Clinical trial NCT01848249: Deceased Donor Biomarkers and Recipient Outcomes
Official title: Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Deceased Donor Kidney Transplant
Acute Kidney Injury
Delayed Graft Function
End Stage Renal Disease
Graft Failure
Keywords: deceased donors
kidney donor
transplant recipients
kidney transplant
delayed graft function
biomarkers
end stage renal disease
graft failure
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Johns Hopkins University
First posted: 2013-05-07
Enrollment: 1679
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

Eligibility 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

Primary outcomes:
measure: Delayed Graft Function
timeFrame: Assessed within first week of receiving renal transplant
measure: Death-Censored Graft Failure (Overall Cohort)
timeFrame: median of 4 years of follow-up
Secondary outcomes:
measure: Graft Function (detailed cohort)
timeFrame: median of 4 years of follow-up
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Waltham
country: United States
facility: New England Organ Bank
state: Massachusetts
city: Ann Arbor
country: United States
facility: Gift of Life Michigan
state: Michigan
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: New Providence
country: United States
facility: New Jersey Sharing Network
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: New York Organ Donor Network
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian/ Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: The New York Hospital (Cornell)
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Gift of Life Donor Program- Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
affiliation: Yale University
name: Chirag R Parikh, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hall IE, Bhangoo RS, Reese PP, Doshi MD, Weng FL, Hong K, Lin H, Han G, Hasz RD, Goldstein MJ, Schroppel B, Parikh CR. Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function. Am J Transplant. 2014 Apr;14(4):886-96. doi: 10.1111/ajt.12635. Epub 2014 Feb 24.
citation: Hall IE, Reese PP, Weng FL, Schroppel 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 Feb 20.
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.
citation: Puthumana J, Hall IE, Reese PP, Schroppel 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. doi: 10.1681/ASN.2016010091. Epub 2016 Jul 22.