DIETARY PROTEIN AND ENDOGENOUS OXALATE SYNTHESIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The amount of oxalate synthesized in the body is a critical factor in the primary hyperoxalurias, which are rare genetic diseases, and also plays an important role in calcium oxalate kidney stone formation. The metabolic pathways and dietary constituents that contribute to this endogenous synthesis of oxalate have not been clearly defined. The liver is the major organ producing endogenous oxalate and experiments in our laboratory with cultured hepatocytes indicate that amino acid metabolism is a primary source of this oxalate. We hypothesize that amino acid metabolism is an important contributor to endogenous oxalate production in humans and that this metabolism will be enhanced on high protein diets. A previous study we conducted suggested that females, but not males, responded to an increased protein intake with an increased endogenous synthesis of oxalate. The interpretation of this study was confounded, however, by a lack of control of dietary oxalate. To test our hypothesis that amino acid metabolism is a significant contributor to endogenous oxalate synthesis in both males and females, we will examine the urinary excretion of oxalate in subjects consuming diets of varying protein content. Diets will be controlled in macro- and micronutrients, including oxalate, to limit the effects of dietary oxalate on urinary oxalate excretion.