Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation.
Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation.
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DOI：
10.1111/ajt.14504
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Cooper JE
中科院分区：
文献类型：
--
作者：
Davis S;Gralla J;Klem P;Tong S;Wedermyer G;Freed B;Wiseman A;Cooper JE
从头供体特异性抗体（dnDSA）与移植物存活率降低有关。他克莫司（TAC）为基础的方案是最常见的免疫抑制在临床实践中使用的今天，但最佳的治疗剂量，以防止dnDSA尚未建立。我们评估了一个队列的538例患者在肾移植第一年的平均TAC C 0和治疗范围内的TAC时间的dnDSA的风险。平均TAC C 0 < 8 ng/ml与6个月（OR 2.51，95% CI 1.32-4.79，p=0.005）和12个月（OR 2.32，95% CI 1.30-4.15，p=0.004）时的dnDSA相关，平均TAC C 0较低时风险分级增加。< 60%治疗范围内的TAC时间与dnDSA相关（OR 2.05，95% CI 1.28-3.30，p=0.003）和急性排斥反应（HR 4.18，95% CI 2.31-7.58，p<0.001）和5年时死亡删失的移植物丢失（HR 3.12，95% CI 1.53-6.37，p=0.002）。TAC最小化可能以较高的dnDSA率为代价，治疗范围内的TAC时间可能是对不良结局风险增加的患者进行分层的有价值策略。
De novo donor-specific antibodies (dnDSA) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common immunosuppression used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSA has not been established. We evaluated mean TAC C0 and TAC time in therapeutic range for the risk of dnDSA in a cohort of 538 patients in the first year of kidney transplant. A mean TAC C0 < 8 ng/ml was associated with dnDSA by 6 months (OR 2.51, 95% CI 1.32-4.79, p=0.005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, p=0.004) and there was a graded increase in risk with lower mean TAC C0. TAC time in therapeutic range of < 60% was associated with dnDSA (OR 2.05, 95% CI 1.28-3.30, p=0.003) and acute rejection (HR 4.18, 95% CI 2.31-7.58, p<0.001) by 12 months and death-censored graft loss by 5 years (HR 3.12, 95% CI 1.53-6.37, p=0.002). TAC minimization may come at a cost of higher rates of dnDSA and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes.
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