Renal Effects of Erythropoietin in Humans

Summary

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.

Conditions

• Renal Effects

Interventions

DRUG

Erythropoietin (Epoetin-beta, NeoRecormon®)

5000 IU/ml of NeoRecormon (Epoetin beta) is given subcutaneously as one ml before 10 O-clock a.m. on day 1,3,5,7,9,11 and 13. On day 1 and 3 5000 IU is given in one syringe and five ml of saline in total is given in five other syringes in order to maintain the double blinding. On day 2 six syringes of a total of 6 ml of saline is given in six syringes.

DRUG

Erythropoietin (Epoetin-beta, NeoRecormon®)

30.000 IU of NeoRecormon (Epoetin beta) is given subcutaneously as a total of six ml (5.000 IU/ml) given in six syringes before 10 O-clock a.m. on day 1,2 and 3. On day 5,7,9,11 and 13 six ml of saline in total is given in six syringes in order to maintain the double blinding.

DRUG

Placebo

1 ml of saline (Sodium Chloride 9 mg/ml) is given subcutaneously before 10 O-clock a.m. on day 1,2,3,5,7,9,11 and 13. On day 1,2 and 3 six ml in total is given in six syringes in order to maintain the double blinding.

Sponsors & Collaborators

• Rigshospitalet, Denmark

  collaborator OTHER

• University of Copenhagen

  lead OTHER

Principal Investigators

• Niels Vidiendal Olsen, M.D., D.M.Sc. · Department of Neuroscience and Pharmacology, University of Copenhagen

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

20 Years

Max Age

40 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-03-31

Primary Completion

2013-08-31

Completion

2013-09-30

Countries

• Denmark

Study Locations