ROSA MARIA AFFONSO MOYSES
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
17 resultados
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conferenceObject Bone and Mineral Metabolism and Fibroblast Growth Factor 23 Levels After Kidney Donation(2014) FERREIRA, G.; GUERRA, G.; SCHIAVENATO, E.; AGENA, F.; MOYSES, R.; DAVID-NETO, E.; WOLF, M.conferenceObject Bone and Mineral Metabolism and Fibroblast Growth Factor 23 Levels After Kidney Donation(2014) FERREIRA, G.; GUERRA, G.; SCHIAVENATO, E.; AGENA, F.; MOYSES, R.; DAVID-NETO, E.; WOLF, M.- Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients(2020) BAPTISTA, A.L.; PADILHA, K.; MALAGRINO, P.A.; VENTURINI, G.; ZERI, A.C.M.; REIS, L.M. dos; MARTINS, J.S.; JORGETTI, V.; PEREIRA, A.C.; TITAN, S.M.; MOYSES, R.M.A.Bone biopsy is still the gold standard to assess bone turnover (T), mineralization (M), and volume (V) in CKD patients, and serum biomarkers are not able to replace histomorphometry. Recently, metabolomics has emerged as a new technique that could allow for the identification of new biomarkers useful for disease diagnosis or for the understanding of pathophysiologic mechanisms, but it has never been assessed in the chronic kidney disease–mineral and bone disorder (CKD–MBD) scenario. In this study, we investigated the association between serum metabolites and the bone TMV classification in patients with end-stage renal disease by using serum NMR spectroscopy and bone biopsy of 49 hemodialysis patients from a single center in Brazil. High T was identified in 21 patients and was associated with higher levels of dimethylsulfone, glycine, citrate, and N-acetylornithine. The receiver-operating characteristic curve for the combination of PTH and these metabolites provided an area under the receiver-operating characteristic curve (AUC) of 0.86 (0.76 to 0.97). Abnormal M was identified in 30 patients and was associated with lower ethanol. The AUC for age, diabetes mellitus, and ethanol was 0.83 (0.71 to 0.96). Low V was identified in 17 patients and was associated with lower carnitine. The association of age, phosphate, and carnitine provided an AUC of 0.83 (0.70 to 0.96). Although differences among the curves by adding selected metabolites to traditional models were not statistically significant, the accuracy of the diagnosis according to the TMV classification seemed to be improved. This is the first study to evaluate the TMV classification system in relation to the serum metabolome assessed by NMR spectroscopy, showing that selected metabolites may help in the evaluation of bone phenotypes in CKD–MBD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Transcription factor HNF4 & alpha;2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy(2023) MARTINEZ-CALLE, Marta; COURBON, Guillaume; HUNT-TOBEY, Bridget; FRANCIS, Connor; SPINDLER, Jadeah; WANG, Xueyan; REIS, Luciene M. dos; MARTINS, Carolina S. W.; SALUSKY, Isidro B.; MALLUCHE, Hartmut; NICKOLAS, Thomas L.; MOYSES, Rosa M. A.; DAVID, Valentin; MARTIN, AlineRenal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4 & alpha; (HNF4 & alpha;), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4 & alpha; expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4 & alpha; resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4 & alpha;1 and Hnf4 & alpha;2, we showed that HNF4 & alpha;2 is the main osseous Hnf4 & alpha; isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4 & alpha;2 prevented bone loss in mice with CKD. Our results showed that HNF4 & alpha;2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.
- Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis(2021) ELIAS, Rosilene M.; MOE, Sharon; MOYSÉS, Rosa M. AAbstract Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.
- 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.
- Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy(2012) SABBAGH, Yves; GRACIOLLI, Fabiana Giorgeti; O'BRIEN, Stephen; TANG, Wen; REIS, Luciene Machado dos; RYAN, Susan; PHILLIPS, Lucy; BOULANGER, Joseph; SONG, Wenping; BRACKEN, Christina; LIU, Shiguang; LEDBETTER, Steven; DECHOW, Paul; CANZIANI, Maria Eugenia F.; CARVALHO, Aluizio B.; JORGETTI, Vanda; MOYSES, Rosa M. A.; SCHIAVI, Susan C.Chronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.
conferenceObject Bone histomorphometric effects of HIV infection and Antiretroviral therapy(2018) RAMALHO, Janaina; MARTINS, Csw; PEREIRA, Rmr; NICKOLAS, Thomas; YIN, Mt; GALVAO, J.; EIRA, Margareth; REIS, Lm; FURUKAWA, Luzia; JORGETTI, Vanda; MOYSES, Rm- A prospective study of the influence of the skeleton on calcium mass transfer during hemodialysis(2018) GOLDENSTEIN, Patricia Taschner; GRACIOLLI, Fabiana Giorgeti; ANTUNES, Gisele Lins; DOMINGUEZ, Wagner Vasques; REIS, Luciene Machado dos; MOE, Sharon; ELIAS, Rosilene Motta; JORGETTI, Vanda; MOYSES, Rosa Maria AffonsoBackground Calcium gradient, the difference between serum calcium and dialysate calcium d[Ca], is the main contributor factor influencing calcium transfer during hemodialysis. The impact, however, of bone turnover, on calcium mass transfer during hemodialysis is still uncertain. Methods This prospective cross-sectional study included 10 patients on hemodialysis for a 57.6 +/- 16.8 months, with severe hyperparathyroidism. Patients were submitted to 3 hemodialysis sessions using d[Ca] of 1.25, 1.5 and 1.75 mmol/l in three situations: pre-parathyroidectomy (pre-PTX), during hungry bone (early post-PTX), and after stabilization of clinical status (late post-PTX). Biochemical analysis and calcium mass transfer were evaluated and serum bone-related proteins were quantified. Results Calcium mass transfer varied widely among patients in each study phase with a median of -89.5, -76.8 and -3 mmol using d[Ca] 1.25 mmol/L, -106, -26.8 and 29.7 mmol using d[Ca] 1.50 mmol/L, and 12.8, -14.5 and 38 mmol using d[Ca] 1.75 mmol/L during pre-PTX, early post-PTX and late post-PTX, respectively, which was significantly different among d[Ca] (p = 0.0001) and among phases (p = 0.040). Ca gradient and delta of Ca also differed among d [Ca] and phases (p<0.05 for all comparisons), whether ultrafiltration was similar. Serum Osteocalcin decreased significantly in late post-PTX, whereas Sclerostin increased earlier, in early post-PTX. Conclusions The skeleton plays a key role in Ca mass transfer during dialysis, either by determining pre-dialysis serum Ca or by controlling the exchangeable Ca pool. Knowing that could help us to decide which d[Ca] should be chosen in a given patient.
conferenceObject Hepatocyte Nuclear Factor 4 alpha is a novel osteoblast transcription factor that regulates osteogenesis and plays a role in ROD pathogenesis(2023) MARTINEZ-CALLE, Marta; COURBON, Guillaume; HUNT-TOBEY, Bridget; FRANCIS, Connor; SPINDLER, Jadeah; WANG, Xueyan; REIS, Luciene M. dos; MARTINS, Carolina S. W.; MOYSES, Rosa M. A.; MARTIN, Aline; DAVID, Valentin