Volume 9 Issue 4
Jul.  2018
Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2018  >  9(4): 278-282
Sun Zhongwei, Fan Yu, Bai Hongwei, et al. Relationship between metabolic rate of tacrolimus and BK virus infection early after renal transplantation[J]. ORGAN TRANSPLANTATION, 2018, 9(4): 278-282. doi: 10.3969/j.issn.1674-7445.2018.04.007
Citation: Sun Zhongwei, Fan Yu, Bai Hongwei, et al. Relationship between metabolic rate of tacrolimus and BK virus infection early after renal transplantation[J]. ORGAN TRANSPLANTATION, 2018, 9(4): 278-282. doi: 10.3969/j.issn.1674-7445.2018.04.007
shu

Relationship between metabolic rate of tacrolimus and BK virus infection early after renal transplantation

doi: 10.3969/j.issn.1674-7445.2018.04.007

  • Medical School of Chinese People' s Liberation Army, Beijing 100853, China

More Information
  • Corresponding author: Qian Yeyong, Email:qianyy@medmail.com.cn
  • Received Date: 2018-04-10
    Available Online: 2021-01-19
  • Publish Date: 2018-07-15
    Abstract
  •   Objective  To investigate the relationship between the metabolic rate of tacrolimus (FK506) and BK virus infection early after renal transplantation.  Methods  Eighty recipients undergoing allogenic renal transplantation in Institute of Organ Transplantation of the 309th Hospital of Chinese People' s Liberation Army were recruited in this study. The polymorphism of cytochrome P450 (CYP) 3A5 gene was detected in 80 recipients. All patients were divided into fast metabolism group (CYP3A5*1/*3 and CYP3A5*1/*1 genotypes, n=38) and slow metabolism group (CYP3A5*3/*3 genotype, n=42) based on the gene detection results. The distribution of CYP3A5 genotypes in 80 recipients was analyzed. The metabolic rate [concentration/dose ratio (C/D value)] of FK506 was statistically compared between two groups. The incidence of BK virus infection events [BK viruria, BK viremia and BK virus nephropathy(BKVN)] within postoperative 6 months were compared between two groups.  Results  Among 80 recipients, 5 cases (6%) were detected with CYP3A5*1/*1 genotype, 33 (41%) with CYP3A5*1/*3 genotype, and 42 (53%) with CYP3A5*3/*3 genotype. Among the 160 alleles in 80 recipients, 117 CYP3A5*3 allele were identified, suggesting that the mutation rate of CYP3A5*3 allele was 73.1%. In the fast metabolism group, the C/D values at postoperative 1, 3, and 6 months were significantly lower than those in the slow metabolism group (all P < 0.01). The incidence rates of BK viruria in the fast and slow metabolism groups were 37% and 29%, 18% and 2% for BK viremia, and 3% and 0 for BKVN, respectively. In the fast metabolism group, the incidence of BK virenia was significantly higher than that in the slow metabolism group (P=0.02). The incidence of BK viruria and BKVN did not significantly differ between two groups (both P > 0.05).  Conclusions  According to the CYP3A5 genotyping outcomes, the recipients with a high metabolic rate of FK506 have a high risk of BK viremia early after renal transplantation.

     

    • FullText(HTML)
  • loading
    • References(17)
  • [1]
    HIRSCH HH, VINCENTI F, FRIMAN S, et al. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study[J]. Am J Transplant, 2013, 13(1): 136-145. DOI: 10.1111/j.1600-6143.2012.04320.x.
    [2]
    SHENAGARI M, MONFARED A, EGHTEDARI H, et al. BK virus replication in renal transplant recipients: analysis of potential risk factors may contribute in reactivation[J]. J Clin Virol, 2017, 96:7-11. DOI: 10.1016/j.jcv.2017.09.004.
    [3]
    GARD L, VAN DOESUM W, NIESTERS HGM, et al. A delicate balance between rejection and BK polyomavirus associated nephropathy; a retrospective cohort study in renal transplant recipients[J]. PLoS One, 2017, 12(6): e0178801. DOI: 10.1371/journal.pone.0178801.
    [4]
    CHEN L, PRASAD GVR. CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment[J]. Pharmgenomics Pers Med, 2018, 11:23-33. DOI: 10.2147/PGPM.S107710.
    [5]
    HAUFROID V, WALLEMACQ P, VANKERCKHOVE V, et al. CYP3A5 and ABCB1 polymorphisms and tacrolimus pharmacokinetics in renal transplant candidates: guidelines from an experimental study[J]. Am J Transplant, 2006, 6(11): 2706-2713. doi: 10.1111/ajt.2006.6.issue-11
    [6]
    THÖLKING G, FORTMANN C, KOCH R, et al. The tacrolimus metabolism rate influences renal function after kidney transplantation[J]. PLoS One, 2014, 9(10): e111128. DOI: 10.1371/journal.pone.0111128.
    [7]
    HUMAR A, MICHAELS M, AST ID Working Group on Infectious Disease Monitoring. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation[J]. Am J Transplant, 2006, 6(2): 262-274. doi: 10.1111/ajt.2006.6.issue-2
    [8]
    LI D, ZHANG GL, LOU YQ, et al. Genetic polymorphisms in MDR1 and CYP3A5 and MDR1 haplotype in mainland Chinese Han, Uygur and Kazakh ethnic groups[J]. J Clin Pharm Ther, 2007, 32(1): 89-95. doi: 10.1111/jcp.2007.32.issue-1
    [9]
    DALIANIS T, RAMQVIST T, ANDREASSON K, et al. KI, WU and Merkel cell polyomaviruses: a new era for human polyomavirus research[J]. Semin Cancer Biol, 2009, 19(4): 270-275. DOI: 10.1016/j.semcancer.2009.04.001.
    [10]
    HIRSCH HH, KNOWLES W, DICKENMANN M, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients[J]. N Engl J Med, 2002, 347(7): 488-496. doi: 10.1056/NEJMoa020439
    [11]
    NICKELEIT V, HIRSCH HH, ZEILER M, et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class Ⅱ expression and rejection in a puzzling game[J]. Nephrol Dial Transplant, 2000, 15(3): 324-332. doi: 10.1093/ndt/15.3.324
    [12]
    张鑫, 刘志红, 郑敬民, 等.细胞色素P450 3A5和多药耐药基因1基因多态性在肾移植患者他克莫司血药浓度监测中的应用[J].肾脏病与透析肾移植杂志, 2004, 13(4): 313-317. DOI: 10.3969/j.issn.1006-298X.2004.04.003.

    ZHANG X, LIU ZH, ZHENG JM, et al. CYP 3A 5 and MDR1 gene polymorphisms is associated with pharmacokinetic variation of tacrolimus in renal transplant patients[J]. Chin J Nephrol Dial Transplant, 2004, 13(4): 313-317. DOI: 10.3969/j.issn.1006-298X.2004.04.003.
    [13]
    LIN YS, DOWLING AL, QUIGLEY SD, et al. Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism[J]. Mol Pharmacol, 2002, 62(1): 162-172. doi: 10.1124/mol.62.1.162
    [14]
    HAN N, HA S, YUN HY, et al. Population pharmacokinetic-pharmacogenetic model of tacrolimus in the early period after kidney transplantation[J]. Basic Clin Pharmacol Toxicol, 2014, 114(5): 400-406. DOI: 10.1111/bcpt.12176.
    [15]
    THÖLKING G, SCHMIDT C, KOCH R, et al. Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation[J]. Sci Rep, 2016, 6:32273. DOI: 10.1038/srep32273.
    [16]
    范宇, 石炳毅, 钱叶勇, 等.肾移植术后BK病毒感染对移植肾功能影响的临床研究[J].器官移植, 2018, 9(1): 51-57. DOI: 10.3969/j.issn.1674-7445.2018.01.007.

    FAN Y, SHI BY, QIAN YY, et al. Clinical study on the effect of BK virus infection on renal allograft function after renal transplantation[J]. Organ Transplant, 2018, 9(1): 51-57. DOI: 10.3969/j.issn.1674-7445.2018.01.007.
    [17]
    GINEVRI F, DE SANTIS R, COMOLI P, et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches[J]. Transplantation, 2003, 75(8):1266-1270. doi: 10.1097/01.TP.0000061767.32870.72
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (107) PDF downloads(10) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return