Deceased-Donor Study
The shortage of kidneys for transplantation is a major dilemma, which has driven efforts to expand the organ supply by using kidneys from deceased donors; however these have higher risk factors for allograft dysfunction. Greater use of kidneys with uncertain quality and the lack of precise tools to measure kidney quality during procurement have led to high organ discard rates and increasing numbers of transplant recipients with allograft dysfunction. Without precise methods to assess kidney quality, it is likely that some useful kidneys are discarded and some low-quality kidneys are transplanted with potentially harmful results. This project has identified novel biomarkers in kidney transplantation associated with allograft outcomes. This study will assess real-time point-of-care biomarker measurements via rapid-testing lateral-flow devices to validate associations with graft outcomes in kidney transplant recipients.
This biomarker study is one of the largest, applied, translational research studies in kidney transplantation. In collaboration with several organ procurement organizations, urine was collected from 1,679 deceased donors at the time of procurement along with samples of transport solution for every pumped kidney. We have measured known injury biomarkers including IL-18, NGAL, KIM-1, LFABP, and cystatin C, with further plans to measure biomarkers of chronic kidney disease, such as uromodulin, albumin, and TGF-ß. We are evaluating rates of delayed graft function and allograft failure in recipients of these kidneys by linkage to the United Network for Organ Sharing database. We are also collecting detailed recipient data about estimated glomerular filtration rate, immunosuppression, acute rejection, and other complications for two years after transplant via chart review at several participating transplant centers. Our ultimate goals are to help maximize the allocation of viable kidneys, develop therapies for ischemia-reperfusion injury, and improve recipient outcomes through the study of noninvasive deceased-donor biomarkers at the time of procurement.
We are using lateral flow devices (LFD) in a real-time point-of-care setting as an innovative approach to assess kidney graft quality for the early determination of kidney allograft prognosis. We have previously identified three urine biomarkers (YKL-40, UMOD, and OPN) that are associated with kidney repair in kidneys. Compared with existing methods, noninvasive donor biomarkers have the potential advantage of rapidly assessing AKI repair mechanisms and immune activation. Fast, cost-effective, and objective biomarker measurement at the time of organ procurement will enable these data to have an impact on transplant centers’ organ quality assessment and acceptance decisions. Donor biomarkers may also be useful in monitoring early management and designing innovative therapies. The workflow for collecting urine samples for real-time point-of-care biomarker measurement is given below:
Some key results from this study are given below:
Funding Information for this Project
The Deceased Donor Study is supported by the NIH/NIDDK (R01DK093770, “Novel Kidney Injury Tools in Deceased Organ Donation to Predict Graft Outcome”)