WAGNER VASQUES DOMINGUEZ

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina

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Assunto: Endocrinology & Metabolism ×

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Agora exibindo 1 - 7 de 7
  • article 14 Citação(ões) na Scopus
    Comparison of clinical, biochemical and histomorphometric analysis of bone biopsies in dialysis patients with and without fractures
    (2019) SANTOS, Melissa F. P.; HERNANDEZ, Mariel J.; OLIVEIRA, Ivone B. de; SIQUEIRA, Flavia R.; DOMINGUEZ, Wagner V.; REIS, Luciene M. dos; CARVALHO, Aluizio B.; MOYSES, Rosa M. A.; JORGETTI, Vanda
    Chronic kidney disease-mineral bone disorders (CKD-MBD) are associated with increased risk of fracture. Studies report about 3% of fractures in CKD patients, and these occur earlier than in the general population, namely 16 and 13years earlier for men and women, respectively. Better understanding of the pathophysiology offractures would probably contribute to new therapeutic approaches. This study aimed to evaluatereport oflong bone fractures from a bone biopsies bank from patients on hemodialysis and compare clinical and biochemical characteristics, as well as the results of the histomorphometric analysis of trabecular and cortical bone of these patients with a control group (without fractures), paired for age, gender, and time on hemodialysis. Bone proteins (SOST, DMP1 and MEPE) were evaluated by immunohistochemistry. Seventeen patients with fracture and controls were studied. Fracture prevalence was 0.82/1000 patients/year. Serum phosphorus levels were significantly lower in the fracture group. Histomorphometric analysis revealed that all the patients had high turnover disease,and the fracture group had smaller volume and trabecular thickness, greater osteoid surface, smaller eroded surface, smaller mineralizing surface, formation rate and longer mineralization lag time when compared to controls; the DMP1 expression in the cortical bone was smaller and the SOST in the trabecular bone was higher in fractured patients. As conclusion, we found low prevalence of fractures. Both groups had high turnover disease, but the fractured ones presentedmore impairedbone microarchitecture, as well as lower formation and greatermineralization defect. Bone proteins expression correlated with parameters involved in bone remodeling.
  • article 0 Citação(ões) na Scopus
    Effects of parathyroidectomy on the biology of bone tissue in patients with chronic kidney disease and secondary hyperparathyroidism (vol 121, pg 277, 2019)
    (2019) PIRES, Geovanna O.; VIEIRA, Itamar O.; HERNANDES, Fabiana R.; TEIXEIRA, Andre L.; OLIVEIRA, Ivone B.; DOMINGUEZ, Wagner V.; REIS, Luciene M. dos; MONTENEGRO, Fabio M.; MOYSES, Rosa M.; CARVALHO, Aluizio B.; JORGETTI, Vanda
  • article 1 Citação(ões) na Scopus
    Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease
    (2023) QUADROS, Kelcia R. S.; ROZA, Noemi A. V.; FRANCA, Renata A.; ESTEVES, Andre B. A.; BARRETO, Joaquim; DOMINGUEZ, Wagner V.; FURUKAWA, Luzia N. S.; CARAMORI, Jacqueline Teixeira; SPOSITO, Andrei C.; OLIVEIRA, Rodrigo Bueno de
    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-KB 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.
  • conferenceObject
    Increased Expression of DKK-1 in an Adynamic Bone Disease Model: Role of Phosphate
    (2023) TRUYTS, Tania; FERREIRA, Juliana; NEVES, Katia; OLIVEIRA, Ivone; DOMINGUEZ, Wagner; JORGETTI, Vanda; MOYSES, Rosa; REIS, Luciene dos
  • article 90 Citação(ões) na Scopus
    Urinary MCP-1 and RBP: Independent predictors of renal outcome in macroalbuminuric diabetic nephropathy
    (2012) TITAN, S. M.; VIEIRA JR., J. M.; DOMINGUEZ, W. V.; MOREIRA, S. R. S.; PEREIRA, A. B.; BARROS, R. T.; ZATZ, R.
    Background: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense. Methods: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis. doubling of serum creatinine or death (primary outcome. PO) in 56 type 2 diabetic patients with macroalbuminuric DN. Results: Mean follow-up time was 30.7 +/- 10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-beta or VEGF. In the Cox regression, urinary RBP. MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p = 0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p = 0.02 for log MCP-1) remained as significant independent predictors of the PO. Conclusion: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated.
  • conferenceObject
    Effects of parathyroidectomy on the biology of bone tissue in patients with chronic kidney disease and secondary hyperparathyroidism
    (2018) PIRES, Geovanna O.; VIEIRA, Itamar O.; HERNANDES, Fabiana R.; TEIXEIRA, Andre L.; OLIVEIRA, Ivone B.; DOMINGUEZ, Wagner V.; REIS, Luciene M. Dos; MONTENEGRO, Fabio M.; MOYSES, Rosa M.; CARVALHO, Aluizio B.; JORGETTI, Vanda
  • article 9 Citação(ões) na Scopus
    Effects of parathyroidectomy on the biology of bone tissue in patients with chronic kidney disease and secondary hyperparathyroidism
    (2019) PIRES, Geovanna O.; VIEIRA, Itamar O.; HERNANDES, Fabiana R.; TEIXEIRA, Andre L.; OLIVEIRA, Ivone B.; DOMINGUEZ, Wagner V.; REIS, Luciene M. dos; MONTENEGRO, Fabio M.; MOYSES, Rosa M.; CARVALHO, Aluizio B.; JORGETTI, Vanda
    Secondary hyperparathyroidism is a complication of chronic kidney disease that compromises skeletal integrity. In patients with secondary hyperparathyroidism undergoing parathyroidectomy, parathyroid hormone levels dramatically decrease. The effects of parathyroidectomy on bone tissue are poorly understood, especially regarding the proteins expressed by osteocytes, such as fibroblast growth factor 23, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, sclerostin, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin, which regulate bone turnover. The objective of this study was to characterize the bone expression of these proteins by immunohistochemistry and correlate these results with those of bone histomor-phometry before and after parathyroidectomy. We studied bone biopsies that were obtained from 23 patients before and 12 months after parathyroidectomy. We observed an improvement in bone microarchitecture, but impaired mineralization after parathyroidectomy. We found significant increases in sclerostin and osteoprotegerin expression and a decrease in the RANKL/osteoprotegerin ratio after parathyroidectomy, suggesting that their expression is regulated by parathormone. These proteins correlated with structural and bone formation parameters. We conclude that after parathyroidectomy, significant changes occur in the bone expression of osteocyte proteins and that these proteins potentially regulate bone remodeling.