Diseases of the urinary tract in newborns can lead to infant death, kidney failure, and in those who survive, to chronic kidney disease (CKD) and early heart disease in adulthood. In the western hemisphere, despite the availability of pre natal maternal care and advanced imaging, obstructive diseases of the urinary tract account for the majority of cases of end stage kidney disease and consume 24% of health care expenditure in this segment of population. In third world countries, where sophisticated maternal care and imaging modalities are not available, these conditions lead to infant mortality. This has necessitated an internationa coordination and integration of efforts in this region- including India for the purpose of early screening for CKD. Most of these conditions do not cause symptoms and therefore are silent killers and go undetected. Current routine urinary testing is not sensitive enough to uncover these conditions. The diagnosis of these serious conditions through the low cost, point of care screening diagnostic test proposed in this grant followed by treatment, can lead to cure in a majority of newborns and infants with congenital diseases of the urinary tract. These conditions have a variable degree of severity and if left undiagnosed or untreated can be progressive and lead to mortality and morbidity. Early detection and treatment has been shown in pilot studies to lessen the burden of chronic kidney and heart disease in adolescents and adults born with these conditions. Based on known incidences, it is anticipated that early detection by this diagnostic test may result in a 10% overall reduction of the CKD burden in adulthood. This objective was clearly identified as a priority at the 2008 Hyderabad workshop, India, which in turn has led to PAR-11-044. For the past 5 years, we discovered urinary biomarkers of congenital obstructive uropathy focusing on human ureteropelvic junction obstruction (UPJO). Using a mass spectrometry (MS)-based proteomics approach we have identified biomarkers of UPJO in infants. Since the advanced MS technology is not suited for routine clinical use, we are proposing to translate this sophisticated technology to an easy to use multiplexed protein array for a point-of-care application. The proposed diagnostic screening kit will be simple and may be operated by mid-level providers. Our overarching hypothesis is that a multiplexed urinary test (dipstick) can be developed to identify the expression levels of up to six candidate protein biomarkers in congenital obstructive uropathy.
Aim 1 : will test that the proposed multiplexed protein array will selectively and precisely capture the biomarkers from a voided urine mixture.
Aim 2 : will test that these multiplex urinary test results are validated by MS-based quantification assays in newborns and infants. The potential clinical impact of the proposed study is substantial. Our goal is to develop a point of care, easy to use, precise, reproducible and accurate diagnostic tool to facilitate early and instantaneous detection of unknown silent obstructive kidney disease and may save many lives.

Public Health Relevance

Childhood kidney disease can lead to kidney failure. Less severe disease can progress over time into various degrees of kidney failure in adolescence and adulthood. Collectively, obstructive diseases of the kidney in newborns and infants consume about a quarter of health care dollars in this segment of the population. We are proposing to develop a new and rapid noninvasive diagnostic test to detect obstructive uropathy in newborns and infants worldwide. The proposal is based on 5 years of research data on the specific condition targeted in this proposal. This data consists of high tech proteomic analysis of urinary specimens in infants with obstructive uropathy. The outcome will help early and instantaneous detection of silent obstructive kidney disease even in low cost resource settings and may save many lives worldwide.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Small Research Grants (R03)
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Special Emphasis Panel (ZRG1)
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Lash, Tiffani Bailey
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University of Wisconsin Milwaukee
United States
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