PATHOPHYSIOLOGY OF DIALYSIS DISEQUILIBRUM SYNDROME

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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.