title: Treating anemia associated with chronic renal failure with erythropoiesis stimulators: recombinant human erythropoietin might be the best among the available choices.
abstract: Chronic renal failure (CRF) is a widespread medical problem commonly accompanied by a hypoproliferative anemia ("renal anemia") due to erythropoietin deficiency. Anemia greatly contributes to reduced quality of life (Hr-QoL) and high morbidity and mortality in CRF patients. Recombinant human erythropoietin (rHu-Epo) was introduced to medical practice some 20years ago. It enables correction of anemia (hemoglobin levels, Hb) with dramatic immediate (Hr-QoL improvement) and long-term effects (reduced morbidity and mortality). Newer experimental data suggest that long-term benefits could be due not only to antianemic effect, but also to a direct organoprotective effect of (rHu)-Epo mediated through a receptor complex different from the "erythropoietic" erythropoietin receptor. During the last decade, two alternative treatments for renal anemia have been approved: darbepoetin and CERA. Both are direct agonists of the "erythropoietic" receptors and both were derived from rHu-Epo. Molecularly, they differ from rHu-Epo in that they are much larger molecules (darbepoetin is genetically modified rHu-Epo with a higher sugar content and CERA is pegylated rHu-Epo) with lower affinity for the erythropoietin receptor but with a longer circulating time. In terms of renal anemia correction, they are non-inferior to rHu-Epo and allow for less frequent dosing. They have never been compared to rHu-Epo regarding the long-term outcomes. It is hypothesized that regarding the long-term outcomes (morbidity, mortality), rHu-Epo might be superior to those larger molecules. The hypothesis is based on two types of observations. First, experimental data emphasize the role of small, erythropoietically less valuable rHu-Epo isoforms in its organoprotective effects. Second, clinical observations suggest that rHu-Epo enables for less variable Hb correction than the larger molecules, and pronounced within-subject Hb variability has been suggested as an independent predictor of poor long-term outcomes of renal anemia management.
authors.affiliation: Department of Pharmacology, Zagreb University School of Medicine, Šalata 11, 10000 Zagreb, Croatia. vtrkulja@mef.hr
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trkulja
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D004921:Erythropoietin / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008954:Models, Biological; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin