Treating anemia associated with chronic renal failure with erythropoiesis stimulators: recombinant human erythropoietin might be the best among the available choices

Znanstveni rad - Izvorni znanstveni rad

• Autor: Vladimir Trkulja
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Kliničke medicinske znanosti

Sažetak (engleski)

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.

• Ključne riječi (engleski): Anemia / drug therapy; Anemia / etiology; Erythropoietin / therapeutic use; Hematinics / therapeutic use; Humans; Kidney Failure, Chronic / complications; Models, Biological; Recombinant Proteins / therapeutic use
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: Medical Hypotheses
• Brojčani podaci: vol. 78, br. 1, str. 157-161
• p-ISSN: 0306-9877
• DOI: https://doi.org/10.1016/j.mehy.2011.10.016
• URN:NBN: urn:nbn:hr:105:400861
• Datum objave publikacije: 2012-01
• URL dokumenta: https://doi.org/10.1016/j.mehy.2011.10.016
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-27 19:13:17