Compared to chronic dialysis, kidney transplantation provides recipients with longer survival and better quality of life at a lower cost. In order to met 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 1,000 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 over 500 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.

Public Health Relevance

Kidney transplantation provides recipients with longer survival and better quality of life at a lower cost compared with chronic dialysis. Novel tools are required to assess the quality of the allograft in order to match it to the appropriate recipient and predic graft survival. This project aims to implement novel tests for measuring injury in the kidney and assess their potential impact in clinical practice in an effort to improve both early and late outcomes following kidney transplantation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK093770-02
Application #
8529513
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Narva, Andrew
Project Start
2012-08-15
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$662,952
Indirect Cost
$195,889
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hall, Isaac E; Reese, Peter P; Weng, Francis L et al. (2014) Preimplant histologic acute tubular necrosis and allograft outcomes. Clin J Am Soc Nephrol 9:573-82
Parikh, Chirag R; Thiessen-Philbrook, Heather (2014) Key concepts and limitations of statistical methods for evaluating biomarkers of kidney disease. J Am Soc Nephrol 25:1621-9
Hall, I E; Bhangoo, R S; Reese, P P et al. (2014) Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function. Am J Transplant 14:886-96
Butala, Neel M; Reese, Peter P; Doshi, Mona D et al. (2013) Is delayed graft function causally associated with long-term outcomes after kidney transplantation? Instrumental variable analysis. Transplantation 95:1008-14