Compared to chronic dialysis, kidney transplantation provides recipients with better survival and quality of life at much lower cost. Efforts to meet the increasing need have resulted in more kidney procurements from older and sicker donors. Unfortunately, these efforts have led to greater discard rates of procured kidneys and more complications for allograft recipients, including reduced allograft function. Available tools to predict allograft quality have poor prognostic ability and do not adequately asses the degree of kidney injury or repair potential at procurement. However, early allograft injury can lead to major consequences for the recipient, such as greater risks of delayed graft function, poor long-term allograft function and premature loss of the transplant. Our proposal is based on the hypotheses that novel biomarkers of injury, inflammation and repair measured in donor urine and transport media at the time of procurement will identify distinct and informative patterns that will predict allograft survival. In collaboration with five organ procurement organizations for Phase 1 of the study, we collected urine samples from over 1500 consecutive deceased donors and perfusate samples from every pumped kidney and measured several kidney injury biomarkers. We linked all recipients from these donors (over 2500 individuals) in the United Network for Organ Sharing (UNOS) database to determine mortality and allograft survival. In Phase 2, we will measure 17 promising novel biomarkers from our biorepository samples that represent various biological processes. We will expand the Recipient Subcohort to include over 1000 recipients to enrich the event rates for important immunological outcomes (i.e., acute rejection and progressive alloimmunity) and collect detailed longitudinal data about allograft function, immunosuppression, and specific complications for up to 5 years after transplant via detailed chart review. With a total of over 25 measured biomarkers, additional clinical events, longer follow-up, and innovative statistical methods, we will create multi-marker panels to assess donor kidney quality and predict critical outcomes. Early, non-invasive and rapid assessment of donor biological processes could drive better allocation decisions and reduce post-transplant complications. These new tools could also provide a platform for therapeutic trials in kidney allografts and recipients aimed at ameliorating injury, augmenting recovery and improving long-term allograft function and survival.

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 donated kidney in order to match it to the appropriate recipient and predict survival after transplant. This project aims to implement high quality 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 #
7R01DK093770-07
Application #
9712307
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Abbott, Kevin C
Project Start
2012-08-15
Project End
2021-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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
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
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
Hall, Isaac E; Reese, Peter P; Doshi, Mona D et al. (2017) Delayed Graft Function Phenotypes and 12-Month Kidney Transplant Outcomes. Transplantation 101:1913-1923
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

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