Reduction in Donor‐Derived Cell‐Free DNA After Rejection Treatment is Associated With Improved Long Term Allograft Function

Donor derived cell-free DNA (dd-cfDNA) has become a useful biomarker for monitoring of kidney transplant rejection, however utilization after rejection is not well established. We conducted a retrospective cohort study of 64 kidney transplant recipients (KTRs) with biopsy-proven rejection and concomitant dd-cfDNA monitoring. The primary outcome was to examine the relationship between changes in dd-cfDNA and allograft function after rejection. Secondary outcomes included the effect of a ≥61% dd-cfDNA reduction on eGFR and proteinuria, and impact of persistently elevated dd-cfDNA. The percent change in dd-cfDNA from rejection to 6 months post-rejection and 1-year post-rejection was negatively correlated with eGFR change at 1, 2, and 3 years. No correlation was seen with dd-cfDNA values at 1 month. KTRs with at least 61% decrease in dd-cfDNA from rejection to 1-year post-rejection showed improvement in eGFR at 1, 2, and 3 years. KTRs with persistently elevated dd-cfDNA showed significantly worse change in eGFR to all time points compared to those without. Incidence of proteinuria at 1, 2, and 3 years trended lower in KTRs with ≥61% decrease in dd-cfDNA. dd-cfDNA was negatively correlated with eGFR, primarily at 6-12 months post-rejection. In conclusion, persistently elevated dd-cfDNA correlates with worse longitudinal changes in eGFR through 3 years post-rejection.