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Title: Diagnostic application of kidney allograft-derived absolute cell-free DNA levels during transplant dysfunction.
Austin Authors: Whitlam, John B ;Ling, Ling;Skene, Alison ;Kanellis, John;Ierino, Francseco L;Slater, Howard R;Bruno, Damien L;Power, David A 
Affiliation: Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Department of Nephrology, St Vincent's Health, Melbourne, Victoria, Australia
Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia
Cyto-molecular Diagnostics Research, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Anatomical Pathology
Department of Nephrology, Monash Health and Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Victoria, Australia
Issue Date: Apr-2019
Date: 2018-10-12
Publication information: American Journal of Transplantation 2019
Abstract: Graft-derived cell-free DNA (donor-derived cell-free DNA) is an emerging marker of kidney allograft injury. Studies examining the clinical validity of this biomarker have previously used the graft fraction, or proportion of total cell-free DNA that is graft-derived. The present study evaluated the diagnostic validity of absolute measurements of graft-derived cell-free DNA, as well as calculated graft fraction, for the diagnosis of graft dysfunction. Plasma graft-derived cell-free DNA, total cell-free DNA and graft fraction were correlated with biopsy diagnosis as well as individual Banff scores. 61 samples were included in the analysis. For the diagnosis of antibody mediated rejection, the receiver-operator characteristic area under the curves of graft-derived cell-free DNA and graft fraction were 0.91 (95% CI 0.82-0.98) and 0.89 (95% CI 0.79-0.98), respectively. Both measures did not diagnose borderline or type 1A cellular mediated rejection. Graft fraction was associated with a broader range of Banff lesions, including lesions associated with cellular mediated rejection, while graft-derived cell-free DNA appeared more specific for antibody mediated rejection. Limitations of this study include a small sample size and lack of a validation cohort. The capacity for absolute quantification, and lower barriers to implementation of this methodology recommend it for further study. This article is protected by copyright. All rights reserved.
DOI: 10.1111/ajt.15142
Journal: American Journal of Transplantation
PubMed URL: 30312536
Type: Journal Article
Subjects: transplant dysfunction
Appears in Collections:Journal articles

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