Hyperoxaluria, defined as the presence of excess oxalic acid and/or oxalate salts in urinary excretions, is a physiological condition associated with an increasing number of common and debilitating chronic diseases whose prevalences are increasing in both the United States and the rest of the world. Oxalic acid is a natural and abundant by-product of metabolism, but also a highly oxidized organic compound with powerful chelating activity that, in high concentrations, can cause death in both animals and humans due to its corrosive effects. More commonly, however, hyperoxaluria is now associated (or correlated) with a variety of pathological disorders, including cardiomyopathy, cardiac conductance disorders, urolithiasis, fungal infections, cystic fibrosis, colitis, primary hyperoxaluria type-I, pyridoxine deficiency, and steatorrhea. Thus, regulating oxalate levels in the body is receiving greater recognition as an important factor in controlling the effects of hyperoxaluria in multiple pathologies. Unfortunately, current testing for hyperoxaluria is expensive, time- consuming and mainly conducted by trained technicians in well-equipped laboratories. This SBIR proposal addresses a serious issue in the field of hyperoxaluria-associated pathologies: the lack of a simple, rapid point- of-care device to monitor oxalate levels in biological fluids. To address this deficiency, we propose to complete the development of a dipstick test that rapidly and accurately measures oxalate levels in urine. To obtain proof- of-concept, the team proposes the following Phase I Specific Aims: 1) Develop a dipstick test from which results can be obtained by visual reading, and 2) Perform in-vitro testing of the dipsticks to determine the sensitivity, specificity, accuracy, and reproducibility. Development of a dipstick for quantifying changes in oxalate levels, similar to the glucometer for measuring glucose levels, would represent a unique advancement for patients suffering with diseases ranging from calcium-oxalate kidney stone disease to cystic fibrosis and primary hyperoxaluria type 1. Our preliminary data suggest the stated aims will be readily achieved. Once proof-of-concept is confirmed, the team will move into Phase II, which will focus on clinical functionality and performance of the dipstick.
Public Health Relevance Statement: PROJECT NARRATIVE Oxalic acid is a naturally-occurring substance that, in high concentrations, is toxic to most organisms. Elevated levels of oxalic acid in urine, referred to as hyperoxaluria, have been found to be present in a number of pathological conditions, including kidney stone disease, primary hyperoxaluria type I, cardiomyopathy, and vulvar pain. Unfortunately, measurement of oxalate is time-consuming and highly technical requiring skilled technicians and sophisticated equipment; thus, patients and physicians are usually unable to quickly obtain urinary oxalate levels reducing patient-physician during visits as a mean to adjust or recommend dietary changes. This SBIR focuses on the development of a urine dipstick that will permit rapid simple point-of-care measurements of oxalate. 1
Project Terms: Address; Animals; Behavior; Biological; Calcium Oxalate; Cardiac; Cardiomyopathies; Cause of Death; Chelating Activity; Chronic Disease; Clinic; Clinical; Colitis; Collection; Consumption; Corrosives; Crohn's disease; Cystic Fibrosis; Data; design; Detection; Development; Devices; Diabetes Mellitus; diabetic; Diagnosis; Diagnostic; Diet; digital; Disease; Dyes; Environment; Equipment; Evaluation; Excretory function; Future; Glucose; glucose monitor; Goals; healthy volunteer; high risk; Home environment; Hour; Human; Hydrogen; Hyperoxaluria; in vitro testing; Individual; Infrastructure; Kidney; Kidney Calculi; Laboratories; Liquid substance; Measurement; Measures; Metabolism; Methods; Mission; Modification; Monitor; Mycoses; Organism; Outpatients; oxalate oxidase; Oxalates; Oxalic Acids; Oxides; Pathologic; Pathology; Patients; Performance; Peroxidases; Phase; phase 1 study; Physicians; Physiological; Plants; point of care; Prevalence; Primary Hyperoxaluria; Reading; Recurrence; Reproducibility; Research; Rest; Salts; Sensitivity and Specificity; Small Business Innovation Research Grant; sound; Specificity; Steatorrhea; Technology; Test Result; Testing; Time; Training; United States; United States Food and Drug Administration; urinary; Urine; urolithiasis; urologic; Vial device; Visit; Visual; Vitamin B 6 Deficiency; vulvar pain; Vulvodynia
