title: Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid.
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.
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco Silva
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: John
authors.initials: J
authors.lastname: Kanellis
authors.forename: Arunas
authors.initials: A
authors.lastname: Zelvys
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
authors.forename: Herwig
authors.initials: H
authors.lastname: Holzer
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Richard D
authors.initials: RD
authors.lastname: Mamelok
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid