SUMMARY
The frequency of kidney stones, of which idiopathic calcium oxalate (CaOx) kidney stones are the most common,
is increasing in the United States, affecting 9% of the population. Environmental factors, lifestyle factors, diet
and metabolic or endogenous factors are known to play a role in the risk of kidney stone disease. Urinary oxalate
excretion influences risk of CaOx kidney stone formation and is derived from both dietary oxalate intake and
endogenous oxalate synthesis. Studies have addressed the contribution of dietary oxalate to urinary oxalate
excretion in healthy subjects, and demonstrated that dietary contribution can vary between 20 to 50%. However,
studies examining the importance of endogenous oxalate synthesis are lacking for patients with CaOx stone
disease. Obesity is linked to CaOx kidney stone risk and may influence urinary oxalate excretion, although the
underlying mechanisms are unknown. Strategies for treatment and prevention of CaOx kidney stones and
research into new treatments would benefit from a better understanding of the sources of endogenous oxalate
synthesis. The current proposal aims to determine if calcium oxalate kidney stone formers and subjects with
obesity have increased rates of endogenous oxalate synthesis compared with healthy volunteers with normal
BMI. An accurate measurement of endogenous oxalate synthesis will be performed using primed, steady-state,
continuous intravenous infusion of the stable isotope of oxalate, 13C2-oxalate, and analysis by ion
chromatography coupled with mass spectrometry, in subjects on a controlled low oxalate diet. 24-hr urinary
oxalate excretions collected on a low oxalate, controlled diet will be compared with the measurement of the
endogenous oxalate synthesis rate calculated by the continuous 13C2-oxalate intravenous infusion method. This
comparison will determine if the utilization of a low oxalate diet and collection of 24 hour urine is an appropriate
and easier approach to assess endogenous oxalate synthesis. The results of this pilot study will form the basis
for a future R01 application to, 1), test the hypothesis that CaOx kidney stone formers have increased
endogenous oxalate synthesis, 2), test the hypothesis that obesity enhances endogenous oxalate synthesis,
and, 3), identify sources of endogenous oxalate synthesis that are altered in obese individuals and those with
CaOx kidney stone disease, which in turn may lead to the development of novel therapeutic approaches to
decrease urinary oxalate excretion.
