Deceased Donor Biomarkers and Recipient Outcomes

Completed

• Conditions: End Stage Renal Disease; Acute Kidney Injury; Delayed Graft Function; Graft Failure; Deceased Donor Kidney Transplant

• Registration Number: NCT01848249
• Lead Sponsor: Yale University

Brief Summary

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.

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 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

Study Timeline

• Study Start: 2010-05-01
• Study First Submitted: 2013-04-30
• Study First Submitted QC: 2013-05-02
• Study First Posted: 2013-05-07
• Primary Completion: 2019-12
• Study Completion: 2020-03
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-08
• Last Update Posted: 2020-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1679

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

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Death-Censored Graft Failure (Overall Cohort)	median of 4 years of follow-up	Requirement of chronic dialysis or retransplantation after renal transplant.
Delayed Graft Function	Assessed within first week of receiving renal transplant	Receipt of dialysis within the first seven days post renal transplant

Secondary Outcome Measures

Name	Time	Method
Graft Function (detailed cohort)	median of 4 years of follow-up	Serum creatinine and estimated glomerular filtration rate at specified time points over a five year period.

Trial Locations

Locations (17)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Gift of Life Michigan; 🇺🇸 Ann Arbor, Michigan, United States

St. Barnabas Medical Center; 🇺🇸 Livingston, New Jersey, United States

Newark Beth Israel Medical Center; 🇺🇸 Newark, New Jersey, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

New Jersey Sharing Network; 🇺🇸 New Providence, New Jersey, United States

Hahnemann University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States

New England Organ Bank; 🇺🇸 Waltham, Massachusetts, United States

Harper University Hospital; 🇺🇸 Detroit, Michigan, United States

New York Organ Donor Network; 🇺🇸 New York, New York, United States

NewYork-Presbyterian/ Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

The New York Hospital (Cornell); 🇺🇸 New York, New York, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

Gift of Life Donor Program- Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Montefiore Medical Center; 🇺🇸 New York, New York, United States