Kidney Week

Abstract: FR-PO884

The Role of Plasma Donor-Derived Cell-Free DNA in Minimal Invasive Graft Monitoring

Session Information

• Transplantation: Translational and Transplant Pathology
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Gielis, Els M., University of Antwerp, Antwerp, Belgium

Els M. Gielis,

• Ledeganck, Kristien J., University of Antwerp, Antwerp, Belgium

Kristien J. Ledeganck,

• Dendooven, Amélie, University Hospital of Antwerp (UZA), Edegem, Belgium

Amélie Dendooven,

• Meysman, Pieter, University of Antwerp, Antwerp, Belgium

Pieter Meysman,

• Beirnaert, Charlie, University of Antwerp, Antwerp, Belgium

Charlie Beirnaert,

• Laukens, Kris, University of Antwerp, Antwerp, Belgium

Kris Laukens,

• De schrijver, Joachim, Agilent Technologies, Niel, Belgium

Joachim De schrijver,

• Van Laecke, Steven, Ghent University Hospital, Ghent, Belgium

Steven Van Laecke,

• Emonds, Marie-Paule, Belgian Red Cross Flanders, Mechelen, Belgium

Marie-Paule Emonds,

• De winter, Benedicte, University of Antwerp, Antwerp, Belgium

Benedicte De winter,

• Bosmans, Jean-Louis, Antwerp University Hospital, Edegem, Belgium

Jean-Louis Bosmans,

• Del favero, Jurgen, Agilent Technologies, Niel, Belgium

Jurgen Del favero,

• Abramowicz, Daniel, Antwerp University Hospital, Edegem, Belgium

Daniel Abramowicz,

Background

After transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to investigate plasma ddcfDNA kinetics in renal transplant recipients thereby evaluating the role of this biomarker in graft monitoring.

Methods

From 107 renal transplant recipients, plasma samples were collected longitudinally from day 1 until 3 months after transplantation within a multicenter set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of total cell-free DNA by next generation sequencing using a targeted, multiplex PCR based method for the analysis of single nucleotide polymorphisms.

Results

Slope normalization analysis was performed in 42 patients that met predefined criteria for stable graft recipients. After an exponential decrease in ddcfDNA, a mean stable baseline level of 0.455% + 0.427 (2 SD) was reached on average 9.85 (± 5.6 days) after transplantation. In the entire cohort, patients that were not stabilized by day 10 (n = 37) had higher individual baseline ddcfDNA values (p = 0.007) and higher ddcfDNA fractions on day 1 (p = 0.0002). Sixteen recipients exhibited abnormal non-exponential ddcfDNA kinetics in the early post-engraftment phase; and this was associated with the occurrence of an early adverse event including a urinary tract infection, a surgical adverse event or episode of hydronephrosis that required treatment, a BKV or CMV infection episode or prerenal acute kidney injury (p=0.0012).
From day 10 onwards, increases of ddcfDNA% above the baseline value of 0.882% (mean+2 SD) were significantly associated with the occurrence of episodes of acute rejection (p = 0.017), acute tubular necrosis (p = 0.011) and pyelonephritis (p = 0.032).

Conclusion

Within 10 days after transplantation, plasma ddcfDNA fractions decrease to a stable baseline level. From day 10 onwards, increases of ddcfDNA% are associated with graft injury related to acute rejection, acute tubular necrosis or pyelonephritis.

Funding

• Government Support - Non-U.S.