Donor-derived cell-free DNA 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 1070 biopsies from 1743 kidney transplant recipients enrolled in the prospective, multicenter Kidney Allograft Outcomes AlloSure Registry. Biopsies were grouped into surveillance or for-cause groups and stratified by dd-cfDNA status: elevated, nonelevated, 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 < .0001). Biopsies with elevated dd-cfDNA and rejection diagnoses more frequently demonstrated antibody-mediated rejection and mixed rejection, whereas biopsies performed with nonelevated dd-cfDNA most often showed no rejection, borderline, or T cell-mediated rejection 1A. The area under the receiving operating characteristic curve for BPAR detection was 0.789. These findings demonstrate that dd-cfDNA levels can improve the pretest probability of BPAR in both surveillance and for-cause settings. Therefore, dd-cfDNA can optimize biopsy utilization by identifying kidney transplant patients who are most likely to have histologic rejection.