Novel non-heart-beating donor kidney storage medium

供体肾脏不能满足目前对肾移植的需求，这是治疗终末期肾衰竭最有效的方法。非心脏跳动（NHB）供体肾脏未得到充分利用，因为目前的技术不允许NHB供体器官承受不可避免的长时间的热缺血和冷缺血。陈氏培养基（CM）是一种新型的生理保存液，对人供体角膜具有良好的保存效果。CM含有β -羟基丁酸盐，一种独特的非乳酸生成高能代谢物，使组织产生高水平的ATP，同时抑制细胞内酸中毒。NHB供体器官经历独特的代谢妥协，其中许多方面可以通过烟酰胺预防。烟酰胺是一种对人体安全的NAD+前体，是保存MHB供体器官的理想选择，因为它可以清除自由基，通过抑制聚（adp -核糖）聚合酶介导的NAD+分解代谢来保持NDA+水平，并抑制损伤后人内皮细胞诱导型一氧化氮合酶和白细胞吸引分子的表达。我们建议用离体灌注猪肾模型的生理、生化和组织学标准来证明烟酰胺CM在NHB供体器官保存方面优于UW和EC溶液。我们的目标是推进移植技术，使未充分利用的NHD供体器官得到有效利用。拟议的商业应用：拟议的研究，如果成功，将有潜在的商业应用。也就是说，CM将能够被标记为非心脏跳动的肾脏保存介质。这是一种孤儿药，在美国的市场规模估计为每年2000万美元，在国外市场的市场规模约为600万至1000万美元。

Donor kidney cannot meet current demand for kidney transplantation, the most effective for end stage renal failure. Non-heart-beating (NHB) donor kidneys are under-utilized because current technology does not allow NHB donor organs to withstand unavoidable extended periods of warm and cold ischemia. Chen Medium (CM), a novel physiological preservation solution, is highly effective for human donor cornea storage and preservation. CM contains beta-hydroxybutyrate, a unique non- lactate-generating high-energy metabolite that enables tissues to generate high levels of ATP while suppressing intracellular acidosis. NHB donor organs undergo unique metabolic compromise, many aspects of which could be prevented by nicotinamide. Nicotinamide, an NAD+ precursor that is safe for humans, is idea for MHB donor organ preservation because it scavenges free radicals, preserves NDA+ levels through inhibition of poly(ADP-ribose) polymerase-mediated NAD+ catabolism, and inhibits both inducible nitric oxide synthase and expression of leukocyte-attracting molecules on human endothelial cells after injury. We propose to use physiological, biochemical and histological criteria with the isolated perfused pig kidney model to demonstrate that CM with nicotinamide is superior to UW and EC solutions for NHB donor organ preservation. Our aim is to advance transplant technology to allow effective utilization of under-utilized NHD donor organs. PROPOSED COMMERCIAL APPLICATIONS: The proposed research, if successful, will have potential commercial application. That is, CM will be able to be marked as a non-heart-beating kidney preservation medium. This is an Orphan product with a market size estimated about $20 million a year in the US and about $6-10 million for the foreign markers combined.