Positive association of serum levels of advanced glycation end products and high mobility group box–1 with asymmetric dimethylarginine in nondiabetic chronic kidney disease patients
Abstract
There is accumulating evidence that engagement of the receptor for advanced glycation end products (RAGE) with ligands such as advanced glycation end products (AGEs) and high mobility group box-1 (HMGB-1) elicits vascular inflammation, thus contributing to the increased risk for cardiovascular disease. Furthermore, enhanced accumulation of asymmetric dimethylarginine (ADMA) plays a role in cardiovascular disease in chronic kidney disease (CKD) patients. However, the relationships among serum levels of AGEs, HMGB-1, soluble form of RAGE (sRAGE), and ADMA are largely unknown. The aim of the present study is to determine their relationships in CKD patients. Twenty nondiabetic normotensive CKD patients with dyslipidemia and 20 age- and sex-matched healthy controls were enrolled. All subjects underwent determination of blood chemistries; urinary proteinuria; and serum levels of AGEs, HMGB-1, sRAGE, and ADMA. Serum AGE, HMGB-1, sRAGE, and ADMA levels in CKD patients were significantly higher than those in control subjects. Circulating levels of AGEs in CKD patients were positively associated with sRAGE and ADMA, and HMGB-1 with ADMA, but not sRAGE. There were no significant associations among these markers and serum creatinine, estimated glomerular filtration rate, proteinuria, and lipid levels. In multiple regression analyses, AGEs and HMGB-1 were independently correlated with ADMA. The present study demonstrated that AGE and sRAGE levels were correlated with each other and that AGEs and HMGB-1 were independently associated with ADMA in nondiabetic CKD patients. Elevation of the RAGE ligands may enhance ADMA levels, suggesting the active involvement of AGE/HMGB-1-RAGE-ADMA axis in CKD patients.
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The RAGE ligand HMGB1 plays a causal role in renal inflammation by enhancing ERK1/2, TNF-α, IL-6, and MCP-1, leading to nephropathy and chronic kidney disease.
“The RAGE ligand HMGB1 also plays a causal role in renal inflammation by enhancing ERK1/2, TNF-α, interleukin (IL)-6, and MCP-1, leading to nephropathy and chronic kidney disease74,75.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [75]
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- Authors
- Nakamura, T., Sato, E., Fujiwara, N., Kawagoe, Y., Ueda, Y., Suzuki, T., Yamada, S., Takeuchi, M., Fukami, K., Ueda, S., Adachi, H., Matsui, T., Okuda, S., & Yamagishi, S.-I.
- Affiliations
- Shinmatsudo Central General Hospital (JP)
- Dokkyo University (JP)
- Shino-Test Corporation (JP)
- Hokuriku University (JP)
- Kurume University (JP)
- Corresponding author
- Yamagishi, Sho-ichi
- ORCID
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 58
- Issue
- 11
- Pages
- 1624-1628
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W1986369605
- Cited by
- 53
- References
- 35
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 3 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 9 · 2012: 6
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- advanced glycation end products, high mobility group box 1, asymmetric dimethylarginine, soluble receptor for advanced glycation end products, chronic kidney disease, vascular inflammation, cardiovascular risk, dyslipidemia, proteinuria
- MeSH terms
- Receptor for Advanced Glycation End Products, Adult, Arginine, Cross-Sectional Studies, Female, Hemodynamics, Humans, Kidney Failure, Chronic, Male, Receptors, Immunologic, Regression Analysis, Glycation End Products, Advanced, HMGB1 Protein, Dyslipidemias
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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