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<sup>®</sup>) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specifie...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/13/8/1205 |
| _version_ | 1797584195994779648 |
|---|---|
| author | Asim Rizvi Sara Faiz Parin H. Thakkar Syed Hussain Ann N. Gamilla-Crudo Michael Kueht Muhammad A. Mujtaba |
| author_facet | Asim Rizvi Sara Faiz Parin H. Thakkar Syed Hussain Ann N. Gamilla-Crudo Michael Kueht Muhammad A. Mujtaba |
| author_sort | Asim Rizvi |
| collection | DOAJ |
| description | Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx<sup>®</sup>) 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<sup>®</sup>. 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 (<i>p</i> = 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 <i>p</i> = 0.01), however, no difference was found for SCr and proteinuria (<i>p</i> > 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<sup>®</sup> 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<sup>®</sup>, and histology has aided in early diagnosis and timely individualized intervention. |
| first_indexed | 2024-03-10T23:48:43Z |
| format | Article |
| id | doaj.art-900cbdab035548d7818abc66439977bf |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T23:48:43Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-900cbdab035548d7818abc66439977bf2023-11-19T01:48:31ZengMDPI AGJournal of Personalized Medicine2075-44262023-07-01138120510.3390/jpm13081205Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management PerspectiveAsim Rizvi0Sara Faiz1Parin H. Thakkar2Syed Hussain3Ann N. Gamilla-Crudo4Michael Kueht5Muhammad A. Mujtaba6Department of Nephrology, Hypertension and Transplant Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Pathology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Nephrology, Hypertension and Transplant Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Nephrology, Hypertension and Transplant Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Nephrology, Hypertension and Transplant Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Transplant Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Nephrology, Hypertension and Transplant Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADonor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx<sup>®</sup>) 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<sup>®</sup>. 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 (<i>p</i> = 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 <i>p</i> = 0.01), however, no difference was found for SCr and proteinuria (<i>p</i> > 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<sup>®</sup> 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<sup>®</sup>, and histology has aided in early diagnosis and timely individualized intervention.https://www.mdpi.com/2075-4426/13/8/1205donor-derived cell-free DNAMolecular Microscope Diagnostic System (MMDx<sup>®</sup>)rejectionantibody-mediated rejectiondonor-specific antibody |
| spellingShingle | Asim Rizvi Sara Faiz Parin H. Thakkar Syed Hussain Ann N. Gamilla-Crudo Michael Kueht Muhammad A. Mujtaba Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective Journal of Personalized Medicine donor-derived cell-free DNA Molecular Microscope Diagnostic System (MMDx<sup>®</sup>) rejection antibody-mediated rejection donor-specific antibody |
| 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 | donor-derived cell-free DNA Molecular Microscope Diagnostic System (MMDx<sup>®</sup>) rejection antibody-mediated rejection donor-specific antibody |
| url | https://www.mdpi.com/2075-4426/13/8/1205 |
| work_keys_str_mv | AT asimrizvi kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective AT sarafaiz kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective AT parinhthakkar kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective AT syedhussain kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective AT annngamillacrudo kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective AT michaelkueht kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective AT muhammadamujtaba kidneyallograftmonitoringbycombiningdonorderivedcellfreednaandmoleculargeneexpressionaclinicalmanagementperspective |