Project 2 wlW test the hypothesis that in non-ICSF most stones do not originate as overgrowths on duct of Bellini crystal plugs. We have established that in ICSF, calcium oxalate stones form as overgrowths on interstitial deposits of hydroxyapatite (Randall's plaque) in patients with large stone burden requiring PNL. We will extend this approach to patients with ICSF and smaller stones who will be treated with URS utilizing digital instrumentation in order to investigate the generalizability of our observation of calcium oxalate overgrovi/th on plaque and, further, that plaque abundance correlates with histologic and metabolic data, as well as clinical stone events. We will also investigate the discordance between acidic bulk urine and tubular deposits of apatie or urate in stone formers with ileostomy and non-bariatric enteric hyperoxaluria utilizing a novel fiberoptic pH microsensor to test the hypothesis that injured BD have local acidification defects enabling deposition of crystals favoring a more alkaline millieu. Finally, we will compare CaP stone content of calyceal stones with a papillary injury scoring system testing the hypothesis that more severely damaged calyces will have more impairment of tubular acidification resulting in a higher percentage of CaP content in stones produced.

Public Health Relevance

Nephrolithiasis is a common condition representing a lifetime occurrence risk of 10% of men and 7% of women. There appear to be at least 3 ways that stones can form in kidneys. Project 2 will study the initiating events in stone formation to determine the sequence of injury that resulting in formation of specific stone types, which will lead to more specific and effective preventive and surgical treatments for these patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-R)
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University of Chicago
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Williams Jr, James C; Borofsky, Michael S; Bledsoe, Sharon B et al. (2018) Papillary Ductal Plugging is a Mechanism for Early Stone Retention in Brushite Stone Disease. J Urol 199:186-192
Worcester, Elaine M; Bergsland, Kristin J; Gillen, Daniel L et al. (2018) Mechanism for higher urine pH in normal women compared with men. Am J Physiol Renal Physiol 314:F623-F629
Bergsland, Kristin J; Coe, Fredric L; Parks, Joan H et al. (2018) Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers. Nephrol Dial Transplant 33:759-770
Kleinguetl, Colin; Williams Jr, James C; Ibrahim, Samar A et al. (2017) Calcium Tartrate Tetrahydrate, Case Report of a Novel Human Kidney Stone. J Endourol Case Rep 3:192-195
Mulay, Shrikant R; Eberhard, Jonathan N; Desai, Jyaysi et al. (2017) Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease. J Am Soc Nephrol 28:761-768
Winfree, Seth; Khan, Shehnaz; Micanovic, Radmila et al. (2017) Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune Cells. J Am Soc Nephrol 28:2108-2118
Borofsky, Michael S; Dauw, Casey A; York, Nadya et al. (2017) Accuracy of daily fluid intake measurements using a ""smart"" water bottle. Urolithiasis :
Winfree, Seth; Ferkowicz, Michael J; Dagher, Pierre C et al. (2017) Large-scale 3-dimensional quantitative imaging of tissues: state-of-the-art and translational implications. Transl Res 189:1-12
Cohen, Andrew J; Borofsky, Michael S; Anderson, Blake B et al. (2017) Endoscopic Evidence That Randall's Plaque is Associated with Surface Erosion of the Renal Papilla. J Endourol 31:85-90
Gilad, Ron; Williams Jr, James C; Usman, Kalba D et al. (2017) Interpreting the results of chemical stone analysis in the era of modern stone analysis techniques. J Nephrol 30:135-140

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