title: Calcineurin inhibitors and hypertension: a role for pharmacogenetics?
abstract: Hypertension is a common side effect of calcineurin inhibitors (CNIs), which are drugs used to prevent rejection after transplantation. Hypertension after kidney transplantation has been associated with earlier graft failure and higher cardiovascular mortality in the recipient. Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension. These insights raise the question whether polymorphisms in the genes encoding these proteins increase the risk of CNI-induced hypertension. Predicting who is at risk for CNI-induced hypertension may be useful for when selecting specific interventions, including dietary salt restriction, thiazide diuretics or a CNI-free immunosuppressive regimen. This review aims to explore the pharmacogenetics of CNI-induced hypertension, highlighting the knowns and unknowns.
authors.affiliation: Department of Internal Medicine, Nephrology & Transplantation, Erasmus  Medical Center, PO Box 2040 - Room H-438, 3000 CA Rotterdam, The Netherlands.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Moes
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
mesh_terms: D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic
chemical_list: D065095:Calcineurin Inhibitors
keywords: ABCB1; CYP3A5; SPAK; WNK4; sodium chloride cotransporter; transplantation