Development of a Urine Test for the Early Detection of Liver Cancer

DESCRIPTION (provided by applicant): While the high costs of healthcare in the U.S. can be felt by everyone in the country, the economic impact to patients with kidney failure is particularl significant as dialysis treatments can reach 85,000 annually, with transplantation being the only known cure. Therefore, kidney transplants today make up more than half of all transplants performed in the U.S., with roughly 17,000 transplants every year. Unfortunately, up to 29% of kidney failure rate is observed for asubset of these transplant patients and delayed graft function also occur in 23% of these kidney recipients. To address this issue, powerful immunosuppressant therapies have been developed to reduce the chances of transplant complications, but such therapies may not be necessary or appropriate for all patients. Therefore, early warning of graft failure has a significant positive economic and health impact by allowing earlier, less intensive, and more effective therapeutic intervention. The current standard practice for evaluating kidney function is through an invasive renal biopsy. Unfortunately, the process of removing a tiny, random tissue sample from patient's kidney leads to significant sampling errors; moreover, the histological evaluation of the biopsies is subjective and can vary amongst pathologists or even the same pathologist reviewing biopsies from opposite poles of the same kidney. Biomarkers such as creatinine, glomerular filtration rate, and proteinuria have also been used for evaluating kidney function; however, they are limited in their prediction power. Among several potential biomarkers for kidney injury, Kidney Injury Molecule-1 (Kim-1) is well studied in the clinical setting and in the animal model. Kim-1 is shed into urine as a solubleform and it is stable for up to 24 hours, therefore its detection in urine is not invasive. In some instance, Kim-1 is more sensitive than histology for allograft injury. Clinical laboratory tests are available for quantifying Kim-1 in the urine as wellas a dipstick test that cn qualitatively detect the presence of Kim-1. Neither test, however, allows for routine quantification of Kim-1 levels at a reasonable cost; being able to monitor the Kim-1 level quantitatively allows the potential for identifyingthe severity of kidney injury, risk stratificaton of patients in clinical setting, to guide therapy and determine if kidney injury is improving or gettig worse. Towards this goal, GlucoSentient is developing a quantitative monitoring device for Kim-1 thatis effective, affordable, and easy to use. We can achieve this goal by developing assays for biomarkers for kidney injury, with Kim-1 as the initial target, to be used with existing glucometers, which are based on low-cost, easy to construct electrochemical sensors. By combining the gold standard antibody based assay with low cost detection technology, GlucoSentient will develop a final product that allows post-kidney-transplant patients to monitor their kidney function by frequently measuring Kim-1 in urine. We believe this product can greatly increase the quality of life for post-transplant patient as well as reduce the associated costs for kidney failure and dysfunction. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: This SBIR Phase I proposal aims to take advantage of existing glucometer technology by employing an innovative technology to develop an assay for quantification of acute urine kidney injury biomarkers, such as Kim-1, which can be used as a surrogate for renal failure post-transplant. Providing patients with a low-cost, convenient, and quantitative device will have a significant impact on reducing kidney transplant failures, saving patients' lives, and deceasing healthcare costs.