RECOMBINANT-HUMAN-ERYTHROPOIETIN - 10 YEARS OF CLINICAL-EXPERIENCE

The need for a renewable source of erythropoietin to treat the anaemia of chronic renal failure was first recognized in the 1960s, but cloni ng and expression of the human gene was not achieved until 1983. Clini cal testing of recombinant human erythropoietin (r-HuEPO) began in 198 5, leading to the first licence as a therapeutic agent in 1988. The fi rst clinical trials showed that an intravenous dose requirement of abo ut 200 IU/kg/week would increase haemoglobin concentrations to 10-12 g /dl in >90% of haemodialysis patients. Subcutaneous administration has subsequently been found to be effective, and may allow lower maintena nce doses. It is now the route of choice in Europe, but not the USA. T he best marker of benefit of the introduction of r-HuEPO is the reduct ion in need for regular blood transfusions. A marked improvement in an aemia-related symptoms has been clearly demonstrated. The most importa nt factor in optimizing the response to r-HuEPO is iron supply. The ma rrow should be stimulated slowly, to allow mobilization of iron stores . Functional or absolute iron deficiency should be pre-empted by regul ar iron supplementation. It is also important to recognize resistant s tates induced by inflammation and bleeding, and to exclude severe hype rparathyroidism, aluminium overload and other haematological diseases. The most important adverse events associated with r-HuEPO are increas ed blood pressure and a possible increased risk of access failure. The se are, however, challenges to improve practice, not reasons to avoid the use of r-HuEPO.