Performance of Donor-Derived Cell-Free DNA in Surveillance and For-Cause Biopsies in Pediatric Kidney Transplant...

Donor-derived cell-free DNA (dd-cfDNA), a biomarker demonstrated to increase with allograft injury, has been considered a possible diagnostic tool for allograft rejection in place of the current gold standard which is invasive kidney biopsies. We tested whether dd-cfDNA levels were predictive of rejection in our single-center cohort of pediatric kidney transplant (KT) recipients.

All primary pediatric KT recipients that had a dd-cfDNA level obtained within a month of any kidney biopsy, either surveillance or for-cause were included. Descriptive analysis was performed stratified by rejection status. Univariate analysis was performed to assess the association between median dd-cfDNA levels and rejection by each biopsy time point. dd-cfDNA levels were then further stratified by rejection type (no rejection, T-cell mediated, antibody mediated, or mixed). Diagnostic performance metrics of dd-cfDNA for detecting rejection were evaluated.

Forty pediatric KT recipients had 44 biopsies, 21 (48%) of which demonstrated rejection. Acute cellular, antibody-mediated, and mixed rejection occurred in 12 (57%), 6 (29%), and 3 (14%) respectively. The median dd-cfDNA level at the time of biopsy in those with and without rejection was 1.7 (95% CI: 0.2, 3.3) and 0.3 (95% CI: 0.2, 0.7), respectively (p = 0.15). dd-cfDNA levels prior to for-cause biopsies were significantly higher in patients with rejection (0.3 vs. 2.7; p = 0.02). dd-cfDNA levels at surveillance biopsies did not differ significantly by rejection status or type of rejection. dd-cfDNA levels ≥ 1 diagnosed rejection with a sensitivity of 52% and specificity of 83%.

Elevated dd-cfDNA levels were associated with rejection in for-cause biopsies but not in surveillance biopsies.