HEMODYNAMIC AND HORMONAL CHANGES DURING ERYTHROPOIETIN THERAPY IN HEMODIALYSIS-PATIENTS

To better understand the mechanism of recombinant human erythropoietin (rhEPO)-induced increase in BP, hemodynamic parameters, body fluid vo lumes, and the hormones implicated in BP regulation were studied in 32 anemic hemodialysis patients before and after 3 to 4 mo of rhEPO ther apy. Hemoglobin levels increased from 83 +/- 1.5 to 119 +/- 2.3 g/L (P < 0.01) after rhEPO therapy (25 to 43 U/kg) administered subcutaneous ly three times weekly. Mean 24-h systolic and diastolic ambulatory BP were significantly increased by 14 +/- 3 and 10 +/- 2 mmHg, respective ly (P < 0.01 for both groups). Systemic vascular resistance consistent ly increased by 28 +/- 5% (P < 0.01), whereas cardiac output was decre ased by 6 +/- 3% (P < 0.05). Red blood cell mass increased by 510 +/- 35 mi (P < 0.01), whereas plasma volume decreased by 420 +/- 66 mi (P < 0.01), which resulted in a nonsignificant increase in total blood vo lume. Extracellular fluid volume and exchangeable sodium were decrease d by 873 +/- 255 mi (P < 0.01) and 125 mmol (P < 0.01), respectively. There was a positive correlation between the changes in exchangeable s odium and in systolic BP (r = 0.41, P < 0.05). Furthermore, a greater increase in 24-h systolic BP was observed in patients in whom exchange able sodium increased or remained unchanged (n = 10) compared with pat ients (n = 22) with decreased exchangeable sodium (20 +/- 4 mmHg versu s 8 +/- 2 mmHg, respectively, P < 0.01). Plasma catecholamines, plasma renin concentration, plasma atrial natriuretic peptide, and plasma en dothelin-l did not significantly change with rhEPO treatment, whereas plasma aldosterone increased significantly (P < 0.01). Although volume -independent mechanisms may contribute to rhEPO-induced BP increase, t he results presented here suggest the importance of optimally reducing extracellular fluid volume to prevent, at least in part, the developm ent of hypertension often observed with improved uremic anemia in thes e patients.