Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications. (1st November 2017)

• Record Type: Journal Article
• Authors: Bromberg, Jonathan S; Brennan, Daniel C; Poggio, Emilio; Bunnapradist, Suphamai; Langone, Anthony; Sood, Puneet; Matas, Arthur J; Mannon, Roslyn B; Mehta, Shikha; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C; Cohen, David J; Zaky, Ziad S; Hiller, David; Woodward, Robert N; Grskovic, Marica; Sninsky, John J; Yee, James P; Bloom, Roy D
• Is Part Of: Journal of applied laboratory medicine. Volume 2:Number 3(2017)
• Page Start: 309
• Page End: 321
• Publication Date: 2017-11-01
• Subjects: Clinical chemistry -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.0756
• DOI: 10.1373/jalm.2016.022731
• Languages: English
• ISSNs: 2576-9456

Abstract

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