Donor-Derived Cell-Free DNA in Stable Pediatric Kidney Transplant Recipients: Influence of Donor Obesity and...

Donor-derived cell-free DNA (dd-cfDNA) is increasingly used as a noninvasive marker of kidney allograft injury, but adult-derived cutoffs may not be applicable to pediatric recipients, particularly in the setting of donor-recipient size mismatch. We evaluated dd-cfDNA levels in stable pediatric kidney transplant (KT) recipients and assessed variation by recipient weight and donor body mass index (BMI).

Retrospective data were collected from seven U.S. pediatric KT centers. Clinically stable recipients < 18 years of age (no de novo donor specific antibody, biopsy-proven rejection or BK viremia/nephropathy), with ≥ 2 dd-cfDNA measurements per year were included. Recipients were stratified by weight at dd-cfDNA collection (< 20 kg, 20-50 kg, > 50 kg). Donor BMI was categorized as underweight (≤ 18.5), normal (18.6-24.9), overweight (25-29.9), or obese (≥ 30). Comparisons were performed using linear mixed-effects models.

Among 178 recipients, mean dd-cfDNA did not differ by recipient weight (< 20 kg: 0.51 ± 0.44; 20-50 kg: 0.65 ± 1.28; > 50 kg: 0.49 ± 0.70). Median dd-cfDNA was similar across donor BMI categories. However, among obese donors, recipients < 20 kg had 1.3-fold higher dd-cfDNA (p = 0.044). Donor-recipient body surface area mismatch > 1.5 was associated with 1.083-fold higher dd-cfDNA up to 5 years post-transplant (p = 0.016).

In stable pediatric KT recipients, dd-cfDNA levels were well below the adult-derived 1% cutoff, reinforcing the generalizability of this cutoff to the pediatric population. Recipients < 20 kg with donor BMI > 30 kg/m² or in the setting of a donor-recipient BSA mismatch > 1.5 were associated with higher dd-cfDNA levels.