title: Pharmacogenetics and drug-induced nephrotoxicity in renal transplant recipients.
abstract: BACKGROUND
  The advent of calcineurin inhibitors (CNIs), as the leading immunosuppressive agents, not only has revolutionized the transplant medicine but also made it a better therapeutic intervention that guarantees the graft outcome and improves the survival rate of patients. However, genetic polymorphism(s) in the CNIs metabolic substrates genes (CYP3A4, CYP3A5) and their transporter such as P-glycoprotein (P-gp) can influence the CNIs metabolism and elicit some possible systemic and intra-renal exposures to drugs and/or metabolites with differential risk of nephrotoxicity, jeopardizing the transplantation.
  
  
  METHODS
  In the current study, we review the recent literatures to evaluate the effects of genetic polymorphisms of the genes involved in development of chronic calcineurin nephrotoxicity and progression of chronic allograft dysfunction (CAD) providing an extensive overview on their clinical impacts.
  
  
  RESULTS
  Identifying the inherited genetic basis for the inter-individual differences in terms of drug responses and determining the risk of calcineurin-mediated nephrotoxicity and CAD allow optimized personalized administration of these agents whith minimal adverse effects.
  
  
  CONCLUSIONS
  Pharmacogenetics characteristics of CYP isoforms (CYP3A) and efflux transporters (P-gp and MRP), involved in metabolism and extracellular transportation of the immunosuppressive CNIs, can be of pivotal information in the pharmacotherapy of the renal-transplant recipients. Such information can be used for the successes clinical interventions to attain an improved drug administration strategy with reduced rates of rejection and toxicity.
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran ; Chronic Kidney Disease Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran ; Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Zununi Vahed
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran ; Chronic Kidney Disease Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Ardalan
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasser
authors.initials: N
authors.lastname: Samadi
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Omidi
keywords: Calcineurin inhibitors; Cytochrome P450; Immunosuppressive agents; Nephrotoxicity; Pharmacogenetics; Renal transplantation