ENTERIC ELIMINATION OF OXALIC ACID

草酸的肠道消除

• 批准号: 2868048
• 负责人: Marguerite Hatch
• 金额: $ 10万
• 依托单位: IXION BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-15 至 2000-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2868048
• 关键词: bacteria characteristic; dietary calcium; gastrointestinal absorption /transport; infection; laboratory rat; membrane channels; microorganism metabolism; nephrocalcinosis; oxalates; primary hyperoxalurias

Every year, approximately one million cases of kidney stone disease are diagnosed in the United States costing about $2 billion in health care. The most common stone is comprised of calcium oxalate (about 80%) and a major risk factor is elevated urinary oxalate concentration. Urinary oxalate is derived directly from food or from metabolic processes and currently there is no pharmacological treatment for reducing hyperoxaluria. The studies proposed here focus on the novel concept of reducing urinary oxalate by innocuously excreting this compound through the intestine where it can be degraded by substrate-specific bacteria (Oxalobacter sp.), present in some, but not all individuals. The specific aims address the hypothesis that Oxalobacter can locally modulate oxalate transport and enhance intestinal elimination. An integral part of the study will examine the effectiveness of Oxalobacter in reducing urinary oxalate under conditions where dietary Ca2+ is manipulated. By developing a more complete understanding of the dynamic interaction between the capacity of the intestinal mucosal barrier to secrete and excrete oxalate coupled with the ability of Oxalobacter sp. To lower intraluminal oxalate activity a novel treatment plan will emerge. The aim is to specifically direct the development of a supplementation therapy which will maximally enhance enteric oxalate excretion and reduce hyperoxaluria. PROPOSED COMMERCIAL APPLICATION: The development of an effective supplementation therapy for the control of hyperoxaluric conditions is timely. Currently, there are 1 million patients with kidney stone disease and there are patients with other oxalate-associated diseases, including primary hyperoxaluria which invariably results in death at an early age due to oxalate-induced kidney failure. The potential for the clinical application of a novel treatment strategy to reduce urinary oxalate excretion is broad-based and highly significant.

在美国，每年大约有100万例肾结石病例被诊断出来，医疗保健费用约为20亿美元。最常见的结石是由草酸钙组成的（约80%），一个主要的危险因素是尿中草酸钙浓度升高。尿草酸盐直接来源于食物或代谢过程，目前还没有减少高草酸尿的药物治疗。这里提出的研究集中在通过肠道无害地排出这种化合物来减少尿草酸盐的新概念上，在肠道中，它可以被存在于某些但不是所有个体中的特定底物细菌（草酸杆菌sp.）降解。具体目的是解决草酸杆菌可以局部调节草酸运输和促进肠道消除的假设。该研究的一个组成部分将检查草酸杆菌在饮食Ca2+被操纵的条件下减少尿草酸盐的有效性。通过更全面地了解肠黏膜屏障分泌和排泄草酸盐的能力与草酸杆菌降低腔内草酸盐活性的能力之间的动态相互作用，一种新的治疗方案将出现。目的是专门指导一种补充疗法的发展，该疗法将最大限度地提高肠内草酸盐排泄并减少高草酸尿。建议的商业应用：开发一种有效的补充疗法来控制高血氧条件是及时的。目前，有100万患者患有肾结石，还有一些患者患有其他草酸盐相关疾病，包括原发性高草酸尿症，由于草酸盐引起的肾衰竭，这种疾病总是导致早期死亡。潜在的临床应用的一种新的治疗策略，以减少尿草酸排泄是广泛的和高度重要的。