title: Increased Synthesis of Liver Erythropoietin with CKD.
abstract: Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0-20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6-9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.
authors.affiliation: Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland; National Center of Competence in Research Kidney.CH, Sophie.deseigneux@hcuge.ch.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Seigneux
authors.affiliation: Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zurich, Switzerland; and.
authors.forename: Anne-Kristine Meinild
authors.initials: AK
authors.lastname: Lundby
authors.affiliation: Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;
authors.forename: Lena
authors.initials: L
authors.lastname: Berchtold
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Berg
authors.affiliation: Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;
authors.forename: Patrick
authors.initials: P
authors.lastname: Saudan
authors.affiliation: National Center of Competence in Research Kidney.CH, Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zurich, Switzerland; and.
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
mesh_terms: D000368:Aged; D004921:Erythropoietin / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*
chemical_list: C554270:EPO protein, human; D004921:Erythropoietin
keywords: anemia; chronic kidney disease; erythropoietin