The Monitoring of Donor-derived Cell-free DNA in Kidney Transplantation.

Cell-free DNA (cfDNA) exists in plasma and can be measured by several techniques. It is now possible to differentiate donor-derived cfDNA (ddcfDNA) from recipient cfDNA in the plasma or urine of solid organ transplant recipients in the absence of donor and recipient genotyping. The assessment of ddcfDNA is being increasingly studied as a noninvasive means of identifying acute rejection (AR) in solid organ transplants, including subclinical AR. We herein review the literature on the correlation of ddcfDNA with AR in kidney transplantation. There have been at least 15 observational studies that have assessed ddcfDNA in urine or plasma using various methodologies with various thresholds for abnormality. Overall, elevated ddcfDNA indicates allograft injury as may occur with AR, infection, or acute tubular injury but may also be found in clinically stable patients with normal histology. Sensitivity is greater for antibody-mediated AR than for cell-mediated AR, and normal levels do not preclude significant cell-mediated rejection. Measurement of ddcfDNA is not a replacement for biopsy that remains the gold standard for diagnosing AR. Serial monitoring of stable patients may allow earlier detection of subclinical AR, but the efficacy of this approach remains to be established. Normal levels should not preclude planned protocol biopsies. There may be roles for following ddcfDNA levels to assess the adequacy of treatment of AR and to guide the intensity of immunosuppression in the individual patient. Randomized controlled trials are necessary to validate the benefit and cost-effectiveness for these various uses. No firm recommendations can be made at this time.