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In this study, a comprehensive method for analysis of these post\u2010translational modifications is established for the clinical diagnostic routine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we analysed albumin \u2013 the most abundant plasma protein in human \u2013 isolated from patients with<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>and healthy controls by chromatographic steps and identified by<jats:styled-content style=\"fixed-case\">MALDI<\/jats:styled-content>mass spectrometry. Post\u2010translational modifications of albumin were identified after digestion by analysing mass signal shifts of albumin peptides using pertinent mass databases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Albumin isolated from plasma of patients with<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>but not from healthy control subjects was specifically post\u2010translationally modified by guanidinylation of lysines at positions 249, 468, 548, 565 and 588. After identification of guanidinylations as post\u2010translational modifications of albumin isolated from patients with<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>, these modifications were quantified by mass spectrometry demonstrating a significant increase in the corresponding mass signal intensities in patients with<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>compared to healthy controls. The relative amount of guanidinylation of lysine at position 468 in patients with<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>was determined as 63\u00a0\u00b1\u00a032% (<jats:italic>N<\/jats:italic>\u00a0=\u00a03). Subsequently, we characterized the pathophysiological impact of the post\u2010translational guanidinylation on the binding capacity of albumin for representative hydrophobic metabolic waste products.<jats:italic>In vitro<\/jats:italic>guanidinylation of albumin from healthy control subjects caused a decreased binding capacity of albumin in a time\u2010dependent manner. Binding of indoxyl sulphate (protein\u2010bound fraction) decreased from 82\u00a0\u00b1\u00a01% of not post\u2010translationally modified albumin to 56\u00a0\u00b1\u00a01% after<jats:italic>in\u00a0vitro<\/jats:italic>guanidinylation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), whereas the binding of tryptophan decreased from 20 to 4%. These results are in accordance with the binding of indoxyl sulphate to albumin from healthy control subjects and patients with<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>(88\u00a0\u00b1\u00a03 vs. 74\u00a0\u00b1\u00a010,<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Thus,<jats:italic>in\u00a0vitro<\/jats:italic>post\u2010translational guanidinylation of albumin had a direct effect on the binding capacity of hydrophobic metabolites such as indoxyl sulphate and tryptophan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We used a mass spectrometry\u2010based method for the characterization of post\u2010translational modification and demonstrated the pathophysiological impact of a representative post\u2010translational modification of plasma albumin. The data described in this study may help to elucidate the pathophysiological role of protein modifications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12518","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T14:36:51Z","timestamp":1430750211000},"page":"13-23","source":"Crossref","is-referenced-by-count":47,"title":["Guanidinylations of albumin decreased binding capacity of hydrophobic metabolites"],"prefix":"10.1111","volume":"215","author":[{"given":"M.","family":"Rueth","sequence":"first","affiliation":[{"name":"eXcorLab Industrie\u2010Center\u2010Obernburg Obernburg Germany"},{"name":"Charit\u00e9\u2010Universitaetsmedizin Berlin Medizinische Klinik IV (CBF) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010D.","family":"Lemke","sequence":"additional","affiliation":[{"name":"eXcorLab Industrie\u2010Center\u2010Obernburg Obernburg 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