Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/jbm4.10727 http://hdl.handle.net/11449/248368 |
Resumo: | Advanced glycation end products (AGEs) accumulation may be involved in the progression of CKD-bone disorders. We sought to determine the relationship between AGEs measured in the blood, skin, and bone with histomorphometry parameters, bone protein, gene expression, and serum biomarkers of bone metabolism in patients with CKD stages 3 to 5D patients. Serum levels of AGEs were estimated by pentosidine, glycated hemoglobin (A1c), and N-carboxymethyl lysine (CML). The accumulation of AGEs in the skin was estimated from skin autofluorescence (SAF). Bone AGEs accumulation and multiligand receptor for AGEs (RAGEs) expression were evaluated by immunohistochemistry; bone samples were used to evaluate protein and gene expression and histomorphometric analysis. Data are from 86 patients (age: 51 ± 13 years; 60 [70%] on dialysis). Median serum levels of pentosidine, CML, A1c, and SAF were 71.6 pmol/mL, 15.2 ng/mL, 5.4%, and 3.05 arbitrary units, respectively. AGEs covered 3.92% of trabecular bone and 5.42% of the cortical bone surface, whereas RAGEs were expressed in 0.7% and 0.83% of trabecular and cortical bone surfaces, respectively. AGEs accumulation in bone was inversely related to serum receptor activator of NF-κB ligand/parathyroid hormone (PTH) ratio (R = −0.25; p = 0.03), and RAGE expression was negatively related to serum tartrate-resistant acid phosphatase-5b/PTH (R = −0.31; p = 0.01). Patients with higher AGEs accumulation presented decreased bone protein expression (sclerostin [1.96 (0.11–40.3) vs. 89.3 (2.88–401) ng/mg; p = 0.004]; Dickkopf-related protein 1 [0.064 (0.03–0.46) vs. 1.36 (0.39–5.87) ng/mg; p = 0.0001]; FGF-23 [1.07 (0.4–32.6) vs. 44.1 (6–162) ng/mg; p = 0.01]; and osteoprotegerin [0.16 (0.08–2.4) vs. 6.5 (1.1–23.7) ng/mg; p = 0.001]), upregulation of the p53 gene, and downregulation of Dickkopf-1 gene expression. Patients with high serum A1c levels presented greater cortical porosity and Mlt and reduced osteoblast surface/bone surface, eroded surface/bone surface, osteoclast surface/bone surface, mineral apposition rate, and adjusted area. Cortical thickness was negatively correlated with serum A1c (R = −0.28; p = 0.02) and pentosidine levels (R = −0.27; p = 0.02). AGEs accumulation in the bone of CKD patients was related to decreased bone protein expression, gene expression changes, and increased skeletal resistance to PTH; A1c and pentosidine levels were related to decreased cortical thickness; and A1c levels were related to increased cortical porosity and Mlt. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
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Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney DiseaseADVANCED GLYCATION END PRODUCTSBONE METABOLISMCHRONIC KIDNEY DISEASEAdvanced glycation end products (AGEs) accumulation may be involved in the progression of CKD-bone disorders. We sought to determine the relationship between AGEs measured in the blood, skin, and bone with histomorphometry parameters, bone protein, gene expression, and serum biomarkers of bone metabolism in patients with CKD stages 3 to 5D patients. Serum levels of AGEs were estimated by pentosidine, glycated hemoglobin (A1c), and N-carboxymethyl lysine (CML). The accumulation of AGEs in the skin was estimated from skin autofluorescence (SAF). Bone AGEs accumulation and multiligand receptor for AGEs (RAGEs) expression were evaluated by immunohistochemistry; bone samples were used to evaluate protein and gene expression and histomorphometric analysis. Data are from 86 patients (age: 51 ± 13 years; 60 [70%] on dialysis). Median serum levels of pentosidine, CML, A1c, and SAF were 71.6 pmol/mL, 15.2 ng/mL, 5.4%, and 3.05 arbitrary units, respectively. AGEs covered 3.92% of trabecular bone and 5.42% of the cortical bone surface, whereas RAGEs were expressed in 0.7% and 0.83% of trabecular and cortical bone surfaces, respectively. AGEs accumulation in bone was inversely related to serum receptor activator of NF-κB ligand/parathyroid hormone (PTH) ratio (R = −0.25; p = 0.03), and RAGE expression was negatively related to serum tartrate-resistant acid phosphatase-5b/PTH (R = −0.31; p = 0.01). Patients with higher AGEs accumulation presented decreased bone protein expression (sclerostin [1.96 (0.11–40.3) vs. 89.3 (2.88–401) ng/mg; p = 0.004]; Dickkopf-related protein 1 [0.064 (0.03–0.46) vs. 1.36 (0.39–5.87) ng/mg; p = 0.0001]; FGF-23 [1.07 (0.4–32.6) vs. 44.1 (6–162) ng/mg; p = 0.01]; and osteoprotegerin [0.16 (0.08–2.4) vs. 6.5 (1.1–23.7) ng/mg; p = 0.001]), upregulation of the p53 gene, and downregulation of Dickkopf-1 gene expression. Patients with high serum A1c levels presented greater cortical porosity and Mlt and reduced osteoblast surface/bone surface, eroded surface/bone surface, osteoclast surface/bone surface, mineral apposition rate, and adjusted area. Cortical thickness was negatively correlated with serum A1c (R = −0.28; p = 0.02) and pentosidine levels (R = −0.27; p = 0.02). AGEs accumulation in the bone of CKD patients was related to decreased bone protein expression, gene expression changes, and increased skeletal resistance to PTH; A1c and pentosidine levels were related to decreased cortical thickness; and A1c levels were related to increased cortical porosity and Mlt. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.National Research CouncilFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Nephrology Division School of Medical Sciences University of Campinas (Unicamp)Laboratory for Evaluation of Mineral and Bone Disorders in Nephrology (LEMON) School of Medical Sciences University of Campinas (Unicamp)Laboratory of Renal Pathophysiology LIM-16 Department of Internal Medicine School of Medicine University of São PauloDepartment of Internal Medicine Botucatu School of Medicine UNESPLaboratory of Atherosclerosis and Vascular Biology Cardiology Division School of Medical Sciences University of Campinas (Unicamp)Department of Internal Medicine Botucatu School of Medicine UNESPFAPESP: 2015/16544-5Universidade Estadual de Campinas (UNICAMP)Universidade de São Paulo (USP)Universidade Estadual Paulista (UNESP)Quadros, Kélcia R. S.Roza, Noemi A. V.França, Renata A.Esteves, André B. A.Barreto, JoaquimDominguez, Wagner V.Furukawa, Luzia N. S.Caramori, Jacqueline Teixeira [UNESP]Sposito, Andrei C.de Oliveira, Rodrigo Bueno2023-07-29T13:42:03Z2023-07-29T13:42:03Z2023-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/jbm4.10727JBMR Plus, v. 7, n. 3, 2023.2473-4039http://hdl.handle.net/11449/24836810.1002/jbm4.107272-s2.0-85148247733Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJBMR Plusinfo:eu-repo/semantics/openAccess2024-08-14T17:23:32Zoai:repositorio.unesp.br:11449/248368Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T17:23:32Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
title |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
spellingShingle |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease Quadros, Kélcia R. S. ADVANCED GLYCATION END PRODUCTS BONE METABOLISM CHRONIC KIDNEY DISEASE |
title_short |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
title_full |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
title_fullStr |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
title_full_unstemmed |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
title_sort |
Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease |
author |
Quadros, Kélcia R. S. |
author_facet |
Quadros, Kélcia R. S. Roza, Noemi A. V. França, Renata A. Esteves, André B. A. Barreto, Joaquim Dominguez, Wagner V. Furukawa, Luzia N. S. Caramori, Jacqueline Teixeira [UNESP] Sposito, Andrei C. de Oliveira, Rodrigo Bueno |
author_role |
author |
author2 |
Roza, Noemi A. V. França, Renata A. Esteves, André B. A. Barreto, Joaquim Dominguez, Wagner V. Furukawa, Luzia N. S. Caramori, Jacqueline Teixeira [UNESP] Sposito, Andrei C. de Oliveira, Rodrigo Bueno |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade de São Paulo (USP) Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Quadros, Kélcia R. S. Roza, Noemi A. V. França, Renata A. Esteves, André B. A. Barreto, Joaquim Dominguez, Wagner V. Furukawa, Luzia N. S. Caramori, Jacqueline Teixeira [UNESP] Sposito, Andrei C. de Oliveira, Rodrigo Bueno |
dc.subject.por.fl_str_mv |
ADVANCED GLYCATION END PRODUCTS BONE METABOLISM CHRONIC KIDNEY DISEASE |
topic |
ADVANCED GLYCATION END PRODUCTS BONE METABOLISM CHRONIC KIDNEY DISEASE |
description |
Advanced glycation end products (AGEs) accumulation may be involved in the progression of CKD-bone disorders. We sought to determine the relationship between AGEs measured in the blood, skin, and bone with histomorphometry parameters, bone protein, gene expression, and serum biomarkers of bone metabolism in patients with CKD stages 3 to 5D patients. Serum levels of AGEs were estimated by pentosidine, glycated hemoglobin (A1c), and N-carboxymethyl lysine (CML). The accumulation of AGEs in the skin was estimated from skin autofluorescence (SAF). Bone AGEs accumulation and multiligand receptor for AGEs (RAGEs) expression were evaluated by immunohistochemistry; bone samples were used to evaluate protein and gene expression and histomorphometric analysis. Data are from 86 patients (age: 51 ± 13 years; 60 [70%] on dialysis). Median serum levels of pentosidine, CML, A1c, and SAF were 71.6 pmol/mL, 15.2 ng/mL, 5.4%, and 3.05 arbitrary units, respectively. AGEs covered 3.92% of trabecular bone and 5.42% of the cortical bone surface, whereas RAGEs were expressed in 0.7% and 0.83% of trabecular and cortical bone surfaces, respectively. AGEs accumulation in bone was inversely related to serum receptor activator of NF-κB ligand/parathyroid hormone (PTH) ratio (R = −0.25; p = 0.03), and RAGE expression was negatively related to serum tartrate-resistant acid phosphatase-5b/PTH (R = −0.31; p = 0.01). Patients with higher AGEs accumulation presented decreased bone protein expression (sclerostin [1.96 (0.11–40.3) vs. 89.3 (2.88–401) ng/mg; p = 0.004]; Dickkopf-related protein 1 [0.064 (0.03–0.46) vs. 1.36 (0.39–5.87) ng/mg; p = 0.0001]; FGF-23 [1.07 (0.4–32.6) vs. 44.1 (6–162) ng/mg; p = 0.01]; and osteoprotegerin [0.16 (0.08–2.4) vs. 6.5 (1.1–23.7) ng/mg; p = 0.001]), upregulation of the p53 gene, and downregulation of Dickkopf-1 gene expression. Patients with high serum A1c levels presented greater cortical porosity and Mlt and reduced osteoblast surface/bone surface, eroded surface/bone surface, osteoclast surface/bone surface, mineral apposition rate, and adjusted area. Cortical thickness was negatively correlated with serum A1c (R = −0.28; p = 0.02) and pentosidine levels (R = −0.27; p = 0.02). AGEs accumulation in the bone of CKD patients was related to decreased bone protein expression, gene expression changes, and increased skeletal resistance to PTH; A1c and pentosidine levels were related to decreased cortical thickness; and A1c levels were related to increased cortical porosity and Mlt. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T13:42:03Z 2023-07-29T13:42:03Z 2023-03-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1002/jbm4.10727 JBMR Plus, v. 7, n. 3, 2023. 2473-4039 http://hdl.handle.net/11449/248368 10.1002/jbm4.10727 2-s2.0-85148247733 |
url |
http://dx.doi.org/10.1002/jbm4.10727 http://hdl.handle.net/11449/248368 |
identifier_str_mv |
JBMR Plus, v. 7, n. 3, 2023. 2473-4039 10.1002/jbm4.10727 2-s2.0-85148247733 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
JBMR Plus |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128164842438656 |