Erythropoietin down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate in humans

Niels Vidiendal Olsen, Niels-Jacob Aachmann-Andersen, Peter Sandor Oturai, Thor Munch-Andersen, Andreas Bornø, Carl Hulston, Niels-Henrik Holstein-Rathlou, Paul Robach, Carsten Lundby

26 Citationer (Scopus)

Abstract

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.
OriginalsprogEngelsk
TidsskriftJournal of Physiology
Vol/bind589
Udgave nummerPt 6
Sider (fra-til)1273-81
Antal sider9
ISSN0022-3751
DOI
StatusUdgivet - 15 mar. 2011

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