
Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin‐angiotensin‐aldosterone system
Author(s) -
AachmannAndersen Niels J.,
Christensen Soren J.,
Lisbjerg Kristian,
Oturai Peter,
Johansson Pär I.,
HolsteinRathlou NielsHenrik,
Olsen Niels V.
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13573
Subject(s) - erythropoietin , medicine , aldosterone , endocrinology , effective renal plasma flow , renal blood flow , renin–angiotensin system , renal sodium reabsorption , plasma renin activity , renal function , reabsorption , kidney , blood pressure , angiotensin ii , hemodynamics
The effect of recombinant erythropoietin (rh EPO ) 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 rh EPO for 2 weeks, or high‐dose rh EPO 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). rh EPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high‐dose rh EPO intervention and tended to decrease GFR . In spite of the decrease in renal perfusion, rh EPO 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 rh EPO induced a prothrombotic state. Our results suggest that rh EPO 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 rh EPO on renal hemodynamics and a decoupling of the renin‐angiotensin‐aldosterone system.