Deceased Donor Biomarkers and Recipient Outcomes

Acute Kidney Injury Clinical Trial

— DDS  

Official title:

Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01848249
• Other study ID #: 1206010465
• Secondary ID: R01DK093770-01A1
• Status: Completed
• Start date: May 1, 2010
• Est. completion date: March 2020

Study information

• Verified date: April 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1679
• Est. completion date: March 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Death
• Deceased Donor Kidney Transplant
• Delayed Graft Function
• End Stage Renal Disease
• Graft Failure
• Kidney Diseases
• Kidney Failure, Chronic

Locations

Country	Name	City	State
United States	Gift of Life Michigan	Ann Arbor	Michigan
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Harper University Hospital	Detroit	Michigan
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	New Jersey Sharing Network	New Providence	New Jersey
United States	Montefiore Medical Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
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	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Gift of Life Donor Program- Philadelphia	Philadelphia	Pennsylvania
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	New England Organ Bank	Waltham	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Hall IE, Bhangoo RS, Reese PP, Doshi MD, Weng FL, Hong K, Lin H, Han G, Hasz RD, Goldstein MJ, Schröppel B, Parikh CR. Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function. Am J Transplant. 2014 — View Citation

Hall IE, Reese PP, Weng FL, Schröppel B, Doshi MD, Hasz RD, Reitsma W, Goldstein MJ, Hong K, Parikh CR. Preimplant histologic acute tubular necrosis and allograft outcomes. Clin J Am Soc Nephrol. 2014 Mar;9(3):573-82. doi: 10.2215/CJN.08270813. Epub 2014 — View Citation

Liu C, Hall IE, Mansour S, Thiessen Philbrook HR, Jia Y, Parikh CR. Association of Deceased Donor Acute Kidney Injury With Recipient Graft Survival. JAMA Netw Open. 2020 Jan 3;3(1):e1918634. doi: 10.1001/jamanetworkopen.2019.18634. — View Citation

Puthumana J, Hall IE, Reese PP, Schröppel B, Weng FL, Thiessen-Philbrook H, Doshi MD, Rao V, Lee CG, Elias JA, Cantley LG, Parikh CR. YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation. J Am Soc Nephrol. 2017 Feb;28(2):661-670. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delayed Graft Function	Receipt of dialysis within the first seven days post renal transplant	Assessed within first week of receiving renal transplant
Primary	Death-Censored Graft Failure (Overall Cohort)	Requirement of chronic dialysis or retransplantation after renal transplant.	median of 4 years of follow-up
Secondary	Graft Function (detailed cohort)	Serum creatinine and estimated glomerular filtration rate at specified time points over a five year period.	median of 4 years of follow-up

External Links

•   Pubmed Link for Deceased Donor Study