Epoetin and cognitive function.
The uremia of chronic renal failure (CRF) can alter brain electrophysiology and cognitive function, even in the well-dialyzed patient. The effect of uremia on brain function can be assessed by electrophysiologic techniques such as electroencephalogram (EEG), sensory-evoked potentials (EPs), and cognitive event-related potentials (ERPs), and through a series of neuropsychologic tests. Five tests have been used clinically to measure the speed and efficiency of cognitive functioning and include the following: Number Cancellation, Trailmaking Test, Symbol Digit Modalities Test, Rey Auditory Verbal Learning Test, and Controlled Oral Word Association Test. Test performance by patients with CRF is often below that of healthy controls. Auditory ERPs, a sensitive indicator of subtle changes in central nervous system (CNS) function in uremia, result in the generation of a P300 component wave that varies in amplitude and latency with patient variables such as attention and effort. Although dialysis tends to normalize P300 latencies, the waves remain somewhat prolonged in most patients. The anemia often observed in patients receiving chronic dialysis appears to aggravate uremic encephalopathy. This effect can be reversed when anemia is corrected following administration of recombinant human erythropoietin (epoetin). Improvement in P300 amplitudes, and, in some cases, decreases in P300 latencies correlated well with epoetin-induced increases in hematocrit levels. With the correction of anemia, that component of brain dysfunction not attributable to retention of uremic toxins can largely be reversed.