Pharmacogenetics and immunosuppressive drugs in solid organ transplantation

Nat Rev Nephrol. 2014 Dec;10(12):725-31. doi: 10.1038/nrneph.2014.172. Epub 2014 Sep 23.

Abstract

The transplantation literature includes numerous papers that report associations between polymorphisms in genes encoding metabolizing enzymes and drug transporters, and pharmacokinetic data on immunosuppressive drugs. Most of these studies are retrospective in design, and although a substantial number report significant associations, pharmacogenetic tests are hardly used in clinical practice. One of the reasons for this poor implementation is the current lack of evidence of improved clinical outcome with pharmacogenetic testing. Furthermore, with efficient therapeutic drug monitoring it is possible to rapidly correct for the effect of genotypic deviations on pharmacokinetics, thereby decreasing the utility of genotype-based dosing. The future of pharmacogenetics will be in treatment models in which patient characteristics are combined with data on polymorphisms in multiple genes. These models should focus on pharmacodynamic parameters, variations in the expression of drug transporter proteins, and predictors of toxicity. Such models will provide more information than the relatively small candidate gene studies performed so far. For implementation of these models into clinical practice, linkage of genotype data to medication prescription systems within electronic health records will be crucial.

Publication types

  • Review

MeSH terms

  • Azathioprine / pharmacokinetics
  • Azathioprine / therapeutic use
  • Cyclosporine / pharmacokinetics
  • Cyclosporine / therapeutic use
  • Drug Monitoring
  • Everolimus
  • Evidence-Based Medicine
  • Female
  • Graft Rejection / genetics*
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Graft Survival / genetics
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods
  • Male
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / therapeutic use
  • Organ Transplantation / adverse effects*
  • Organ Transplantation / methods
  • Pharmacogenetics / methods*
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacokinetics
  • Sirolimus / therapeutic use
  • Tacrolimus / pharmacokinetics
  • Tacrolimus / therapeutic use
  • Transplantation Immunology / drug effects*
  • Transplantation Immunology / genetics

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Mycophenolic Acid
  • Azathioprine
  • Sirolimus
  • Tacrolimus