VANDA JORGETTI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
11 resultados
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- Is arterial calcification in children and adolescents with end-stage renal disease a rare finding?(2019) MENEZES, Fernanda L. de; KOCH-NOGUEIRA, Paulo C.; VAL, Maria L. D. M. do; PESTANA, Jose O. M.; JORGETTI, Vanda; REIS, Marlene A. dos; MONTEIRO, Maria L. G. dos Reis; LEITE, Heitor P.Aim To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. Methods In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. Results No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 mu m (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). Conclusion Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.
- Thyrotoxicosis Involves beta 2-Adrenoceptor Signaling to Negatively Affect Microarchitecture and Biomechanical Properties of the Femur(2019) NEOFITI-PAPI, Bianca; ALBUQUERQUE, Ruda P.; MIRANDA-RODRIGUES, Manuela; GONCALVES, Natalia J. N.; JORGETTI, Vanda; BRUM, Patricia C.; FERREIRA, Julio C. B.; GOUVEIA, Cecilia H. A.Background: Thyrotoxicosis increases bone turnover, resulting in net bone loss. Sympathetic nervous system (SNS) activation, via beta 2-adrenoceptor (beta 2-AR) signaling, also has osteopenic effects. Because thyroid hormones (TH) interact with the SNS to regulate several physiological processes, we hypothesized that this interaction also occurs to regulate bone mass. Previous studies support this hypothesis, as alpha 2-AR knockout (KO) mice are less susceptible to thyrotoxicosis-induced osteopenia. Here, we evaluated whether TH-SNS interactions in bone involve beta 2-AR signaling. Methods: Thyrotoxicosis was induced in 120-day-old female and male mice with beta 2-AR gene inactivation (beta 2-AR(-/-)) by daily treatment with supraphysiological doses of triiodothyronine (T3) for 12 weeks. The impact of thyrotoxicosis on femoral bone microarchitecture, remodeling, fracture risk, and gene expression of the receptor activator of nuclear factor-kappa-B (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) pathway was evaluated. In addition, the effect of the beta 2-AR-specific agonist clenbuterol (CL) on cAMP accumulation was determined in osteoblastic (MC3T3-E1) cells treated with T3 and/or 17 beta-estradiol (E2). Results: Thyrotoxicosis negatively affected trabecular bone microarchitecture in wild-type (WT) females, but this effect was milder or nonexistent in beta 2-AR(-/-) animals, whereas the opposite was seen in males. T3 treatment increased the femoral RANKL/OPG mRNA ratio and the endosteal perimeter and medullary area of the diaphysis in WT females and males, but not in beta 2-AR(-/-) mice, suggesting that T3 promotes endosteal resorption in cortical bone, in a mechanism that involves beta 2-AR signaling. T3 treatment increased endocortical mineral apposition rate only in WT females but not in beta 2-AR(-/-) mice, suggesting that TH also induce bone formation in a beta 2-AR signaling-dependent mechanism. T3 treatment decreased femoral resistance to fracture only in WT females, but not in KO mice. E2 and CL similarly increased cAMP accumulation in MC3T3-E1 cells; whereas T3 alone had no effect, but it completely blocked E2-stimulated cAMP accumulation, suggesting that some T3 effects on bone may involve E2/cAMP signaling in osteoblasts. Conclusions: These findings sustain the hypothesis that T3 interacts with the SNS to regulate bone morphophysiology in a beta 2-AR signaling-dependent mechanism. The data also reveal sex as an important modifier of skeletal manifestations of thyrotoxicosis, as well as a modifier of the TH-SNS interactions to control bone microarchitecture, remodeling, and resistance to fracture.
- A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation(2019) MARQUES, Igor Denizarde Bacelar; ARAUJO, Maria Julia Correia Lima Nepomuceno; GRACIOLLI, Fabiana Giorgetti; REIS, Luciene Machado dos; PEREIRA, Rosa Maria R.; ALVARENGA, Jackeline C.; CUSTODIO, Melani Ribeiro; JORGETTI, Vanda; ELIAS, Rosilene Motta; MOYSES, Rosa Maria Affonso; DAVID-NETO, EliasBackground Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). Methods In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. Results Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. Conclusions Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.
- 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, VandaChronic 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.
conferenceObject Evaluation of Cortical Microarchitecture and Biomechanical Properties 6-12 Months after Atypical Femoral Fracture(2019) PEREZ, Mariana; DOMICIANO, Diego; PEREIRA, Rosa; JORGETTI, Vanda- Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin(2019) ARAUJO, Maria Julia Correia Lima Nepomuceno; MARQUES, Igor Denizarde Bacelar; GRACIOLLI, Fabiana Giorgetti; FUKUHARA, Luzia; REIS, Luciene Machado dos; CUSTODIO, Melani; JORGETTI, Vanda; ELIAS, Rosilene Mota; DAVID-NETO, Elias; MOYSES, Rosa M. A.In an attempt to clarify the mechanisms of post-transplant bone disease we investigated the bone content and gene expression of several bone-related proteins. After a successful kidney transplant, the content of sclerostin in bone biopsies was found to be increased as measured by immunohistochemistry, multiplex assay, and gene expression despite a concomitant decrease of sclerostin in the serum. The phosphorylation of beta-catenin was increased, confirming Wnt pathway inhibition, an effect accompanied by an increase of the receptor activator of nuclear factor kappa-B ligand (RANKL) and a decrease of osteoprotegerin protein levels in both serum and bone. Thus, changes in circulating biomarkers after kidney transplantation cannot be easily extrapolated to concomitant changes occurring in the bone. Hence, overall treatment decisions post kidney transplant should not be based on serum biochemistry alone.
- Treatment of Human Immunodeficiency Virus Infection With Tenofovir Disoproxil Fumarate-Containing Antiretrovirals Maintains Low Bone Formation Rate, But Increases Osteoid Volume on Bone Histomorphometry(2019) RAMALHO, Janaina; MARTINS, Carolina Steller Wagner; GALVAO, Juliana; FURUKAWA, Luzia N.; DOMINGUES, Wagner V.; OLIVEIRA, Ivone B.; REIS, Luciene M. dos; PEREIRA, Rosa M. R.; NICKOLAS, Thomas L.; YIN, Michael T.; EIRA, Margareth; JORGETTI, Vanda; MOYSES, Rosa M. A.Bone mineral density (BMD) loss is a known complication of human immunodeficiency virus (HIV) infection and its treatment, particularly with tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens. Although renal proximal tubular dysfunction and phosphaturia is common with TDF, it is unknown whether BMD loss results from inadequate mineralization. We evaluated change in BMD by dual-energy X-ray absorptiometry (DXA) and bone histomorphometry by tetracycline double-labeled transiliac crest biopsies in young men living with HIV before (n = 20) and 12 months after (n = 16) initiating TDF/lamivudine/efavirenz. We examined relationships between calciotropic hormones, urinary phosphate excretion, pro-inflammatory and pro-resorptive cytokines, and bone remodeling-related proteins with changes in BMD and histomorphometry. Mean age was 29.6 +/- 5.5 years, with mean CD4 + T cell count of 473 +/- 196 cells/mm(3). At baseline, decreased bone formation rate and increased mineralization lag time were identified in 16 (80%) and 12 (60%) patients, respectively. After 12 months, we detected a 2% to 3% decrease in lumbar spine and hip BMD by DXA. By histomorphometry, we observed no change in bone volume/total volume (BV/TV) and trabecular parameters, but rather, increases in cortical thickness, osteoid volume, and osteoblast and osteoclast surfaces. We did not observe significant worsening of renal phosphate excretion or mineralization parameters. Increases in PTH correlated with decreased BMD but not histomorphometric parameters. Overall, these data suggest abnormalities in bone formation and mineralization occur with HIV infection and are evident at early stages. With TDF-containing antiretroviral therapy (ART), there is an increase in bone remodeling, reflected by increased osteoblast and osteoclast surfaces, but a persistence in mineralization defect, resulting in increased osteoid volume. (c) 2019 American Society for Bone and Mineral Research
- 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
- Quality of life after surgery in secondary hyperparathyroidism comparing subtotal parathyroidectomy to total parathyroidectomy with immediate parathyroid autograft - a prospective randomized trial (vol 164, pg 978, 2018)(2019) ALVES FILHO, Wellington; PLAS, Willemijn Y. van der; BRESCIA, Marilia D. G.; NASCIMENTO JR., Climerio R.; GOLDENSTEIN, Patricia T.; MASSONI NETO, Ledo M.; ARAP, Sergio S.; CUSTODIO, Melani R.; BUENO, Rodrigo O.; MOYSES, Rosa M. A.; JORGETTI, Vanda; KRUIJF, Schelto; MONTENEGRO, Fabio L. M.
- Chronic kidney disease is associated with low BMD at the hip but not at the spine(2019) CARVALHO, K. S. Bezerra de; VASCO, R. F. V.; CUSTODIO, M. R.; JORGETTI, V.; MOYSES, R. M. A.; ELIAS, R. M.The SummaryAlthough chronic kidney disease is associated withotherbonedisorders, osteoporosis can be found in this context, and itis defined based on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry. As CKD progresses, the percentage of normal BMD decreases, whereas that of osteopenia/osteoporosis increases, mostly due to hip involvement, particularly in patients with reduced renal function.IntroductionOsteoporosis is a highly prevalent disease in patients with chronic kidney disease (CKD). We investigated the features of bone mineral density (BMD) in patients with assorted kidney diseases and hypothesized that low BMD, as measured by dual-energy X-ray absorptiometry (DXA), would be more prevalent as kidney function decreased and would correlate with biomarkers of mineral and bone disease.MethodsDXA obtained from January 1, 2008, to December 31, 2017, clinical, demographic, and biochemical data at the time of image acquisition were recorded. Data from 1172 patients were included in this study (81.3% women, 79.9% white, and 8.1% diabetic).ResultsOsteopenia and osteoporosis in at least one site (total hip or spine) were found in 32.7% and 20.0% of patients, respectively. As CKD progressed, the percentage of patients with normal BMD decreased, whereas the percentage of osteopenia and osteoporosis increased, which was mostly due to the total hip involvement, particularly in patients with estimated glomerular filtration rate (eGFR) <60ml/min/1.73m(2). Older age and hyperparathyroidism were independent risk factors for osteopenia/osteoporosis at the total hip; female gender, older age, and higher iCa were independently associated with the risk of osteopenia/osteoporosis at the spine. With eGFR >90ml/min as reference, the odds ratios for osteoporosis/osteopenia at the hip were 1.51 (95% CI 1.01-2.24) and 1.91 (95% CI 1.13-3.20) for patients with eGFR 30-60 and 15-30ml/min/1.73m(2), respectively. No CKD stage was significantly associated with the risk of osteoporosis/osteopenia at the spine.ConclusionOur results highlighted that low BMD in patients with CKD is associated with age and hyperparathyroidism, and affects predominantly the hip.