Influence of Obesity on Endogenous Oxalate Synthesis

点击翻译按钮获取中文摘要

The prevalence of both obesity and kidney stones is increasing with calcium oxalate as the major component in 70 – 80% of stones. The amount of oxalate excreted in urine is a risk factor for the development of calcium oxalate stones and several studies have identified that obese individuals excrete more oxalate than individuals with normal BMI. The prevalence of both obesity and stone disease is high in both Alabama and Texas, indicating that these states are ideally suited to identify whether they are inter-related. In this project we will assess 3 possible reasons for this greater excretion including an increased contribution of endogenous oxalate synthesis to the urinary oxalate pool, enhanced net gastrointestinal oxalate absorption, and augmented renal oxalate secretion. We will merge the skill sets and knowledge present on the UAB campus in the Center for research on Obesity and Oxalate Kidney Stones (COOKS) with those in the UTSW Center for Mineral Metabolism and Clinical Research (CMMCR) in order to address this hypothesis. This joint endeavor will facilitate subject recruitment and enhance skill sets originating in urology, biochemistry, obesity, nutrition and physiology at UAB with those in endocrinology, urology, GI Medicine/hepatology and nephrology at UTSW. We aim to identify factors contributing to an increased urinary oxalate excretion in obese calcium oxalate stone formers. In Specific Aim 1 we will examine endogenous oxalate synthesis which will be the predominant source of urinary oxalate on a very low oxalate diet. In Specific Aim 2, we will examine transport processes in the gut and kidney to identify the contributions of gastrointestinal absorption and renal secretion of oxalate. Body fat content and its distribution will also be measured to determine if it correlates with oxalate synthesis or transport. The successful completion of these aims may identify therapeutic strategies that decrease urinary oxalate excretion and stone risk. The amalgamation of expertise in these Centers should be a pathway for strong future collaborative research focused on therapeutic interventions.