{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:31:22Z","timestamp":1791851482078,"version":"4.3.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We sampled venous blood at patient surveillance visits (typically at posttransplant months 1\u20134, 6, 9, and 12) in a 14-center observational study. Patients with stable renal allograft function spanning \u22653 serial visits were selected. We used AlloSure\u00ae, 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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%\u20130.39%) 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%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>Clinicaltrials.gov Identifier: NCT02424227<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1373\/jalm.2016.022731","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T18:26:32Z","timestamp":1532370392000},"page":"309-321","source":"Crossref","is-referenced-by-count":88,"title":["Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications"],"prefix":"10.1093","volume":"2","author":[{"given":"Jonathan S","family":"Bromberg","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Transplantation, University of Maryland, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C","family":"Brennan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Poggio","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suphamai","family":"Bunnapradist","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Langone","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, and Medical Specialties Clinic, Veteran Affairs Hospital Renal Transplant Program, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneet","family":"Sood","sequence":"additional","affiliation":[{"name":"Thomas Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J","family":"Matas","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roslyn B","family":"Mannon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, and Division of Transplantation, University of Alabama School of Medicine, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikha","family":"Mehta","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, and Division of Transplantation, University of Alabama School of Medicine, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Sharfuddin","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplant, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Fischbach","sequence":"additional","affiliation":[{"name":"Baylor Research Institute, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohanram","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Texas A&M Health Science Center College of Medicine, Temple, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley C","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA"},{"name":"Division of Nephrology, Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Columbia University Medical Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad S","family":"Zaky","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hiller","sequence":"additional","affiliation":[{"name":"Biostatistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N","family":"Woodward","sequence":"additional","affiliation":[{"name":"Research and Development, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marica","family":"Grskovic","sequence":"additional","affiliation":[{"name":"Research and Development, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Sninsky","sequence":"additional","affiliation":[{"name":"Research and Development, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P","family":"Yee","sequence":"additional","affiliation":[{"name":"Clinical Research, CareDx, Inc., Brisbane, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy D","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Perelman School of Medicine and Penn Kidney Pancreas Transplant Program, Pennsylvania, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"2022020109102454200_B1","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1111\/ajt.13387","article-title":"Cell-free DNA: an upcoming biomarker in transplantation","volume":"15","author":"Gielis","year":"2015","journal-title":"Am J 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