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Title: | Diagnostic application of kidney allograft-derived absolute cell-free DNA levels during transplant dysfunction. | Authors: | Bruno D.L.;Slater H.R.;Whitlam J.B.;Ling L.;Skene A.;Kanellis J.;Ierino F.L.;Power D.A. | Institution: | (Whitlam, Power) Department of Nephrology, Austin Health, Melbourne, VIC, Australia (Whitlam, Ling, Slater) Cyto-molecular Diagnostics Research Melbourne, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia (Whitlam, Ierino, Power) Department of Medicine, University of Melbourne, Melbourne, VIC, Australia (Skene) Department of Anatomical Pathology, Austin Health, Melbourne, VIC, Australia (Kanellis) Department of Nephrology, Department of Medicine, Monash Health and Centre for Inflammatory Diseases, Monash University, Melbourne, VIC, Australia (Ierino) Department of Nephrology, St Vincent's Health, Melbourne, VIC, Australia (Slater) Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia (Bruno) Victorian Clinical Genetics Services Melbourne, Murdoch Children's Research Institute, Melbourne, VIC, Australia | Issue Date: | 2-Apr-2019 | Copyright year: | 2019 | Publisher: | Blackwell Publishing Ltd | Place of publication: | United Kingdom | Publication information: | American Journal of Transplantation. 19 (4) (pp 1037-1049), 2019. Date of Publication: April 2019. | Journal: | American Journal of Transplantation | 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. Sixty-one 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.Copyright © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1111/ajt.15142 | PubMed URL: | 30312536 [http://www.ncbi.nlm.nih.gov/pubmed/?term=30312536] | ISSN: | 1600-6135 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/35734 | Type: | Article | Subjects: | *renal graft dysfunction/dt [Drug Therapy] cyclosporine/dt [Drug Therapy] *DNA/ec [Endogenous Compound] mammalian target of rapamycin/dt [Drug Therapy] mycophenolic acid/dt [Drug Therapy] OKT 3/dt [Drug Therapy] prednisolone/dt [Drug Therapy] tacrolimus/dt [Drug Therapy] adult antibody mediated rejection antibody specificity article blood sampling cohort analysis comparative study controlled study creatinine blood level cross-sectional study diagnostic test accuracy study droplet digital polymerase chain reaction female genotype histopathology human human tissue immunosuppressive treatment *kidney allograft major clinical study priority journal prospective study proteinuria *renal graft dysfunction/di [Diagnosis] male *renal graft dysfunction/pc [Prevention] sensitivity and specificity azathioprine/dt [Drug Therapy] basiliximab/dt [Drug Therapy] creatinine/ec [Endogenous Compound] cohort analysis blood sampling Article antibody specificity antibody mediated rejection adult diagnostic test accuracy study droplet digital polymerase chain reaction *renal graft dysfunction / *diagnosis / *drug therapy / *prevention sensitivity and specificity cross-sectional study creatinine blood level controlled study comparative study female genotype histopathology human human tissue immunosuppressive treatment *kidney allograft major clinical study male priority journal prospective study proteinuria |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
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