Extended Validation of Donor-derived Cell-free DNA in Kidney Transplant Recipients (VALiDATE)

September 3, 2026 updated by: Paris Translational Research Center for Organ Transplantation

Multinational Study to Evaluate the Performance of Donor-derived Cell-free DNA in Detecting Kidney Allograft Rejection Across Context of Use, Populations, and Injury Phenotypes

This is a multinational, multi-center, observational cohort study.

Kidney allograft rejection is poorly detected by standard-of-care biomarkers. Although dd-cfDNA has been associated with improved rejection detection when added to standard-of-care biomarkers and clinical parameters, little is known about its performance across Banff 2022 rejection phenotypes and injury patterns, in various clinical scenarios and populations, and when measured repeatedly over time.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Allograft rejection remains a leading cause of kidney transplant failure, and standard-of-care monitoring detects it late.

Recently, combining dd-cfDNA with functional, immunological and clinical parameters has been shown to improve rejection detection under the Banff 2019 framework. However, the Banff 2022 revision formally recognized microvascular inflammation without DSA or C4d (MVI, DSA-negative, C4d-negative) and probable antibody-mediated rejection as distinct rejection phenotypes, raising the question of whether dd-cfDNA can help detecting these phenotypes. Its performance also remains unclear across the broader spectrum of Banff rejection phenotypes and injury patterns, when the complete diagnostic workup is unavailable, in the early post-transplant period, in specific populations, and when measured repeatedly over time.

The investigators therefore aim to evaluate the association between dd-cfDNA and Banff rejection phenotypes and its added diagnostic value to detect them, across the clinical situations in which the biomarker is used.

The study has three objectives:

  • To assess the association between dd-cfDNA and Banff 2022 rejection phenotypes and injury patterns, including antibody-mediated, T cell-mediated and mixed rejection, borderline changes, probable antibody-mediated rejection and MVI, DSA-negative, C4d-negative, together with its relationship to the severity of the underlying lesions, with particular attention to microvascular inflammation.
  • To assess the diagnostic value of dd-cfDNA, alone and within the integrative dd-cfDNA model, for the detection of biopsy-proven rejection as defined by the Banff 2022 classification, and beyond standard-of-care monitoring.
  • To assess whether this performance is maintained across clinical scenarios and populations, including incomplete diagnostic workup, the first month post-transplant, delayed graft function, and specific subpopulations.

Secondarily, the investigators aim to assess whether serial dd-cfDNA improves the detection of rejection, and its prognostic value for death-censored allograft failure.

Study Type

Observational

Enrollment (Estimated)

5000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
        • Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
  • Brazil
      • São Paulo, Brazil
        • Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil
  • France
      • Paris, France
        • Hôpital Necker
      • Paris, France, 75015
        • Department of Nephrology and Dialysis, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
      • Paris, France
        • 11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
      • Paris, France
        • Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;
      • Toulouse, France
        • Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France
  • Germany
      • Berlin, Germany
        • Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin
  • South Korea
      • Seoul, South Korea
        • Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
  • Spain
      • Barcelona, Spain
        • Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Switzerland
      • Geneva, Switzerland, 1205
        • Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
      • Los Angeles, California, United States, 90048
        • Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
      • Los Angeles, California, United States, 90095
        • Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    • Florida
      • Tampa, Florida, United States, 33606
        • Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Division of Pediatric Nephrology, Emory University School of Medicine, Atlanta, GA, USA
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
      • St Louis, Missouri, United States, 63110
        • Division of Pediatric Nephrology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA
    • New York
      • New York, New York, United States, 10065
        • Division of Nephrology, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, NY, USA
    • Ohio
      • Cleveland, Ohio, United States, 44195-0001
        • Cleveland Clinic, 2050 East 96th Street, Cleveland, OH
    • Texas
      • Dallas, Texas, United States, 75390-8856
        • Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    • Utah
      • Murray, Utah, United States, 84107
        • Transplant Services, Intermountain Medical Center, Murray, UT, USA
      • Salt Lake City, Utah, United States, 84132
        • Division of Nephrology, Department of Medicine, University of Utah Health, Salt Lake City, UT, USA
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Kidney transplant recipients of all age and sexes with at least one kidney biopsy performed concurrently with dd-cfDNA measurement.

Description

Inclusion Criteria:

  • Recipients transplanted from a deceased or living donor
  • Kidney allograft biopsy concomitantly with dd-cfDNA measurement
  • Written informed consent at the time of transplantation for inclusion the center database

Exclusion Criteria:

  • Combined organ transplantation
  • Pregnant women
  • Grafts from monozygotic twins
  • Recipient of a bone marrow transplant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
French Cohort
Necker and Saint Louis Hospitals Kidney Transplant Recipients Cohorts
Diagnostic test: Donor-derived cell-free DNA
Cell-free DNA (cfDNA) is fragmented extracellular DNA released in the bloodstream from cells undergoing apoptosis or necrosis. In transplantation, donor-derived cfDNA (dd-cfDNA) is detected in the blood of kidney recipients and has been proposed as a noninvasive biomarker to detect rejection.
External Validation Cohort
Multinational cohort comprising transplant centers across Europe, North America, South America and Asia (see involved transplant centres in contacts and locations).
Diagnostic test: Donor-derived cell-free DNA
Cell-free DNA (cfDNA) is fragmented extracellular DNA released in the bloodstream from cells undergoing apoptosis or necrosis. In transplantation, donor-derived cfDNA (dd-cfDNA) is detected in the blood of kidney recipients and has been proposed as a noninvasive biomarker to detect rejection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Allograft active injury
Time Frame: Periprocedural (At time of biopsy)
Antibody-mediated rejection (active or chronic active) T cell-mediated rejection (active or chronic active) Mixed rejection Microvascular Inflammation, DSA-negative, C4d-negative Probable AMR
Periprocedural (At time of biopsy)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Allograft loss
Time Frame: Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
Return to dialysis or re-transplantation
Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Paris Translational Research Center for Organ Transplantation

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
Fondation pour la Recherche Médicale
Paris Cardiovascular Research Center (Inserm U970)
Université Paris Cité

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

August 24, 2026

First Submitted That Met QC Criteria

September 3, 2026

First Posted (Actual)

September 4, 2026

Study Record Updates

Last Update Posted (Actual)

September 4, 2026

Last Update Submitted That Met QC Criteria

September 3, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • VALIDATE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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