Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris
About this trial
Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential diagnostic tool to monitor the rejection status of the kidney transplant. It has been suggested that dd-cfDNA is increasing in the blood of kidney transplant patient presenting a graft rejection. In this project, investigators proposed a different approach to predict and characterize kidney transplant rejection/dysfunction based on the quantification of epigenetic signatures present on the donor-cell-free DNA. In 2018, Moss et al. develops a deconvolution model capable of identifying the tissue origin of circulating DNA by taking advantage of its epigenetic properties. The study confirmed that the cell-free DNA circulating in healthy subjects comes mainly from blood cells and endothelial cells, but not from kidney cells.
In this study, researchers investigate the evolution of blood renal-specific cell-free DNA amount in patient with chronic kidney disease before and after the transplantation surgery by testing a set of renal-specific epigenetic markers. The purpose of this study is to identify the biological noise of "native kidney" on renal-specific cell-free DNA and to compare it with signal coming from "transplanted kidney".
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years old
With end-stage renal failure
Summoned for a kidney transplant at Pitié Salpêtrière Hospital
Having been informed of the study and not objecting to the study having given free and informed written consent for the genetic analysis
Disqualifiers
None
Trial population
Adult subjects with end-stage renal disease about to receive a kidney transplant from a deceased donor.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
determination of circulating biomarkers of renal origin circulating biomarkers of renal origin
GeneticThe extracted circulating DNA will be extracted and converted using the methylation kit. Finally, circulating DNA will be analyzed using the PCR mix developed by CGenetix, quantifying tubular and glomerular biomarkers (patented technology).
Treatment groups
No treatment groups listed
Trial outcomes
Primary outcomes
1
Amount of renal circulating cell-free DNA
The amount of renal-cell-free DNA (glomerular and tubular markers) will be measured 6 hours before the kidney transplant is performed and 12-24 hours after the kidney transplant by digital multiplex PCR
Time frame
6 hours before kidney transplantation and 12 to 24 after transplantation surgerySecondary outcomes
1
Estimating the inter-individual variations of the free circulating methylome of renal origin in patients with end-stage chronic insufficiency
The amount of renal-cell-free DNA (glomerular and tubular markers) measured will be compared between individuals.
Time frame
6 hours before kidney transplantation and 12 to 24 after transplantation surgery2
Identify by a method without a priori (methyl seq) specific markers of acute renal injury in terms of epigenetic signature
Comparison of two biomarkers quantification methods (whole genome methyl-Sequencing and multiplex digital-PCR)
Time frame
6 hours before kidney transplantation and 12 to 24 after transplantation surgery3
Study the statistical association between the presence of free circulating methylated sequences of renal origin and the resumption of graft function
Comparison of circulating free methylome of renal origin between the groups of patients with immediate recovery of function and delayed recovery of function (defined on the performance of a dialysis session in the first 7 days and on the reduction ratio serum creatinine between the 1st and 2nd day after the transplant).
Time frame
7 day after the transplantSponsors and contacts
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Source ClinicalTrials.gov