Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial
Donor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and Decemb...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Transplant International |
| Subjects: | |
| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11899/full |
| _version_ | 1811153564444131328 |
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| author | Louise Benning Christian Morath Annette Fink Markus Rudek Claudius Speer Florian Kälble Christian Nusshag Jörg Beimler Constantin Schwab Rüdiger Waldherr Martin Zeier Caner Süsal Caner Süsal Thuong Hien Tran |
| author_facet | Louise Benning Christian Morath Annette Fink Markus Rudek Claudius Speer Florian Kälble Christian Nusshag Jörg Beimler Constantin Schwab Rüdiger Waldherr Martin Zeier Caner Süsal Caner Süsal Thuong Hien Tran |
| author_sort | Louise Benning |
| collection | DOAJ |
| description | Donor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and December 2022 to validate the clinical value of dd-cfDNA in a cohort of German patients. dd-cfDNA was quantified at biopsy and correlated to histopathology. Additionally, dd-cfDNA was determined on days 7, 30, and 90 post-biopsy and analyzed for potential use to monitor response to anti-rejection treatment. dd-cfDNA levels were with a median (IQR) % of 2.00 (0.48–3.20) highest in patients with ABMR, followed by 0.92 (0.19–11.25) in patients with TCMR, 0.44 (0.20–1.10) in patients with borderline changes and 0.20 (0.11–0.53) in patients with no signs of rejection. The AUC for dd-cfDNA to discriminate any type of rejection including borderline changes from no rejection was at 0.72 (95% CI 0.62–0.83). In patients receiving anti-rejection treatment, dd-cfDNA levels significantly decreased during the 7, 30, and 90 days follow-up compared to levels at the time of biopsy (p = 0.006, p = 0.002, and p < 0.001, respectively). In conclusion, dd-cfDNA significantly discriminates active rejection from no rejection. Decreasing dd-cfDNA following anti-rejection treatment may indicate response to therapy.Clinical Trial Registration: https://drks.de/search/de/trial/DRKS00023604, identifier DRKS00023604. |
| first_indexed | 2024-04-24T12:59:04Z |
| format | Article |
| id | doaj.art-dd27de4fe00d46a19c12bf2a47c50f5f |
| institution | Directory Open Access Journal |
| issn | 1432-2277 |
| language | English |
| last_indexed | 2024-04-24T12:59:04Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj.art-dd27de4fe00d46a19c12bf2a47c50f5f2024-04-05T16:34:27ZengFrontiers Media S.A.Transplant International1432-22772023-11-013610.3389/ti.2023.1189911899Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center TrialLouise Benning0Christian Morath1Annette Fink2Markus Rudek3Claudius Speer4Florian Kälble5Christian Nusshag6Jörg Beimler7Constantin Schwab8Rüdiger Waldherr9Martin Zeier10Caner Süsal11Caner Süsal12Thuong Hien Tran13Department of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Immunology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Nephrology, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Immunology, Heidelberg University Hospital, Heidelberg, GermanyTransplant Immunology Research Center of Excellence, Koç University Hospital, Istanbul, TürkiyeInstitute of Immunology, Heidelberg University Hospital, Heidelberg, GermanyDonor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and December 2022 to validate the clinical value of dd-cfDNA in a cohort of German patients. dd-cfDNA was quantified at biopsy and correlated to histopathology. Additionally, dd-cfDNA was determined on days 7, 30, and 90 post-biopsy and analyzed for potential use to monitor response to anti-rejection treatment. dd-cfDNA levels were with a median (IQR) % of 2.00 (0.48–3.20) highest in patients with ABMR, followed by 0.92 (0.19–11.25) in patients with TCMR, 0.44 (0.20–1.10) in patients with borderline changes and 0.20 (0.11–0.53) in patients with no signs of rejection. The AUC for dd-cfDNA to discriminate any type of rejection including borderline changes from no rejection was at 0.72 (95% CI 0.62–0.83). In patients receiving anti-rejection treatment, dd-cfDNA levels significantly decreased during the 7, 30, and 90 days follow-up compared to levels at the time of biopsy (p = 0.006, p = 0.002, and p < 0.001, respectively). In conclusion, dd-cfDNA significantly discriminates active rejection from no rejection. Decreasing dd-cfDNA following anti-rejection treatment may indicate response to therapy.Clinical Trial Registration: https://drks.de/search/de/trial/DRKS00023604, identifier DRKS00023604.https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11899/fulldonor-derived cell-free DNAdd-cfDNAkidney transplantationrejectionresponse to therapy |
| spellingShingle | Louise Benning Christian Morath Annette Fink Markus Rudek Claudius Speer Florian Kälble Christian Nusshag Jörg Beimler Constantin Schwab Rüdiger Waldherr Martin Zeier Caner Süsal Caner Süsal Thuong Hien Tran Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial Transplant International donor-derived cell-free DNA dd-cfDNA kidney transplantation rejection response to therapy |
| title | Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial |
| title_full | Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial |
| title_fullStr | Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial |
| title_full_unstemmed | Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial |
| title_short | Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial |
| title_sort | donor derived cell free dna dd cfdna in kidney transplant recipients with indication biopsy results of a prospective single center trial |
| topic | donor-derived cell-free DNA dd-cfDNA kidney transplantation rejection response to therapy |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11899/full |
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