Biology Reference
In-Depth Information
Use of recombinant erythropoietins in the setting of
renal disease
Iain C. Macdougall
Renal Unit, King's College Hospital, East Dulwich Grove, London SE22 8PT, UK
Introduction
Recombinant human erythropoietin (rHuEPO) therapy was introduced for the
treatment of renal anemia in the mid-1980s, and since that time, several mil-
lion patients have been treated worldwide. The market for this product has
expanded considerably, and is currently valued at approximately US$7
billion. In the context of renal disease, the treatment has proved highly effec-
tive, largely because the major cause of renal anemia is a relative deficiency in
circulating amounts of endogenous EPO. The history and development of
rHuEPO is discussed elsewhere in this topic (see Chapter 2), as are the phar-
macokinetics (see Chapter 6) and biological effects of this therapy (see
Chapter 10). This chapter will,therefore, discuss the clinical use of rHuEPO
in patients with renal disease, focusing in turn on the hematologic response,
the secondary benefits associated with this treatment, and possible adverse
effects.
Currently available erythropoietic agents for treating renal anemia
Worldwide, quite a number of erythropoietins/erythropoietin analogues are
manufactured using recombinant DNA technology for the treatment of anemia
in patients with kidney disease. Several of these products breach patent regu-
lations but are produced for local use in their country of origin, and/or for lim-
ited export to some of the less industrialized countries of the world. Excluding
these, there are three major erythropoietic agents produced for the developed
world, and these include two rHuEPOs (epoetin alfa and epoetin beta), and a
second-generation erythropoietin analogue (darbepoetin alfa). Epoetin alfa
and epoetin beta share structural homology with the endogenous hormone,
while darbepoetin alfa is a modified EPO molecule that was designed to be
longer acting. All erythropoietic agents act on the erythropoietin receptor
(EPOR)(see Chapters 3 and 5 for further information), and all enhance the pro-
liferation and survival of erythroid progenitor cells in the bone marrow, thus
