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Parathyroidectomy effects on bone tissue, body composition, energy metabolism in patients with chronic kidney disease and secondary hyperparathyroidism

Grant number: 15/13126-8
Support Opportunities:Regular Research Grants
Duration: February 01, 2016 - May 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Vanda Jorgetti
Grantee:Vanda Jorgetti
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Luciene Machado dos Reis ; Rosa Maria Affonso Moysés


Patients with chronic kidney disease (CKD) develop numerous complications. Changes of mineral metabolism and bone diseases are part of them and occur in the early stages of the disease. The loss of renal function compromise phosphorus excretion and synthesis of calcitriol, causing accumulation of phosphorus, decreased intestinal calcium absorption and increased production of parathyroid hormone, which progressively leads to secondary hyperparathyroidism (SHPT). Fibroblast growth factor 23 (FGF-23), a phosphatonin which promotes phosphaturia and whose serum levels rise even before parathyroid hormone, also participates in the development of SHPT. FGF-23 is produced primarily by osteocytes, bone cells that regulate bone turnover. These cells also produce other factors such as osteocalcin, which act in the energetic metabolism. The non-carboxylated fraction of osteocalcin directly stimulates pancreatic cells, increasing insulin production and insulin sensitivity, as well as energy expenditure, decreasing serum glucose levels. On the other hand, bone cells respond to hormones involved in energy metabolism such as leptin, which interfere in the growth and mineralization ability of these cells. SHPT presents several comorbidities, such as extreme poor quality of life due to worsening of anemia, vascular calcifications, cognitive disorders, pruritus, bone and muscle pain, tendon rupture, bone demineralization, increased number of fractures and protein catabolism, as well as protein-energy malnutrition and increased mortality of patients affected. In recent years, the use of medications such as selective activators of vitamin D and calcimimetics have improved control of this complication. However, 5 to 30% of the patients need to control it with surgical intervention, parathyroidectomy (PTx). In such cases, patients go from a very high PTH situation to another where hormone levels drop dramatically. The effects of this decline are poorly studied in bone tissue, especially in the proteins expressed by osteocytes that regulate both bone remodeling and mineral homeostasis, as well as the interaction between bone tissue and the energetic metabolism. This project has two objectives: to evaluate the expression of proteins produced by osteocytes in bone biopsies from patients with SHPT before and after PTx; in addition, to analyze the effects of PTx in body composition and energy metabolism of patients with CKD and SHPT. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PIRES, GEOVANNA O.; VIEIRA, ITAMAR O.; HERNANDES, FABIANA R.; TEIXEIRA, ANDRE L.; OLIVEIRA, IVONE B.; DOMINGUEZ, WAGNER V.; DOS REIS, LUCIENE M.; MONTENEGRO, FABIO M.; MOYSES, ROSA M.; CARVALHO, ALUIZIO B.; et al. Effects of parathyroidectomy on the biology of bone tissue in patients with chronic kidney disease and secondary hyperparathyroidism. BONE, v. 121, p. 277-283, . (15/13126-8)
DE SIQUEIRA, FLAVIA RAMOS; DE OLIVEIRA, KARIN CARNEIRO; DOMINGUEZ, WAGNER VASQUES; MADID TRUYTS, CESAR AUGUSTO; AFFONSO MOYSES, ROSA MARIA; DOS REIS, LUCIENE MACHADO; JORGETTI, VANDA. Effect of parathyroidectomy on bone tissue biomarkers and body composition in patients with chronic kidney disease and secondary hyperparathyroidism. European Journal of Clinical Nutrition, v. 75, n. 7, p. 1126-1133, . (15/13126-8)

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