The Journal of Practical Medicine >

2023 , Vol. 39 >Issue 17: 2215 - 2220

DOI: https://doi.org/10.3969/j.issn.1006-5725.2023.17.011

Clinical Research

Correlation of tacrolimus concentration and metabolic rate with prognosis in the early stage after heart transplantation

  • Lin GUO ,
  • Zhenzhen WANG ,
  • Xiangli ZHANG ,
  • Yunfei LIU ,
  • Mian ZHANG ,
  • Hua ZHENG ,
  • Chang′an. WANG
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  • *.Department of Critical Care Medicine，Zhengzhou Seventh People's Hospital，Zhengzhou 450016，China

Received date: 2023-02-13

  Online published: 2023-09-27

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Abstract

Objective To evaluate the correlation of tacrolimus trough concentration， metabolic rate and their variability with postoperative infection， rejection and death in the early stage of heart transplantation. Methods The information of recipients who underwent heart transplantation in our hospitalwas reviewed， and the tacrolimus trough concentration （C0） monitoring value and tacrolimus dose were collected within 30 days after surgery. The mean C0 value， metabolic rate （C0/D） and their variability were calculated. The postoperative infection， rejection and death of recipients were followed up， and the correlation between early exposure of tacrolimus and these prognosis was analyzed. Results A total of 172 heart transplant recipients were finally included as research subjects. The mean and peak value of tacrolimus C0 had no statistical correlation with prognosis （all P > 0.05）. The C0/D values of recipients with overall infection， hospitalized infection and rehospitalization due to infection were significantly higher than those without infection， and the differences were statistically significant （2.044， 2.432 and 2.816， P = 0.007、0.044 and 0.017， respectively）. In terms of rejection and death， there was no statistical difference in C0/D value （P > 0.05）. The subjects were divided into concentration < 10 ng/mL group （n = 132）， 10 ~ 15 ng/mL group （n = 34） and > 15 ng/mL group （n = 6）， there was no significant difference in postoperative infection， rejection and death （all P > 0.05）. The SD values of C0/D in recipients with hospitalized infection， infection rehospitalization or overall infection were significantly higher than those without infection （Z = 2.044， 2.432 and 2.816， P = 0.041， 0.015 and 0.005， respectively）. The SD value of C0/D in death recipients was also higher than that in survival recipients （Z = 2.255， P = 0.024）. Conclusion Tacrolimus C0 is not significantly associated with rejection， overall infection， and death； tacrolimus slow metabolizers are more prone to postoperative infection than fast metabolizers； the variability of tacrolimus metabolic rate is related to the incidence of postoperative infection， and the higher variability of metabolic rate of tacrolimus is a risk factor for poor prognosis after heart transplantation.

Key words： heart transplantation; tacrolimus; trough concentration; metabolic rate; variability

Cite this article

Lin GUO , Zhenzhen WANG , Xiangli ZHANG , Yunfei LIU , Mian ZHANG , Hua ZHENG , Chang′an. WANG . Correlation of tacrolimus concentration and metabolic rate with prognosis in the early stage after heart transplantation[J]. The Journal of Practical Medicine, 2023 , 39(17) : 2215 -2220 . DOI: 10.3969/j.issn.1006-5725.2023.17.011

References

1 LUND L H， KHUSH K K， CHERIKH W S， et al. The Registry of the International Society for Heart and Lung Transplantation： Thirty-fourth Adult Heart Transplantation Report-2017； Focus Theme： Allograft ischemic time［J］. J Heart Lung Transplant， 2017，36（10）：1037-1046.
2 GRIMM M， RINALDI M， YONAN N A， et al. Superior Prevention of Acute Rejection by Tacrolimus vs. Cyclosporine in Heart Transplant Recipients-A Large European Trial［J］. Am J Transplant， 2006，6（6）：1387-1397.
3 LUND L H， EDWARDS L B， DIPCHAND A I， et al. The Registry of the International Society for Heart and Lung Transplantation： Thirty-third Adult Heart Transplantation Report-2016； Focus Theme： Primary Diagnostic Indications for Transplant［J］. J Heart Lung Transplant， 2016，35（10）：1158-1169.
4 COSTANZO M R， DIPCHAND A， STARLING R， et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients［J］. J Heart Lung Transplant， 2010，29（8）：914-956.
5 陈文倩， 张雷， 张弋，等. 实体器官移植他克莫司个体化治疗专家共识［J］. 中国医院用药评价与分析， 2021， 21（12）：16.
6 黄洁. 心脏移植免疫抑制诱导和维持治疗［J］. 中华移植杂志（电子版）， 2018，12（2）：49-54.
7 RODRíGUEZ-PERáLVAREZ M， GERMANI G， PAPASTERGIOU V， et al. Early tacrolimus exposure after liver transplantation： Relationship with moderate/severe acute rejection and long-term outcome［J］. J Hepatol， 2012，58（2）：262-270.
8 倪晓洁， 蔡勇， 王瑾珺， 等. 肾移植受者妊娠期CNI血药浓度变异性对移植肾功能及妊娠和胎儿的影响［J］. 中华移植杂志（电子版）， 2020，14（3）：159-163.
9 杨志伟， 刘君昌， 高小林， 等. 他克莫司代谢率与肾移植后早期BK病毒感染的关系［J］. 中国组织工程研究， 2022，26（5）：712-716.
10 王真珍，郑华，刘云霏，等. 他克莫司个体内变异性与心脏移植预后的相关性分析［J］. 实用医学杂志，2022， 38（24）： 3145-3149.
11 余文静，高兴莲，王曾妍，等. 146例脑死亡器官捐献心脏移植手术期管理［J］. 临床心血管病杂志，2016，32（4）：418-421.
12 孟中如， 朱怀军， 葛卫红. 他克莫司个体内浓度变异度与肝肾移植预后关系的研究进展［J］. 药学与临床研究， 2018，26（4）：278-280.
13 BRUNET M， VAN GELDER T， ASBERG A， et al. Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy： Second Consensus Report［J］. Ther Drug Monit， 2019，41（3）：261-307.
14 周峻臣， 李丹滢， 方芸，等. 服用他克莫司的肾移植患者ABCB1基因多态性与术后感染的相关性［J］. 中国医院药学杂志， 2016， 36（4）：5.
15 吴云， 王家莹， 卢映蓉， 等. 器官移植患者他克莫司血药浓度影响因素的研究进展［J］. 医药导报， 2022，41（5）：669-674.
16 CHEN L， PRASAD G. CYP3A5 polymorphisms in renal transplant recipients： influence on tacrolimus treatment［J］. Pharmgenomics Pers Med， 2018，11：23-33.
17 刘冰洋， 黄洁， 廖中凯， 等. CYP3A5基因多态性对心脏移植受者他克莫司的血药浓度/剂量比值和长期预后的影响［J］. 中国循环杂志， 2018，33（S1）：95.
18 LIU B， CHEN W， CHEN Z， et al. The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients［J］. Eur J Drug Metab Pharmacokinet， 2019，44（6）：771-776.
19 张海燕， 张小明， 吴小丽， 等. CYP3A5基因多态性对中国肾移植受者他克莫司血药浓度和疗效的影响［J］. 器官移植， 2011，2（6）：328-331.
20 KUYPERS D R J. Intrapatient Variability of Tacrolimus Exposure in Solid Organ Transplantation： A Novel Marker for Clinical Outcome［J］. Clin Pharmacol Ther， 2019，107（2）：347-358.
21 SHUKER N， BOUAMAR R， HESSELINK D A， et al. Intrapatient Variability in Tacrolimus Exposure Does Not Predict The Development of Cardiac Allograft Vasculopathy After Heart Transplant［J］. Exp Clin Transplant， 2018，16（3）：326-332.
22 GUETA I， MARKOVITS N， YARDEN-BILAVSKY H， et al. High tacrolimus trough level variability is associated with rejections after heart transplant［J］. Am J Transplant， 2018，18（10）：2571-2578.
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