Kidney Week

Abstract: FR-PO1194

Association of Donor-Derived Cell-Free DNA Elevation with Outcomes in Borderline and T-Cell-Mediated Rejection (TCMR)

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

• Kumar, Dhiren, Virginia Commonwealth University, Richmond, Virginia, United States

Dhiren Kumar, MD

• Vaishnav, Sakshi, Medical University of South Carolina, Charleston, South Carolina, United States

Sakshi Vaishnav, MD

• Huang, Edmund, Cedars-Sinai, Los Angeles, California, United States

Edmund Huang, MD, MS

• Chuang, Peale, CareDx Inc, Brisbane, California, United States

Peale Chuang, MD, FASN

• Ponsirenas, Renata, CareDx Inc, Brisbane, California, United States

Renata Ponsirenas, PhD

• Shen, Ling, CareDx Inc, Brisbane, California, United States

Ling Shen, PhD, MPH

• Xue, Jiashu, CareDx Inc, Brisbane, California, United States

Jiashu Xue, MSc

• Jagadeesan, Muralidharan, The George Washington University Hospital, Washington, District of Columbia, United States

Muralidharan Jagadeesan, MD, MBBS, FASN

• Tanriover, Bekir, Banner - University Medical Center South, Tucson, Arizona, United States

Bekir Tanriover, MD, MBA, MPH

• Brennan, Daniel C., Johns Hopkins University, Baltimore, Maryland, United States

Daniel C. Brennan, MD

Group or Team Name

• KOAR Principal Investigators

Background

Management of borderline and of TCMR remains heterogeneous, in part because the histologic findings do not consistently reflect clinically meaningful allograft injury and may prompt unnecessary treatment. Donor-derived cell-free DNA (dd-cfDNA) is a biomarker of active allograft injury. In this study, we evaluated the association between dd-cfDNA elevation and clinical outcomes among kidney transplant recipients (KTR) with borderline changes and TCMR.

Methods

We analyzed KTRs enrolled in the multicenter KOAR study with biopsy-proven borderline changes or TCMR and a paired dd-cfDNA test within 30 days of biopsy. Patients were stratified by paired dd-cfDNA level (≥1% vs <1%), and clinical characteristics were compared between groups. Outcomes were evaluated using time-to-event analyses and included the primary composite outcome of ≥30% decline in eGFR from baseline or allograft loss, and the secondary outcome of subsequent rejection. KTRs were followed from the time of biopsy until outcome or administrative censoring at 3 years post-transplant.

Results

From 131 KTRs with paired dd-cfDNA testing and biopsy-proven borderline (N=66) or TCMR (N=65), 91 (69%) KTRs had dd-cfDNA <1%, and 40 (31%) had dd-cfDNA ≥1%. Recipients with dd-cfDNA ≥1% were younger (43.7 vs. 54.5, p=0.012) and more frequently developed TCMR or borderline later post-transplant (year 1, 53% vs. 80%; year 2, 18% vs. 14%; year 3, 30% vs. 6%, p<0.001). Rates of subsequent rejection did not differ significantly between recipients with dd-cfDNA ≥1% and those with dd-cfDNA <1% (30% vs. 27%, p=0.834). dd-cfDNA ≥1% was independently associated with an increased risk of the composite outcome (HR [95% CI], 2.78 [1.43–5.40]; P=0.002) (Figure 1).

Conclusion

dd-cfDNA ≥1% was independently associated with a 2.78-fold higher risk of kidney allograft loss or decline in function in KTRs with borderline changes or TCMR on biopsy. These findings support the potential role of dd-cfDNA in risk-stratifying borderline and TCMR biopsy findings and identifying clinically meaningful allograft injury.