Deceased Donor Biomarkers and Recipient Outcomes (DDS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Yale University
Sponsor:
Information provided by (Responsible Party):
Chirag Parikh, Yale University
ClinicalTrials.gov Identifier:
NCT01848249
First received: April 30, 2013
Last updated: May 2, 2013
Last verified: May 2013
  Purpose

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 kidney injury 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 four organ procurement organizations, we will collect urine samples from consecutive deceased donors and samples of transport solution for every pumped kidney. We will measure five acute injury markers and three chronic injury markers. We will determine mortality and allograft survival in all patients by linkage to th United Network for Organ Sharing (UNOS) database. Additionally, we will perform a detailed chart review of a subset of recipients and will also examine associations between biomarkers and longitudinal graft function over two 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.


Condition
Deceased Donor Kidney Transplant
Acute Kidney Injury
Delayed Graft Function
End Stage Renal Disease
Graft Failure

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Delayed Graft Function [ Time Frame: Assessed within first week of receiving renal transplant ] [ Designated as safety issue: No ]
    Receipt of dialysis within the first seven days post renal transplant

  • Death-Censored Graft Failure [ Time Frame: Within two years of receiving renal transplant ] [ Designated as safety issue: No ]
    Requirement of chronic dialysis or retransplantation after renal transplant.


Secondary Outcome Measures:
  • Graft Function [ Time Frame: Within two years of receiving renal transplant ] [ Designated as safety issue: No ]
    Serum creatinine and estimated glomerular filtration rate at specified time points over a two year period.


Biospecimen Retention:   Samples Without DNA

((A)) Urine Samples: At time of deceased donor nephrectomy ((B)) Perfusates: At time of initiation and stopping of machine perfusion


Estimated Enrollment: 1600
Study Start Date: May 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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)

Detailed Description:

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 500 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 two years after transplantation, including acute rejection and estimated glomerular filtration rate at the time of transplantation and at months 1, 3, 6, 12 and 24 after transplant.

  5. Acute and chronic kidney injury biomarkers will be measured in urine and perfusate
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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.

Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01848249

Contacts
Contact: Chirag R Parikh, MD PhD chirag.parikh@yale.edu
Contact: Isaac E Hall, MD MS isaac.hall@yale.edu

Locations
United States, Massachusetts
New England Organ Bank Recruiting
Waltham, Massachusetts, United States, 02451
Contact: Christopher Curran       christopher.curran@neob.org   
United States, Michigan
Gift of Life Michigan Recruiting
Ann Arbor, Michigan, United States, 48108
Contact: Burton Mattice, CPTC MBA       bmattice@giftoflifemichigan.org   
Harper University Hospital Recruiting
Detroit, Michigan, United States, 48201
Contact: Mona Doshi, MD       mdoshi@med.wayne.edu   
Principal Investigator: Mona Doshi, MD         
United States, New Jersey
St. Barnabas Medical Center Recruiting
Livingston, New Jersey, United States, 07039
Contact: Francis Weng, MD       fweng@barnabashealth.org   
Principal Investigator: Francis Weng, MD         
New Jersey Sharing Network Recruiting
New Providence, New Jersey, United States, 07974
Contact: Carolyn Welsh       CWelsh@njsharingnetwork.org   
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Bernd Schroppel, MD       bernd.schroppel@mountsinai.org   
Principal Investigator: Bernd Schroppel, MD         
New York Organ Donor Network Recruiting
New York, New York, United States, 10001
Contact: Harvey Lerner       hlerner@nyodn.org   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Peter Reese, MD MSCE       peter.reese@uphs.upenn.edu   
Principal Investigator: Peter Reese, MD MSCE         
Gift of Life Donor Program- Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Richard Hasz       rhasz@donors1.org   
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Chirag R Parikh, MD PhD Yale University
  More Information

Additional Information:
No publications provided

Responsible Party: Chirag Parikh, Associate Professor of Medicine, Yale University
ClinicalTrials.gov Identifier: NCT01848249     History of Changes
Other Study ID Numbers: DK093770-01A1
Study First Received: April 30, 2013
Last Updated: May 2, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Yale University:
deceased donors
kidney donor
transplant recipients
kidney transplant
delayed graft function
biomarkers
end stage renal disease
graft failure

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Acute Kidney Injury
Delayed Graft Function
Death
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Pathologic Processes

ClinicalTrials.gov processed this record on September 18, 2014