Dietary Oxalate and Kidney Stone Formation

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DESCRIPTION (provided by applicant): 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 is 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 is 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.