Extended Validation of Donor-derived Cell-free DNA in Kidney Transplant Recipients (VALiDATE)
3. september 2026 oppdatert av: 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.
Studieoversikt
Status
Aktiv, ikke rekrutterende
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Observasjonsmessig
Registrering (Antatt)
5000
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Leuven, Belgia
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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São Paulo, Brasil
- Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil
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California
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Los Angeles, California, Forente stater, 90048
- Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Los Angeles, California, Forente stater, 90048
- Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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Los Angeles, California, Forente stater, 90095
- Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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Florida
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Tampa, Florida, Forente stater, 33606
- Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Division of Pediatric Nephrology, Emory University School of Medicine, Atlanta, GA, USA
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Missouri
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St Louis, Missouri, Forente stater, 63110
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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St Louis, Missouri, Forente stater, 63110
- Division of Pediatric Nephrology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA
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New York
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New York, New York, Forente stater, 10065
- Division of Nephrology, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, NY, USA
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Ohio
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Cleveland, Ohio, Forente stater, 44195-0001
- Cleveland Clinic, 2050 East 96th Street, Cleveland, OH
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Texas
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Dallas, Texas, Forente stater, 75390-8856
- Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Utah
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Murray, Utah, Forente stater, 84107
- Transplant Services, Intermountain Medical Center, Murray, UT, USA
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Salt Lake City, Utah, Forente stater, 84132
- Division of Nephrology, Department of Medicine, University of Utah Health, Salt Lake City, UT, USA
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Virginia
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Richmond, Virginia, Forente stater, 23219
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
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Wisconsin
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Madison, Wisconsin, Forente stater, 53705
- Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
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Paris, Frankrike
- Hopital Necker
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Paris, Frankrike, 75015
- Department of Nephrology and Dialysis, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
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Paris, Frankrike
- 11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
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Paris, Frankrike
- Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;
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Toulouse, Frankrike
- Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France
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Barcelona, Spania
- Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
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Geneva, Sveits, 1205
- Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland
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Seoul, Sør -Korea
- Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Berlin, Tyskland
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
Kidney transplant recipients of all age and sexes with at least one kidney biopsy performed concurrently with dd-cfDNA measurement.
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
Intervensjon / Behandling |
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French Cohort
Necker and Saint Louis Hospitals Kidney Transplant Recipients Cohorts
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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.
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External Validation Cohort
Multinational cohort comprising transplant centers across Europe, North America, South America and Asia (see involved transplant centres in contacts and locations).
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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.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Allograft active injury
Tidsramme: Periprocedural (At time of biopsy)
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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
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Periprocedural (At time of biopsy)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Allograft loss
Tidsramme: Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
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Return to dialysis or re-transplantation
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Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
15. juni 2024
Primær fullføring (Antatt)
1. desember 2026
Studiet fullført (Antatt)
31. desember 2026
Datoer for studieregistrering
Først innsendt
24. august 2026
Først innsendt som oppfylte QC-kriteriene
3. september 2026
Først lagt ut (Faktiske)
4. september 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
4. september 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
3. september 2026
Sist bekreftet
1. september 2026
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- VALIDATE
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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