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Deceased Donor Biomarkers and Recipient Outcomes (DDS)

8 april 2020 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Detaljerad beskrivning

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

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.
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.
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.
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.
Novel biomarkers will be measured in urine and perfusate

Studietyp

Observationell

Inskrivning (Faktisk)

1679

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

Barn
Vuxen
Äldre vuxen

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Testmetod

Sannolikhetsprov

Studera befolkning

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.

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

Observationsmodeller: Kohort
Tidsperspektiv: Blivande

Antal grupper/kohorter

Kohorter och interventioner

Grupp / Kohort
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.

Vad mäter studien?

Primära resultatmått

Resultatmått	Åtgärdsbeskrivning	Tidsram
Delayed Graft Function Tidsram: 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) Tidsram: median of 4 years of follow-up	Requirement of chronic dialysis or retransplantation after renal transplant.	median of 4 years of follow-up

Sekundära resultatmått

Resultatmått	Åtgärdsbeskrivning	Tidsram
Graft Function (detailed cohort) Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Yale University

Samarbetspartners

Johns Hopkins University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Utredare

Huvudutredare: Chirag R Parikh, MD PhD, Yale University

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Pubmed Link for Deceased Donor Study

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 maj 2010

Primärt slutförande (Faktisk)

1 december 2019

Avslutad studie (Faktisk)

1 mars 2020

Studieregistreringsdatum

Först inskickad

30 april 2013

Först inskickad som uppfyllde QC-kriterierna

2 maj 2013

Första postat (Uppskatta)

7 maj 2013

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

9 april 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

8 april 2020

Senast verifierad

1 april 2020

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

1206010465
R01DK093770-01A1 (U.S.S. NIH-anslag/kontrakt)

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