, Volume 64, Issue 5, pp 499–509 | Cite as

Differentiating Factors Between Erythropoiesis-Stimulating Agents

A Guide to Selection for Anaemia of Chronic Kidney Disease
  • Robert DeicherEmail author
  • Walter H. Hörl
Review Article


Endogenous erythropoietin (EPO) consists of a central polypeptide core covered by post-translationally linked carbohydrates. Three of the four currently available erythropoiesis stimulating agents (ESA) — epoetin-α, epoetin-β and epoetin-ω — are composed of an identical amino acid sequence, but glycosylation varies as a result of type- and host cell-specific differences in the production process.

Epoetin-α and epoetin-β resemble each other with respect to molecular characteristics and pharmacokinetic data, although epoetin-β has a higher molecular weight, a lower number of sialylated glycan residues and possibly slight pharmacokinetic advantages such as a longer terminal elimination half-life. A serious adverse effect of long-term administration of ESA is pure red cell aplasia. This effect has been observed predominantly with subcutaneous use of epoetin-α produced outside the US after albumin was removed from the formulation. In comparison with the intravenous route, subcutaneous administration of epoetin has been reported to have a dose-sparing effect in some studies. Epoetin-β has been the subject of studies aimed at proving efficacy with a reduced administration frequency but results are not unequivocal.

Epoetin-co is produced in a different host cell than all other erythropoietic agents, hence glycosylation and pharmacokinetics are different. Small-scale clinical studies found epoetin-ω to be slightly more potent than epoetin-α.

Epoetin-δ is a recently approved agent produced by human cells that are genetically engineered to transcribe and translate the EPO gene under the control of a newly introduced regulatory DNA sequence. However, epoetin-δ is not yet on the market and few data are available.

The erythropoietin analogue darbepoetin-α carries two additional glycosylation sites that permit a higher degree of glycosylation. Consequently, in comparison with the other epoetins, darbepoetin-a has a longer serum half-life and a higher relative potency, which further increases with extension of the administration interval. Dosage requirements of darbepoetin-α do not appear to differ between the intravenous and subcutaneous routes of administration. The less frequent administration of darbepoetin-α in comparison to the other epoetins may reduce drug costs in the long term, but the variability in dosage or dosage frequency required within a single patient is high.

Further studies should be aimed at defining predictors of the individual demand for erythropoietic agents, thereby allowing nephrologists to prescribe a cost-effective, individualised regimen.


Chronic Kidney Disease Subcutaneous Administration Peritoneal Dialysis Patient Sialic Acid Residue Erythropoiesis Stimulate Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of the manuscript. Non-personal research grants to the Division of Nephrology and Dialysis, Department of Medicine III, University of Vienna, are provided by Amgen, Baxter, Jansen-Cilag and Roche. Professor Dr Dr W.H. Hörl, FRCP, is a consultant to Baxter and Amgen. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.


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Authors and Affiliations

  1. 1.Division of Nephrology and Dialysis, Department of Medicine IIIUniversity of ViennaViennaAustria

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