Abstract: FR-OR69
Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients with Indication Biopsy: Results of a Prospective German Single-Center Trial
Session Information
- Kidney Transplantation: Biomarkers, New and Old
November 03, 2023 | Location: Room 115, Pennsylvania Convention Center
Abstract Time: 05:42 PM - 05:51 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Benning, Louise, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Morath, Christian, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Fink, Annette, Transplantation Immunology, Heidelberg Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany
- Rudek, Markus A., Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Speer, Claudius, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Nusshag, Christian, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Kälble, Florian, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Mahler, Christoph Friedrich, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Schwab, Constantin, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
- Zeier, Martin G., Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
- Süsal, Caner, Transplantation Immunology, Heidelberg Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany
- Tran, Thuong Hien, Transplantation Immunology, Heidelberg Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany
Background
Donor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. With a number of studies investigating the benefit of dd-cfDNA in US American transplant cohorts, we aimed at evaluating the performance of dd-cfDNA in a cohort of German kidney transplant recipients.
Methods
We enrolled 106 kidney transplant recipients with clinically indicated biopsy between November 2020 and March 2023 at the Department of Nephrology at Heidelberg University Hospital. dd-cfDNA was quantified using the AlloSeq cfDNA assay (CareDx) at time of biopsy to correlate dd-cfDNA levels with histopathological reporting and on days 7, 30 and 90 following biopsy to assess the utility of dd-cfDNA in monitoring treatment response.
Results
Of the 108 allograft biopsies, 36 (33%) were classified as different types of rejection. Patients with ABMR or TCMR (N=13) showed significantly higher dd-cfDNA levels with a median (IQR) of 1.60% (0.38–3.35) compared to the 0.44% (0.20–1.10) in patients with borderline changes (N=23) and the 0.2% (0.11–0.53) in patients with no signs of rejection (N=72) (P<0.05 and P<0.001, respectively). The AUC for dd-cfDNA to differentiate any type of rejection including Borderline changes from no rejection was at 0.72 (95% CI 0.62–0.83). The optimal cut point for dd-cfDNA to discriminate active rejection was at a threshold of 0.57%, yielding a sensitivity of 53% (95% CI 37–68%), a specificity of 81% (95% CI 70–88%), a PPV of 58% (95% CI 41–73%), and a NPV of 77% (95% CI 67–85%). In patients receiving anti-rejection treatment, dd-cfDNA levels decreased significantly 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).
Conclusion
Our data verify the good performance of dd-cfDNA to correctly identify kidney transplant recipients with active rejection at a German transplant center. We show that dd-cfDNA may aid the clinician in recognizing patients at risk and in decision-making regarding the need for a graft biopsy. The potential benefit of dd-cfDNA to assess response to therapy needs further validation.
Funding
- Commercial Support – CareDX