Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy-Results of a Prospective Single-Center Trial

Louise Benning; Christian Morath; Annette Fink; Markus Rudek; Claudius Speer; Florian Kälble; Christian Nusshag; Jörg Beimler; Constantin Schwab; Rüdiger Waldherr; Martin Zeier; Caner Süsal; Thuong Hien Tran

doi:10.3389/ti.2023.11899

Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy-Results of a Prospective Single-Center Trial

Transpl Int. 2023 Nov 3:36:11899. doi: 10.3389/ti.2023.11899. eCollection 2023.

Affiliations

¹ Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
² Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany.
³ Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Transplant Immunology Research Center of Excellence, Koç University Hospital, Istanbul, Türkiye.

Abstract

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.

Keywords: dd-cfDNA; donor-derived cell-free DNA; kidney transplantation; rejection; response to therapy.

Publication types

Clinical Trial

MeSH terms

Biopsy
Cell-Free Nucleic Acids*
Graft Rejection / diagnosis
Humans
Kidney Transplantation* / adverse effects
Prospective Studies
Tissue Donors
Transplant Recipients

Substances

Cell-Free Nucleic Acids

Grants and funding

LB is funded by the Olympia Morata Program of Heidelberg University. CSp is funded by the Physician Scientist Program of the Heidelberg Faculty of Medicine. CSü is funded by the European Union’s Horizon 2020 Research and Innovation Programme (grant no. 952512). For the publication fee we acknowledge financial support by Deutsche Forschungsgemeinschaft within the funding program “Open Access Publikationskosten” as well as by Heidelberg University.