Introduction: Surveillance of allograft health is a critical component of post-kidney transplant care. Invasive protocol biopsies are associated with secondary complications and often provide results that warrant no treatment. Based on these limitations, there is considerable need for a rapid and noninvasive biomarker capable of performing better in early detection of allograft damage secondary to rejection.

Methods: Thirteen pediatric kidney transplant recipients were prospectively enrolled at a single center between June 2015 and July 2016. Donor-derived cell-free DNA (dd-cfDNA) and biopsy results were evaluated longitudinally post-transplant. Circulating plasma dd-cfDNA was quantified by an analytically validated clinical-grade next-generation sequencing assay utilizing single nucleotide polymorphisms (SNPs) distributed across the genome to differentiate donor and recipient sequences. Five patients with no biopsies to date and one patient who developed a de novo DSA post-transplant were excluded.

Results: Two patients with biopsy-proven acute cellular rejection (ACR) also exhibited significantly elevated dd-cfDNA levels greater than 2%. These elevated dd-cfDNA levels were observed 7 weeks and 31 weeks prior to biopsy-proven ACR. The difference was statistically significant when compared to those patients (n=5) without episodes of biopsy-proven ACR (p=0.0476). All patients without biopsy-proven ACR post-transplant exhibited normal (baseline) levels of dd-cfDNA.

Conclusion: dd-cfDNA is a safe, rapid and cost effective test that is associated with detecting ACR episodes in a small pilot study of pediatric kidney transplant recipients. These data suggest that dd-cfDNA may serve as a novel first-line screening tool for ACR and may have the potential to improve transplant outcomes and treatment paradigms.

CITATION INFORMATION: Stoltz D, Brubaker A, Grskovic M, Woodward R, Gallo A. Donor-Derived Cell-Free DNA Predicts Biopsy-Proven Acute Cellular Rejection in Pediatric Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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