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中华移植杂志(电子版) ›› 2020, Vol. 14 ›› Issue (01) : 58 -61. doi: 10.3877/cma.j.issn.1674-3903.2020.01.015

所属专题: 文献

综述

肾移植术后常用免疫抑制剂诱发胃肠道症状的机制探讨
宋文彬1, 马葵芬2, 李兴德1, 张阳1, 宋沧桑1,()   
  1. 1. 650224 昆明市第一人民院 昆明医科大学附属甘美医院药学部
    2. 310009 杭州,浙江大学医学院附属第一医院药学部
  • 收稿日期:2019-10-28 出版日期:2020-02-25
  • 通信作者: 宋沧桑
  • 基金资助:
    云南省医疗卫生单位内设研究机构科研项目(2014NS205)

The mechanisms of gastrointestinal symptoms induced by immunosuppressive agents in kidney transplant recipients

Wenbin Song1, Kuifen Ma2, Xingde Li1, Yang Zhang1, Cangsang Song1,()   

  1. 1. Department of Pharmacy, Calmette Hospital Affiliated to Kunming Medical University, Kunming First People′s Hospital, Kunming 650224, China
    2. Department of Pharmacy, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
  • Received:2019-10-28 Published:2020-02-25
  • Corresponding author: Cangsang Song
  • About author:
    Corresponding author: Song Cangsang, Email:
引用本文:

宋文彬, 马葵芬, 李兴德, 张阳, 宋沧桑. 肾移植术后常用免疫抑制剂诱发胃肠道症状的机制探讨[J]. 中华移植杂志(电子版), 2020, 14(01): 58-61.

Wenbin Song, Kuifen Ma, Xingde Li, Yang Zhang, Cangsang Song. The mechanisms of gastrointestinal symptoms induced by immunosuppressive agents in kidney transplant recipients[J]. Chinese Journal of Transplantation(Electronic Edition), 2020, 14(01): 58-61.

他克莫司和吗替麦考酚酯是诱发肾移植术后胃肠道症状的主要免疫抑制剂,其机制可能与药物暴露增加以及二者对肠道相关淋巴组织的抑制作用相关。他克莫司暴露受细胞色素P450 3A4、3A5和P-糖蛋白基因多态性以及胃肠道功能和肠道内菌群丰度变化等多重因素的影响,他克莫司高暴露可促进胃肠道蠕动和霉酚酸类药物吸收。霉酚酸类药物胃肠道不良反应可能与其抗胃肠道上皮细胞增殖特性有关。

Tacrolimus and mycophenolate mofetil are the main cause of gastrointestinal symptoms in kidney transplant recipients. The possible induced mechanisms include the increase of drug exposure and inhibition on gut associated lymph tissue. Tacrolimus exposure is associated with the genetic polymorphisms of CYP 3A4, 3A5 and P-glycoprotein, and changes in the gastrointestinal function and abundance of intestinal bacterial flora, and so on. Increasing tacrolimus exposure promotes gastrointestinal motility and mycophenolic acid (MPA) absorption. MPA induced gastrointestinal side effects is associated with its antiproliferative effect on the basal epithelial cells of the gastrointestinal tract.

1
Ekberg H, Kyllönen L, Madsen S, et al. Increased prevalence of gastrointestinal symptoms associated with impaired quality of life in renal transplant recipients[J]. Transplantation, 2007,83(3):282-289.
2
Zhu Y, Zhou Y, Zhang L, et al. Efficacy of interventions for adherence to the immunosuppressive therapy in kidney transplant recipients: a meta-analysis and systematic review[J]. J Investig Med, 2017,65(7):1049-1056.
3
Nevins TE, Nickerson PW, Dew MA. Understanding medication nonadherence after kidney transplant[J]. J Am Soc Nephrol, 2017,28(8):2290-2301.
4
Kim JE, Ha J, Kim YS, et al. Effect of severe diarrhea on kidney transplant outcomes[J]. Nephrology, 2019.[Epub ahead of print]
5
Malinowski M, Martus P, Lock JF, et al. Systemic influence of immunosuppressive drugs on small and large bowel transport and barrier function[J]. Transpl Int, 2011, 24(2):184-193.
6
Angarone M, Snydman DR; AST ID Community of Practice. Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice[J]. Clin Transplant, 2019,33(9):e13550.
7
Tielemans MM, van Boekel GAJ, van Gelder T, et al. Immunosuppressive drugs and the gastrointestinal tract in renal transplant patients[J]. Transplant Rev (Orlando), 2019, 33(2):55-63.
8
Ginsburg PM, Thuluvath PJ. Diarrhea in liver transplant recipients: etiology and management[J]. Liver Transpl, 2005,11(8):881-890.
9
Maes BD, Vanwalleghem J, Kuypers D, et al. Differences in gastric motor activity in renal transplant recipients treated with FK-506 versus cyclosporine[J]. Transplantation, 1999,68(10):1482-1485.
10
Park JM, Lake KD, Cibrik DM. Impact of changing from cyclosporine to tacrolimus on pharmacokinetics of mycophenolic acid in renal transplant recipients with diabetes[J]. Ther Drug Monit, 2008,30(5):591-596.
11
Camilleri M, Parkman HP, Shafi MA, et al; American College of Gastroenterology. Clinical guideline: management of gastroparesis[J]. Am J Gastroenterol, 2013, 108(1):18-37.
12
Hesselink DA, van Hest RM, Mathot RA, et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2[J]. Am J Transplant, 2005,5(5):987-994.
13
Kumar M, Chapman A, Javed S, et al. The investigation and treatment of diabetic gastroparesis[J]. Clin Ther, 2018,40(6):850-861.
14
van Boekel GA, Aarnoutse RE, van der Heijden JJ, et al. Effect of mild diarrhea on tacrolimus exposure[J]. Transplantation, 2012,94(7):763-767.
15
Canaparo R, Finnström N, Serpe L, et al. Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum[J]. Clin Exp Pharmacol Physiol, 2007,34(11):1138-1144.
16
Stefanović NZ, Cvetković TP, Jevtović-Stoimenov TM, et al. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function[J]. Exp Ther Med, 2015,10(3):1149-1156.
17
Muller J, Keiser M, Drozdzik M, et al. Expression, regulation and function of intestinal drug transporters: an update[J]. Biol Chem, 2017,398(2):175-192.
18
Mouly S, Paine MF. P-glycoprotein increases from proximal to distal regions of human small intestine[J]. Pharm Res, 2003,20(10):1595-1599.
19
Kawauchi S, Nakamura T, Miki I, et al. Downregulation of CYP3A and P-glycoprotein in the secondary inflammatory response of mice with dextran sulfate sodium-induced colitis and its contribution to cyclosporine A blood concentrations[J]. J Pharmacol Sci, 2014,124(2):180-191.
20
Evers R, Piquette-Miller M, Polli JW, et al. Disease-associated changes in drug transporters may impact the pharmacokinetics and/or toxicity of drugs: a White Paper from the International Transporter Consortium[J]. Clin Pharmacol Ther, 2018,104(5):900-915.
21
Guo Y, Crnkovic CM, Won KJ, et al. Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites[J]. Drug Metab Dispos, 2019,47(3):194-202.
22
Lee JR, Muthukumar T, Dadhania D, et al. Gut microbiota and tacrolimus dosing in kidney transplantation[J]. PLoS One, 2015, 10(3):e0122399.
23
Lee JR, Muthukumar T, Dadhania D, et al. Gut microbial community structure and complications after kidney transplantation: a pilot study[J]. Transplantation, 2014,98(7):697-705.
24
Lee JR, Magruder M, Zhang L, et al. Gut microbiota dysbiosis and diarrhea in kidney transplant recipients[J]. Am J Transplant, 2019,19(2):488-500.
25
Rangel EB, Melaragno CS, Sá JR, et al. Mycophenolate mofetil versus enteric-coated mycophenolate sodium after simultaneous pancreas-kidney transplantation[J]. Transplant Proc, 2009,41(10):4265-4269.
26
Chan L, Mulgaonkar S, Walker R, et al. Patient-reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium[J]. Transplantation, 2006, 81(9):1290-1297.
27
孟凡航,郭雪坤,陈志勇,等. 麦考酚钠肠溶片治疗肾移植后远期吗替麦考酚酯相关性腹泻患者的临床疗效[J]. 世界华人消化杂志,2014,22(30):4691-4694.
28
Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action[J]. Immunopharmacology, 2000,47(2-3):85-118.
29
Aiyangar A, Rajput P, Shah BV. Mycophenolate induced diarrhoea[J]. J Assoc Physicians India, 2010,58:192-194.
30
Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management[J]. Drug Saf, 2001,24(9):645-663.
31
Heischmann S, Dzieciatkowska M, Hansen K, et al. The immunosuppressant mycophenolic acid alters nucleotide and lipid metabolism in an intestinal cell model[J]. Sci Rep, 2017,7:45088.
32
Satoh S, Tada H, Murakami M, et al. The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation[J]. Transplant Proc, 2005,37(4):1751-1753.
33
Cristelli MP, Tedesco-Silva H, Medina-Pestana JO, et al. Safety profile comparing azathioprine and mycophenolate in kidney transplant recipients receiving tacrolimus and corticosteroids[J]. Transpl Infect Dis, 2013,15(4):369-378.
34
芦泽兰,乔宇琪,冉志华. Th17细胞和肠道菌群在炎症性肠病发病中的作用[J]. 胃肠病学,2015, 20(10):619-621.
35
蒋学佩,吴小丽,黄智铭. Treg细胞和Th17细胞在炎症性肠病治疗中的作用[J]. 胃肠病学,2018, 23(2):109-112.
36
Abadja F, Atemkeng S, Alamartine E, et al. Impact of mycophenolic acid and tacrolimus on Th17-related immune response[J]. Transplantation, 2011,92(4):396-403.
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