Donor-Derived Cell-Free DNA Levels and Prediction of Resolution of Rejection in Kidney Transplant Recipients

The gold standard approach to the diagnosis of rejection in kidney transplant recipients currently relies on tissue obtained during biopsies. However, repeat performance of biopsies is cumbersome, and use of dd-cfDNA in conjunction with eGFR may help inform whether ongoing rejection may be persistent after a diagnosis of rejection is made by biopsy and anti-rejection treatment administered. In this single-center prospective study, 52 patients with rejection were followed longitudinally over time with quarterly dd-cfDNA measurements, of whom 78% had repeat biopsies to confirm the presence or absence of persistent rejection. With every 1 percentage point higher baseline ("first") dd-cfDNA levels drawn at time of enrollment, the odds of persistent rejection were 1.35 (95% CI 1.18-1.55) higher. With every 1 percentage point increase in the slope of dd-cfDNA levels over time, the odds of persistent rejection were 1.62 times higher (95% CI 1.10-2.38). Models including only baseline and the slope of dd-cfDNA provided moderate risk discrimination for rejection (c = 0.73), which improved to c = 0.75 with the addition of eGFR at baseline and change in eGFR over time. Monitoring of dd-cfDNA may offer reasonable discrimination of the likelihood of persistent rejection following anti-rejection therapy. Further validation of these findings is needed.