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

NCT07805343 | Active Not Recruiting

• 1 other identifier: VALIDATE
• Study Type: observational
• Target: 5,000
• Locations: 8 countries
• Sites: 25

Brief 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 performance across Banff 2022 rejection phenotypes and injury patterns, in various clinical scenarios and populations, and when measured repeatedly over time.

Conditions

Kidney Rejection Transplant; Rejection Acute Renal; Rejection Chronic Renal; Transplantation

Keywords

donor-derived cell-free DNA; organ rejection; kidney rejection transplant

Outcome Measures

Primary Outcomes (1)

• 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

  Periprocedural (At time of biopsy)

Secondary Outcomes (1)

• Allograft loss

  Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)

Study Arms (2)

French Cohort

Necker and Saint Louis Hospitals Kidney Transplant Recipients Cohorts

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).

Diagnostic Test: Donor-derived cell-free DNA

Interventions

Donor-derived cell-free DNA DIAGNOSTIC_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.

External Validation Cohort; French Cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Recipients transplanted from a deceased or living donor
• Kidney allograft biopsy concomitantly with dd-cfDNA measurement

You may not qualify if:

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

Sponsors & Collaborators

• Paris Translational Research Center for Organ Transplantation: lead
• Fondation pour la Recherche Médicale: collaborator
• Université Paris Cité: collaborator
• Paris Cardiovascular Research Center (Inserm U970): collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (25)

Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Los Angeles, California, 90048, United States

Location

Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Los Angeles, California, 90048, United States

Location

Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Los Angeles, California, 90095, United States

Location

Department of Nephrology, Tampa General Hospital, Tampa, FL, USA

Tampa, Florida, 33606, United States

Location

Division of Pediatric Nephrology, Emory University School of Medicine, Atlanta, GA, USA

Atlanta, Georgia, 30322, United States

Location

Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

St Louis, Missouri, 63110, United States

Location

Division of Pediatric Nephrology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA

St Louis, Missouri, 63110, United States

Location

Division of Nephrology, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, NY, USA

New York, New York, 10065, United States

Location

Cleveland Clinic, 2050 East 96th Street, Cleveland, OH

Cleveland, Ohio, 44195-0001, United States

Location

Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Dallas, Texas, 75390-8856, United States

Location

Transplant Services, Intermountain Medical Center, Murray, UT, USA

Murray, Utah, 84107, United States

Location

Division of Nephrology, Department of Medicine, University of Utah Health, Salt Lake City, UT, USA

Salt Lake City, Utah, 84132, United States

Location

Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA

Richmond, Virginia, 23219, United States

Location

Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Madison, Wisconsin, 53705, United States

Location

Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium

Leuven, Belgium

Location

Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil

São Paulo, Brazil

Location

Department of Nephrology and Dialysis, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France

Paris, 75015, France

Location

11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

Paris, France

Location

Hôpital Necker

Paris, France

Location

Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;

Paris, France

Location

Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France

Toulouse, France

Location

Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin

Berlin, Germany

Location

Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

Seoul, South Korea

Location

Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain

Barcelona, Spain

Location

Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland

Geneva, 1205, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 38824959 BACKGROUND

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: September 4, 2026
• Study Start: June 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 4, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); ES (1); BE (1); US (14); BR (1); KR (1); FR (5); CH (1)