Use of pharmacogenomics in pediatric renal transplant recipients

Front Genet. 2015 Feb 18:6:41. doi: 10.3389/fgene.2015.00041. eCollection 2015.

Abstract

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.

Keywords: GWAS; acute rejection; adverse reactions; drug metabolism; genotype; graft survival; immunosuppression; pharmacogenomics.

Publication types

  • Review