Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics.
Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics.
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DOI：
10.1111/tri.12155
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
DeKAF Genomics Investigators
中科院分区：
文献类型：
--
作者：
Israni AK;Riad SM;Leduc R;Oetting WS;Guan W;Schladt D;Matas AJ;Jacobson PA;DeKAF Genomics Investigators
大多数基于钙调神经磷酸酶抑制剂（CNI）的方案在临床稳定的肾移植受者中减少移植后约2-3个月的血谷目标。减少后，CNI目标谷水平以防止排斥尚不清楚。采用多变量考克斯比例风险模型，我们确定了随时间变化的他克莫司（TAC）谷浓度与移植后前6个月发生的急性排斥反应（AR）的相关性，但我们特别在3个月后评估了这种相关性。在一项前瞻性研究中，1，930例患者在AR前接受了基于TAC的免疫抑制治疗。在151例（7.8%）发生AR的患者中，47例在移植后3个月发生AR。在校正的时变多变量模型中，前6个月内TAC谷浓度每降低1 ng/mL，AR风险增加7.2%[HR=1.07，95% CI（1.01，1.14）P=0.03]。在第3-6个月，TAC谷水平每降低1 ng/mL，AR风险额外增加23%[HR=1.23，95% CI（1.06，1.43）P=0.008]。总之，较低的TAC谷值水平与移植后前6个月内AR风险增加显著相关，并且在移植后3-6个月之间存在额外的AR风险。TAC剂量减少的时机和做法应根据个人的风险因素进行个性化。
Most calcineurin inhibitor (CNI) based protocols reduce blood trough goals approximately 2–3 months post-transplant in clinically stable kidney transplant recipients. The CNI target trough level to prevent rejection, after reduction, is unknown. Using a multivariate Cox proportional hazards model we determined the association of time-varying tacrolimus (TAC) trough levels with acute rejection (AR) occurring in the first 6 months post-transplant, but specifically we assessed this association after 3 months. 1,930 patients received TAC based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time varying multivariate model, each 1 ng/mL decrease in TAC trough levels was associated with a 7.2% increased risk of AR [HR=1.07, 95% CI (1.01, 1.14) P=0.03] in the first 6 months. There was an additional 23% increased risk of AR with each 1 ng/mL decrease in the TAC trough levels in months 3–6 [HR=1.23, 95% CI (1.06, 1.43) P=0.008]. In conclusion, lower TAC trough levels were significantly associated with increased risk of AR in the first 6 months post-transplant with additional risk of AR between months 3–6 post-transplant. The timing and practice of TAC dose reduction should be personalized based on the individual’s risk factors.
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影响因子：
6.2
作者：
Jacobson PA;Oetting WS;Brearley AM;Leduc R;Guan W;Schladt D;Matas AJ;Lamba V;Julian BA;Mannon RB;Israni A;DeKAF Investigators
通讯作者：
DeKAF Investigators
影响因子：
1.3
作者：
Filler, G;Webb, NJA;Trompeter, R
通讯作者：
Trompeter, R
影响因子：
8.8
作者：
Sellares, J.;de Freitas, D. G.;Halloran, P. F.
通讯作者：
Halloran, P. F.
影响因子：
158.5
作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
通讯作者：
Halloran, Philip F.
影响因子：
8.8
作者：
Gaston, R.;Kaplan, B.;Bloom, R. D.
通讯作者：
Bloom, R. D.