Kidney stone disease is a significant health problem that consumes billions of dollars annually in health care costs and lost productivity. The bulk of these stones consist primarily of calcium oxalate. The amount of calcium and oxalate in urine are thus significant risk factors for the disease. Until recently, dietary oxalate was believed to make only a minor contribution to the amount of oxalate in urine. However, using diets carefully controlled in their content of oxalate and other nutrients, we were able to show that it contributed on average half of the oxalate excreted in urine. The goal of this research project is to determine how dietary oxalate most contributes to stone risk and to design therapeutic strategies that will offset this stone risk and prevent stobe recurrence. To date, our investigations have shown that differences in the renal handling of oxalate do not contribute to renal injury or oxidative stress following transient increases in the filtered load of oxalate produced by oral oxalate loads. We did observe that the absorption of dietary oxalate does differ in individuals, particularly that occurring in the large intestine.
The first aim of this project is to identify the prevalence of hyperabsorption in normal individuals and stone formers and to determine what features are associated with this hyperabsorption.
The second aim i s to clarify the role of the oxalate-degrading organism, Oxalobacter formigenes in large intestinal absorption.
The third aim seeks to translate these findings into directed therapies that prevent stone recurrence. We will test an interactive Internet-based program that will utilize several dietary modifications to help patients modify their diet and reduce stone risk. This translation of laboratory based findings to the clinic should be adatable to reducing a number of dietary associated risk factors and in individuals with stones other than calcium oxalate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK062284-08
Application #
7789575
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Kirkali, Ziya
Project Start
2002-06-01
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2013-03-31
Support Year
8
Fiscal Year
2010
Total Cost
$294,359
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Urology
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
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
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
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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