Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid.
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.
van Gelder
Teun
T
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
Tedesco Silva
Helio
H
de Fijter
Johan W
JW
Budde
Klemens
K
Kuypers
Dirk
D
Arns
Wolfgang
W
Soulillou
Jean Paul
JP
Kanellis
John
J
Zelvys
Arunas
A
Ekberg
Henrik
H
Holzer
Herwig
H
Rostaing
Lionel
L
Mamelok
Richard D
RD
D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D009173:Mycophenolic Acid / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid