Title: Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid
Authors: van Gelder, Teun ×
Tedesco Silva, Helio
de Fijter, Johan W
Budde, Klemens
Kuypers, Dirk
Arns, Wolfgang
Soulillou, Jean Paul
Kanellis, John
Zelvys, Arunas
Ekberg, Henrik
Holzer, Herwig
Rostaing, Lionel
Mamelok, Richard D #
Issue Date: Mar-2010
Publisher: Lippincott Williams & Wilkins
Series Title: Transplantation vol:89 issue:5 pages:595-599
Abstract: 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.
ISSN: 0041-1337
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Nephrology
× corresponding author
# (joint) last author

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