Pharmacogenomics in kidney transplant recipients and potential for integration into practice

Tam T. Nguyen, Rachael A. Pearson, Moataz E. Mohamed, David P. Schladt, Danielle Berglund, Zachary Rivers, Debra J. Skaar, Baolin Wu, Weihua Guan, Jessica van Setten, Brendan J. Keating, Casey Dorr, Rory P. Remmel, Arthur J. Matas, Roslyn B. Mannon, Ajay K. Israni, William S. Oetting, Pamala A. Jacobson

Research output: Contribution to journalArticlepeer-review

Abstract

What is known and objective: Pharmacogenomic biomarkers are now used in many clinical care settings and represent one of the successes of precision medicine. Genetic variants are associated with pharmacokinetic and pharmacodynamic changes leading to medication adverse effects and changes in clinical response. Actionable pharmacogenomic variants are common in transplant recipients and have implications for medications used in transplant, but yet are not broadly incorporated into practice. Methods: From the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines, and PharmGKB databases, 12 pharmacogenomic genes with 30 variants were selected and used to create diplotypes and actionable pharmacogenomic phenotypes. A total of 853 kidney allograft recipients who had genomic information available from a genome-wide association study were included. Results: Each recipient had at least one actionable pharmacogenomic diplotype/phenotype, whereas the majority (58%) had three or four actionable diplotypes/phenotypes and 17.4% had five or more among the 12 genes. The participants carried actionable diplotypes/phenotypes for multiple medications, including tacrolimus, azathioprine, clopidogrel, warfarin, simvastatin, voriconazole, antidepressants and proton-pump inhibitors. What is new and conclusion: Pharmacogenomic variants are common in transplant recipients, and transplant recipients receive medications that have actionable variants. Clinical trial: Genomics of Transplantation, clinicaltrials.gov (NCT01714440).

Original languageEnglish (US)
Pages (from-to)1457-1465
Number of pages9
JournalJournal of Clinical Pharmacy and Therapeutics
Volume45
Issue number6
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
Pharmacogenomic biomarkers are emerging into clinical practice to guide selection of medications and doses. Clinical implementation of pharmacogenomics has been hastened by the several important initiatives. The Clinical Pharmacogenetic Implementation Consortium (CPIC), sponsored by the National Institute of Health (NIH), evaluates the pharmacogenomic literature and creates peer‐reviewed, evidence‐based actionable drug‐gene practice guidelines. The Dutch Pharmacist Working Group (DPWG) is a European organization that peer reviews and develops pharmacogenomic‐based therapeutic recommendations in the form of guidelines. The PharmGKB is a NIH‐supported pharmacogenomic knowledge database that collects curates and disseminates knowledge about the impact of variation on drug response. There are also over 250 Food and Drug Administration (FDA)‐approved drugs with genetic biomarker information provided in the drug labelling, and the FDA recently released a list of drug‐gene pairs that they believe there is sufficient evidence that certain genotypes are likely to have altered drug metabolism and differential therapeutic and adverse effects. 1 2 3

Funding Information:
This project was supported by grants (U19‐AI070119 and U01‐AI058013) from the National Institute of Allergy and Infectious Disease (AM, PJ, AI, WO) and by Melendy Student Research Scholarships, University of Minnesota, College of Pharmacy (RP, TN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or National Institute of Allergy and Infectious Disease.

Funding Information:
This project was supported by grants (U19-AI070119 and U01-AI058013) from the National Institute of Allergy and Infectious Disease (AM, PJ, AI, WO) and by Melendy Student Research Scholarships, University of Minnesota, College of Pharmacy (RP, TN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or National Institute of Allergy and Infectious Disease. We acknowledge the contributions of our generous patients. We also acknowledge the dedication and hard work of our coordinators at University of Alberta, Nicoleta Bobocea, Tina Wong, Adrian Geambasu and Alyssa Sader; University of Minnesota, Mandi DeGrote and Monica Meyers; Hennepin County Medical Center, Lisa Berndt; Mayo Clinic, Tom DeLeeuw; University of Alabama, Jacquelin Vaughn, Valencia Stephens and Tena Hilario. We also acknowledge the dedicated work of our research scientists Marcia Brott and Amutha Muthusamy.

Publisher Copyright:
© 2020 John Wiley & Sons Ltd

Keywords

  • clinical pharmacy
  • kidney transplantation
  • pharmacogenetics
  • pharmacogenomics

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