| Grant number: | 15/13126-8 |
| Support Opportunities: | Regular Research Grants |
| Start date: | February 01, 2016 |
| End date: | 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 |
| City of the host institution: | São Paulo |
| Associated researchers: | Luciene Machado dos Reis ; Rosa Maria Affonso Moysés |
Abstract
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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