PATHOPHYSIOLOGY OF DIALYSIS DISEQUILIBRUM SYNDROME

透析失衡综合征的病理生理学

• 批准号: 3247177
• 负责人: YEONG-HAU H. LIEN
• 金额: $ 14万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1997-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3247177
• 关键词: brain cell; brain edema; chronic renal failure; hemodialysis; laboratory rat; magnetic resonance imaging; nuclear magnetic resonance spectroscopy; renal failure; syndrome; tissue /cell culture; uremias

Currently, more than 200,000 patients in the United States are treated for end stage renal disease (ESRD). Among them, about 60% are treated with hemodialysis. These patients frequently suffer from dialysis disequilibrium syndrome (DDS) which includes symptoms varying from seizure and coma to muscle cramps, anorexia, and restlessness. DDS is caused by brain edema when uremia is corrected too rapidly with hemodialysis. It has been debated whether brain edema is due to the retention of urea in the brain or due to the generation of unknown molecules, so-called "idiogenic osmoles" after hemodialysis. In either case, water would be shifted into the brain to cause brain edema. Since these "idiogenic osmoles" have not been identified, the real mechanisms of DDS remain unclear. As a result, proper ways to diagnose and to treat DDS have not yet been established. Previously, the investigators have successfully identified the dehydration-induced "idiogenic osmoles" in the rat brain by using 1H-nuclear magnetic resonance (NMR) spectroscopy and other biochemistry methods. They propose to use the similar approaches to characterize the "idiogenic osmoles" responsible to the development of DDS. Furthermore, they will apply the advanced NMR techniques, such as magnetic resonance imaging and localized NMR spectroscopy, to observe the changes of these "idiogenic osmoles" and associated changes in cell size, cell energy level, acid content and other metabolites in the brain and thigh muscle of living animals during the course of hemodialysis. To further delineate the role of different types of brain cells on the development of DDS, investigators will study the effects of addition and subsequent withdrawal of urea on cultured brain cells of a single cell type in a NMR-compatible system recently developed by them. The molecular basis of the generation of "idiogenic osmoles" will also be investigated in these cultured brain cells. These results would shed light on the mechanisms of DDS and provide information of the metabolic consequence of ESRD and hemodialysis. Potentially, new methods of diagnosing, treating and preventing DDS may be developed, thus, the quality of life of hemodialysis patients will be significantly improved.

目前，美国有20多万名患者接受治疗 用于终末期肾病(ESRD)。其中，约60%的人接受了治疗 进行血液透析。这些患者经常需要进行透析。 不平衡综合征(DDS)，包括以下症状 癫痫发作和昏迷到肌肉痉挛、食欲不振和躁动。DDS是 尿毒症纠正得太快时引起的脑水肿 血液透析。人们一直在争论，脑水肿是否由 尿素滞留在大脑中或由于未知的产生 分子，即血液透析后的“自发性渗透压”。在任何一种中 在这种情况下，水会被转移到大脑中，导致脑水肿。自.以来 这些“天然渗透分子”还没有被发现，真正的机制是 DDS的具体情况仍不清楚。因此，正确的诊断和治疗方法 DDS尚未建立。此前，调查人员已经 成功地鉴定了由脱水引起的“天然渗透压” 用~1H-核磁共振波谱研究大鼠脑 和其他生物化学方法。他们建议使用类似的 表征“天然渗透分子”的方法 DDS的发展。此外，他们还将应用先进的核磁共振技术 磁共振成像和定位核磁共振等技术 光谱分析，观察这些“天然渗透压”的变化和 细胞大小、细胞能级、酸含量和 活体动物大脑和大腿肌肉中的其他代谢物 血液透析的过程。为了进一步界定不同组织的作用 脑细胞类型对DDS发展的影响，研究人员将进行研究 添加和停用尿素对培养物生长的影响 最近在核磁共振兼容系统中的单个细胞类型的脑细胞 由他们开发的。“独生性”产生的分子基础 “渗透分子”也将在这些培养的脑细胞中进行研究。 研究结果将有助于阐明DDS的发病机制，并提供信息 终末期肾病和血液透析的代谢后果。潜在的，新的 可以开发诊断、治疗和预防DDS的方法， 因此，血液透析患者的生活质量将显著提高 改进了。