title: Patients with anaemia can shift from kidney to liver production of erythropoietin as shown by glycoform analysis.
abstract: The primary production site of erythropoietin (EPO) is shifted from the liver to the kidney shortly after birth. Under conditions of lost or reduced kidney production, it is valuable to measure the production capacity of the liver. However, there is a lack of urine or serum based methods that can distinguish endogenous EPO produced in different cell types. Here is presented a method based on chromatographic interaction with the lectin wheat germ agglutinin (WGA) that can distinguish presumably liver-produced EPO, found in anaemic patients receiving epoetin and darbepoetin, from kidney-produced EPO found in healthy individuals. All the tested samples from haemodialysis patients with end-stage renal disease showed a presence of liver EPO. In some samples, the liver-produced EPO made up 90-100% of total EPO at a concentration of 8-10 ng/L in urine, which indicates that the liver has a quite high production capacity, although not adequate for the degree of anaemia. This glycoform analysis has made it possible to affirm that some anaemic patients can increase their liver-production of EPO. The use of such a method can give better insight into the regulation of non-renal endogenous EPO production, a potential source of EPO intended to replace administration of exogenous EPO.
authors.affiliation: Analytical Chemistry, Department of Chemistry - BMC, Uppsala University, Uppsala, Sweden. maria.lonnberg@kemi.uu.se
authors.forename: Maria
authors.initials: M
authors.lastname: Lönnberg
authors.forename: Mats
authors.initials: M
authors.lastname: Garle
authors.forename: Lina
authors.initials: L
authors.lastname: Lönnberg
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegård
mesh_terms: D000328:Adult; D000740:Anemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D016022:Case-Control Studies; D002846:Chromatography, Affinity / Q000379:methods*; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000032:analysis* / Q000096:biosynthesis / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis; D014909:Wheat Germ Agglutinins / Q000737:chemistry; D055815:Young Adult
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D014909:Wheat Germ Agglutinins; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa