1. Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay
- Author
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Gielis, Els, Beirnaert, Charlie, Dendooven, Amélie, Meysman, Pieter, Laukens, Kris, De Schrijver, Joachim, Van Laecke, Steven, Van Biesen, Wim, Emonds, Marie-Paule, De Winter, Benedicte, Bosmans, Jean-Louis, Del-Favero, Jurgen, Abramowicz, Daniel, and Ledeganck, Kristien
- Subjects
0301 basic medicine ,HEMODIALYSIS ,CLEARANCE ,Cardiovascular Procedures ,medicine.medical_treatment ,Blood Donors ,Artificial Gene Amplification and Extension ,030230 surgery ,Polymerase Chain Reaction ,0302 clinical medicine ,Medicine and Health Sciences ,Renal Transplantation ,Medicine ,Longitudinal Studies ,Prospective Studies ,Respiratory System Procedures ,Prospective cohort study ,Kidney transplantation ,Multidisciplinary ,Cardiac Transplantation ,Multidisciplinary Sciences ,Cell-free fetal DNA ,REJECTION ,UNIVERSAL BIOMARKER ,Science & Technology - Other Topics ,Hemodialysis ,Anatomy ,Engineering sciences. Technology ,Cell-Free Nucleic Acids ,Research Article ,medicine.medical_specialty ,Heart-Lung Transplantation ,Science ,Kinetics ,Immunology ,Urology ,CIRCULATION ,Single-nucleotide polymorphism ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Polymorphism, Single Nucleotide ,Urinary System Procedures ,03 medical and health sciences ,Digestive System Procedures ,Transplantation Immunology ,Multiplex polymerase chain reaction ,Genetics ,Humans ,Molecular Biology Techniques ,Biology ,Molecular Biology ,Alleles ,Computer. Automation ,Transplantation ,Science & Technology ,business.industry ,Transplant Rejection ,Biology and Life Sciences ,Kidneys ,Organ Transplantation ,Renal System ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Liver Transplantation ,030104 developmental biology ,Genetic Loci ,Clinical Immunology ,Human medicine ,Clinical Medicine ,business ,Multiplex Polymerase Chain Reaction - 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. ispartof: PLOS ONE vol:13 issue:12 ispartof: location:United States status: published
- Published
- 2018