Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01848249
Other study ID # 1206010465
Secondary ID R01DK093770-01A1
Status Completed
Phase
First received
Last updated
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
Health authority
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

Study Design


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
See also
  Status Clinical Trial Phase
Recruiting NCT05538351 - A Study to Support the Development of the Enhanced Fluid Assessment Tool for Patients With Acute Kidney Injury
Recruiting NCT06027788 - CTSN Embolic Protection Trial N/A
Completed NCT03938038 - Guidance of Ultrasound in Intensive Care to Direct Euvolemia N/A
Recruiting NCT05805709 - A Patient-centered Trial of a Process-of-care Intervention in Hospitalized AKI Patients: the COPE-AKI Trial N/A
Recruiting NCT05318196 - Molecular Prediction of Development, Progression or Complications of Kidney, Immune or Transplantation-related Diseases
Recruiting NCT05897840 - Continuous Central Venous Oxygen Saturation Measurement as a Tool to Predict Hemodynamic Instability Related to Renal Replacement Therapy in Critically Ill Patients N/A
Recruiting NCT04986137 - Fractional Excretion of Urea for the Differential Diagnosis of Acute Kidney Injury in Cirrhosis
Terminated NCT04293744 - Acute Kidney Injury After Cardiac Surgery N/A
Completed NCT04095143 - Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury
Not yet recruiting NCT06026592 - Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients
Not yet recruiting NCT06064305 - Transcriptional and Proteomic Analysis of Acute Kidney Injury
Terminated NCT03438877 - Intensive Versus Regular Dosage For PD In AKI. N/A
Terminated NCT03305549 - Recovery After Dialysis-Requiring Acute Kidney Injury N/A
Completed NCT05990660 - Renal Assist Device (RAD) for Patients With Renal Insufficiency Undergoing Cardiac Surgery N/A
Completed NCT04062994 - A Clinical Decision Support Trial to Reduce Intraoperative Hypotension
Terminated NCT02860130 - Clinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT) Phase 3
Completed NCT06000098 - Consol Time and Acute Kidney Injury in Robotic-assisted Prostatectomy
Not yet recruiting NCT05548725 - Relation Between Acute Kidney Injury and Mineral Bone Disease
Completed NCT02665377 - Prevention of Akute Kidney Injury, Hearttransplant, ANP Phase 3
Terminated NCT03539861 - Immunomodulatory Biomimetic Device to Treat Myocardial Stunning in End-stage Renal Disease Patients N/A