The broad, long-term goal of this work is to measure kidney nephron and glomerular volume endowment in humans, in vivo. Each nephron contains a glomerulus, which functions as a high-pressure filter of blood macromolecules. Deficits in nephrons and glomeruli have been correlated with renal diseases such as diabetes, obesity, and hypertension. There is currently no noninvasive technique to count the total number of functioning renal glomeruli and nephrons in vivo. Such a technique would enable studies of kidney and systemic disease in humans, and would open a new area of animal studies of the susceptibility to renal disease. We propose that contrast-enhanced MRI, using MRI-detectable nanoparticles targeted to the glomerular basement membrane, can be used to accurately count the total number of glomeruli and measure glomerular volume in the whole, intact kidney. This proposal is focused on establishing this technique in mice. We further propose to assess the accuracy of the technique in the presence of systemic deficits in nephron endowment in mice. Once completed, the proposed work will open the possibility of real-time, in vivo glomerular counts and volume in studies of renal and systemic diseases in animals and humans.

Public Health Relevance

The purpose of this project is to develop a molecular MRI technique to count the number of kidney glomeruli and volume ex vivo and in vivo. This work will lay the foundation for the use of MRI-detectable nanoparticle probes to study single nephron structure and function in animal models and humans.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Pathobiology of Kidney Disease Study Section (PBKD)
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Ketchum, Christian J
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University of Hawaii
Schools of Arts and Sciences
United States
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Beeman, Scott C; Cullen-McEwen, Luise A; Puelles, Victor G et al. (2014) MRI-based glomerular morphology and pathology in whole human kidneys. Am J Physiol Renal Physiol 306:F1381-90
Clavijo Jordan, M Veronica; Beeman, Scott C; Baldelomar, Edwin J et al. (2014) Disruptive chemical doping in a ferritin-based iron oxide nanoparticle to decrease r2 and enhance detection with T1-weighted MRI. Contrast Media Mol Imaging 9:323-32
Bertram, John F; Cullen-McEwen, Luise A; Egan, Gary F et al. (2014) Why and how we determine nephron number. Pediatr Nephrol 29:575-80
Bennett, K M; Bertram, John F; Beeman, Scott C et al. (2013) The emerging role of MRI in quantitative renal glomerular morphology. Am J Physiol Renal Physiol 304:F1252-7
Charlton, Jennifer R; Beeman, Scott C; Bennett, Kevin M (2013) MRI-detectable nanoparticles: the potential role in the diagnosis of and therapy for chronic kidney disease. Adv Chronic Kidney Dis 20:479-87