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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究場所
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California
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Los Angeles、California、アメリカ、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、アメリカ、90048
- Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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Los Angeles、California、アメリカ、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、アメリカ、33606
- Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
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Georgia
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Atlanta、Georgia、アメリカ、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、アメリカ、63110
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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St Louis、Missouri、アメリカ、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、アメリカ、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、アメリカ、44195-0001
- Cleveland Clinic, 2050 East 96th Street, Cleveland, OH
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Texas
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Dallas、Texas、アメリカ、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、アメリカ、84107
- Transplant Services, Intermountain Medical Center, Murray, UT, USA
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Salt Lake City、Utah、アメリカ、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、アメリカ、23219
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
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Wisconsin
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Madison、Wisconsin、アメリカ、53705
- Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
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Geneva、スイス、1205
- Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland
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Barcelona、スペイン
- Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
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Berlin、ドイツ
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin
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Paris、フランス
- Hopital Necker
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Paris、フランス、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、フランス
- 11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
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Paris、フランス
- Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;
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Toulouse、フランス
- Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France
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São Paulo、ブラジル
- Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil
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Leuven、ベルギー
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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Seoul、韓国
- Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Allograft active injury
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Allograft loss
時間枠：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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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- VALIDATE
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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