Erythropoietin down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate in humans.
Recombinant human erythropoietin (rHuEPO) elevates haemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin–aldosterone system and renal function. Sixteen healthy males were given rHuEPO for 28 days in doses raising the haematocrit to 48.3±4.1%.Renal clearance studieswith urine collections (N = 8) were done at baseline and at days 4, 11, 29 and 42. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA.Renal clearance of lithium (CLi)was used as an index of proximal tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in haematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO decreased plasma levels of renin and aldosterone (N = 8) by 21–33% (P < 0.05) and 15–36% (P < 0.05), respectively. After cessation of rHuEPO, values returned to baseline. On days 11 and 29, CLi increased (P < 0.02) indicating a significant 10–16% decrease in absolute proximal reabsorption of sodium and water (APR = GFR − CLi, P < 0.05). GFR decreased slightly, albeit significantly, on day 4 (P < 0.05). In conclusion, rHuEPO promptly, and before any changes in blood volumes and haematocrit can be detected, causes a down-regulation of the renin–aldosterone system. The results are compatible with a rHuEPO-induced reduction in proximal reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in GFR. Therefore, treatment with rHuEPO may result in suppression of endogenous EPO synthesis secondary to a decrease in intrarenal oxygen consumption.
Olsen
Niels Vidiendal
NV
Department of Neuroanaesthesia, The Neuroscience Centre, Investigation, Rigshospitalet, Copenhagen, Denmark.
Aachmann-Andersen
Niels-Jacob
NJ
Oturai
Peter
P
Munch-Andersen
Thor
T
Bornø
Andreas
A
Hulston
Carl
C
Holstein-Rathlou
Niels-Henrik
NH
Robach
Paul
P
Lundby
Carsten
C
D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000328:Adult; D048429:Cell Size / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage*; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007279:Injections, Subcutaneous; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D004921:Erythropoietin