Use of pharmacogenomics in pediatric renal transplant recipients.
Transplant recipients receive potent immunosuppressive drugs in order to prevent graft rejection. Therapeutic drug monitoring is the current approach to guide the dosing of calcineurin inhibitors, mammalian target of rapamycin inhibitors (mTORi) and mofetil mycophenolate. Target concentrations used in pediatric patients are extrapolated from adult studies. Gene polymorphisms in metabolizing enzymes and drug transporters such as cytochromes CYP3A4 and CYP3A5, UDP-glucuronosyl transferase, and P-glycoprotein are known to influence the pharmacokinetics and dose requirements of immunosuppressants. The implications of pharmacogenomics in this patient population is discussed. Genetic information can help with achieving target concentrations in the early post-transplant period, avoiding adverse drug reactions and drug-drug interactions. Evidence about genetic studies and transplant outcomes is revised.
Laboratorio de Investigación en Nefrología y Metabolismo Mineral, Hospital Infantil de México Federico Gómez México, México ; Departamento de Farmacología, Facultad de Medicina UNAM México, México ; Pharmaceutical Outcomes Programme, Pediatrics, BC Children's Hospital, University of British Columbia Vancouver, BC, Canada.
Mara
M
Medeiros
Departamento de Farmacología, Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional México, México.
Gilberto
G
Castañeda-Hernández
Pharmaceutical Outcomes Programme, Pediatrics, BC Children's Hospital, University of British Columbia Vancouver, BC, Canada ; Division of Translational Therapeutics, Department of Paediatrics, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Child and Family Research Institute, University of British Columbia Vancouver, BC, Canada.
Colin J D
CJ
Ross
Pharmaceutical Outcomes Programme, Pediatrics, BC Children's Hospital, University of British Columbia Vancouver, BC, Canada ; Division of Translational Therapeutics, Department of Paediatrics, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Child and Family Research Institute, University of British Columbia Vancouver, BC, Canada.
Bruce C
BC
Carleton
GWAS; acute rejection; adverse reactions; drug metabolism; genotype; graft survival; immunosuppression; pharmacogenomics