Erythropoietin: Biology and clinical applications

Research output: Contribution to journalArticlepeer-review

Abstract

Cloning of the human erythropoietin (Epo) gene and production of recombinant human Epo (rhEpo) have allowed impressive advances in our understanding of Epo biology and have provided clinicians with a very powerful agent for treatment of anaemia. Epo is a glycoprotein with a molecular weight of 30,400 D: glycosylation is important for survival in vivo but not for biological activity in vitro. More than 85% of Epo synthesis takes place primarily in the kidney in the adult. Epo producing cells are grouped in interstitial foci mostly adjacent to proximal convoluted tubules in the inner cortex, and are likely to be peritubular capillary endothelial cells. Epo exerts its effects on erythropoiesis by binding to a surface Epo receptor. It is essentially a survival factor for colony-forming unit-erythroid and early proerythroblasts, preventing apoptosis or programmed cell death of these cells. Moreover, it stimulates biochemical processes in erythroid cells and induces terminal erythroid maturation. Assessment of serum Epo is now a routine diagnostic procedure and allows evaluation of appropriateness of Epo response to anaemia in the individual patient. Blunted Epo production is the major cause of anaemia in various disorders, including anaemia of chronic renal failure, prematurity, rheumatoid arthritis, AIDS, malignancy and bone marrow transplantation. Recombinant human Epo corrects anaemia, eliminates the need for transfusion, improves quality of life and is cost effective in anaemic patients with renal failure. Anaemic patients with AIDS who are treated with zidovudine and who have inadequate endogenous Epo production can benefit from treatment with rhEpo. Autologous blood donation can be significantly potentiated by administering rhEpo to subjects with haematocrit values lower than 40% in order to avoid exposure to allogeneic blood. Functional iron deficiency is an important limiting factor for erythroid response, so that iron supplementation is essential in these subjects. Recombinant human Epo is also effective in several other anaemias, although only a portion of these patients are responsive. Due to the very high costs of rhEpo it is necessary to identify factors predicting response, in order to define those patients for whom treatment is both medically and cost effective.

Original languageEnglish
Pages (from-to)344-361
Number of pages18
JournalFORUM - Trends in Experimental and Clinical Medicine
Volume3
Issue number4
Publication statusPublished - 1993

Keywords

  • anaemia
  • erythropoiesis
  • erythropoietin
  • iron therapy
  • red cell

ASJC Scopus subject areas

  • Medicine(all)

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