DIALYSIS DISEQUILIBRIUM SYNDROME (DDS) IN THE RAT - ROLE OF THE REVERSE UREA EFFECT

DDS is characterized by neurologic deterioration and cerebral edema which occurs after hemodialysis. To investigate the pathogenesis of DDS, we studied the effects of rapid hemodialysis on plasma and brain electrolytes, urea, and osmolality in the rat. Forty-two hours after bilateral nephrectomy, nine uremic rats were hemodialyzed for 90 minutes against dialysate without urea (model of DDS), yielding a decrease in plasma urea from 72 +/- 2 mm to 34 +/- 2 mm (P < 0.01) and an 8% (29 mOsm/kg) decrease in plasma osmolality. This group was compared to three control groups: 11 uremic animals dialyzed against a bath with urea added so that no fall in plasma urea occurred, and 15 uremic and 12 nonuremic animals that were not dialyzed. In animals dialyzed without urea, compared to uremic non-dialyzed animals, there was a 6% increase in brain water (3.89 +/- 0.04 liter/kg dry wt vs. 3.67 +/- 0.03, P < 0.01) and an increase in the brain to plasma (urea) ratio (1.30 +/- 0.06 vs. 0.79 +/- 0.05, P < 0.01). Comparison of these parameters in animals dialyzed without urea versus other control groups yielded similar results. In animals dialyzed without urea, the 53% decrease in plasma urea was associated with only a 13% decrease in brain urea content. Brain content of sodium and potassium was not significantly different among groups. Retention of brain urea despite the large decrease in plasma urea was able to account for the increased brain water observed in animals dialyzed without urea. The brain to plasma osmolality ratio in animals dialyzed without urea (1.00 +/- 0.04) was not significantly different from the three control groups. We conclude that the cerebral edema in our model of DDS appears primarily due to a large brain to plasma urea gradient.