Plasma Donor-derived Cell-free DNA Kinetics After Kidney Transplantation Using a Single Tube Multiplex PCR Assay

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Dec 7

PMID 30521549

Citations 32

Authors

Els M Gielis

Charlie Beirnaert

Amelie Dendooven

Pieter Meysman

Kris Laukens

Joachim De Schrijver

Steven van Laecke

Wim Van Biesen

Marie-Paule Emonds

Benedicte Y De Winter

Jean-Louis Bosmans

Jurgen Del Favero

Daniel Abramowicz

Kristien J Ledeganck

Affiliations

Soon will be listed here.

Abstract

Background: After transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient's circulation. We aimed to quantify ddcfDNA levels in plasma of kidney transplant recipients thereby investigating the kinetics of this biomarker after transplantation and determining biological variables that influence ddcfDNA kinetics in stable and non-stable patients.

Materials And Methods: From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (day 1-3 months) within a multicenter 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 PCR-based method for the analysis of single nucleotide polymorphisms. A subgroup of stable renal transplant recipients was identified to determine a ddcfDNA threshold value.

Results: In stable transplant recipients, plasma ddcfDNA% decreased to a mean (SD) ddcfDNA% of 0.46% (± 0.21%) which was reached 9.85 (± 5.6) days after transplantation. A ddcfDNA threshold value of 0.88% (mean + 2SD) was determined in kidney transplant recipients. Recipients that did not reach this threshold ddcfDNA value within 10 days after transplantation showed a higher ddcfDNA% on the first day after transplantation and demonstrated a higher individual baseline ddcfDNA%.

Conclusion: In conclusion, plasma ddcfDNA fractions decreased exponentially within 10 days after transplantation to a ddcfDNA threshold value of 0.88% or less. To investigate the role of ddcfDNA for rejection monitoring of the graft, future research is needed to determine causes of ddcfDNA% increases above this threshold value.

Citing Articles

Integrating Donor Derived Cell-Free DNA Fraction and Absolute Quantification for Enhanced Rejection Diagnosis in Kidney Transplant Recipients.

Nie W, Wang Y, Fu Q, Wu C, Deng R, Yu X Diagnostics (Basel). 2025; 15(3).

PMID: 39941167 PMC: 11817499. DOI: 10.3390/diagnostics15030237.

Clinical use of donor-derived cell-free DNA in kidney transplantation.

Jaikaransingh V, Makadia B, Khan H, Hasan I World J Transplant. 2024; 14(4):97219.

PMID: 39697447 PMC: 11438940. DOI: 10.5500/wjt.v14.i4.97219.

A review of cell-free DNA and epigenetics for non-invasive diagnosis in solid organ transplantation.

Sebastian A, Silvy M, Coiffard B, Reynaud-Gaubert M, Magdinier F, Chiaroni J Front Transplant. 2024; 3:1474920.

PMID: 39619700 PMC: 11605403. DOI: 10.3389/frtra.2024.1474920.

Graft-derived cell free DNA: used for assessment of early graft status and its implications for long-term kidney function.

Wei L, Zhao Y, Deng S, Wu S, Wang H, Luo X Front Physiol. 2024; 15:1440799.

PMID: 39619094 PMC: 11604621. DOI: 10.3389/fphys.2024.1440799.

Application of graft-derived cell-free DNA for solid organ transplantation.

Zhang W, Liu B, Jia D, Wang R, Cao H, Wu H Front Immunol. 2024; 15:1461480.

PMID: 39376561 PMC: 11456428. DOI: 10.3389/fimmu.2024.1461480.

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