ENTERIC ELIMINATION OF OXALIC ACID

在美国，每年大约有一百万例肾结石患者被诊断为肾结石，花费在医疗保健上的费用约为20亿美元。最常见的结石是草酸钙(约80%)，一个主要的危险因素是尿草酸浓度升高。尿草酸直接来自食物或代谢过程，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泄这种化合物来减少尿草酸的新概念，在那里它可以被底物特定细菌(草杆菌属)降解，这种细菌存在于一些人中，但不是所有人。具体的目的是解决这样的假设，即草酸杆菌可以局部调节草酸的运输并促进肠道消除。这项研究的一个组成部分将检验草酸杆菌在控制膳食钙离子的条件下减少尿草酸的有效性。通过更全面地了解肠粘膜屏障分泌和排泄草酸的能力与草酸杆菌能力之间的动态相互作用。为了降低管腔内草酸的活性，一种新的治疗计划将会出现。其目的是专门指导一种补充疗法的开发，这种疗法将最大限度地增加肠道草酸排泄，减少高草酸尿。拟议的商业应用：开发一种有效的补充疗法来控制高草酸状况是及时的。目前，有100万名肾结石患者，还有其他草酸相关疾病的患者，包括原发性高草酸尿症，由于草酸诱导的肾功能衰竭，这种疾病总是会导致早年死亡。临床应用一种新的治疗策略来减少尿草酸排泄的潜力是广泛的和非常重要的。

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.