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

ABSTRACT

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.