Role of dialysable solutes in the mediation of uremic encephalopathy in the rat

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This study addresses mechanisms of the clinical, encephalopathic uremic illness and its suppression by dialysis. Renoprival rats were treated with peritoneal dialysis (8 exchanges per day, 30 min dwell), or untreated (attrition group), and their EEG's were automatically sampled overnight and subjected to power spectrum analysis as an index of encephalopathy. As in man the background rhythm of the quantified EEG (Q.EEG) in the attrition group slowed with time as extracellular fluid composition became increasingly abnormal; these changes were normalized by therapeutic dialysis (TD) using standard, commercial dialysate. However, Q.EEG slowing was only partially normalized by solute-specific dialysis using "mock uremic dialysate" (M-UD), prepared from laboratory chemicals to equal plasma concentrations in preterminal uremic rats of urea, creatinine, potassium, phosphorus, calcium, magnesium, bicarbonate, sodium, and chloride. When only phosphate was added to TD, the Q.EEG slowed to the same level achieved after M-UD. We conclude that uremic encephalopathy in this model is produced by an unknown neurotoxin and augmented by one or more of the M-UD solutes, phosphate being a likely candidate. To localize the encephalopathic effect, regional brain glucose uptake was estimated in 20 discrete brain areas. Significance of reduced uptake in three areas is discussed.