Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with...

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Main Authors: Alexandre Loupy, Anaïs Certain, Narin S. Tangprasertchai, Maud Racapé, Cindy Ursule-Dufait, Kawthar Benbadi, Marc Raynaud, Evgeniya Vaskova, Corina Marchis, Sílvia Casas, Tim Hague, Oriol Bestard, Delphine Kervella, Carmen Lefaucheur, Thierry Viard, Olivier Aubert
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Transplant International
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Online Access:https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13919/full
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author Alexandre Loupy
Alexandre Loupy
Anaïs Certain
Narin S. Tangprasertchai
Maud Racapé
Cindy Ursule-Dufait
Kawthar Benbadi
Marc Raynaud
Evgeniya Vaskova
Corina Marchis
Sílvia Casas
Tim Hague
Oriol Bestard
Delphine Kervella
Carmen Lefaucheur
Carmen Lefaucheur
Thierry Viard
Olivier Aubert
Olivier Aubert
author_facet Alexandre Loupy
Alexandre Loupy
Anaïs Certain
Narin S. Tangprasertchai
Maud Racapé
Cindy Ursule-Dufait
Kawthar Benbadi
Marc Raynaud
Evgeniya Vaskova
Corina Marchis
Sílvia Casas
Tim Hague
Oriol Bestard
Delphine Kervella
Carmen Lefaucheur
Carmen Lefaucheur
Thierry Viard
Olivier Aubert
Olivier Aubert
author_sort Alexandre Loupy
collection DOAJ
description Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study. 580 kidney allograft recipients from 3 referral centers were included for 603 total evaluations. Correlation between assays was evaluated using r-squared (r2) and Spearman’s rank correlation test, and associations with rejection using logistic regression analyses and discrimination using area under the curve. Mean dd-cfDNA levels from decentralized and centralized tests were 0.51% ± 0.81% and 0.43% ± 0.78%, respectively. The assays were highly correlated, with r2 = 0.95 and Spearman’s rank correlation 0.88 (p < 0.0001). Both tests showed significant association with allograft rejection (p < 0.0001) and good and similar discriminations to predict rejection (AUC: 0.758 for the decentralized and AUC: 0.760 for the centralized dd-cfDNA; p = 0.8466). Consistency between the assays was also confirmed across clinical scenarios including post-transplant timepoint, allograft stability, and allograft rejection subcategories. This decentralized dd-cfDNA assessment demonstrates high accuracy and value to non-invasively monitor kidney recipients.
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spelling doaj-art-4b63188cb64c4e4d9b05e9d5b57be3082025-08-20T01:58:27ZengFrontiers Media S.A.Transplant International1432-22772024-12-013710.3389/ti.2024.1391913919Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection MonitoringAlexandre Loupy0Alexandre Loupy1Anaïs Certain2Narin S. Tangprasertchai3Maud Racapé4Cindy Ursule-Dufait5Kawthar Benbadi6Marc Raynaud7Evgeniya Vaskova8Corina Marchis9Sílvia Casas10Tim Hague11Oriol Bestard12Delphine Kervella13Carmen Lefaucheur14Carmen Lefaucheur15Thierry Viard16Olivier Aubert17Olivier Aubert18Université Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceDepartment of Kidney Transplantation, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, FranceUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceCareDx, Brisbane, CA, United StatesUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceCareDx, Brisbane, CA, United StatesCareDx, Brisbane, CA, United StatesCareDx, Brisbane, CA, United StatesCareDx, Brisbane, CA, United StatesDepartment of Nephrology and Kidney Transplantation, Vall d’Hebron University Hospital, Vall d’ Hebrón Research Institute, Vall d’ Hebrón Barcelona Campus Hospital, Barcelona Autonomous University, Barcelona, SpainDepartment of Nephrology and Kidney Transplantation, Vall d’Hebron University Hospital, Vall d’ Hebrón Research Institute, Vall d’ Hebrón Barcelona Campus Hospital, Barcelona Autonomous University, Barcelona, SpainUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceKidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, FranceCareDx, Brisbane, CA, United StatesUniversité Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, FranceDepartment of Kidney Transplantation, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, FranceDonor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study. 580 kidney allograft recipients from 3 referral centers were included for 603 total evaluations. Correlation between assays was evaluated using r-squared (r2) and Spearman’s rank correlation test, and associations with rejection using logistic regression analyses and discrimination using area under the curve. Mean dd-cfDNA levels from decentralized and centralized tests were 0.51% ± 0.81% and 0.43% ± 0.78%, respectively. The assays were highly correlated, with r2 = 0.95 and Spearman’s rank correlation 0.88 (p < 0.0001). Both tests showed significant association with allograft rejection (p < 0.0001) and good and similar discriminations to predict rejection (AUC: 0.758 for the decentralized and AUC: 0.760 for the centralized dd-cfDNA; p = 0.8466). Consistency between the assays was also confirmed across clinical scenarios including post-transplant timepoint, allograft stability, and allograft rejection subcategories. This decentralized dd-cfDNA assessment demonstrates high accuracy and value to non-invasively monitor kidney recipients.https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13919/fullAlloSeqdd-cfDNAliquid biopsyallograft rejectionnon-invasive diagnosis
spellingShingle Alexandre Loupy
Alexandre Loupy
Anaïs Certain
Narin S. Tangprasertchai
Maud Racapé
Cindy Ursule-Dufait
Kawthar Benbadi
Marc Raynaud
Evgeniya Vaskova
Corina Marchis
Sílvia Casas
Tim Hague
Oriol Bestard
Delphine Kervella
Carmen Lefaucheur
Carmen Lefaucheur
Thierry Viard
Olivier Aubert
Olivier Aubert
Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
Transplant International
AlloSeq
dd-cfDNA
liquid biopsy
allograft rejection
non-invasive diagnosis
title Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
title_full Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
title_fullStr Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
title_full_unstemmed Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
title_short Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
title_sort evaluation of a decentralized donor derived cell free dna assay for kidney allograft rejection monitoring
topic AlloSeq
dd-cfDNA
liquid biopsy
allograft rejection
non-invasive diagnosis
url https://www.frontierspartnerships.org/articles/10.3389/ti.2024.13919/full
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