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Deceased Donor Biomarkers and Recipient Outcomes (DDS)

8 avril 2020 mis à jour par: Yale University

Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes

Compared to chronic dialysis, kidney transplantation provides recipients with longer survival and better quality of life at a lower cost. In order to meet increasing demands for kidney allografts, kidneys from older and sicker donors are being procured. This has led to greater discard rates of donated kidneys as well as more complications for recipients, including shorter allograft survival. Available clinical models to predict kidney allograft quality have poor prognostic ability and do not asses the degree of kidney allograft injury. However, allograft injury near the time of procurement can lead to major consequences for the transplant recipient: greater risks of delayed graft function, poor allograft function and premature loss of the transplant. Our proposal is based on the hypotheses that novel biomarkers measured in donor urine and transport media at the time of procurement can assess acute and chronic kidney injury and that distinct biomarker patterns will predict allograft survival. In collaboration with five organ procurement organizations, we will collect urine samples from consecutive deceased donors and samples of transport solution for every pumped kidney. We will measure markers of injury, repair, inflammation and fibrosis. We will determine mortality and allograft survival in all patients by linkage to the United Network for Organ Sharing (UNOS) database (Overall Cohort). Additionally, we will perform a detailed chart review of a subset of recipients (detailed cohort) and will also examine associations between biomarkers and longitudinal graft function over five years after transplant. Early, non-invasive and rapid assessment of donor kidney injury could drive better allocation decisions and potentially reduce the rates of post-transplant complications. Further, these new tools could provide a platform for clinical trials of therapies for allografts and kidney transplant recipients aimed at ameliorating allograft injury.

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

Our study has several key processes that we have developed and tested to address our scientific aims:

  1. Enrollment

    We will collect urine samples from approximately 1600 deceased donors and approximately 600 perfusate samples from machine-pumped kidneys from participating organ procurement organizations (OPOs). We estimate that our final donor group will be comprised of 55% standard criteria donors, 25% expanded-criteria donors and 10% donors after cardiac death. Approximately, 20% of the kidneys will be discarded.

  2. Donor Data

    Donor variables come from two sources: the United Network for Organ Sharing (UNOS) database and detailed data abstraction from each OPO. The UNOS database provides data on all donors with demographics and other important clinical characteristics. The additional data collected by the OPO staff captures granular information on events surrounding donor death, which are not included in the UNOS database. These data will be available on all enrolled donors and include variables such as serial serum creatinine, nadir blood pressures, medication and vasopressor use, and machine pump parameters.

  3. Overall Recipient Cohort

    Over 2000 recipients will have received kidneys from the deceased donors in our study. The Overall Cohort will comprise all of these recipients General demographic and clinical characteristics about recipients in the Overall Cohort will come from the UNOS database. For the Overall Recipient Cohort, we will ascertain delayed graft function (DGF) through center reports to UNOS. We will ascertain allograft failure through center reports to UNOS and new episodes of wait-listing and re-transplant collected by UNOS, Recipient mortality will be ascertained through the center reports to UNOS/SRTR and through the Social Security Death Master File.

  4. Detailed Recipient Cohort

    A subset of over 1100 recipients of the Overall Cohort who had transplantation at any of our collaborating transplant centers will comprise this cohort. For the Detailed Subcohort, on-site coordinators will perform manual chart review and abstract more extensive data about each recipient including dialysis indications post-transplant, comorbidities, and specific doses of immunosuppression. For the Detailed Subcohort, we will also collect data on clinical events for up to five years after transplantation, including acute rejection and estimated glomerular filtration rate at the time of transplantation and at months 1, 3, 6, 12, 18, 24, 30, 36, 48 and 60 months after transplant.

  5. Novel biomarkers will be measured in urine and perfusate

Type d'étude

Observationnel

Inscription (Réel)

1679

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Connecticut
      • New Haven, Connecticut, États-Unis, 06510
        • Yale New Haven Hospital
    • Maryland
      • Baltimore, Maryland, États-Unis, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Waltham, Massachusetts, États-Unis, 02451
        • New England Organ Bank
    • Michigan
      • Ann Arbor, Michigan, États-Unis, 48108
        • Gift of Life Michigan
      • Detroit, Michigan, États-Unis, 48201
        • Harper University Hospital
    • New Jersey
      • Livingston, New Jersey, États-Unis, 07039
        • St. Barnabas Medical Center
      • New Providence, New Jersey, États-Unis, 07974
        • New Jersey Sharing Network
      • Newark, New Jersey, États-Unis, 07112
        • Newark Beth Israel Medical Center
    • New York
      • New York, New York, États-Unis, 10029
        • Mount Sinai School of Medicine
      • New York, New York, États-Unis, 10467
        • Montefiore Medical Center
      • New York, New York, États-Unis, 10001
        • New York Organ Donor Network
      • New York, New York, États-Unis, 10032
        • NewYork-Presbyterian/ Columbia University Irving Medical Center
      • New York, New York, États-Unis, 10065
        • The New York Hospital (Cornell)
    • Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, États-Unis, 19102
        • Hahnemann University Hospital
      • Philadelphia, Pennsylvania, États-Unis, 19104
        • Gift of Life Donor Program- Philadelphia

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant
  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon de probabilité

Population étudiée

The population from which our Deceased-Donor Cohort will be selected is all potential deceased organ donors located in the regions serviced by our participating organ procurement organizations (OPOs).

The recipient cohorts will be defined by the deceased donors enrolled in the study, and thus, the study population for this group is all recipients of kidneys from deceased organ donors procured in the regions serviced by our participating OPOs.

La description

Inclusion Criteria:

  • Donor Cohort: Appropriate informed consent for research according to OPO policies
  • Recipient Cohorts: Any recipient of at least one kidney from a deceased donor enrolled by our participating OPOs

Exclusion Criteria:

• Donor Cohort: Lack of adequate biospecimen quantity or quality as per protocol

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Modèles d'observation: Cohorte
  • Perspectives temporelles: Éventuel

Cohortes et interventions

Groupe / Cohorte
Deceased-Donor Cohort
We will collect urine samples from approximately 1600 deceased donors and approximately 600 perfusate samples from machine-pumped kidneys from participating organ procurement organizations (OPOs).
Recipient Cohort (Overall and Detailed)
No samples will be collected from the recipients. Only clinical data and outcomes will be collected from the recipients.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Delayed Graft Function
Délai: Assessed within first week of receiving renal transplant
Receipt of dialysis within the first seven days post renal transplant
Assessed within first week of receiving renal transplant
Death-Censored Graft Failure (Overall Cohort)
Délai: median of 4 years of follow-up
Requirement of chronic dialysis or retransplantation after renal transplant.
median of 4 years of follow-up

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Graft Function (detailed cohort)
Délai: median of 4 years of follow-up
Serum creatinine and estimated glomerular filtration rate at specified time points over a five year period.
median of 4 years of follow-up

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Yale University

Collaborateurs

Johns Hopkins University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Les enquêteurs

  • Chercheur principal: Chirag R Parikh, MD PhD, Yale University

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mai 2010

Achèvement primaire (Réel)

1 décembre 2019

Achèvement de l'étude (Réel)

1 mars 2020

Dates d'inscription aux études

Première soumission

30 avril 2013

Première soumission répondant aux critères de contrôle qualité

2 mai 2013

Première publication (Estimation)

7 mai 2013

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 avril 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

8 avril 2020

Dernière vérification

1 avril 2020

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 1206010465
  • R01DK093770-01A1 (Subvention/contrat des NIH des États-Unis)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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