Disruptive technologies for rapid detection of renal transplant rejection

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Kidney transplantation is the most effective treatment for end-stage kidney failure, which affects over 0.5 million people in the EU; however, 1 in 3 patients may experience acute rejection within the first year of receiving a transplant. Early detection is critical to maximize graft function and improve the quality of life for patients with transplants. Currently, renal transplant monitoring is performed with invasive biopsies or with tests that cannot specifically report on acute transplant rejection. There is a need for noninvasive technologies that can rapidly measure acute organ rejection and monitor disease progression and response to therapy. This unmet patient need drives the development of the project RENO.The ERC CoG project DYNAFLUORS delivered the first fluorescent chemical toolbox for imaging immune cell activity. After organ transplantation, the activity of immune cells is indicative on how patients respond to the transplanted organ. Granzyme B is a protein secreted by over-activated immune cells during acute transplant rejection, with high levels of granzyme B in urine correlating to early stages of kidney rejection and with disease severity. We propose to develop a simple test to measure active granzyme B in urine in real time. This test will enable early identification of acute rejection, reduce the need for invasive biopsies, and encourage prompt treatment to prolong the life of a renal transplant for patients.Funding for this project will allow us to: 1) commercialize our fluorescent reagents for biomedical research through licensing with industry, and 2) establish the foundations for point-of-care technologies to measure granzyme B activity in the urine of patients that have undergone renal transplantation. This project will be guided by input from existing and new industrial and clinical partners, and will create opportunities for accelerating the research, early detection and effective treatment of kidney rejection.