dd-cfDNA Significantly Improves Rejection Yield in Kidney Transplant Biopsies

Donor-derived cell-free DNA (dd-cfDNA) is a biomarker that enables the early detection of immune-mediated graft injury. This study evaluated the clinical utility of dd-cfDNA in predicting the presence of biopsy-proven rejection (BPAR). We analyzed 1,070 biopsies from 1,743 kidney transplant recipients enrolled in the prospective, multicenter Kidney Allograft Outcomes AlloSure Registry (KOAR). Biopsies were grouped into surveillance or for-cause groups and stratified by dd-cfDNA status: elevated, non-elevated, or not tested. Rejection yield was significantly higher when dd-cfDNA was elevated: 39% vs. 7% in the surveillance group and 47% vs. 12% in the for-cause group (p<0.0001). Biopsies with elevated dd-cfDNA and rejection diagnoses more frequently demonstrated ABMR and mixed rejection, whereas biopsies performed with non-elevated dd-cfDNA most often showed no rejection, borderline, or TCMR 1A. The AUROC for BPAR detection was 0.789. These findings demonstrate dd-cfDNA levels can improve the pre-test probability of BPAR in both surveillance and for-cause settings. Therefore, dd-cfDNA can optimize biopsy utilization by identifying renal transplant patients who are most likely to have histological rejection.