EPO explained - What it Is and How it Acts

In 1836 Richard Bright described the connection between anaemia and kidney failure. At the turn of the century it was pointed out that a serum factor - incidentally at that time unknown - was able to stimulate the formation of red blood cells in the bone marrow, but it wasnt until 1953 that the Danish scientist Erslev described a factor (today we will call it a hormone) who was able to stimulate the formation of red blood cells and which a few years later was named Erythropoietin (EPO).

Some years later it was established, that the kidney was the endocrine organ which regulated the erythropoiesis - i.e. the formation of red blood cells.

Approximately 10 years later the reversed relation between haematocrit (the procentual number of red blood cells) and the plasma levels of EPO was established.

In 1974 Erslev proved that EPO-producing cells in the kidneys regulated the production of red blood cells depending on the oxygen tension in the kidneys.

For the first time in 1977 EPO was successfully extracted from the urine of a patient with aplastic anaemia (a chronic disease of the bonemarrow where the red cells are produced) and this allowed the possibility to map the structure of the molecule and led to the gene technological production of the substance.

Today EPO is produced from gene manipulated ovary cells from Chinese hamsters, which in unlimited quantity can be cultivated in tissue-culture from which the hormone can be harvested.

EPO improves the lives of kidney patients
The first clinical experiment with this gene spliced hormone happened during the years 1985 86. At the turn of the year 1986-87 the first clinical results on kidney patients were published.

In addition to itching, nausea, indigestion and cerebral disturbances, the uraemic syndrome also consists of a distinct fatigue and general feeling of sickness. These symptoms have always more or less been put down to well defined uraemic toxins, but after the introduction of the EPO-treatment, it appears that a great part of the uraemic patients discomforts vanish like dew before the sun. A reduction in days of admittance, a normalisation of the heart's pumping ability, an improved maximum O2-absorption (VO2 max.), an improved cognitive function plus a measurable improvement in quality of life- and last but not least- a better survival, is the result of an almost normal haemoglobin concentration.

Thus one must conclude, that the chronic state of anaemia, in which the patients have been, and which only necessarily and intermittently has been correctable through blood transfusions, is the main reason for the poor condition of the uraemic patients.

The treatment with EPO has thus markedly revolutionised the life of the chronic uraemic patient, that one can regard this treatment as the biggest revolution in the therapy of chronic kidney insufficiency since the dialysis treatment became generally accessible.

Today EPO is prescribed subcutaneously 1-3 times weekly in the magnitude 2000-4000 units per treatment.

EPO-resistance is never the less seen in several situations, but the most essential factor - and regrettably often also overlooked - is iron deficiency. Small or emptied iron stores will make the patients resistant to EPO-treatment.

The effect of EPO is apart from an accelerated ripening process of the earliest erythrocyte precursor (BFU and CFU) so that the differentiation is encouraged, also a stimulation of the haemoglobin synthesis and incorporation of iron in the unmature red cells. Clinically it is therefore very important to draw the attention to the patients' iron stores which means that they have enough iron in their bodies to make haemoglobin.

Infectious diseases, cancer diseases and surgical stress are factors, which fully or partly can impede the effect of EPO, for which reason one always ought to be aware of these factors in case a patient doesn't react satisfactorily to the therapy.

No reason to give EPO to healthy people
The treatment is costly. Estimated it will cost approximately 4000 $ per patient a year, if the aim is a haemoglobin level of the lower normal limit.

Approximately 90% of all patients on dialysis would probably benefit from the treatment, and in addition to this is a significant amount of pre-dialysis patients, whose general condition, physical yielding ability and social functions over a longer period of time can be kept intact.

A new EPO analogue has recently been marketed. It is called NESP (novel erythropoisis stimulating protein). Biochemically it is very close to EPO but it has the advantage that it can be prescribed with bigger intervals than EPO and also given intravenously to patients on haemodialysis in the same amount in contrast to EPO where the dose is higher in intravenously use.

There are certain other more unusual indications for EPO treatment, but exclusively to patients suffering from specific diseases. There are no reasons except stupidity to give this hormone to healthy people!