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Tolerability of mycophenolate sodium in renal transplant recipients

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Abstract

Background Kidney transplant recipients (KTR) receive fixed daily doses of mycophenolate sodium as part of the immunosuppressive regimen. Dose reductions occur primarily due to adverse events and may be associated with an increased risk of acute rejection and graft loss. Objectives To evaluate the tolerability of mycophenolate in kidney transplant recipients receiving tacrolimus and prednisone. Setting The study was performed at Hospital do Rim, Federal University of São Paulo in Brazil. Method This was a retrospective cohort study including 506 patients. Tolerability of mycophenolate sodium was classified into the following groups: Temporary reduction (TR), definitive reduction (DR), temporary interruption (TI), permanent discontinuation (PD) and without modification (WM). Main outcome measure The cause of mycophenolate dose change and its influence on rejection-free survival during the first 3 years after transplantation. Results The cumulative incidence of dose change was 51.2% (11%TR, 44%DR, 24%TI, and 21%PD). Gastrointestinal (45.3%), infection (31.9%) and hematological (14.9%) systems accounted for most of the dose changes. The adverse events with higher incidence were diarrhea, cytomegalovirus (CMV) infection and leukopenia. Changes in dose of mycophenole were associated with reduced acute rejection-free survival compared with patients WM group (71.4%TR, 58.9%DR, 56.7%TI, 53.7%PD vs. 74.2%WM, p = 0.020). Only patients with PD showed inferior patient (59.3% vs. 94.4%, p = 0.001) and death-censored graft (83.3% vs. 92.5%, p = 0.074) survivals compared to patients WM. Conclusion In this cohort, changes in the dose of mycophenolate were associated with increased risk of acute rejection and permanent discontinuation was associated with inferior patient and graft survival.

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Abbreviations

AUC-MPA:

Area under the curve of mycophenolic acid

BPAR:

Biopsy-proven acute rejection

CMV:

Cytomegalovirus

CTCAE:

Common terminology criteria for adverse events

DGF:

Delayed graft function

DNA:

Deoxyribonucleic acid

DR:

Definitive reduction

IMPDH:

Inosine monophosphate dehydrogenase

MMF:

Mycophenolate mofetil

MPA:

Mycophenolate acid

MPS:

Mycophenolate sodium

PD:

Permanent discontinuation

PRED:

Prednisone

r-ATG:

Rabbit anti-thymocyte globulin

RNA:

Ribonucleic acid

TAC:

Tacrolimus

TI:

Temporary interruption

TR:

Temporary reduction

WM:

Without modification

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Acknowledgements

Liliane Hiramoto received a research grant from “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq).

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Authors and Affiliations

  1. Nephrology Division, Hospital do Rim, Federal University of São Paulo, Rua Borges Lagoa, 960, 11º andar, São Paulo, SP, 04038-002, Brazil

    Liliane L. Hiramoto, Helio Tedesco-Silva, Jose O. Medina-Pestana & Claudia R. Felipe

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  1. Liliane L. Hiramoto
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  2. Helio Tedesco-Silva
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  3. Jose O. Medina-Pestana
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  4. Claudia R. Felipe
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Correspondence to Helio Tedesco-Silva.

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This study was supported by grants from CNPq.

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The authors declare that they have no conflict of interest.

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Hiramoto, L.L., Tedesco-Silva, H., Medina-Pestana, J.O. et al. Tolerability of mycophenolate sodium in renal transplant recipients. Int J Clin Pharm 40, 1548–1558 (2018). https://doi.org/10.1007/s11096-018-0727-4

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  • DOI: https://doi.org/10.1007/s11096-018-0727-4

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