Hemodynamic and hormonal changes during erythropoietin therapy in hemodialysis patients

Abstract

To better understand the mechanism of recombinant human erythropoietin (rhEPO)-induced increase in BP, hemodynamic parameters, body fluid volumes, and the hormones implicated in BP regulation were studied in 32 anemic hemodialysis patients before and after 3 to 4 mo of rhEPO therapy. 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 subcutaneously three times weekly. Mean 24-h systolic and diastolic ambulatory BP were significantly increased by 14 ± 3 and 10 ± 2 mmHg, respectively (P < 0.01 for both groups). Systemic vascular resistance consistently increased by 28 ± 5% (P < 0.01), whereas cardiac output was decreased by 6 ± 3% (P < 0.05). Red blood cell mass increased by 510 ± 35 ml (P < 0.01), whereas plasma volume decreased by 420 ± 66 ml (P < 0.01), which resulted in a nonsignificant increase in total blood volume. Extracellular fluid volume and exchangeable sodium were decreased by 873 ± 255 ml (P < 0.01) and 125 mmol (P < 0.01), respectively. There was a positive correlation between the changes in exchangeable sodium 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 exchangeable sodium increased or remained unchanged (n = 10) compared with patients (n = 22) with decreased exchangeable sodium (20 ± 4 mmHg versus 8 ± 2 mmHg, respectively, P < 0.01). Plasma catecholamines, plasma renin concentration, plasma atrial natriuretic peptide, and plasma endothelin-1 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, the results presented here suggest the importance of optimally reducing extracellular fluid volume to prevent, at least in part, the development of hypertension often observed with improved uremic anemia in these patients.