Donor-derived Cell-free DNA as a Noninvasive Biomarker of Kidney Allograft Rejection in Pediatric Kidney Transplantation

BACKGROUND: Allograft biopsy remains the gold standard to diagnose rejection. New noninvasive biomarkers are needed to avoid unnecessary biopsies and to diagnose early rejection. We studied the performance of donor derived cell-free DNA (dd-cfDNA) to detect rejection in an unselected cohort of pediatric kidney transplant recipients (pKTRs) and determined whether dd-cfDNA could improve standard-of-care monitoring and detection of kidney allograft rejection in children. METHODS: We included 196 pKTRs, who underwent 367 biopsies with concomitant dd-cfDNA assessment. We assessed the association of dd-cfDNA with histological lesions and with rejection using a Cox regression model and compared the discrimination of 3 models: standard of care, dd-cfDNA alone, and combined. RESULTS: We found a significant increase in dd-cfDNA levels with higher degree of inflammation on the biopsies. dd-cfDNA was strongly and independently associated with the presence of allograft rejection (odds ratio 1.89, 95% confidence interval [CI], 1.40-2.60). dd-cfDNA alone had a fair discrimination of 0.76 (95% CI, 0.69-0.81) to detect rejection and its addition to standard of care resulted in a significant increase in discrimination from 0.80 (95% CI, 0.71-0.85) to 0.84 (95% CI, 0.79-0.90), P = 0.01. CONCLUSIONS: dd-cfDNA combined with standard of care improves the prediction of rejection in pKTRs. Further specific studies are needed to better define how to use this promising biomarker in various contexts of use in children.