Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin‐angiotensin‐aldosterone system

Recombinant erythropoietin acutely decreases renal perfusion and decouples the... The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double‐blinded, cross‐over study. Sixteen healthy subjects were tested with placebo, or low‐dose rhEPO for 2 weeks, or high‐dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high‐dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin‐angiotensin‐aldosterone system from changes in renal hemodynamics. This may serve as a negative feed‐back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin‐angiotensin‐aldosterone system. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Physiological Reports Wiley

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin‐angiotensin‐aldosterone system

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Publisher
Wiley
Copyright
© 2018 Published by the American Physiological Society and The Physiological Society
ISSN
2051-817X
eISSN
2051-817X
D.O.I.
10.14814/phy2.13573
Publisher site
See Article on Publisher Site

Abstract

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double‐blinded, cross‐over study. Sixteen healthy subjects were tested with placebo, or low‐dose rhEPO for 2 weeks, or high‐dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high‐dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin‐angiotensin‐aldosterone system from changes in renal hemodynamics. This may serve as a negative feed‐back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin‐angiotensin‐aldosterone system.

Journal

Physiological ReportsWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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