Eligibility

Ages Eligible for Study

20 years to 40 years

Genders Eligible for Study

M

Keywords

Erythropoietin, Glomerular filtration rate, Tubular reabsorption, Renal function, and Renal perfusion

Sponsors

Other

Rigshospitalet, Denmark

Other

University of Copenhagen

Inclusion Criteria

- Male

- Age between 20-40 years

- Non smoker for min. a year

- BP below 140/90

- No medicine use

- BMI below 25

Exclusion Criteria

- Participation in other medical trails

- Allergi towards Erythropoietin

- Malignity diseases

- Epilepsy

- Staying above 1500 meters within the last 3 months

- Polycythemia

- Elite athlete

- Haematocrit above 55%

Detailed Description

Erythropoietin (EPO) is a glycoprotein produced mainly in the kidney. After its release to the bloodstream EPO binds to its receptor predominantly located within the bone marrow where erythropoiesis is stimulated. Recently, we have shown that recombinant human EPO (rHuEPO) down-regulates circulating levels of renin and aldosterone. Concomitant clearance studies revealed a decrease in proximal tubular reabsorption of sodium and water and a fall in glomerular filtration rate (GFR). These results for the first time demonstrate a link between EPO and renal function: By inhibiting proximal tubular reabsorption, which in turn results in rapid declines in GFR and renin/aldosterone levels, EPO may directly reduce the major oxygen consuming factor in the kidney. The expected result will be an increase of the oxygen tension in the environment of renal EPO producing cells, in this way initiating an appropriate signal for down-regulation of endogenous EPO synthesis when circulating levels of EPO are high. The aim of this project is to test this hypothesis by investigating the renal effects of rHuEPO in humans. In a double-blinded manner healthy subjects will be tested with placebo, or low-dose rHuEPO for two weeks, or high-dose rHuEPO for three days. Accurate sodium balance studies will be conducted together with renal clearance studies for measurements of renal plasma flow (131I-Hippuran clearance with renal venous sampling), GFR (51Cr-EDTA clearance) and the segmentel tubular handling of sodium and water (lithium clearance). EPO is the sole haematopoietic growth factor that is mainly produced in the kidneys and the project will provide new information about basic physiological issues regarding the association between renal function and the regulation of EPO synthesis.