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Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients

Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in the CYP3A5 g...

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Autores principales: Obayemi, Joy, Keating, Brendan, Callans, Lauren, Lentine, Krista L., Schnitzler, Mark A., Caliskan, Yasar, Xiao, Huiling, Dharnidharka, Vikas R., Mannon, Roslyn B., Axelrod, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529042/
https://www.ncbi.nlm.nih.gov/pubmed/36204191
http://dx.doi.org/10.1097/TXD.0000000000001379
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author Obayemi, Joy
Keating, Brendan
Callans, Lauren
Lentine, Krista L.
Schnitzler, Mark A.
Caliskan, Yasar
Xiao, Huiling
Dharnidharka, Vikas R.
Mannon, Roslyn B.
Axelrod, David A.
author_facet Obayemi, Joy
Keating, Brendan
Callans, Lauren
Lentine, Krista L.
Schnitzler, Mark A.
Caliskan, Yasar
Xiao, Huiling
Dharnidharka, Vikas R.
Mannon, Roslyn B.
Axelrod, David A.
author_sort Obayemi, Joy
collection PubMed
description Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in the CYP3A5 gene and therefore retain a rapid metabolism phenotype and higher clearance of tacrolimus. Patients with this rapid metabolism typically require higher dosing to achieve therapeutic trough concentrations. This study aims to further characterize the impact of CYP3A5 genotype on clinical outcomes and financial expenditure. METHODS. The CYP3A5 phenotype status was identified in 438 adult kidney transplant (KTx) recipients (96% were African American) using 3 LoF alleles (CYP3A5*3, *6 or *7). Individuals were categorized as rapid metabolism phenotype without LoF alleles‚ intermediate phenotype for 1 LoF allele‚ and slow phenotype for 2 LoF alleles. KTx outcomes (patient/kidney survival and Medicare spending) were determined using linked transplant registry and claims data. RESULTS. Among the cohort, 23% had a rapid, 47% intermediate, and 30% a slow metabolism phenotype based on genotype. At 3 y, the rate of death censored graft failure and all cause graft failure was highest in the rapid metabolism phenotype and lowest in the intermediate metabolism phenotype group. First-year Medicare reimbursement differed significantly by genotype (rapid: $79 535, intermediate: $72 796, slow: $79 346, P = 0.03). After adjustment for donor and recipient characteristics, care for patients with intermediate metabolism was $4790 less expensive (P = 0.003). CONCLUSIONS. Pharmacogenomic assessment of African American KTx recipients may be useful to guide therapy when as CYP3A5 functional variants appear to be associated with differential outcome and spending after transplant.
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spelling pubmed-95290422022-10-05 Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients Obayemi, Joy Keating, Brendan Callans, Lauren Lentine, Krista L. Schnitzler, Mark A. Caliskan, Yasar Xiao, Huiling Dharnidharka, Vikas R. Mannon, Roslyn B. Axelrod, David A. Transplant Direct Kidney Transplantation Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in the CYP3A5 gene and therefore retain a rapid metabolism phenotype and higher clearance of tacrolimus. Patients with this rapid metabolism typically require higher dosing to achieve therapeutic trough concentrations. This study aims to further characterize the impact of CYP3A5 genotype on clinical outcomes and financial expenditure. METHODS. The CYP3A5 phenotype status was identified in 438 adult kidney transplant (KTx) recipients (96% were African American) using 3 LoF alleles (CYP3A5*3, *6 or *7). Individuals were categorized as rapid metabolism phenotype without LoF alleles‚ intermediate phenotype for 1 LoF allele‚ and slow phenotype for 2 LoF alleles. KTx outcomes (patient/kidney survival and Medicare spending) were determined using linked transplant registry and claims data. RESULTS. Among the cohort, 23% had a rapid, 47% intermediate, and 30% a slow metabolism phenotype based on genotype. At 3 y, the rate of death censored graft failure and all cause graft failure was highest in the rapid metabolism phenotype and lowest in the intermediate metabolism phenotype group. First-year Medicare reimbursement differed significantly by genotype (rapid: $79 535, intermediate: $72 796, slow: $79 346, P = 0.03). After adjustment for donor and recipient characteristics, care for patients with intermediate metabolism was $4790 less expensive (P = 0.003). CONCLUSIONS. Pharmacogenomic assessment of African American KTx recipients may be useful to guide therapy when as CYP3A5 functional variants appear to be associated with differential outcome and spending after transplant. Lippincott Williams & Wilkins 2022-09-15 /pmc/articles/PMC9529042/ /pubmed/36204191 http://dx.doi.org/10.1097/TXD.0000000000001379 Text en Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Kidney Transplantation
Obayemi, Joy
Keating, Brendan
Callans, Lauren
Lentine, Krista L.
Schnitzler, Mark A.
Caliskan, Yasar
Xiao, Huiling
Dharnidharka, Vikas R.
Mannon, Roslyn B.
Axelrod, David A.
Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients
title Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients
title_full Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients
title_fullStr Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients
title_full_unstemmed Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients
title_short Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients
title_sort impact of cyp3a5 status on the clinical and financial outcomes among african american kidney transplant recipients
topic Kidney Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529042/
https://www.ncbi.nlm.nih.gov/pubmed/36204191
http://dx.doi.org/10.1097/TXD.0000000000001379
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