肺移植术后前三个月他克莫司血药浓度处于治疗范围的时间与急性排斥反应之间的关联。
Association between time in therapeutic range of tacrolimus blood concentration and acute rejection within the first three months after lung transplantation.
作者信息
Katada Yoshiki, Nakagawa Shunsaku, Itohara Kotaro, Suzuki Takuya, Kato Ryota, Endo Hiroki, Sugimoto Mitsuhiro, Yonezawa Atsushi, Nakagawa Takayuki, Ohsumi Akihiro, Nakajima Daisuke, Date Hiroshi, Terada Tomohiro
机构信息
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Kyoto, Sakyo-ku, 606-8507, Japan.
Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Kyoto, Sakyo-ku, 606-8507, Japan.
出版信息
J Pharm Health Care Sci. 2022 Oct 1;8(1):25. doi: 10.1186/s40780-022-00256-9.
BACKGROUND
Tacrolimus is a key drug in immunosuppressive therapy following lung transplantation. The blood tacrolimus levels are likely to fluctuate in the early postoperative period, and failure to maintain the tacrolimus trough level in target ranges is a risk factor for rejection. However, there is little information about the relationship between the time in therapeutic range (TTR) of the tacrolimus trough level (tacrolimus TTR) and clinical outcomes. This study aimed to evaluate the association between tacrolimus TTR and acute rejection (AR) within the first three months after lung transplantation.
METHODS
This was a retrospective study of patients who underwent lung transplantation at a single center. The target tacrolimus trough levels were 10-15 ng/mL, and tacrolimus TTR was calculated using the Rosendaal method. The cut-off value of the tacrolimus TTR was estimated by receiver operating characteristic analysis based on AR.
RESULTS
The study included 90 patients. AR was observed in 26 patients. In this study, ''early-AR'' was defined as any AR within 2 weeks post-transplant (n = 22) and ''late-AR'' was defined as any AR after 1-month post-transplant (n = 4). For early AR, the relationship between tacrolimus TTR and the onset of AR was examined. There were no differences in the tacrolimus TTR between the early-AR group and non-AR group (35.7 ± 22.4 vs 31.5 ± 19.9%, P = 0.416). For late-AR, the relationship with tacrolimus TTR was examined every 10 d. The tacrolimus TTR during postoperative days (POD) 21-30 and POD 31-onset was significantly lower in the late-AR group than the no-AR group (50.0 ± 7.1 vs. 71.8 ± 18.0% and 37.0 ± 26.6 vs. 68.9 ± 31.5%, P < 0.05, respectively). The cutoff value of the tacrolimus TTR during POD 21-30 was estimated as 55.0%.
CONCLUSIONS
Our findings suggest that a lower tacrolimus TTR is a predictor of late AR. A tacrolimus TTR of 55% or higher is necessary to reduce the risk of AR during this period after lung transplantation.
背景
他克莫司是肺移植术后免疫抑制治疗的关键药物。术后早期血他克莫司水平可能波动，未能将他克莫司谷浓度维持在目标范围内是排斥反应的一个危险因素。然而，关于他克莫司谷浓度的治疗时间范围（TTR）（他克莫司TTR）与临床结局之间的关系，目前信息较少。本研究旨在评估肺移植术后前三个月内他克莫司TTR与急性排斥反应（AR）之间的关联。
方法
这是一项对在单一中心接受肺移植患者的回顾性研究。他克莫司谷浓度的目标值为10 - 15 ng/mL，并使用Rosendaal法计算他克莫司TTR。基于AR通过受试者工作特征分析估计他克莫司TTR的截断值。
结果
该研究纳入90例患者。26例患者观察到AR。在本研究中，“早期AR”定义为移植后2周内发生的任何AR（n = 22），“晚期AR”定义为移植后1个月后发生的任何AR（n = 4）。对于早期AR，研究了他克莫司TTR与AR发生之间的关系。早期AR组与非AR组之间的他克莫司TTR无差异（35.7±22.4 vs 31.5±19.9%，P = 0.416）。对于晚期AR，每10天研究其与他克莫司TTR的关系。晚期AR组术后第21 - 30天和第31天至发病期间的他克莫司TTR显著低于无AR组（50.0±7.1 vs. 71.8±18.0%以及37.0±26.6 vs. 68.9±31.5%，P均<0.05）。术后第21 - 30天他克莫司TTR的截断值估计为55.0%。
结论
我们的研究结果表明，较低的他克莫司TTR是晚期AR的一个预测指标。肺移植术后此期间，他克莫司TTR达到55%或更高对于降低AR风险是必要的。
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