Introduction: Whether an early, short-term, adequate exposure to mycophenolic acid (MPA) under tacrolimus-based immunosuppression regimen in kidney transplantation from donation after circulatory death (DCD) was effective and safe is yet unknown. Material and Methods: The study was a single-center, retrospective, cohort study of DCD transplantation in China. Intensified and standard dosage regimens of enteric-coated mycophenolate sodium (EC-MPS) were week 1, 2,160 vs. 1,440 mg/day. The incidences of biopsy-proven acute rejection (BPAR), delayed graft function, infection, and patient and graft survival were compared between the 2 groups. Results: A total of 209 patients (n = 82 in intensified group and n = 127 in standard group) were enrolled from August 2013 to December 2014. The incidence of BPAR at 12 months was significantly lower in the intensified group as compared to that of the standard group. (2.4 vs. 10.2%, p = 0.035). The mean MPA area under curve (AUC) levels at day 7 was significantly higher in the intensified group than that in the standard group (66.18 ± 35.48 vs. 45.30 ± 23.5 mg·h/L, p < 0.001). MPA AUC levels were significantly decreased in patients with BPAR as compared to those with NO-BPAR. Conclusion: An early, short-term regimen of intensified EC-MPS with tacrolimus increased early MPA exposure and achieved a low rate of BPAR in kidney transplantation from DCD.

1.
Zhang L, Zeng L, Gao X, Wang H, Zhu Y: Transformation of organ donation in China. Transpl Int 2015; 28: 410–415.
2.
Xiaoming P, Xiang H, LinJuan L, Chenguang D, Ren L: Preliminary results of transplantation with kidneys donated after cardiac death: a path of hope for organ transplantation in China. Nephrol Dial Transplant 2015; 30: 1590–1596.
3.
Wang C, Fu Q, Liu L, et al: Kidney transplantation from donation after cardiac death donors in China – a single-center experience. Transplant Proc 2012; 44: 862–864.
4.
Chen GD, Shiu-Chung Ko D, Wang CX, et al: Kidney transplantation from donors after cardiac death: an initial report of 71 cases from China. Am J Transplant 2013; 13: 1323–1326.
5.
Wang C, Liu L, Fu Q, et al: Kidney transplantation from donors after brain or cardiac death in China – a clinical analysis of 94 cases. Transplant Proc 2013; 45: 1323–1326.
6.
van Gelder T, Silva HT, de Fijter JW, et al: Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: The fixed-dose concentration-controlled trial. Transplantation 2008; 86: 1043–1051.
7.
Budde K, Tedesco-Silva H, Arns W, et al: Improved rejection prophylaxis with an initially intensified dosing regimen of enteric-coated mycophenolate sodium in de novo renal transplant recipients. Transplantation 2011; 92: 321–327.
8.
Kiberd BA, Lawen J, Fraser AD, Keough-Ryan T, Belitsky P: Early adequate mycophenolic acid exposure is associated with less rejection in kidney transplantation. Am J Transplant 2004; 4: 1079–1083.
9.
van Gelder T, Tedesco Silva H, de Fijter JW, et al: Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid. Transplantation 2010; 89: 595–599.
10.
Beal JL, Jones CE, Taylor PJ, Tett SE: Evaluation of an immunoassay (EMIT) for mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatography assay. Ther Drug Monit 1998; 20: 685–690.
11.
Haas M, Sis B, Racusen LC, et al: Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014; 14: 272–283.
12.
Matsushita K, Mahmoodi BK, Woodward M, et al: Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA 2012; 307: 1941–1951.
13.
Masson I, Flamant M, Maillard N, et al: MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients. Transplantation 2013; 95: 1211–1217.
14.
Sommerer C, Glander P, Arns W, et al: Safety and efficacy of intensified versus standard dosing regimens of enteric-coated mycophenolate sodium in de novo renal transplant patients. Transplantation 2011; 91: 779–785.
15.
Budde K, Tedesco-Silva H, Arns W, et al: Improved rejection prophylaxis with an initially intensified dosing regimen of enteric-coated mycophenolate sodium in de novo renal transplant recipients. Transplantation 2011; 92: 321–327.
16.
Glander P, Sommerer C, Arns W, et al: Pharmacokinetics and pharmacodynamics of intensified versus standard dosing of mycophenolate sodium in renal transplant patients. Clin J Am Soc Nephrol 2010; 5: 503–511.
17.
Barraclough KA, Staatz CE, Isbel NM, Johnson DW: Therapeutic monitoring of mycophenolate in transplantation: is it justified? Curr Drug Metab 2009; 10: 179–187.
18.
van Gelder T, Silva HT, de Fijter H, et al: How delayed graft function impacts exposure to mycophenolic acid in patients after renal transplantation. Ther Drug Monit 2011; 33: 155–164.
19.
Ding C, Xue W, Tian P, et al: Outcomes of standard dose EC-MPS with low exposure to CsA in DCD renal transplantation recipients with DGF. Int J Clin Pract Suppl 2015; 183: 8–15.
20.
Tahir W, Hakeem A, Dawrant M, et al: Early sirolimus conversion as rescue therapy in kidneys with prolonged delayed graft function in deceased donor renal transplant. Transplant Proc 2015; 47: 1610–1615.
21.
Le Meur Y, Aulagnon F, Bertrand D, et al: Effect of an early switch to belatacept among calcineurin inhibitor-intolerant graft recipients of kidneys from extended-criteria dsonors. Am J Transplant 2016; 16: 2181–2186.
22.
Arns W, Sommerer C, Glander P, et al: A randomized trial of intensified vs. standard dosing for enteric-coated mycophenolate sodium in de novo kidney transplant recipients: results at 1 year. Clin Nephrol 2013; 79: 421–431.
23.
Gourishankar S, Houde I, Keown PA, et al: The CLEAR study: a 5-day, 3-g loading dose of mycophenolate mofetil versus standard 2-g dosing in renal transplantation. Clin J Am Soc Nephrol 2010; 5: 1282–1289.
24.
Sommerer C, Müller-Krebs S, Schaier M, et al: Pharmacokinetic and pharmacodynamic analysis of enteric-coated mycophenolate sodium: limited sampling strategies and clinical outcome in renal transplant patients. Br J Clin Pharmacol 2010; 69: 346–357.
25.
Wang W, Xu S, Ren Z, Jiang J, Zheng S: Gut microbiota and allogeneic transplantation. J Transl Med 2015; 13: 275.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.