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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Narva, Andrew
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Hall, Isaac E; Parikh, Chirag R; Schröppel, Bernd et al. (2018) Procurement Biopsy Findings Versus Kidney Donor Risk Index for Predicting Renal Allograft Survival. Transplant Direct 4:e373
Mansour, Sherry G; Hall, Isaac E; Reese, Peter P et al. (2018) Reliability of deceased-donor procurement kidney biopsy images uploaded in United Network for Organ Sharing. Clin Transplant 32:e13441
Hall, Isaac E; Akalin, Enver; Bromberg, Jonathan S et al. (2018) Deceased-donor acute kidney injury is not associated with kidney allograft failure. Kidney Int :
Moledina, Dennis G; Parikh, Chirag R (2018) Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine. Semin Nephrol 38:3-11
Harhay, Meera Nair; Jia, Yaqi; Thiessen-Philbrook, Heather et al. (2018) The association of discharge decisions after deceased donor kidney transplantation with the risk of early readmission: Results from the deceased donor study. Clin Transplant 32:e13215
Doshi, Mona D; Reese, Peter P; Hall, Isaac E et al. (2017) Utility of Applying Quality Assessment Tools for Kidneys With KDPI ?80. Transplantation 101:1125-1133
Puthumana, Jeremy; Hall, Isaac E; Reese, Peter P et al. (2017) YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation. J Am Soc Nephrol 28:661-670
Chi, Jingmao; Ma, Yiwei; Weng, Francis L et al. (2017) Surface-enhanced Raman scattering analysis of urine from deceased donors as a prognostic tool for kidney transplant outcome. J Biophotonics 10:1743-1755
Mansour, S G; Puthumana, J; Reese, P P et al. (2017) Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes. Kidney Int Rep 2:749-758
Moledina, Dennis G; Hall, Isaac E; Thiessen-Philbrook, Heather et al. (2017) Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury. Am J Kidney Dis 70:807-816

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