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Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid.

van Gelder, Teun; Tedesco Silva, Helio; de Fijter, Johan W; Budde, Klemens; Kuypers, Dirk; Arns, Wolfgang; Soulillou, Jean Paul; Kanellis, John; Zelvys, Arunas and Ekberg, Henrik LU , et al. (2010) In Transplantation 89. p.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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
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Transplantation
volume
89
pages
595 - 599
publisher
Lippincott Williams & Wilkins
external identifiers
  • WOS:000275719900014
  • PMID:20124953
  • Scopus:77949385812
ISSN
1534-6080
DOI
10.1097/TP.0b013e3181ca7d84
language
English
LU publication?
yes
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f71ab873-7bce-40b3-82bc-50d8ed2389dd (old id 1553032)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20124953?dopt=Abstract
date added to LUP
2010-03-02 15:40:50
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2016-11-06 04:27:24
@misc{f71ab873-7bce-40b3-82bc-50d8ed2389dd,
  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.},
  author       = {van Gelder, Teun and Tedesco Silva, Helio and de Fijter, Johan W and Budde, Klemens and Kuypers, Dirk and Arns, Wolfgang and Soulillou, Jean Paul and Kanellis, John and Zelvys, Arunas and Ekberg, Henrik and Holzer, Herwig and Rostaing, Lionel and Mamelok, Richard D},
  issn         = {1534-6080},
  language     = {eng},
  pages        = {595--599},
  publisher    = {ARRAY(0x9131c68)},
  series       = {Transplantation},
  title        = {Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid.},
  url          = {http://dx.doi.org/10.1097/TP.0b013e3181ca7d84},
  volume       = {89},
  year         = {2010},
}