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Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study
BACKGROUND: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (E...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692010/ https://www.ncbi.nlm.nih.gov/pubmed/31408493 http://dx.doi.org/10.1371/journal.pone.0221058 |
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author | Martens, Remy J. H. Broers, Natascha J. H. Canaud, Bernard Christiaans, Maarten H. L. Cornelis, Tom Gauly, Adelheid Hermans, Marc M. H. Konings, Constantijn J. A. M. van der Sande, Frank M. Scheijen, Jean L. J. M. Stifft, Frank Wirtz, Joris J. J. M. Kooman, Jeroen P. Schalkwijk, Casper G. |
author_facet | Martens, Remy J. H. Broers, Natascha J. H. Canaud, Bernard Christiaans, Maarten H. L. Cornelis, Tom Gauly, Adelheid Hermans, Marc M. H. Konings, Constantijn J. A. M. van der Sande, Frank M. Scheijen, Jean L. J. M. Stifft, Frank Wirtz, Joris J. J. M. Kooman, Jeroen P. Schalkwijk, Casper G. |
author_sort | Martens, Remy J. H. |
collection | PubMed |
description | BACKGROUND: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS: We examined cross-sectional Spearman’s rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N(∈)-(carboxymethyl)lysine (CML), N(∈)-(carboxyethyl)lysine (CEL), N(δ)-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS: After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS: In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI. |
format | Online Article Text |
id | pubmed-6692010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-66920102019-08-30 Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study Martens, Remy J. H. Broers, Natascha J. H. Canaud, Bernard Christiaans, Maarten H. L. Cornelis, Tom Gauly, Adelheid Hermans, Marc M. H. Konings, Constantijn J. A. M. van der Sande, Frank M. Scheijen, Jean L. J. M. Stifft, Frank Wirtz, Joris J. J. M. Kooman, Jeroen P. Schalkwijk, Casper G. PLoS One Research Article BACKGROUND: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS: We examined cross-sectional Spearman’s rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N(∈)-(carboxymethyl)lysine (CML), N(∈)-(carboxyethyl)lysine (CEL), N(δ)-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS: After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS: In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI. Public Library of Science 2019-08-13 /pmc/articles/PMC6692010/ /pubmed/31408493 http://dx.doi.org/10.1371/journal.pone.0221058 Text en © 2019 Martens et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Martens, Remy J. H. Broers, Natascha J. H. Canaud, Bernard Christiaans, Maarten H. L. Cornelis, Tom Gauly, Adelheid Hermans, Marc M. H. Konings, Constantijn J. A. M. van der Sande, Frank M. Scheijen, Jean L. J. M. Stifft, Frank Wirtz, Joris J. J. M. Kooman, Jeroen P. Schalkwijk, Casper G. Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study |
title | Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study |
title_full | Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study |
title_fullStr | Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study |
title_full_unstemmed | Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study |
title_short | Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study |
title_sort | relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: a cross-sectional observational study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692010/ https://www.ncbi.nlm.nih.gov/pubmed/31408493 http://dx.doi.org/10.1371/journal.pone.0221058 |
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