PATHOPHYSIOLOGY OF DIALYSIS DISEQUILIBRUM SYNDROME

透析失衡综合征的病理生理学

• 批准号: 2144869
• 负责人: YEONG-HAU H. LIEN
• 金额: $ 19.16万
• 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/2144869
• 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，美国有超过20万名患者接受治疗 终末期肾病（ESRD） 其中，约60%的人接受治疗 血液透析。这些患者经常遭受透析 不平衡综合征（DDS），包括以下症状 癫痫和昏迷到肌肉痉挛厌食和坐立不安 DDS是 由于尿毒症纠正过快而引起脑水肿， 血液透析。 关于脑水肿是否是由于 尿素在脑中的滞留或由于产生未知的 分子，即血液透析后所谓的“特发性渗透压”。 在任一 在这种情况下，水会转移到大脑中，导致脑水肿。 以来 这些“特发性渗透压”尚未确定，其真实的机制 DDS的情况仍不清楚。 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 成功鉴定了脱水诱导的“特发性渗透压”， 用1H-核磁共振（NMR）波谱法测定大鼠脑 和其他生物化学方法。 他们建议使用类似的 方法来表征“独特的渗透压”负责 DDS的发展。 此外，他们将应用先进的核磁共振技术， 技术，例如磁共振成像和局部核磁共振 光谱法，观察这些“自发渗透压摩尔”的变化， 在细胞大小、细胞能量水平、酸含量和 其他代谢物在活体动物的大脑和大腿肌肉中， 血液透析的过程。 为了进一步阐明不同的 类型的脑细胞对DDS的发展，研究人员将研究 添加和随后取消尿素对培养的 最近，在NMR兼容系统中的单个细胞类型的脑细胞 由他们开发的。 “特基因”产生的分子基础 还将在这些培养的脑细胞中研究”渗透压“。 这些 结果将揭示DDS的机制，并提供信息 终末期肾病和血液透析的代谢后果。 可能，新 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， 提高