High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury

Erik Stites, Dhiren Kumar, Oyedolamu Olaitan, Sidney John Swanson, Nicolae Leca, Matthew Weir, Jonathan Bromberg, Joseph Melancon, Irfan Agha, Hasan Fattah, Tarek Alhamad, Yasir Qazi, Alexander Wiseman, Gaurav Gupta

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The clinical importance of subclinical, early T cell–mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA. Forty-two patients had elevated dd-cfDNA (≥0.5%) and 37 patients had low levels (<0.5%). Elevated levels of dd-cfDNA predicted adverse clinical outcomes: among patients with elevated cfDNA, estimated glomerular filtration rate declined by 8.5% (interquartile rate [IQR] −16.22% to −1.39%) (−3.50 mL/min/1.73 m2 IQR −8.00 to −1.00) vs 0% (−4.92%, 4.76%) in low dd-cfDNA patients (P =.004), de novo donor-specific antibody formation was seen in 40% (17/42) vs 2.7% (P <.0001), and future or persistent rejection occurred in 9 of 42 patients (21.4%) vs 0% (P =.003). The use of dd-cfDNA may complement the Banff classification and to risk stratify patients with borderline/TCMR 1A identified on biopsy.

Original languageEnglish
Pages (from-to)2491-2498
Number of pages8
JournalAmerican Journal of Transplantation
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • biomarker
  • cellular transplantation (non-islet)
  • clinical research/practice
  • kidney (allograft) function/dysfunction
  • kidney failure/injury
  • monitoring: immune
  • rejection: T cell mediated (TCMR)

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