Kidney Week

Abstract: FR-PO1198

Histopathological Correlates and Diagnostic Utility of Donor-Derived Cell-Free DNA in Kidney Allograft Injury

Session Information

• Transplantation: Clinical - Rejection, Biomarkers, and Pharmacology
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• Kim, Bioh, The Catholic University of Korea Seoul St Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)

Bioh Kim, MD, MS

• Lee, Hanbi, The Catholic University of Korea Seoul St Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)

Hanbi Lee, MD

• Kim, Hyung Duk, The Catholic University of Korea Eunpyeong St Mary's Hospital, Eunpyeong-gu, Seoul, Korea (the Republic of)

Hyung Duk Kim, MD

• Yoon, Hye Eun, The Catholic University of Korea Seoul St Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)

Hye Eun Yoon, MD, PhD

• Chung, Byung ha, The Catholic University of Korea Seoul St Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)

Byung ha Chung, MD, PhD

Background

The aim of this study is to investigate whether clinically meaningful elevations in donor-derived cell-free DNA (dd-cfDNA) are associated with specific histopathological findings that cause allograft kidney injury, thereby exploring the clinical contexts in which dd-cfDNA may be most useful.

Methods

This retrospective observational study included 178 kidney transplant recipients with clinically suspected allograft rejection who concurrently underwent dd-cfDNA testing and an indicated biopsy. The dd-cfDNA testing was performed immediately before allograft biopsy. We excluded patients who were within one-month post-transplantation or had received a re-transplantation. Allograft biopsy specimens were evaluated according to the Banff classification. We analyzed the association between histological diagnoses, Banff scoring system and dd-cfDNA levels and evaluated the predictive performance of dd-cfDNA for each type of allograft rejection, incorporating donor-specific antibody (DSA) status.

Results

Patients were stratified into high and low groups based on a dd-cfDNA cut-off of 1.0%. The incidences of biopsy-proven rejection (BPR), antibody-mediated rejection (AMR), T-cell-mediated rejection (TCMR), and severe microvascular inflammation (MVI) were significantly higher in the high dd-cfDNA group (BPR: 23.4% vs. 66.0%, p < 0.001; AMR: 17.2% vs. 54.0%, p < 0.001; TCMR: 7.8% vs. 28.0%, p < 0.001; severe MVI: 22.0% vs. 64.0%, p < 0.001). Multivariate analysis identified C4d and MVI scores as significant factors associated with the high dd-cfDNA group, with the MVI score being the strongest predictor (odds ratio: 1.572). The dd-cfDNA test showed favorable predictive power for BPR (AUC = 0.748), likewise good performance for AMR (AUC = 0.710), TCMR (AUC = 0.786), and severe MVI (AUC = 0.727). In DSA-positive patients, using the 1.0% cut-off yielded a positive predictive value (PPV) of 85.7% for AMR. A retrospective review of four DSA-positive patients with dd-cfDNA > 1.0% but no initial AMR diagnosis revealed that three had findings consistent with AMR or later developed AMR.

Conclusion

The dd-cfDNA test is an excellent predictor of allograft rejection and MVI. Furthermore, its high PPV for diagnosing AMR, especially in DSA-positive patients, highlights its potential as a strong non-invasive diagnostic tool for the diagnosis of ABMR to serve as an alternative to allograft kidney biopsies.