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Red blood cell lifespan, erythropoiesis and hemoglobin control.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
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2008 (English)In: Contributions to Nephrology, ISSN 0302-5144, Vol. 161, 247-254 p.Article in journal (Refereed) Published
Abstract [en]

Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

Place, publisher, year, edition, pages
2008. Vol. 161, 247-254 p.
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-110007DOI: 10.1159/000130698ISI: 000257307700034PubMedID: 18451684OAI: oai:DiVA.org:uu-110007DiVA: diva2:275007
Available from: 2009-11-02 Created: 2009-11-02 Last updated: 2009-11-11Bibliographically approved

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