ENTERIC ELIMINATION OF OXALIC ACID

每年，在美国诊断出大约100万例肾结石疾病，花费约20亿美元的医疗保健费用。最常见的结石由草酸钙（约80%）组成，主要的风险因素是尿草酸盐浓度升高。尿草酸盐直接来源于食物或代谢过程，目前没有减少高尿酸血症的药物治疗。本文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盐的新概念，在肠道中，这种化合物可以被底物特异性细菌（草酸盐属）降解，存在于某些人身上，但不是所有人。具体目的是解决奥沙利铂可以局部调节草酸盐转运和增强肠道消除的假设。本研究的一个组成部分将检查在控制饮食Ca2+的条件下，草酸盐在减少尿草酸盐方面的有效性。通过更全面地了解肠粘膜屏障分泌和排泄草酸盐的能力与Oxalobacter sp.降低腔内草酸盐活性的能力之间的动态相互作用，将出现一种新的治疗计划。其目的是专门指导开发一种补充疗法，该疗法将最大限度地增强肠道草酸盐排泄并减少高尿酸血症。拟议的商业应用：开发一种有效的补充疗法来控制高尿酸状况是及时的。目前，有100万肾结石患者，还有其他尿酸盐相关疾病的患者，包括原发性高尿酸血症，由于尿酸盐诱导的肾衰竭，原发性高尿酸血症总是导致早期死亡。一种新的治疗策略，以减少尿草酸排泄的临床应用的潜力是广泛的和高度显着的。

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.