Rejection Acute RenalVALiDATENCT07805343
Extended Validation of Donor-derived Cell-free DNA in Kidney Transplant Recipients
An observational study of Rejection Acute Renal and Rejection Chronic Renal, run by Paris Translational Research Center for Organ Transplantation at 25 sites in 8 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Rejection Acute Renal, Rejection Chronic Renal, Transplantation
- What is being tested?
- Donor-derived cell-free DNA
- How many people
- 5,000 participants
- Where
- 25 sitesin 8 countries
- Study dates
- 15 Jun 2024to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Kidney transplant recipients of all age and sexes with at least one kidney biopsy performed concurrently with dd-cfDNA measurement.
Who may be able to join
- 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
Who cannot join
- Combined organ transplantation
- Pregnant women
- Grafts from monozygotic twins
- Recipient of a bone marrow transplant
Trial locations and contacts
25 sites in 8 countries.
25 sites in 8 countries
United States14 sites
Division of Pediatric Nephrology, Emory University School of Medicine, Atlanta, GA, USA
Atlanta, Georgia, 30322
Cleveland Clinic, 2050 East 96th Street, Cleveland, OH
Cleveland, Ohio, 44195-0001
Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Dallas, Texas, 75390-8856
Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Los Angeles, California, 90048
Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Los Angeles, California, 90048
Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Los Angeles, California, 90095
Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Madison, Wisconsin, 53705
Transplant Services, Intermountain Medical Center, Murray, UT, USA
Murray, Utah, 84107
Division of Nephrology, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, NY, USA
New York, New York, 10065
Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
Richmond, Virginia, 23219
Division of Nephrology, Department of Medicine, University of Utah Health, Salt Lake City, UT, USA
Salt Lake City, Utah, 84132
Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
St Louis, Missouri, 63110
Division of Pediatric Nephrology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA
St Louis, Missouri, 63110
Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
Tampa, Florida, 33606
France5 sites
Department of Nephrology and Dialysis, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
Paris, 75015
11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Paris
Hôpital Necker
Paris
Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;
Paris
Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France
Toulouse
Belgium1 site
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
Leuven
Brazil1 site
Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil
São Paulo
Germany1 site
Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin
Berlin
South Korea1 site
Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
Seoul
Spain1 site
Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
Barcelona
Switzerland1 site
Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland
Geneva, 1205
About this study
Official title: 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.
Read the 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.
- Conditions
- Rejection Acute Renal, Rejection Chronic Renal, Transplantation, Kidney Rejection Transplant
- Being tested
- Donor-derived cell-free DNA
- Keywords
- donor-derived cell-free DNA, organ rejection, kidney rejection transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor-derived cell-free DNADiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| French Cohort | Necker and Saint Louis Hospitals Kidney Transplant Recipients Cohorts Receives: Diagnostic Test: Donor-derived cell-free DNA | |
| External Validation Cohort | Multinational cohort comprising transplant centers across Europe, North America, South America and Asia (see involved transplant centres in contacts and locations). Receives: Diagnostic Test: Donor-derived cell-free DNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Allograft active injury
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
Measured: Periprocedural (At time of biopsy)
Secondary outcomes (1)
Allograft loss
Return to dialysis or re-transplantation
Measured: Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2026
- Study start15 Jun 2024
- Primary completion1 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rejection Acute RenalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Paris Translational Research Center for Organ Transplantation
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation pour la Recherche Médicale, Université Paris Cité, Paris Cardiovascular Research Center (Inserm U970), Institut National de la Santé Et de la Recherche Médicale, France
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07805343
- Sponsor's protocol ID
- VALIDATE
- Acronym
- VALiDATE
- Status last verified
- Sep 2026
- First submitted
- 24 Aug 2026
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Aubert O, Ursule-Dufait C, Brousse R, Gueguen J, Racape M, Raynaud M, Van Loon E, Pagliazzi A, Huang E, Jordan SC, Chavin KD, Gupta G, Kumar D, Alhamad T, Anand S, Sanchez-Garcia J, Abdalla BA, Hogan J, Garro R, Dadhania DM, Jain P, Mandelbrot DA, Naesens M, Dandamudi R, Dharnidharka VR, Anglicheau D, Lefaucheur C, Loupy A. Cell-free DNA for the detection of kidney allograft rejection. Nat Med. 2024 Aug;30(8):2320-2327. doi: 10.1038/s41591-024-03087-3. Epub 2024 Jun 2.
PubMed 38824959
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07805343
- Acronym / sponsor ID
- VALiDATE / VALIDATE
- Conditions
- Rejection Acute Renal, Rejection Chronic Renal, Transplantation, Kidney Rejection Transplant
- Keywords
- donor-derived cell-free DNA, organ rejection, kidney rejection transplant
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 5,000 participants (estimated)
- Lead sponsor
- Paris Translational Research Center for Organ TransplantationUniversity, hospital or other
- Collaborators
- Fondation pour la Recherche Médicale, Université Paris Cité, Paris Cardiovascular Research Center (Inserm U970), Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 15 Jun 2024 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 4 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| French Cohort | – | Diagnostic Test: Donor-derived cell-free DNANecker and Saint Louis Hospitals Kidney Transplant Recipients Cohorts |
| External Validation Cohort | – | Diagnostic Test: Donor-derived cell-free DNAMultinational cohort comprising transplant centers across Europe, North America, South America and Asia (see involved transplant centres in contacts and locations). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Kidney transplant recipients of all age and sexes with at least one kidney biopsy performed concurrently with dd-cfDNA measurement.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- Combined organ transplantation
- Pregnant women
- Grafts from monozygotic twins
- Recipient of a bone marrow transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Donor-derived cell-free DNACell-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. | Diagnostic test | External Validation Cohort, French Cohort |
Primary outcome
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
1 secondary outcome
Allograft loss
Time frame: Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Background: PubMed 38824959Aubert O, Ursule-Dufait C, Brousse R, Gueguen J, Racape M, Raynaud M, Van Loon E, Pagliazzi A, Huang E, Jordan SC, Chavin KD, Gupta G, Kumar D, Alhamad T, Anand S, Sanchez-Garcia J, Abdalla BA, Hogan J, Garro R, Dadhania DM, Jain P, Mandelbrot DA, Naesens M, Dandamudi R, Dharnidharka VR, Anglicheau D, Lefaucheur C, Loupy A. Cell-free DNA for the detection of kidney allograft rejection. Nat Med. 2024 Aug;30(8):2320-2327. doi: 10.1038/s41591-024-03087-3. Epub 2024 Jun 2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rejection Acute Renal and Rejection Chronic Renal, run by Paris Translational Research Center for Organ Transplantation at 25 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, France, Belgium, Brazil, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Allograft active injury (time frame: Periprocedural (At time of biopsy)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07805343, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.