title: Detection of Free Advanced Glycation End Products in Vivo during Hemodialysis.
abstract: Advanced glycation end products (AGEs) are often regarded as glycotoxins, which are normally removed by the kidney. Patients with end-stage renal failure rely on hemodialysis (HD) treatment to eliminate these compounds. In the present work, a highly selective LC-MS/MS method was used for quantitation of AGE levels in plasma and in dialysis fluids of HD patients, with a focus on AGE-free adducts. A broad range of 19 amino acid modifications was identified and quantitated. It was expected that the AGE-free adducts are successfully eliminated by dialysis treatment. Indeed, with a mean elimination rate of 71%, this assumption proved to be valid for all target analytes with the exception of pyrraline, which showed an opposite behavior. Here, plasma and dialysate levels increased during the treatment by about 59%. The notions that pyrraline was formed in high amounts in the patient's bloodstream (I) after intake of the corresponding precursor compound 3-deoxyglucosone with the dialysis fluid or (II) by catalytic effects on the formation by the dialysis membrane were ruled out. In contrast, in a dietary study, the comparison of pyrraline concentrations in plasma before and after food consumption confirmed that the increase in pyrraline originates solely from digestion of glycated food proteins. Additionally, by detailed analyses of the food consumed during dialysis sessions, bread rolls with a pyrraline content of about 21.7 μmol per serving were identified as the main source.
authors.affiliation: Institute of Chemistry, Food Chemistry, Martin-Luther-University Halle-Wittenberg , Halle/Salle, Germany.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0003-2476-9925
authors.initials: C
authors.lastname: Hohmann
authors.affiliation: Institute of Chemistry, Food Chemistry, Martin-Luther-University Halle-Wittenberg , Halle/Salle, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Liehr
authors.affiliation: Institute of Chemistry, Food Chemistry, Martin-Luther-University Halle-Wittenberg , Halle/Salle, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Henning
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg , Halle/Salle, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Fiedler
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg , Halle/Salle, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Girndt
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH , Hechingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gebert
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH , Hechingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hulko
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH , Hechingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Storr
authors.affiliation: Institute of Chemistry, Food Chemistry, Martin-Luther-University Halle-Wittenberg , Halle/Salle, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Glomb
mesh_terms: D002853:Chromatography, Liquid; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009646:Norleucine / Q000031:analogs & derivatives / Q000097:blood; D011758:Pyrroles / Q000097:blood; D006435:Renal Dialysis; D053719:Tandem Mass Spectrometry
chemical_list: D017127:Glycation End Products, Advanced; D011758:Pyrroles; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine
keywords: advanced glycation end products; carboxymethyl-lysine; dietary study; end-stage renal failure; hemodialysis; pyrraline