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Donor-Derived Cell-Free DNA Parallels Increases in Donor Specific Antibodies in Pediatric Kidney Transplant Recipients.

D. Stoltz,1 A. Brubaker,1 M. Grskovic,2 R. Woodward,2 A. Gallo.1

1Surgery, Stanford University, Palo Alto, CA
2CareDx, Brisbane, CA

Meeting: 2017 American Transplant Congress

Abstract number: D27

Keywords: Antibodies, Kidney transplantation, Pediatric

Session Information

Session Name: Poster Session D: Diagnostics/Biomarkers Session II

Session Type: Poster Session

Date: Tuesday, May 2, 2017

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Introduction: Anti-HLA antibody screening is a critical component of post-kidney transplant surveillance. Existing protocols and treatment plans are not standard/consistent across institutions. As increasing numbers of highly sensitized patients are transplanted, the need to understand how best to monitor and treat these patients is crucial.

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), protocol donor specific antibody (DSA) monitoring (3, 6, 12 months), 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. Patients with isolated cellular rejection were excluded.

Results: Two patients who developed de novo DSAs post-transplant (either C1q negative or C1q positive) also exhibited significantly elevated dd-cfDNA levels. The single patient with a simultaneous biopsy also demonstrated biopsy-proven antibody mediated rejection (AMR). Elevated dd-cfDNA levels appeared within one month of this histologic change. The difference was statistically significant when compared to those (n=10) without DSA changes (p=0.0046). All patients without de novo DSA production post-transplant exhibited normal (baseline) levels of dd-cfDNA.

Conclusion: dd-cfDNA is a cost effective and convenient test that is associated with de novo DSAs and AMR in pediatric kidney transplant recipients. These data suggest that dd-cfDNA may serve as a novel first line screening tool for AMR 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 Parallels Increases in Donor Specific Antibodies in Pediatric Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Stoltz D, Brubaker A, Grskovic M, Woodward R, Gallo A. Donor-Derived Cell-Free DNA Parallels Increases in Donor Specific Antibodies in Pediatric Kidney Transplant Recipients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-parallels-increases-in-donor-specific-antibodies-in-pediatric-kidney-transplant-recipients/. Accessed May 25, 2025.

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