Title: UGT1A9-275T > A/-2152C > T Polymorphisms Correlate With Low MPA Exposure and Acute Rejection in MMF/Tacrolimus-Treated Kidney Transplant Patients
Authors: van Schaik, R. H. N ×
van Agteren, M
de Fijter, J. W
Hartmann, A
Schmidt, J
Budde, K
Kuypers, Dirk
Le Meur, Y
van der Werf, M
Mamelok, R
van Gelder, T #
Issue Date: Sep-2009
Publisher: Nature publishing group
Series Title: Clinical pharmacology & therapeutics vol:86 issue:3 pages:319-327
Abstract: Mycophenolate mofetil (MMF) is an immunosuppressive drug commonly used in the context of kidney transplantation. exposure to the active metabolite mycophenolic acid (MPA) is associated with risk of allograft rejection. MPA pharmacokinetics varies between individuals, the potential cause being the presence of genetic polymorphisms in key enzymes. We genotyped 338 kidney transplant patients for UGT1A8, UGT1A9, UGT2B7, and MRP2 polymorphisms and recorded MPA exposure and biopsy-proven acute rejections (BPARs) during a 1-year follow-up. Tacrolimus-treated patients who were UGT1A9-275T>A and/or -2152C>T carriers displayed a 20% lower MPA area under the concentration-time curve from 0 to 12 h (AUC(0-12)) (P = 0.012). UGT1A9*3 carriers displayed a 49% higher MPA AUC(0-12) when treated with tacrolimus and a 54% higher MPA AUC(0-12) when treated with cyclosporine (P < 0.005). Cyclosporine-treated UGT1A8*2/*2 (518GG) patients had an 18% higher MPA AUC(0-12) compared with noncarriers. Carrying the UGT1A9-275T>A and/or -2152C>T polymorphism significantly predicted acute rejection in fixed-dose (FD) MMF-treated patients receiving tacrolimus (odds ratio 13.3, 95% confidence interval 1.1-162.3; P < 0.05). UGT1A9-275T>A and/or -2152C>T genotyping may identify patients at risk of MPA underexposure and acute rejection when receiving treatment with MMF and tacrolimus.
ISSN: 0009-9236
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Nephrology
× corresponding author
# (joint) last author

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