The clinical value of donor-derived cell-free DNA measurements in kidney transplantation

Early diagnosis is critical to minimizing the damage rejection can do to the transplanted kidney. Donor-derived cell-free DNA (dd-cfDNA) represents non-encapsulated fragmented DNA that is continuously shed into the bloodstream from the allograft undergoing injury, with a half-life of about 30 min. This article reviews the available evidence regarding the diagnostic value of dd-cfDNA in kidney transplantation, as a result of which two assays, Allosure and Prospera, have garnered Medicare approval. We provide information on important scenarios and contexts including antibody-mediated rejection, T-cell mediated rejection, pre-test probability of rejection, timing of the test, repeat transplants, and background cell-free DNA levels to help our understanding of the test characteristics and utility of these assays in clinical practice. Data on multimodality assays including gene expression profiles and serial monitoring of dd-cfDNA in high risk situations are emerging.