Normalizing hematocrit in dialysis patients improves brain function.

Recombinant human erythropoietin (rHuEPO) treatment has been shown to improve brain and cognitive function in anemic dialysis patients. Significant debate continues, however, regarding the appropriate target hematocrit (Hct) that will lead to the greatest benefits while considering possible side effects and costs of rHuEPO. Current practice results in an Hct averaging only 31% to 32% in dialysis patients, a level less than that achieved in the initial clinical trials and well less than normal. This study was designed to evaluate dialysis patients at the current practice Hct levels versus normal Hct levels (40% to 45%) to see if improvement in brain function resulted. Twenty patients with end-stage renal disease (ESRD) currently being treated with rHuEPO (mean Hct, 31.6%) were administered additional rHuEPO to reach normal Hct levels (mean, 42. 8%). Electroencephalogram (EEG) frequency analysis showed a significant decrease in EEG slowing at greater Hct values, and the auditory oddball and Continuous Performance Task tasks yielded significant electrode and time-by-electrode effects for P300 amplitude. Changes in P300 latency significantly correlated with increased Hct in the auditory oddball task. These findings suggest that further correction of anemia to normal Hct levels may result in continued improvement in neurocognitive function by improving the ability to sustain attention in easier tasks and by enhancing the ability to recognize, discriminate, and hold stimuli in memory for more difficult tasks.

The use of recombinant human erythropoietin in the correction of anemia in predialysis patients and its effect on renal function: a double-blind, placebo-controlled trial.

Fourteen nondialyzed patients with chronic renal insufficiency (serum creatinine 265 to 972 mumol/L [3.0 to 11.0 mg/dL]) and severe anemia (hematocrit less than 30%) were randomized to receive either recombinant human erythropoietin (r-HuEPO) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38% to 40%. Anemia was significantly ameliorated in the treated patients. No acceleration in the progression of renal failure (1/serum creatinine v time) or change in serum potassium was noted for either the placebo or treated group over the 12-week period. Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation (plasma iron/total iron-binding capacity). This resulted in functional iron deficiency and the requirement for iron supplementation. The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study. Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group. This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period. Improved patient well-being as a result of the correction of anemia resulted in one patient refusing appropriate initiation of dialysis therapy.