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Association of Blood Donor-derived Cell-free DNA Levels with Banff Scores and Histopathological Lesions in Kidney Allograft Biopsies: Results from an Observational Study

Akifova A, Budde K, Choi M, Amann KU, Büttner-Herold M, Oellerich M, Beck J, Bornemann-Kolatzki K, Schütz E, Bachmann F, Halleck F, Schrezenmeier EV, Seelow E, Zukunft B, Hammett C, Pohl NA, Mordà B, Kowald J, Lachmann N, Stauch D, Osmanodja B (2025)

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Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 11

Pages Range: e1794-

Journal Issue: 5

DOI: 10.1097/TXD.0000000000001794

Abstract

Background. Donor-derived cell-free DNA (dd-cfDNA) is an emerging biomarker of kidney allograft injury, mainly investigated in the context of rejection. However, the dd-cfDNA dynamics in other graft pathologies merit further investigation. Methods. In this single-center observational study, we prospectively collected dd-cfDNA at indication biopsies. To evaluate the association between dd-cfDNA and different histological patterns, we correlated absolute and relative dd-cfDNA (thresholds of 50 copies/mL and 0.5%, respectively) with the Banff 2022 lesion scores and the assigned diagnoses. Results. We examined 151 dd-cfDNA paired biopsies in 131 kidney transplant recipients and found significantly higher absolute dd-cfDNA levels in antibody-mediated rejection (n, median, IQR: 45, 63 copies/mL, 42-89), microvascular inflammation (MVI) without donor-specific antibodies or C4d-deposition (6, 102 copies/mL, 61-134), mixed rejection (8, 140 copies/mL, 77-171), and BK virus-Associated nephropathy (6, 213 copies/mL, 83-298) compared with glomerulonephritis (20, 12 copies/mL, 8-18), calcineurin toxicity (19, 10 copies/mL, 7-16), interstitial fibrosis/tubular atrophy (12, 10 copies/mL, 9-16) and normal histology (6, 9 copies/mL, 7-16). In the multivariable analysis, absolute and relative dd-cfDNA correlated with the peritubular capillaritis (ptc), glomerulitis (g), and tubulitis (t) scores. In the receiver operating characteristic analysis, absolute dd-cfDNA showed best discrimination for MVI of any cause (area under the curve [AUC] 0.88, sensitivity 0.71, specificity 0.86, positive predictive value [PPV] 0.76, negative predictive value [NPV] 0.82), followed by antibody-mediated rejection including mixed rejection (AUC 0.85, sensitivity 0.72, specificity 0.83, PPV 0.69, NPV 0.84), and overall rejection (AUC 0.83, sensitivity 0.66, specificity 0.85, PPV 0.76, NPV 0.77). T cell-mediated rejection was only detectable by dd-cfDNA when associated with vascular lesions. Conclusions. Altogether, we conclude that dd-cfDNA-release is not limited to rejection-related injury phenotypes and is mainly driven by MVI in kidney allografts.

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APA:

Akifova, A., Budde, K., Choi, M., Amann, K.U., Büttner-Herold, M., Oellerich, M.,... Osmanodja, B. (2025). Association of Blood Donor-derived Cell-free DNA Levels with Banff Scores and Histopathological Lesions in Kidney Allograft Biopsies: Results from an Observational Study. Transplantation Direct, 11(5), e1794-. https://doi.org/10.1097/TXD.0000000000001794

MLA:

Akifova, Aylin, et al. "Association of Blood Donor-derived Cell-free DNA Levels with Banff Scores and Histopathological Lesions in Kidney Allograft Biopsies: Results from an Observational Study." Transplantation Direct 11.5 (2025): e1794-.

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