Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid

Teun Van Gelder, Helio Tedesco Silva, Johan W.W. de Fijter, Klemens Budde, Dirk Kuypers, Wolfgang Arns, Jean Paul Soulillou, John Kanellis, Arunas Zelvys, Henrik Ekberg, Herwig Holzer, Lionel Rostaing, Richard D. Mamelok

    Research output: Contribution to journalArticleResearchpeer-review

    40 Citations (Scopus)


    Background: To better define subpopulations in which achieving adequate mycophenolic acid (MPA) concentrations quickly would be important, a post hoc exploratory analysis on the fixed-dose concentration-controlled database was performed, comparing high-versus low-risk renal transplant patients. Methods: Renal transplant patients were treated with mycophenolate mofetil, corticosteroids, and cyclosporine A or tacrolimus. Patients were defined as "high risk" if they had one or more of the following characteristics: delayed graft function, second or third transplantation, panel reactive antibodies >15%, four or more human leukocyte antigen mismatches, or were of black race. Results: A total of 549 patients (61%) were classified as high risk, of whom 284 were on cyclosporine A treatment and 265 on tacrolimus. In high-risk patients, the difference in rejection incidence was 14.3% in the MPA-area under the concentration (AUC) less than 30 mg hr/L vs. 7.8% in the MPA-AUC more than or equal to 30 mg hr/L groups (P=0.025) during the first month after transplantation; whereas, in low-risk patients, there were similar rejection rates (5.7% vs. 4.5%). In the subgroup of high-risk tacrolimus-treated patients, the difference in acute rejection incidence in the first month between patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was most pronounced: 16 of 67 patients (23.9%) vs. 18 of 173 patients (10.4%); P=0.012. Conclusions: The incidence of acute rejection is higher in high-risk patients if MPA-AUC0-12 is below 30 mg hr/L. In contrast, a difference in acute rejection incidence in low-risk patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was not observed. This supports the use of a higher mycophenolate mofetil starting dose in selected patient populations early after transplantation.

    Original languageEnglish
    Pages (from-to)595-599
    Number of pages5
    Issue number5
    Publication statusPublished - Mar 2010


    • Graft rejection
    • Mycophenolate mofetil
    • Therapeutic drug monitoring
    • Transplantation

    Cite this