Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health
Joint Authors
Winklhofer-Roob, Brigitte M.
Rabbani, Naila
Thornalley, Paul J.
Masania, Jinit
Faustmann, Gernot
Anwar, Attia
Hafner-Giessauf, Hildegard
Rajpoot, Nasir
Grabher, Johanna
Rajpoot, Kashif
Tiran, Beate
Obermayer-Pietsch, Barbara
Roob, Johannes M.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-19
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease.
Related modified amino acids formed by proteolysis are excreted in urine.
We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen.
We recruited 200 human subjects with early-stage health decline and healthy controls.
Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry.
Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility.
Urinary analyte changes were as follows: impaired metabolic health—increased Nε-carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health—increased glucosepane; and impaired renal health—increased BCAAs and decreased Nε-(γ-glutamyl)lysine.
Algorithms combining subject age, BMI, and BCAAs discriminated between healthy controls and impaired metabolic, vascular, and renal health study groups with accuracy of 84%, 72%, and 90%, respectively.
In 2-step analysis, algorithms combining subject age, BMI, and urinary Nε-fructosyl-lysine and valine discriminated between healthy controls and impaired health (any type), accuracy of 78%, and then between types of health impairment with accuracy of 69%-78% (cf.
random selection 33%).
From likelihood ratios, this provided small, moderate, and conclusive evidence of early-stage cardiovascular, metabolic, and renal disease with diagnostic odds ratios of 6 – 7, 26 – 28, and 34 – 79, respectively.
We conclude that measurement of urinary glycated, oxidized, crosslinked, and branched-chain amino acids provides the basis for a noninvasive health screen for early-stage health decline in metabolic, vascular, and renal health.
American Psychological Association (APA)
Masania, Jinit& Faustmann, Gernot& Anwar, Attia& Hafner-Giessauf, Hildegard& Rajpoot, Nasir& Grabher, Johanna…[et al.]. 2019. Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1203867
Modern Language Association (MLA)
Masania, Jinit…[et al.]. Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1203867
American Medical Association (AMA)
Masania, Jinit& Faustmann, Gernot& Anwar, Attia& Hafner-Giessauf, Hildegard& Rajpoot, Nasir& Grabher, Johanna…[et al.]. Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1203867
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203867