Role of pharmacogenomics in dialysis and transplantation

Curr Opin Nephrol Hypertens. 2014 Nov;23(6):570-7. doi: 10.1097/MNH.0000000000000065.

Abstract

Purpose of review: Pharmacogenomics is the study of differences in drug response on the basis of individual genetic background. With rapidly advancing genomic technologies and decreased costs of genotyping, the field of pharmacogenomics continues to develop. Application to patients with kidney disease provides growing opportunities for improving drug therapy.

Recent findings: Pharmacogenomics studies are lacking in patients with chronic kidney disease and dialysis, but are abundant in the kidney transplant field. A potentially clinically actionable genetic variant exists in the CYP3A5 gene, with the initial tacrolimus dose selection being optimized based on CYP3A5 genotype. Although many pharmacogenomics studies have focused on transplant immunosuppression pharmacokinetics, an expanding literature on pharmacodynamic outcomes, such as calcineurin inhibitor toxicity and new onset diabetes, is providing new information on patients at risk.

Summary: Appropriately powered pharmacogenomics studies with well-defined phenotypes are needed to validate existing studies and unearth new findings in patients with kidney disease, especially the chronic kidney disease and dialysis population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / pharmacokinetics
  • Calcineurin Inhibitors / therapeutic use*
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Genotype
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Pharmacogenetics*
  • Phenotype
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / therapy*

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A