Calcium oxalate kidney stone formation affects a significant number of individuals in the United States and contributes billions of dollars to health care costs. Urinary oxalate excretion plays a major role in the formation of these calculi as it influences the supersaturation of urine with calcium oxalate, a prerequisite for calcium oxalate stone formation. Recent investigations have shown that a significant amount of urinary oxalate is derived from dietary sources. Therefore, reducing oxalate consumption or its absorption from the intestinal tract may prove to be useful methods for limiting an individual's risk of forming stones. Experiments with cultured cells and animal models have demonstrated that oxalate has the potential to damage renal tissue through the generation of chemicals called oxygenated free radicals. This process may play a causative role in calcium oxalate stone formation. Therefore, attenuating this response may also limit stone generation.There are three specific aims in this research proposal. The first is to compare the response of stone forming and non-stone forming adults to dietary oxalate.
The second aim i s to compare renal oxalate clearance in both of the aforementioned groups. These studies will determine whether there are any differences in the renal handling of oxalate between these two groups.
The third aim i s to determine whether urinary oxalate excretion and renal proximal tubular cell injury can be reduced with calcium supplements, vitamin E supplements, administration of oxalate degrading bacteria, or a combination of all three of these regimens. All of these studies will be conducted in our General Clinical Research Center where carefully controlled diets can be administered. Various responses will be assessed including gastrointestinal oxalate absorption, urinary supersaturation, oxalate excretion, oxidative stress and markers of renal proximal tubular cell injury. These studies will aid in the development of strategies to prevent kidney stone formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK062284-04
Application #
6878638
Study Section
Special Emphasis Panel (ZRG1-GRM (04))
Program Officer
Kirkali, Ziya
Project Start
2002-06-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2005
Total Cost
$275,401
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Surgery
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Holmes, Ross P; Knight, John; Assimos, Dean G (2016) Lowering urinary oxalate excretion to decrease calcium oxalate stone disease. Urolithiasis 44:27-32
Lange, Jessica N; Mufarrij, Patrick W; Easter, Linda et al. (2014) Fish oil supplementation and urinary oxalate excretion in normal subjects on a low-oxalate diet. Urology 84:779-81
Lange, Jessica N; Easter, Linda; Amoroso, Robert et al. (2013) Internet program for facilitating dietary modifications limiting kidney stone risk. Can J Urol 20:6922-6
Knight, John; Deora, Rajendar; Assimos, Dean G et al. (2013) The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease. Urolithiasis 41:187-96
Manny, Ted B; Mufarrij, Patrick W; Lange, Jessica N et al. (2012) Gas-containing renal stones: findings from five consecutive patients. Urology 80:1203-8
Lange, Jessica N; Mufarrij, Patrick W; Wood, Kyle D et al. (2012) The association of cardiovascular disease and metabolic syndrome with nephrolithiasis. Curr Opin Urol 22:154-9
Lange, Jessica N; Wood, Kyle D; Wong, Hayes et al. (2012) Sensitivity of human strains of Oxalobacter formigenes to commonly prescribed antibiotics. Urology 79:1286-9
Lange, Jessica N; Wood, Kyle D; Mufarrij, Patrick W et al. (2012) The impact of dietary calcium and oxalate ratios on stone risk. Urology 79:1226-9
Knight, John; Jiang, Juquan; Wood, Kyle D et al. (2011) Oxalate and sucralose absorption in idiopathic calcium oxalate stone formers. Urology 78:475.e9-475.e13
Jiang, Juquan; Knight, John; Easter, Linda H et al. (2011) Impact of dietary calcium and oxalate, and Oxalobacter formigenes colonization on urinary oxalate excretion. J Urol 186:135-9

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