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...

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Main Authors: Benning, Louise (Author) , Morath, Christian (Author) , Fink, Annette (Author) , Rudek, Markus (Author) , Speer, Claudius (Author) , Kälble, Florian (Author) , Nußhag, Christian (Author) , Beimler, Jörg (Author) , Schwab, Constantin (Author) , Waldherr, Rüdiger (Author) , Zeier, Martin (Author) , Süsal, Caner (Author) , Tran, Thuong Hien (Author)
Format: Article (Journal)
Language:English
Published: 03 November 2023
In: Transplant international
Year: 2023, Volume: 36, Pages: 1-11
ISSN:1432-2277
DOI:10.3389/ti.2023.11899
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/ti.2023.11899
Verlag, kostenfrei, Volltext: https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11899/full
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Author Notes:Louise Benning, Christian Morath, Annette Fink, Markus Rudek, Claudius Speer, Florian Kälble, Christian Nusshag, Jörg Beimler, Constantin Schwab, Rüdiger Waldherr, Martin Zeier, Caner Süsa and Thuong Hien Tran
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Summary: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-day 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.
Item Description:Gesehen am 22.03.2024
Physical Description:Online Resource
ISSN:1432-2277
DOI:10.3389/ti.2023.11899