Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health
- PMID: 31827677
- PMCID: PMC6885816
- DOI: 10.1155/2019/4851323
Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health
Abstract
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 N ε -carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health-increased glucosepane; and impaired renal health-increased BCAAs and decreased N ε -(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 N ε -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.
Copyright © 2019 Jinit Masania et al.
Conflict of interest statement
The authors declare that they have no conflict of interest in relation to this work.
Figures
Similar articles
-
Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism - a source of biomarkers for clinical diagnosis.Mol Autism. 2018 Feb 19;9:3. doi: 10.1186/s13229-017-0183-3. eCollection 2018. Mol Autism. 2018. PMID: 29479405 Free PMC article.
-
Reading patterns of proteome damage by glycation, oxidation and nitration: quantitation by stable isotopic dilution analysis LC-MS/MS.Essays Biochem. 2020 Feb 17;64(1):169-183. doi: 10.1042/EBC20190047. Essays Biochem. 2020. PMID: 32065835 Review.
-
Detection of oxidized and glycated proteins in clinical samples using mass spectrometry--a user's perspective.Biochim Biophys Acta. 2014 Feb;1840(2):818-29. doi: 10.1016/j.bbagen.2013.03.025. Epub 2013 Apr 2. Biochim Biophys Acta. 2014. PMID: 23558060 Review.
-
High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes.Sci Rep. 2020 Jul 29;10(1):12709. doi: 10.1038/s41598-020-69350-y. Sci Rep. 2020. PMID: 32728119 Free PMC article.
-
Urinary excretion of amino acids and their advanced glycation end-products (AGEs) in adult kidney transplant recipients with emphasis on lysine: furosine excretion is associated with cardiovascular and all-cause mortality.Amino Acids. 2021 Nov;53(11):1679-1693. doi: 10.1007/s00726-021-03091-8. Epub 2021 Oct 24. Amino Acids. 2021. PMID: 34693489 Free PMC article. Clinical Trial.
Cited by
-
Alterations of Urinary Microbial Metabolites and Immune Indexes Linked With COVID-19 Infection and Prognosis.Front Immunol. 2022 Mar 29;13:841739. doi: 10.3389/fimmu.2022.841739. eCollection 2022. Front Immunol. 2022. PMID: 35422810 Free PMC article.
-
Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease.Int J Mol Sci. 2022 Dec 21;24(1):152. doi: 10.3390/ijms24010152. Int J Mol Sci. 2022. PMID: 36613596 Free PMC article.
-
AGEomics Biomarkers and Machine Learning-Realizing the Potential of Protein Glycation in Clinical Diagnostics.Int J Mol Sci. 2022 Apr 21;23(9):4584. doi: 10.3390/ijms23094584. Int J Mol Sci. 2022. PMID: 35562975 Free PMC article. Review.
-
CKD Urine Metabolomics: Modern Concepts and Approaches.Pathophysiology. 2023 Sep 29;30(4):443-466. doi: 10.3390/pathophysiology30040033. Pathophysiology. 2023. PMID: 37873853 Free PMC article. Review.
-
Decreased methylglyoxal-mediated protein glycation in the healthy aging mouse model of ectopic expression of UCP1 in skeletal muscle.Redox Biol. 2023 Feb;59:102574. doi: 10.1016/j.redox.2022.102574. Epub 2022 Dec 6. Redox Biol. 2023. PMID: 36521306 Free PMC article.
References
-
- Lim S. S., Vos T., Flaxman A. D., et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;380(9859):2224–2260. doi: 10.1016/S0140-6736(12)61766-8. - DOI - PMC - PubMed
-
- Ceriello A., Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24(5):816–823. doi: 10.1161/01.ATV.0000122852.22604.78. - DOI - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical