title: Clinical implementation of pharmacogenetics in kidney transplantation: calcineurin inhibitors in the starting blocks.
abstract: Pharmacogenetics has generated many expectations for its potential to individualize therapy proactively and improve medical care. However, despite the huge amount of reported genetic associations with either pharmacokinetics or pharmacodynamics of drugs, the translation into patient care is still slow. In fact, strong evidence for a substantial clinical benefit of pharmacogenetic testing is still limited, with a few exceptions. In kidney transplantation, established pharmacogenetic discoveries are being investigated for application in the clinic to improve efficacy and to limit toxicity associated with the use of immunosuppressive drugs, especially the frequently used calcineurin inhibitors (CNIs) tacrolimus and ciclosporin. The purpose of the present review is to picture the current status of CNI pharmacogenetics and to discuss the most promising leads that have been followed so far.
authors.affiliation: Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCL), Brussels, Belgium; Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam.
authors.forename: Laure
authors.initials: L
authors.lastname: Elens
authors.forename: Rachida
authors.initials: R
authors.lastname: Bouamar
authors.forename: Nauras
authors.initials: N
authors.lastname: Shuker
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
mesh_terms: D000483:Alleles; D065095:Calcineurin Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005820:Genetic Testing; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D016030:Kidney Transplantation / Q000379:methods*; D010597:Pharmacogenetics; D016559:Tacrolimus / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D016559:Tacrolimus
keywords: calcineurin inhibitors; ciclosporin; kidney transplantation; pharmacogenetics; tacrolimus