Donor-Derived Cell-Free DNA Normal Range and Biological Variation Defined in a Reference Population.
1University of Maryland, Baltimiore, MD
2Washington University, St. Louis, MO
3Cleveland Clinic, Cleveland, OH
4CareDx, Brisbane, CA
5University of Pennsylvania, Philadelphia, PA
Meeting: 2017 American Transplant Congress
Abstract number: B78
Keywords: Monitoring, Multicenter studies, Non-invasive diagnosis, Rejection
Session Information
Session Name: Poster Session B: Antibody Mediated Rejection in Kidney Transplant Recipients II
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose: Donor-derived cell-free DNA (dd-cfDNA) in the circulating blood of transplant recipients has shown promise as a non-invasive biomarker of acute rejection. This analysis was performed to establish clinical reference ranges for dd-cfDNA in renal transplant recipients and identify the normal biological variation in serial testing to enhance interpretation of dd-cfDNA results.
Methods: We sampled venous blood at surveillance visits (post-transplant months 1,2,3,4 and 6) in a 14-center observational study. Patients with stable renal allograft function spanning at least three serial visits were selected as the reference population. We used an analytically-validated targeted next-generation sequencing based approach to measure dd-cfDNA in the plasma (analytical coefficient of variation (CV) 6.8%). Results were used to compute the intra-individual (CVI) and inter-individual (or group, CVG), coefficients of variation, and the reference change value (RCV).
Results: There were 93 patients that met the criteria for analysis, with a total of 380 serial blood samples (minimum 3, average 4.1 per patient). Of these 93 patients, 63% were deceased donor kidney recipients. The dd-cfDNA median value was 0.21% (interquartile range 0.12-0.39%) across all 380 samples, and the 97.5th percentile was 1.20%. Over 96% of the measurements were less than 1.0%. In 18 patients with all measurement values greater than the limit of quantification of 0.2%, the CVI was 21%, CVG was 37%, and RCV was 61%.
Conclusions: The reference range for dd-cfDNA in this renal transplant population identified 1.2% as a cutoff for defining out of range and potentially abnormal values. A serial increase of less than 61% in dd-cfDNA may be attributable to biological variation, whereas greater changes may be indicative of pathological influences.
CITATION INFORMATION: Bromberg J, Brennan D, Poggio E, Hiller D, Woodward R, Yee J, Sninsky J, Bloom R. Donor-Derived Cell-Free DNA Normal Range and Biological Variation Defined in a Reference Population. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Bromberg J, Brennan D, Poggio E, Hiller D, Woodward R, Yee J, Sninsky J, Bloom R. Donor-Derived Cell-Free DNA Normal Range and Biological Variation Defined in a Reference Population. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-normal-range-and-biological-variation-defined-in-a-reference-population/. Accessed May 13, 2025.« Back to 2017 American Transplant Congress