Deceased Donor Biomarkers and Recipient Outcomes (DDS)
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.
Deceased Donor Kidney Transplant
Acute Kidney Injury
Delayed Graft Function
End Stage Renal Disease
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes|
- 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.
- 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
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
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)|
Our study has several key processes that we have developed and tested to address our scientific aims:
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 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 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.
- Acute and chronic kidney injury biomarkers will be measured in urine and perfusate
Please refer to this study by its ClinicalTrials.gov identifier: NCT01848249
|United States, Massachusetts|
|New England Organ Bank|
|Waltham, Massachusetts, United States, 02451|
|United States, Michigan|
|Gift of Life Michigan|
|Ann Arbor, Michigan, United States, 48108|
|Harper University Hospital|
|Detroit, Michigan, United States, 48201|
|United States, New Jersey|
|St. Barnabas Medical Center|
|Livingston, New Jersey, United States, 07039|
|New Jersey Sharing Network|
|New Providence, New Jersey, United States, 07974|
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|New York Organ Donor Network|
|New York, New York, United States, 10001|
|United States, Pennsylvania|
|Gift of Life Donor Program- Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Chirag R Parikh, MD PhD||Yale University|