The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation

Nephrol Dial Transplant. 2020 Apr 1;35(4):714-721. doi: 10.1093/ndt/gfz091.


Background: After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient's circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection.

Methods: From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms.

Results: Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P = 0.017), acute tubular necrosis (P = 0.011) and acute pyelonephritis (P = 0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection.

Conclusions: Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.

Keywords: acute kidney rejection; biomarker; donor-derived cell-free DNA; kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood*
  • Cell-Free Nucleic Acids / blood*
  • Cell-Free Nucleic Acids / genetics
  • Female
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Graft Rejection / etiology
  • Graft Survival
  • Humans
  • Kidney Diseases / blood*
  • Kidney Diseases / genetics
  • Kidney Diseases / surgery
  • Kidney Transplantation / adverse effects*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Postoperative Complications / blood
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / etiology
  • Prognosis
  • ROC Curve
  • Survival Rate
  • Tissue Donors / supply & distribution*
  • Young Adult


  • Biomarkers
  • Cell-Free Nucleic Acids