Diagnostic application of kidney allograft-derived absolute cell-free DNA levels during transplant dysfunction

John B. Whitlam, Ling Ling, Alison Skene, John Kanellis, Francseco L. Ierino, Howard R. Slater, Damien L. Bruno, David A. Power

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1037-1049
Number of pages13
JournalAmerican Journal of Transplantation
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2019

Keywords

  • biomarker
  • clinical research/practice
  • diagnostic techniques and imaging
  • genetics
  • kidney (allograft) function/dysfunction
  • kidney transplantation/nephrology
  • organ transplantation in general
  • rejection
  • rejection: antibody-mediated (ABMR)
  • translational research/science

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