Influence of Obesity on Endogenous Oxalate Synthesis

肥胖和肾结石的患病率都在增加，草酸钙是肾结石的主要成分。 70%-80%的结石。尿液中草酸排泄量是钙形成的危险因素。 草酸盐结石和几项研究已经证实，肥胖的人比个人排出更多的草酸 体重指数正常。在阿拉巴马州和德克萨斯州，肥胖症和结石病的患病率都很高，这表明 这些状态非常适合用来确定它们是否相互关联。在这个项目中，我们将评估3个 这种更大排泄的可能原因包括内源性草酸合成的增加 尿草酸池，增强胃肠道草酸净吸收，并增加肾草酸 分泌物。我们将把UAB园区现有的技能和知识整合到中心进行研究 肥胖和草酸肾结石(厨师)与UTSW矿物代谢和临床中心的厨师 研究(CMMCR)，以解决这一假设。这一联合努力将促进学科招募 并加强UAB在泌尿学、生化、肥胖、营养和生理学方面的技能 在内分泌学、泌尿科、胃肠内科/肝病和肾脏科。我们的目标是确定因素 导致肥胖的草酸钙结石患者尿草酸排泄增加。在特定目标中1 我们将检查内源性草酸合成，它将是尿草酸的主要来源。 低草酸饮食。在具体目标2中，我们将检查肠道和肾脏的转运过程，以确定 草酸的胃肠吸收和肾脏分泌的贡献。体脂含量及其分布 也将进行测量，以确定它是否与草酸盐的合成或运输有关。圆满完成 这些目标之一可能会确定减少尿草酸排泄和结石风险的治疗策略。这个 这些中心的专业知识融合应该是未来强有力的合作研究的途径 关于治疗干预。

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.