Extended Validation of Donor-derived Cell-free DNA in Kidney Transplant Recipients (VALiDATE)
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.
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
연락처 및 위치
연구 장소
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Seoul, 대한민국
- Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Berlin, 독일
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin
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California
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Los Angeles, California, 미국, 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, 미국, 90048
- Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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Los Angeles, California, 미국, 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, 미국, 33606
- Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
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Georgia
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Atlanta, Georgia, 미국, 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, 미국, 63110
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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St Louis, Missouri, 미국, 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, 미국, 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, 미국, 44195-0001
- Cleveland Clinic, 2050 East 96th Street, Cleveland, OH
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Texas
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Dallas, Texas, 미국, 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, 미국, 84107
- Transplant Services, Intermountain Medical Center, Murray, UT, USA
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Salt Lake City, Utah, 미국, 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, 미국, 23219
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
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Wisconsin
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Madison, Wisconsin, 미국, 53705
- Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
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Leuven, 벨기에
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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São Paulo, 브라질
- Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil
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Geneva, 스위스, 1205
- Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland
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Barcelona, 스페인
- Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
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Paris, 프랑스
- Hopital Necker
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Paris, 프랑스, 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, 프랑스
- 11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
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Paris, 프랑스
- Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;
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Toulouse, 프랑스
- Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France
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참여기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
샘플링 방법
연구 인구
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
개입 / 치료 |
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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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Allograft active injury
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Allograft loss
기간: 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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공동 작업자 및 조사자
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
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