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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.

Background The prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era. Aims To detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation. Methods This is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered. Results 275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41–56) vs. 55 (43–61) years; p = 0.026], had lower body mass index [23.5 (21.6–25.5) vs. 24.3 (22.1–27.8) kg/m2; p = 0.017], higher dialysis vintage [108 (48–183) vs. 71 (28–132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0–3) vs. 0 (0–3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176–17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000–1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439–6.804; p = 0.004) and HR = 2.785 (CI: 1.120–6.928; p = 0.028]. Conclusions An elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.

Background: This study determines whether -week high-fat diet (HFD) consumption alters insulin sensitivity, kidney function, and blood pressure (BP) in female rats when compared with standard rodent diet (ND) intake in gender- and age-matched rats. Methods: The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD) compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. Results: The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: ±2.8 vs. HFD: 87±3.8 mg/dL) associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL) in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9), homeostasis model assessment of insulin resistance (HOMA-IR) index, and the first-order rate constant for the disappearance of glucose (Kitt) were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P