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Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective
Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx(®)) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by u...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455393/ https://www.ncbi.nlm.nih.gov/pubmed/37623456 http://dx.doi.org/10.3390/jpm13081205 |
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author | Rizvi, Asim Faiz, Sara Thakkar, Parin H. Hussain, Syed Gamilla-Crudo, Ann N. Kueht, Michael Mujtaba, Muhammad A. |
author_facet | Rizvi, Asim Faiz, Sara Thakkar, Parin H. Hussain, Syed Gamilla-Crudo, Ann N. Kueht, Michael Mujtaba, Muhammad A. |
author_sort | Rizvi, Asim |
collection | PubMed |
description | Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx(®)) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx(®). Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69–0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx(®) was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx(®), and histology has aided in early diagnosis and timely individualized intervention. |
format | Online Article Text |
id | pubmed-10455393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104553932023-08-26 Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective Rizvi, Asim Faiz, Sara Thakkar, Parin H. Hussain, Syed Gamilla-Crudo, Ann N. Kueht, Michael Mujtaba, Muhammad A. J Pers Med Article Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx(®)) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx(®). Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69–0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx(®) was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx(®), and histology has aided in early diagnosis and timely individualized intervention. MDPI 2023-07-29 /pmc/articles/PMC10455393/ /pubmed/37623456 http://dx.doi.org/10.3390/jpm13081205 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rizvi, Asim Faiz, Sara Thakkar, Parin H. Hussain, Syed Gamilla-Crudo, Ann N. Kueht, Michael Mujtaba, Muhammad A. Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective |
title | Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective |
title_full | Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective |
title_fullStr | Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective |
title_full_unstemmed | Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective |
title_short | Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective |
title_sort | kidney allograft monitoring by combining donor-derived cell-free dna and molecular gene expression: a clinical management perspective |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455393/ https://www.ncbi.nlm.nih.gov/pubmed/37623456 http://dx.doi.org/10.3390/jpm13081205 |
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