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

TL;DR

The study examines whether donor-derived cell-free DNA can detect kidney transplant rejection in children, finding it effective for for-cause biopsies but not surveillance biopsies.

Contribution

Shows dd-cfDNA levels correlate with rejection in for-cause biopsies but not surveillance biopsies in pediatric kidney transplant recipients.

Findings

dd-cfDNA levels were significantly higher before for-cause biopsies with rejection (p=0.02).

dd-cfDNA levels ≥1 had 52% sensitivity and 83% specificity for diagnosing rejection.

No significant association between dd-cfDNA and rejection in surveillance biopsies.

Abstract

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.

Elevated dd‐cfDNA levels were associated with rejection in for‐cause biopsies but not surveillance biopsies in a single‐center pediatric kidney transplant cohort.

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