Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD)

Michael Keller, Errol Bush, Joshua M. Diamond, Pali Shah, Joby Matthew, Anne W. Brown, Junfeng Sun, Irina Timofte, Hyesik Kong, Ilker Tunc, Helen Luikart, Aldo Iacono, Steven D. Nathan, Kiran K. Khush, Jonathan Orens, Moon Jang, Sean Agbor-Enoh

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

BACKGROUND: Primary graft dysfunction (PGD) is a risk factor for chronic lung allograft dysfunction (CLAD). However, the association between PGD and degree of allograft injury remains poorly defined. In this study, we leverage a novel biomarker for allograft injury, percentage donor-derived cell-free DNA (%ddcfDNA), to study the association between PGD, degree of allograft injury, and the development of CLAD. METHODS: This prospective cohort study recruited 99 lung transplant recipients and collected plasma samples on days 1, 3, and 7 for %ddcfDNA measurements. Clinical data on day 3 was used to adjudicate for PGD. %ddcfDNA levels were compared between PGD grades. In PGD patients, %ddcfDNA was compared between those who developed CLAD and those who did not. RESULTS: On posttransplant day 3, %ddcfDNA was higher in PGD than in non-PGD patients (median [IQR]: 12.2% [8.2, 22.0] vs 8.5% [5.6, 13.2] p = 0.01). %ddcfDNA correlated with the severity grade of PGD (r = 0.24, p = 0.02). Within the PGD group, higher levels of %ddcfDNA correlated with increased risk of developing CLAD (log OR(SE) 1.38 (0.53), p = 0.009). PGD patients who developed CLAD showed ∼2-times higher %ddcfDNA levels than patients who did not develop CLAD (median [IQR]: 22.4% [11.8, 27.6] vs 9.9% [6.7, 14.9], p = 0.007). CONCLUSION: PGD patients demonstrated increased early posttransplant allograft injury, as measured by %ddcfDNA, in comparison to non-PGD patients, and these high %ddcfDNA levels were associated with subsequent development of CLAD. This study suggests that %ddcfDNA identifies PGD patients at greater risk of CLAD than PGD alone.

Original languageEnglish (US)
Pages (from-to)488-493
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume40
Issue number6
DOIs
StatePublished - Jun 2021
Externally publishedYes

Keywords

  • Chronic lung allograft dysfunction (CLAD)
  • Donorderived cell-free DNA (ddcfDNA)
  • Primary graft dysfunction (PGD)
  • Rejection

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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