Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation

Background and objectives Donor-derived cellfree DNA (cfDNA) is a less-invasive marker of allograft injury compared with kidney biopsy. However, donor-derived cfDNA has not yet been extensively tested in children, wherethetestmayhavedifferentcharacteristics. Design, setting, participants, & measurements We assayed donor-derived cfDNA (AlloSure; CareDx) from 290 stored plasma samples from a prospective biobank at our center, collected from 57 children monthly in the first year postkidney transplant between January 2013 and December 2019. We assessed the kinetic changes in donor-derived cfDNA levels within the first year post-transplant. We analyzed donor-derived cfDNA levels for associations with biopsy-proven acute rejection using area under the receiver operating characteristic curve to longitudinal plasma and urine BK viral loads using linear mixed models. We analyzed the prognostic effect of an elevated donor-derived cfDNA level on the eGFR 30 days after the assay via Kolmogorov–Smirnov two-sample tests or on measured GFR or interstitial fibrosis at 12 months post-transplant. Results The donor-derived cfDNA levels in children remained persistently elevated for at least 4 months post-transplant, more so if there is greater disparity in size between the donor and the recipient, before reaching a steady low level. A donor-derived cfDNA level of >1% discriminated between biopsy-proven acute rejection with a receiver operating characteristic area under the curve of 0.82 (95% confidence interval, 0.71 to 0.93). During BK viruria or viremia, patients had a significantly higher median donor-derived cfDNA than before or after and a significant rise within the same patient. A donor-derived cfDNA of >0.5% predicted a wider spread in the eGFR over the next 30 days but not the 12-month outcomes. Conclusions In children, donor-derived cfDNA is a valuable, less invasive biomarker for assessment of allograft rejection and injury.