out of 38 patients, 19 (50%) developed de novo DSA. In the logistic regression model, after adjusting for age, rejection history, maintenance immunosuppression, and CV, for every 10% increase in tacrolimus variability, the odds of developing de novo DSA increased by 53% (p = 0.048, CI 1.0005, 1.11). Age at transplant was also an independent risk factor for DSA development; every 1 year increase in age was associated with a 31% increase in the odds of developing DSA (p = 0.03, CI 1.03, 1.67). At a CV cut-point >= 30%, higher tacrolimus variability was associated with an increased incidence of allograft rejection (0% vs 42%, < 30 and >= 30% respectively, p = 0.07). As there were few graft loss events (n = 4) in our study population, an association could not be determined between tacrolimus variability and graft loss.Conclusion Tacrolimus variability and age at transplant were identified as independent risk factors for de novo DSA development. There was an association between tacrolimus variability and rejection in pediatric renal transplant recipients. Adding the assessment of tacrolimus variability to current monitoring methods may be an important step towards improving graft outcomes.