ROSA MARIA AFFONSO MOYSES
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- EVALUATION OF BONE MICROARCHITECTURE BY HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY IN PATIENTS WITH CHRONIC KIDNEY DISEASE: COMPARISON WITH TRANSILIAC BONE BIOPSY(2015) MARQUES, Igor; ARAUJO, Maria Julia; GRACIOLLI, Fabiana; REIS, Luciene dos; CUSTODIO, Melani; PEREIRA, Rosa; JAMAL, Sophie; JORGETTI, Vanda; DAVID-NETO, Elias; MOYSES, Rosa
- Turning over renal osteodystrophy dogma: direct actions of FGF23 on osteoblast beta-catenin pathway(2016) SCHIAVI, Susan C.; MOYSES, Rosa M. A.Although recognized as a major complication of chronic kidney disease (CKD), the pathophysiology of the CKD-related mineral and bone disorder (CKD-MBD) is not completely understood. Recently, the inhibition of Wnt/beta-catenin pathway in osteocytes by sclerostin has been shown to play a role in CKD-MBD. The study by Carrilo-Lopez et al. confirms this inhibition in an experimental model of CKD. Moreover, they describe direct actions of FGF23-Klotho on osteoblasts, increasing the expression of DKK1, another Wnt/beta-catenin pathway inhibitor.
- The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease(2017) GRACIOLLI, Fabiana G.; NEVES, Katia R.; BARRETO, Fellype; BARRETO, Daniela V.; REIS, Luciene M. dos; CANZIANI, Maria E.; SABBAGH, Yves; CARVALHO, Aluizio B.; JORGETTI, Vanda; ELIAS, Rosilene M.; SCHIAVI, Susan; MOYSES, Rosa M. A.Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated beta-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.
- A microRNA Approach to Discriminate Cortical Low Bone Turnover in Renal Osteodystrophy(2020) NICKOLAS, Thomas L.; CHEN, Neal; MCMAHON, Donald J.; DEMPSTER, David; ZHOU, Hua; II, James Dominguez; APONTE, Maria A.; SUNG, Joshua; EVENEPOEL, Pieter; D'HAESE, Patrick C.; MAC-WAY, Fabrice; MOYSES, Rosa; MOE, SharonA main obstacle to diagnose and manage renal osteodystrophy (ROD) is the identification of intracortical bone turnover type (low, normal, high). The gold standard, tetracycline-labeled transiliac crest bone biopsy, is impractical to obtain in most patients. The Kidney Disease Improving Global Outcomes Guidelines recommend PTH and bone-specific alkaline phosphatase (BSAP) for the diagnosis of turnover type. However, PTH and BSAP have insufficient diagnostic accuracy to differentiate low from non-low turnover and were validated for trabecular turnover. We hypothesized that four circulating microRNAs (miRNAs) that regulate osteoblast (miRNA-30b, 30c, 125b) and osteoclast development (miRNA-155) would provide superior discrimination of low from non-low turnover than biomarkers in clinical use. In 23 patients with CKD 3-5D, we obtained tetracycline-labeled transiliac crest bone biopsy and measured circulating levels of intact PTH, BSAP, and miRNA-30b, 30c, 125b, and 155. Spearman correlations assessed relationships between miRNAs and histomorphometry and PTH and BSAP. Diagnostic test characteristics for discriminating low from non-low intracortical turnover were determined by receiver operator curve analysis; areas under the curve (AUC) were compared by chi(2) test. In CKD rat models of low and high turnover ROD, we performed histomorphometry and determined the expression of bone tissue miRNAs. Circulating miRNAs moderately correlated with bone formation rate and adjusted apposition rate at the endo- and intracortical envelopes (rho = 0.43 to 0.51; p < 0.05). Discrimination of low versus non-low turnover was 0.866, 0.813, 0.813, and 0.723 for miRNA-30b, 30c, 125b, and 155, respectively, and 0.509 and 0.589 for PTH and BSAP, respectively. For all four miRNAs combined, the AUC was 0.929, which was superior to that of PTH and BSAP alone and together (p < 0.05). In CKD rats, bone tissue levels of the four miRNAs reflected the findings in human serum. These data suggest that a panel of circulating miRNAs provide accurate noninvasive identification of bone turnover in ROD. (C) 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Can we compare serum sclerostin results obtained with different assays in hemodialysis patients?(2015) MOYSES, Rosa M. A.; JAMAL, Sophie A.; GRACIOLLI, Fabiana G.; REIS, Luciene M. dos; ELIAS, Rosilene M.Sclerostin, secreted by osteocytes, plays a key role in antagonizing bone formation. Recent studies, which seldom include chronic kidney disease (CKD) patients, have reported on the association of sclerostin and mortality, with contradictory results. The assay-linked variability may contribute to these discrepant results. We have compared sclerostin results obtained with two assays (TECO and Biomedica) in a cohort of 91 CKD patients undergoing hemodialysis. We found a strong correlation (r = 0.870, p < 0.0001) between the serum sclerostin concentrations measured by the two assays. Bland-Altman plot shows that, although there was a partial agreement between the assays, differences found for individual values (-0.27 +/- A 0.54; ranging from -1.3 to 0.8 ng/ml) were quite unpredictable. By using TECO, there was a significant relationship between serum sclerostin, and calcitonin (r = 0.224), IL-6 (r = 0.251) and FGF23 (r = 0.331) levels while no correlation was found with PTH or total alkaline phosphatase. Regarding Biomedica, there was a significant correlation with calcitonin (r = 0.260), and beta(2) microglobulin (r = 0.210), but no correlation with PTH or total alkaline phosphatase. Overall, 25.3 % among the patients had different classifications as to normal or high values, according to the manufacturer. Sclerostin levels should be interpreted with caution, as they can vary widely according to the assay used. Further studies are clearly needed before considering sclerostin as a true marker of mortality. Moreover, we do not know at present which serum sclerostin levels should be regarded as either normal or potentially dangerous in patients with CKD.
- Fractures in chronic kidney disease: pursuing the best screening and management(2015) GOLDENSTEIN, Patricia T.; JAMAL, Sophie A.; MOYSES, Rosa M. A.Purpose of review Osteoporotic fractures are common and cause increased sickness and death. Men and women with chronic kidney disease (CKD) are at particularly high risk of osteoporotic fractures. Currently, however, there are no guidelines concerning noninvasive methods to assess fracture risk in CKD. Further, approved treatments to prevent fractures in otherwise healthy men and women are only recommended for use with caution in those with CKD. This review focuses on the recent data that support the use of noninvasive methods to assess fracture risk in CKD and highlights new therapies that could be used in fracture prevention in CKD. Recent findings Data from prospective studies demonstrate that low bone mineral density predicts fracture in CKD patients. Post-hoc analyses demonstrate that agents approved for the treatment of postmenopausal osteoporosis (bisphosphonates, denosumab and teriparatide) when given to those with CKD are well tolerated and potentially efficacious with respect to fracture risk reduction. Summary To date, patients, and nephrologists taking care of them, have largely ignored fracture risk assessment and treatment in CKD. This should change given recent data. Further studies are needed, specifically bone histomorphometric studies, which will increase our understanding of CKD-mineral bone disease (MBD) pathophysiology, and randomized clinical trials of therapy in patients with CKD.