Suppression of the renin-angiotensin-aldosterone axis with erythropoietin therapy by a negative feedback loop

To investigate the pathophysiology of hypertension in patients receiving recombinant human erythropoietin (rHuEpo) we studied its effects on the renin-aldosterone axis of chronic haemodialysis (HD) patients not receiving antihypertensive drugs. Nine severely anaemic normotensive HD patients received rHuEpo 50 U/kg bodyweight, thrice weekly after each HD. The dose was increased by 25 U/kg bodyweight every 4 weeks to a maximum of 100 U/kg or until an increase of Hb or Hct of 2 g/dl or 7% was achieved. Blood samples were taken after 30 min supine rest and while seated 10 min later after gentle ambulation. Results expressed as mean±SEM: Both parameters decreased in all patients during rHuEpo therapy, but there were no changes in mean arterial pressure (89 ± 5 versus 89 ± 5 mmHg) or bodyweight (62 ±5 versus 62 ±5 kg). Haemoglobin (g/dl) and haematocrit (%) increased from 6.2 ±0.6 and 19.1 ±0.8 to 8.2±1.3 and 24.5±1.14 respectively (P<0.01). We therefore conclude that suppression of the renin-aldosterone axis occurs during rHuEpotherapy in normotensive HD patients by a negative feedback loop, before the development of hypertension.