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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK056788-14
Application #
8730121
Study Section
Special Emphasis Panel (ZDK1-GRB-R)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
14
Fiscal Year
2014
Total Cost
$169,059
Indirect Cost
$45,392
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Williams Jr, James C; Lingeman, James E; Coe, Fredric L et al. (2015) Micro-CT imaging of Randall's plaques. Urolithiasis 43 Suppl 1:13-7
Connors, Bret A; Evan, Andrew P; Blomgren, Philip M et al. (2014) Comparison of tissue injury from focused ultrasonic propulsion of kidney stones versus extracorporeal shock wave lithotripsy. J Urol 191:235-41
Evan, Andrew P; Lingeman, James E; Worcester, Elaine M et al. (2014) Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones. Anat Rec (Hoboken) 297:731-48
Handa, Rajash K; Evan, Andrew P; Connors, Bret A et al. (2014) Shock wave lithotripsy targeting of the kidney and pancreas does not increase the severity of metabolic syndrome in a porcine model. J Urol 192:1257-65
Williams Jr, James C; McAteer, James A (2013) Retention and growth of urinary stones: insights from imaging. J Nephrol 26:25-31
Bergsland, Kristin J; Worcester, Elaine M; Coe, Fredric L (2013) Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria. Am J Physiol Renal Physiol 305:F592-9
Childs, M Adam; Mynderse, Lance A; Rangel, Laureano J et al. (2013) Pathogenesis of bladder calculi in the presence of urinary stasis. J Urol 189:1347-51
Xu, Hongshi; Zisman, Anna L; Coe, Fredric L et al. (2013) Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother 14:435-47
Worcester, Elaine M; Bergsland, Kristin J; Gillen, Daniel L et al. (2013) Evidence for increased renal tubule and parathyroid gland sensitivity to serum calcium in human idiopathic hypercalciuria. Am J Physiol Renal Physiol 305:F853-60
Lingeman, James E (2013) Pathogenesis of nephrolithiasis. J Urol 189:417-8

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