Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial

Akifova A, Budde K, Amann KU, Büttner-Herold M, Choi M, Oellerich M, Beck J, Bornemann-Kolatzki K, Schütz E, Bachmann F, Halleck F, Von Hoerschelmann E, Koch N, Schrezenmeier E, Seelow E, Waiser J, Zukunft B, Eckardt KU, Halbritter J, Kettritz R, López Del Moral C, Lachmann N, Stauch D, Niemann M, Schmidt D, Halloran PF, Osmanodja B (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Nephrology Dialysis Transplantation Oxford University Press (OUP): Policy B

Book Volume: 40

Pages Range: 1384-1395

Journal Issue: 7

DOI: 10.1093/ndt/gfae282

Abstract

Background Donor-derived cell-free DNA (dd-cfDNA) shows good diagnostic performance for the detection of antibody-mediated rejection (AMR) in kidney transplant recipients (KTR). However, the clinical benefits of dd-cfDNA monitoring need to be established. Early diagnosis of AMR at potentially reversible stages may be increasingly important due to emerging treatment options for AMR. We hypothesized that monitoring dd-cfDNA in KTR with de novo donor-specific anti-HLA antibodies (dnDSA) and performing kidney biopsy in case of increased dd-cfDNA may reduce time to AMR diagnosis in comparison with clinical indication biopsy. Methods In this diagnostic, single-center, open-label, randomized clinical trial, we assigned 40 KTR with prevalent dnDSA and estimated glomerular filtration rate ≥20 mL/min/1.73 m2, but without previous biopsy-proven AMR, to either dd-cfDNA-guided biopsy (intervention group) or clinician-guided biopsy (control group) over a 12-month period. In both groups, dd-cfDNA was assessed at inclusion and 1, 3, 6, 9 and 12 months. In the intervention group, dd-cfDNA >50 copies/mL indicated a biopsy. Biopsies for clinical indication could be performed at any point during the study period in both groups. A protocol biopsy was scheduled after 12 months for patients without dd-cfDNA-guided biopsy or clinical indication biopsy until study completion. The primary endpoint was time from study inclusion to diagnosis of active or chronic active AMR. Results Thirty-nine of 40 patients had functioning grafts at study completion. From these, 26 patients underwent biopsy, 13 in each group. AMR was diagnosed earlier in the intervention group than in the control group [median 2.8 months, interquartile range (IQR) 1.7-5.3 vs median 14.5 months, IQR 13.3-16.7, P =. 003]. Longitudinal dd-cfDNA monitoring had 77% positive predictive value and 85% negative predictive value for AMR. Conclusions Dd-cfDNA-guided biopsy in KTR with prevalent dnDSA can reduce the time to AMR diagnosis and hereby expedite therapy initiation.

Authors with CRIS profile

Kerstin Ute Amann Department of Nephropathology Maike Büttner-Herold Department of Nephropathology

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) PIRCHE AG DE Germany (DE) University of Alberta CA Canada (CA) Universitätsklinikum Göttingen DE Germany (DE) Chronix Biomedical GmbH DE Germany (DE)

How to cite

APA:

Akifova, A., Budde, K., Amann, K.U., Büttner-Herold, M., Choi, M., Oellerich, M.,... Osmanodja, B. (2025). Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial. Nephrology Dialysis Transplantation, 40(7), 1384-1395. https://doi.org/10.1093/ndt/gfae282

MLA:

Akifova, Aylin, et al. "Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial." Nephrology Dialysis Transplantation 40.7 (2025): 1384-1395.

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