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临床试验/NCT01848249
NCT01848249已完成不适用

Deceased Donor Urinary Biomarkers to Predict Kidney Transplant Outcomes

Yale University17 个研究点 分布在 1 个国家目标入组 1,679 人开始时间: 2010年5月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
1,679
试验地点
17
主要终点
Death-Censored Graft Failure (Overall Cohort)

研究概览

简要总结

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.

详细描述

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

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

性别
All
接受健康志愿者

入选标准

  • 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

排除标准

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

结局指标

主要结局

Death-Censored Graft Failure (Overall Cohort)

时间窗: median of 4 years of follow-up

Requirement of chronic dialysis or retransplantation after renal transplant.

Delayed Graft Function

时间窗: Assessed within first week of receiving renal transplant

Receipt of dialysis within the first seven days post renal transplant

次要结局

  • Graft Function (detailed cohort)(median of 4 years of follow-up)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (17)

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