SEARCHCOHORTnephrology, endocrinology

cohort·nephrology, endocrinology, internal medicine, preclinical research, research methods·PMC10020922

Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease

JBMR Plus · 10 authors, 5 centres

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TL;DR

This cross-sectional study of 86 CKD patients found that advanced glycation end products (AGEs) accumulate in bone and are associated with altered bone protein and gene expression, while serum AGE markers correlate with structural bone deficits.

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AGEs were measured in serum (pentosidine, CML, A1c), skin autofluorescence, and bone via immunohistochemistry. Bone AGEs accumulation was inversely related to the serum RANKL/PTH ratio, and RAGE expression was negatively related to the TRACP-5b/PTH ratio. Serum A1c was associated with increased cortical porosity and mineralization lag time, while both A1c and pentosidine correlated with decreased cortical thickness.

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cohort

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nephrology

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ORIGINAL PAPER

PMC10020922

Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease

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ABSTRACT

ABSTRACT 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.

CITATION EXPORT

Kélcia R. S. Quadros, Noemi A. V. Roza, Renata A. França et al.. Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease. JBMR Plus. (2023). https://doi.org/10.1002/jbm4.10727

AUTHORS

10 · 5 CENTRES

Kélcia R. S. Quadros, Noemi A. V. Roza, Renata A. França, André B. A. Esteves, Joaquim Barreto, Wagner V. Dominguez, Luzia N. S. Furukawa, Jacqueline Teixeira Caramori, Andrei C. Sposito, Rodrigo Bueno de Oliveira

1 Nephrology Division, School of Medical Sciences University of Campinas (Unicamp) Campinas Brazil
2 Laboratory for Evaluation of Mineral and Bone Disorders in Nephrology (LEMON), School of Medical Sciences University of Campinas (Unicamp) Campinas Brazil
3 Laboratory of Renal Pathophysiology, LIM‐16, Department of Internal Medicine, School of Medicine University of São Paulo São Paulo Brazil
4 Department of Internal Medicine, Botucatu School of Medicine UNESP São Paulo Brazil
5 Laboratory of Atherosclerosis and Vascular Biology, Cardiology Division School of Medical Sciences, University of Campinas (Unicamp) Campinas Brazil