Novel Kidney Injury Tools in Deceased Organ Donation to Predict Graft Outcome

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Project Summary 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.