Kidney Week

Abstract: FR-PO774

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

Session Information

• Transplantation: Clinical - Biomarkers
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• Benning, Louise, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg, Germany

Louise Benning,

• Fink, Annette, Transplantation Immunology, Heidelberg Institute of Immunology, University Hospital Heidelberg, Germany, Heidelberg, Germany

Annette Fink,

• Kälble, Florian, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg, Germany

Florian Kälble,

• Speer, Claudius, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg, Germany

Claudius Speer,

• Nusshag, Christian, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg, Germany

Christian Nusshag,

• Zeier, Martin G., Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg, Germany

Martin G. Zeier,

• Süsal, Caner, Transplant Immunology Research Center of Excellence, Koç University Hospital, Istanbul, Turkey, Istanbul, Turkey

Caner Süsal,

• Morath, Christian, Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg, Germany

Christian Morath,

• Tran, Thuong Hien, Transplantation Immunology, Heidelberg Institute of Immunology, University Hospital Heidelberg, Germany, Heidelberg, Germany

Thuong Hien Tran,

Background

Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in kidney transplant recipients (KTR). Little is known about the possible use of dd-cfDNA in evaluating response to anti-rejection treatment.

Methods

This far, we enrolled 84 KTR with indication biopsy between November 2020 and May 2022. Besides routine transplant laboratory, AlloSeq dd-cfDNA was quantified at time of biopsy and on days 7, 30, and 90 following biopsy.

Results

27/84 (32%) biopsies were graded as different types of rejection, whereof 19/27 (70%) showed borderline changes, 5/27 (19%) antibody-mediated rejections (ABMR) and 3/27 (11%) T-cellular mediated rejections (TCMR). Patients with signs of active rejection, including borderline changes, had significantly higher levels of dd-cfDNA at time of biopsy than patients without any signs for rejection, whereas estimated glomerular filtration rate did not differ significantly between the two groups (P<0.001 and P>0.99, respectively, Figure 1A). Patients with ABMR or TCMR showed highest dd-cfDNA levels with a median (IQR) of 2.6% (0.57–9.13) compared to 0.44% (0.20–1.10) in patients with borderline changes and 0.18% (0.11–0.50) in patients with no signs of rejection. dd-cfDNA levels decreased in most of these patients with ABMR or TCMR following initiation of anti-rejection therapy (pooled slope -0.02, Figure 1B). In patients with borderline changes and low levels of dd-cfDNA (<1%) at time of biopsy we see an increase in eGFR after initiation of corticosteroid pulse therapy, whereas patients with high levels of dd-cfDNA (≥1%) show subsequent eGFR decline (Figure 1C).

Conclusion

dd-cfDNA significantly discriminates active rejection at time of biopsy in KTR. Decreasing levels of dd-cfDNA may indicate treatment response in patients with ABMR and TCMR. dd-cfDNA may further help to identify borderline changes with favorable outcome from changes where additional therapy and closer monitoring is needed.

Funding

• Commercial Support – CareDX