Full Text:   <1444>

Summary:  <1228>

CLC number: R969.3

On-line Access: 2018-06-04

Received: 2017-06-20

Revision Accepted: 2018-01-25

Crosschecked: 2018-05-14

Cited: 0

Clicked: 2295

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Chen-guang Ding

https://orcid.org/0000-0001-9306-9709

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.6 P.481-489

http://doi.org/10.1631/jzus.B1700315


Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients


Author(s):  Li-zi Jiao, Chen-guang Ding, Pu-xun Tian, Xiao-ming Ding, Xiao-ming Pan, He-li Xiang, Xiao-hui Tian, Yang Li, Jin Zheng, Wu-jun Xue

Affiliation(s):  Department of Kidney Transplantation, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China; more

Corresponding email(s):   doctor_ding@126.com, xwujun@126.com

Key Words:  Enteric-coated mycophenolate sodium (EC-MPS), Tacrolimus, Delayed graft function (DGF), Donation after cardiac death (DCD), Kidney transplantation


Li-zi Jiao, Chen-guang Ding, Pu-xun Tian, Xiao-ming Ding, Xiao-ming Pan, He-li Xiang, Xiao-hui Tian, Yang Li, Jin Zheng, Wu-jun Xue. Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients[J]. Journal of Zhejiang University Science B, 2018, 19(6): 481-489.

@article{title="Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients",
author="Li-zi Jiao, Chen-guang Ding, Pu-xun Tian, Xiao-ming Ding, Xiao-ming Pan, He-li Xiang, Xiao-hui Tian, Yang Li, Jin Zheng, Wu-jun Xue",
journal="Journal of Zhejiang University Science B",
volume="19",
number="6",
pages="481-489",
year="2018",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1700315"
}

%0 Journal Article
%T Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients
%A Li-zi Jiao
%A Chen-guang Ding
%A Pu-xun Tian
%A Xiao-ming Ding
%A Xiao-ming Pan
%A He-li Xiang
%A Xiao-hui Tian
%A Yang Li
%A Jin Zheng
%A Wu-jun Xue
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 6
%P 481-489
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700315

TY - JOUR
T1 - Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients
A1 - Li-zi Jiao
A1 - Chen-guang Ding
A1 - Pu-xun Tian
A1 - Xiao-ming Ding
A1 - Xiao-ming Pan
A1 - He-li Xiang
A1 - Xiao-hui Tian
A1 - Yang Li
A1 - Jin Zheng
A1 - Wu-jun Xue
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 6
SP - 481
EP - 489
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1700315


Abstract: 
Effective use of immunosuppressive agents to avoid the occurrence of nephrotoxicity and rejection in recipients with delayed graft function (DGF) is a concern for physicians. We investigated the outcomes of treatment with enteric-coated mycophenolate sodium (EC-MPS) in combination with a low-dose of tacrolimus (Tac) in renal transplantation for recipients with a high risk of DGF. We conducted a retrospective study of 61 recipients with a high risk of DGF who were treated with EC-MPS and low-dose Tac. The recipients were separated into a no-DGF group and a DGF group, based on whether DGF actually occurred. The results showed that although EC-MPS and Tac doses were similar in both groups, the percentage of recipients whose mycophenolic acid area under the curve 0–12 h (MPA-AUC0–12 h) was below 30 (mg·h)/L was significantly higher and the Tac trough concentration significantly lower in the DGF group one week after transplantation. Notably, a higher incidence of biopsy-proven acute rejection (BPAR) was found in the DGF group and among all recipients whose MPA-AUC0–12 h was less than 30 (mg·h)/L at one week after transplantation. One-year graft survival, patient survival, allograft function, and the incidence of the most common adverse events were similar in the two groups. In conclusion, the immunosuppressive regime is applicable to Chinese kidney transplant recipients, and early low exposure to EC-MPS was related to acute rejection in the recipients at a high risk of DGF.

DCD肾移植中DGF高风险受者应用EC-MPS 联合低剂量他克莫司治疗的预后分析

目的:分析心脏死亡供体(DCD)肾移植中移植物功能延迟恢复(DGF)高风险受者应用米芙(EC-MPS)联合低剂量他克莫司治疗术后1年的有效性及安全性,指导临床用药.
创新点:对比DGF高风险受者术后发生DGF及正常恢复受者的免疫抑制剂药代动力学特征.
方法:将本中心进行肾移植的61例DGF高风险受者按照实际病情纳入DGF组及正常恢复组,均行米芙联合低剂量他克莫司免疫抑制治疗.对比两组免疫抑制剂血药浓度及预后各项指标.
结论:DGF组及正常恢复组间米芙及他克莫司剂量无显著差异.术后1周DGF组EC-MPS血药浓度曲线下面积小于30 (mg·h)/L的比率显著高于正常恢复组,同时他克莫司谷浓度显著低于正常恢复组,DGF组经活检证实的急排反应的发生率显著高于正常恢复组,术后1周的EC-MPS血药浓度曲线下面积低于30 (mg·h)/L的受者中经活检证实的急排反应的发生率显著高于其他受者.1年移植物存活率、移植物功能及常见不良反应在两组间未见明显差异.

关键词:米芙(EC-MPS);他克莫司;移植物功能延迟恢复(DGF);心脏死亡供体(DCD);肾移植

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Arns W, Cibrik DM, Walker RG, et al., 2006. Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature. Transplantation, 82(8):1004-1012.

[2]Budde K, Glander P, Kramer BK, et al., 2007. Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant recipients receiving tacrolimus: clinical, pharmacokinetic, and pharmacodynamic outcomes. Transplantation, 83(4):417-424.

[3]Cortinovis M, Gotti E, Pradini S, et al., 2011. Renal graft function and low-dose cyclosporine affect mycophenolic acid pharmacokinetics in kidney transplantation. Transplantation, 92(5):550-556.

[4]Daher Abdi Z, Premaud A, Essig M, et al., 2014. Exposure to mycophenolic acid better predicts immunosuppressive efficacy than exposure to calcineurin inhibitors in renal transplant patients. Clin Pharmacol Ther, 96:508-515.

[5]de Winter BC, Mathot RA, van Hest RM, et al., 2007. Therapeutic drug monitoring of mycophenolic acid: does it improve patient outcome? Expert Opin Drug Metab Toxicol, 3(2):251-261.

[6]Ding C, Xue W, Tian P, et al., 2014. Which is more suitable for kidney transplantation at the early post-transplantation phase in China—low dosing or standard dosing of enteric-coated mycophenolate sodium? Int J Clin Pract Suppl, 68(181):10-16.

[7]Ding C, Xue W, Tian P, et al., 2015. Outcomes of standard dose EC-MPS with low exposure to CsA in DCD renal transplantation recipients with DGF. Int J Clin Pract, 69(S183):8-15.

[8]Dominguez-Gil B, Duranteau J, Mateos A, et al., 2016. Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme. Transpl Int, 29(8):842-859.

[9]Ekberg H, Tedesco-Silva H, Demirbas A, et al., 2007. Reduced exposure to calcineurin inhibitors in renal transplantation. NEJM, 357(25):2562-2575.

[10]Gaston RS, Kaplan B, Shah T, et al., 2009. Fixed- or controlled-dose mycophenolate mofetil with standard- or reduced-dose calcineurin inhibitors: the Opticept trial. Am J Transpl, 9(7):1607-1619.

[11]Gaynor JJ, Ciancio G, Guerra G, et al., 2016. Lower tacrolimus trough levels are associated with subsequently higher acute rejection risk during the first 12 months after kidney transplantation. Transpl Int, 29(2):216-226.

[12]Heilman RL, Mathur A, Smith ML, et al., 2016. Increasing the utilization of kidneys from unconventional and higher risk deceased donors. Am J Transpl, 16(11):3086-3092.

[13]Huang CT, Shu KH, Ho HC, et al., 2016. Higher variability of tacrolimus trough level increases risk of acute rejection in kidney transplant recipients. Transplant Proc, 48(6):1978-1980.

[14]Huang J, Wang H, Fan ST, et al., 2013. The national program for deceased organ donation in China. Transpl J, 96(1):5-9.

[15]Huang J, Millis JM, Mao Y, et al., 2015. Voluntary organ donation system adapted to Chinese cultural values and social reality. Liver Transpl, 21(4):419-422.

[16]Irish WD, Ilsley JN, Schnitzler MA, et al., 2010. A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transpl, 10(10):2279-2286.

[17]Kamar N, Garrigue V, Karras A, et al., 2006. Impact of early or delayed cyclosporine on delayed graft function in renal transplant recipients: a randomized, multicenter study. Am J Transpl, 6(5p1):1042-1048.

[18]Kaplan B, Meier-Kriesche HU, Minnick P, et al., 2005. Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co-administered enteric-coated mycophenolate sodium. Clin Transplant, 19(4):551-558.

[19]Lu XY, Huang HF, Sheng-Tu JZ, et al., 2005. Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients. J Zhejiang Univ-Sci, 6B(9):885-891.

[20]Nyberg SL, Matas AJ, Rogers M, et al., 2001. Donor scoring system for cadaveric renal transplantation. Am J Transpl, 1(2):162-170.

[21]Perico N, Cattaneo D, Sayegh MH, et al., 2004. Delayed graft function in kidney transplantation. Lancet, 364(9447):1814-1827.

[22]Salvadori M, Holzer H, Mattos A, et al., 2004. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil inde novorenal transplant patients. Am J Transpl, 4(2):231-236.

[23]Sánchez F, Ana I, Isabel MD, et al., 2012. Limited-sampling strategy for mycophenolic acid in renal transplant recipients reciving enteric-coated mycophenolate sodium and tacrolimus. Ther Drug Monit, 34(3):298-305.

[24]Shaw LMK, Denofrio D, Brayman KL, 2001. Pharmacokinetic, pharmacodynamic, and outcome investigations as the basis for mycophenolic acid therapeutic drug monitoring in renal and heart transplant patients. Clin Biochem, 34(1):17-22.

[25]Singh RP, Farney AC, Rogers J, et al., 2011. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post-transplant outcomes. Clin Transpl, 25(2):255-264.

[26]Solez K, Colvin RB, Racusen LC, et al., 2007. Banff ’05 meeting report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (‘CAN’). Am J Transplant, 7(3):518-526.

[27]Sommerer C, Glander P, Arns W, et al., 2011. Safety and efficacy of intensified versus standard dosing regimens of enteric-coated mycophenolate sodium in de novo renal transplant patients. Transplantation, 91(7):779-785.

[28]Stracke S, Shipkova M, Mayer J, et al., 2012. Pharmacokinetics and pharmacodynamics of mycophenolate sodium (EC-MPS) co-administered with cyclosporine in the early-phase post-kidney transplantation. Clin Transpl, 26(1):57-66.

[29]van Gelder T, Silva HT, de Fijter JW, et al., 2010, Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid. Transplantation, 89:595-599.

[30]Zhang L, Zeng L, Gao X, et al., 2015. Transformation of organ donation in China. Transpl Int, 28(4):410-415.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE