Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications
Year: 2017
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Previous studies have demonstrated that donor-derived cell-free DNA (dd-cfDNA) found in circulating blood of transplant recipients may serve as a noninvasive biomarker of allograft rejection. To better interpret the clinical meaning of dd-cfDNA, it is essential to understand the biological variation of this biomarker in stable healthy recipients. This report establishes the biological variation and clinical reference intervals of dd-cfDNA in renal transplant recipients by using an analytically validated assay that has a CV of 6.8%. METHODS: We sampled venous blood at patient surveillance visits (typically at posttransplant months 1-4, 6, 9, and 12) in a 14-center observational study. Patients with stable renal allograft function spanning ≥3 serial visits were selected. We used AlloSure®, a targeted next-generation sequencing-based approach, to measure dd-cfDNA in the plasma and computed the intraindividual CV (CVI) and interindividual CV (CVG), the index of individuality (II), and reference change value (RCV). RESULTS: Of 93 patients, 61% were men, 56% were Caucasian, mean age was 49 years, and 63% were deceased donor kidney recipients. Of 380 blood samples, the dd-cfDNA median value was 0.21% (interquartile range 0.12%-0.39%) and the 97.5th percentile was 1.20%. In 18 patients with an average of 4.1 tests, the CVI was 21%, CVG was 37%, II was 0.57, and RCV was 61%. CONCLUSIONS: In a renal transplant recipient, a dd-cfDNA level above 1.2% is out of range and potentially abnormal. A serial increase of up to 61% in level of dd-cfDNA in a patient may be attributable to biological variation.Clinicaltrials.gov Identifier: NCT02424227.
Authors: Jonathan S Bromberg, Daniel C Brennan, Emilio Poggio, Suphamai Bunnapradist, Anthony Langone, Puneet Sood, Arthur J Matas, Roslyn B Mannon, Shikha Mehta, Asif Sharfuddin, Bernard Fischbach, Mohanram Narayanan, Stanley C Jordan, David J Cohen, Ziad S Zaky, David Hiller, Robert N Woodward, Marica Grskovic, John J Sninsky, James P Yee, Roy D Bloom
Institutions: University of Maryland, Baltimore, Washington University in St. Louis, Cleveland Clinic, University of California, Los Angeles, VA Tennessee Valley Healthcare System, Nashville VA Medical Center, Vanderbilt University Medical Center, University of Pittsburgh Medical Center, University of Minnesota, University of Alabama, University of Alabama at Birmingham, UAB Medicine, Indiana University Indianapolis, Indiana University School of Medicine, Texas A&M Health Science Center, Cedars-Sinai Medical Center, Columbia University Irving Medical Center, CareDx, Inc. (United States), University of Pennsylvania
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2596790126