Use of graft-derived cell-free DNA as a novel biomarker to predict allograft function after kidney transplantation

Int J Urol. 2021 Oct;28(10):1019-1025. doi: 10.1111/iju.14638. Epub 2021 Jul 6.

Abstract

Objective: To investigate the association between graft-derived cell-free DNA and pretransplantation clinical variables, and to determine whether the former could be used as a novel biomarker to predict renal function.

Methods: A total of 87 recipients who underwent primary kidney transplantation were recruited to the study. For each recipient, 10 mL peripheral blood was collected on days 1, 7, 14-20, and 30-45 after transplantation. The fractional abundance of graft-derived cell-free DNA was determined using droplet digital polymerase chain reaction.

Results: For most recipients, graft-derived cell-free DNA fraction values were significantly elevated on the first day after transplantation, followed by a rapid decline, and reaching baseline values of graft-derived cell-free DNA fraction in the range of <1% at 7 days. Statistical analysis showed that longer cold ischemia time was significantly associated with higher graft-derived cell-free DNA fraction values (P = 0.02). Moreover, we also found that graft-derived cell-free DNA fraction values among recipients with delayed graft function were significantly higher than those of recipients without delayed graft function on the first day after transplantation. Kaplan-Meier analysis showed that recipients who had a graft-derived cell-free DNA fraction value of <1% at 7 days had a significantly lower probability of an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 at 90 days. Using a random forest regression model, the predicted values of estimated glomerular filtration rate at 90 days were almost the same as the actual values.

Conclusions: Our findings suggest that graft-derived cell-free DNA might be used as a novel biomarker to predict delayed graft function and renal function.

Keywords: cold ischemia time; delayed graft function; estimated glomerular filtration rate; graft-derived cell-free DNA; kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Biomarkers
  • Cell-Free Nucleic Acids*
  • Glomerular Filtration Rate
  • Graft Rejection / diagnosis
  • Graft Survival
  • Humans
  • Kidney
  • Kidney Transplantation* / adverse effects
  • Transplantation, Homologous

Substances

  • Biomarkers
  • Cell-Free Nucleic Acids