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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

Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal...

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Autores principales: Rabbani, Naila, Adaikalakoteswari, Antonysunil, Larkin, James R., Panagiotopoulos, Sianna, MacIsaac, Richard J., Yue, Dennis K., Fulcher, Gregory R., Roberts, Matthew A., Thomas, Merlin, Ekinci, Elif, Thornalley, Paul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820473/
https://www.ncbi.nlm.nih.gov/pubmed/36613596
http://dx.doi.org/10.3390/ijms24010152
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author Rabbani, Naila
Adaikalakoteswari, Antonysunil
Larkin, James R.
Panagiotopoulos, Sianna
MacIsaac, Richard J.
Yue, Dennis K.
Fulcher, Gregory R.
Roberts, Matthew A.
Thomas, Merlin
Ekinci, Elif
Thornalley, Paul J.
author_facet Rabbani, Naila
Adaikalakoteswari, Antonysunil
Larkin, James R.
Panagiotopoulos, Sianna
MacIsaac, Richard J.
Yue, Dennis K.
Fulcher, Gregory R.
Roberts, Matthew A.
Thomas, Merlin
Ekinci, Elif
Thornalley, Paul J.
author_sort Rabbani, Naila
collection PubMed
description Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2–4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2–4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD.
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spelling pubmed-98204732023-01-07 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 Rabbani, Naila Adaikalakoteswari, Antonysunil Larkin, James R. Panagiotopoulos, Sianna MacIsaac, Richard J. Yue, Dennis K. Fulcher, Gregory R. Roberts, Matthew A. Thomas, Merlin Ekinci, Elif Thornalley, Paul J. Int J Mol Sci Article Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2–4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2–4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD. MDPI 2022-12-21 /pmc/articles/PMC9820473/ /pubmed/36613596 http://dx.doi.org/10.3390/ijms24010152 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rabbani, Naila
Adaikalakoteswari, Antonysunil
Larkin, James R.
Panagiotopoulos, Sianna
MacIsaac, Richard J.
Yue, Dennis K.
Fulcher, Gregory R.
Roberts, Matthew A.
Thomas, Merlin
Ekinci, Elif
Thornalley, Paul J.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820473/
https://www.ncbi.nlm.nih.gov/pubmed/36613596
http://dx.doi.org/10.3390/ijms24010152
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