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
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- Parathyroidectomy Improves Restless Leg Syndrome in Patients on Hemodialysis(2016) SANTOS, Roberto Savio Silva; COELHO, Fernando Morgadinho Santos; SILVA, Bruno Caldin da; GRACIOLLI, Fabiana Giorgeti; DOMINGUEZ, Wagner Velasquez; MONTENEGRO, Fabio Luiz de Menezes; JORGETTI, Vanda; MOYSES, Rosa Maria Affonso; ELIAS, Rosilene MottaBackground Restless leg syndrome (RLS) is a sleep disorder with high prevalence among patients on hemodialysis. It has been postulated that high phosphate and high parathyroid hormone may be implicated in its pathogenesis. Standard international criteria and face-to-face interview are not always applied. Methods this was an interventional prospective study in which 19 patients (6 men, aged 48+/-11 years) with severe hyperparathyroidism were evaluated. RLS diagnosis and rating scale were accessed based on the International RLS Study Group pre- and post-parathyroidectomy. Patients also underwent standard polysomnography. Results At baseline, RLS was present in 10 patients (52.6%), and pain was the most reported symptom associated with the diagnosis. Patients with RLS had higher serum phosphate (p = 0.008) that remained independently associated with RLS in a logistic regression model, adjusted for hemoglobin, age and gender (HR = 7.28; CI = 1.14-46.3, p = 0.035). After parathyroidectomy, there was a reduction of serum parathyroid hormone, phosphate, calcium and alkaline phosphatase, and an increase of 25(OH)-vitamin D, and Fetuin-A. Parathyroidectomy alleviated RLS (from 52% to 21%; p = 0.04), which was accompanied by a decrease in severity scale, in association with relief of pain and pruritus. Polysomnography in these patients showed an improvement of sleep parameters as measured by sleep efficiency, sleep latency and percentage of REM sleep. Conclusion RLS is associated with high levels of phosphate in patients with severe secondary hyperparathyroidism on hemodialysis. Pain is most reported complain in these patients. Parathyroidectomy provided an opportunity to relief RLS. Whether the reduction of serum phosphorus or parathyroid hormone contributed to this improvement merits further investigation.
- Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function(2012) CANCELA, Ana Ludimila; SANTOS, Raul Dias; TITAN, Silvia Maria; GOLDENSTEIN, Patricia Taschner; ROCHITTE, Carlos Eduardo; LEMOS, Pedro Alves; REIS, Luciene Machado dos; GRACIOLLI, Fabiana Giorgetti; JORGETTI, Vanda; MOYSES, Rosa MariaHigh serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m(2). Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score <= 10 (3.63 +/- 0.55 versus 3.49 +/- 0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6 +/- 0.5 versus 3.5 +/- 0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score ( p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function.
- Parathyroidectomy Improves Survival In Patients with Severe Hyperparathyroidism: A Comparative Study(2013) GOLDENSTEIN, Patricia Taschner; ELIAS, Rosilene Motta; CARMO, Lilian Pires de Freitas do; COELHO, Fernanda Oliveira; MAGALHAES, Luciene Pereira; ANTUNES, Gisele Lins; CUSTODIO, Melani Ribeiro; MONTENEGRO, Fabio Luiz de Menezes; TITAN, Silvia Maria; JORGETTI, Vanda; MOYSES, Rosa Maria AffonsoBackground and objectives: Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery. Methods: This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012. Results: Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group. Conclusions: Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients.
- Bone Plasticity in Response to Exercise Is Sex-Dependent in Rats(2013) VICENTE, Wagner S.; REIS, Luciene M. dos; GRACIOLLI, Rafael G.; GRACIOLLI, Fabiana G.; DOMINGUEZ, Wagner V.; WANG, Charles C.; FONSECA, Tatiana L.; VELOSA, Ana P.; ROSCHEL, Hamilton; TEODORO, Walcy R.; GUALANO, Bruno; JORGETTI, VandaPurpose: To characterize the potential sexual dimorphism of bone in response to exercise. Methods: Young male and female Wistar rats were either submitted to 12 weeks of exercise or remained sedentary. The training load was adjusted at the mid-trial (week 6) by the maximal speed test. A mechanical test was performed to measure the maximal force, resilience, stiffness, and fracture load. The bone structure, formation, and resorption were obtained by histomorphometric analyses. Type I collagen (COL I) mRNA expression and tartrate-resistant acid phosphatase (TRAP) mRNA expression were evaluated by quantitative real-time PCR (qPCR). Results: The male and female trained rats significantly improved their maximum speed during the maximal exercise test (main effect of training; p<0.0001). The male rats were significantly heavier than the females, irrespective of training (main effect of sex; p<0.0001). Similarly, both the weight and length of the femur were greater for the male rats when compared with the females (main effect of sex; p<0.0001 and p<0.0001, respectively). The trabecular volume was positively affected by exercise in male and female rats (main effect of training; p = 0.001), whereas the trabecular thickness, resilience, mineral apposition rate, and bone formation rate increased only in the trained males (within-sex comparison; p<0.05 for all parameters), demonstrating the sexual dimorphism in response to exercise. Accordingly, the number of osteocytes increased significantly only in the trained males (within-sex comparison; p<0.05). Pearson's correlation analyses revealed that the COL I mRNA expression and TRAP mRNA expression were positively and negatively, respectively, related to the parameters of bone remodeling obtained from the histomorphometric analysis (r = 0.59 to 0.85; p<0.05). Conclusion: Exercise yielded differential adaptations with respect to bone structure, biomechanical proprieties, and molecular signaling in male and female rats.
- Effect of aluminum accumulation on bone and cardiovascular risk in the current era(2023) CARBONARA, Cinthia E. M.; ROZA, Noemi A. V.; QUADROS, Kelcia R. S.; FRANCA, Renata A.; ESTEVES, Andre B. A.; PAVAN, Celia R.; BARRETO, Joaquim; REIS, Luciane M. dos; JORGETTI, Vanda; SPOSITO, Andrei C.; OLIVEIRA, Rodrigo BuenoBackgroundThe prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era. AimsTo detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation. MethodsThis is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered. Results275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41-56) vs. 55 (43-61) years; p = 0.026], had lower body mass index [23.5 (21.6-25.5) vs. 24.3 (22.1-27.8) kg/m(2); p = 0.017], higher dialysis vintage [108 (48-183) vs. 71 (28-132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0-3) vs. 0 (0-3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176-17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000-1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439-6.804; p = 0.004) and HR = 2.785 (CI: 1.120-6.928; p = 0.028]. ConclusionsAn elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.
- 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.
- Effects of Dietary Phosphate on Adynamic Bone Disease in Rats with Chronic Kidney Disease - Role of Sclerostin?(2013) FERREIRA, Juliana C.; FERRARI, Guaraciaba O.; NEVES, Katia R.; CAVALLARI, Raquel T.; DOMINGUEZ, Wagner V.; REIS, Luciene M. dos; GRACIOLLI, Fabiana G.; OLIVEIRA, Elizabeth C.; LIU, Shiguang; SABBAGH, Yves; JORGETTI, Vanda; SCHIAVI, Susan; MOYSES, Rosa M. A.High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/beta-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+ PTx 1.2%. In the two Nx+ PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+ PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+ PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx +PTx 0.6% group. Nx+ PTx 0.6% rat had very low serum sclerostin levels, and Nx+ PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.
- The effect of vitamin D and zoledronic acid in bone marrow adiposity in kidney transplant patients: A post hoc analysis(2018) HERNANDEZ, Mariel J.; REIS, Luciene M. dos; MARQUES, Igor D.; ARAUJO, Maria J.; TRUYTS, Cesar A. M.; OLIVEIRA, Ivone B.; BARRETO, Fellype C.; DAVID-NETO, Elias; CUSTODIO, Melani R.; MOYSES, Rosa M.; BELLORIN-FONT, Ezequiel; JORGETTI, VandaPurpose Osteoblasts and adipocytes are derived from mesenchymal stem cells. An imbalance in the differentiation of these lineages could affect the preservation of bone integrity. Several studies have suggested the importance of this imbalance in the pathogenesis of osteoporosis after kidney transplant (KT), but the role of bone marrow adiposity in this process is not well known, and if the treatment with the anti-absorptive (zoledronic acid-ZA) drugs could attenuate bone loss. Thus, our objective was compare bone marrow adiposity, osteoblasts and osteocytes before and after KT, verify an association between bone remodeling process (Turnover, Volume, and Mineralization-TMV classification), the osteocyte sclerostin expression to evaluate if there is a role of Wnt pathway, as well as the effect of ZA on these cells. Methods We studied 29 new living-adonor KT patients. One group received ZA at the time of KT plus cholecalciferol for twelve months, and the other group received only cholecalciferol. Bone biopsies were performed at baseline and after 12 months of treatment. Histomorphometric evaluation was performed in bone and bone marrow adipocytes. Sclerostin (Scl) expression in osteocytes was evaluated by immunohistochemistry. Results Some bone marrow adiposity parameters were increased before KT. After KT, some of them remained increased and they worsened with the use of ZA. In the baseline, lower bone Volume and Turnover, were associated with increased bone marrow adiposity parameters (some of them). After KT, both groups showed the same associations. Osteocyte Scl expression after KT decreased with the use of ZA. We observed also an inverse association between bone adiposity parameters and lower osteocyte sclerostin expression 12 months after KT. Conclusion In conclusion, the present study suggests that KT fails to normalize bone marrow adiposity, and it even gets worse with the use of ZA. Moreover, bone marrow adiposity is inversely associated with bone Volume and Turnover, which seems to be accentuated by the antiresorptive therapy.
- Bone Disease in Newly Diagnosed Lupus Nephritis Patients(2014) RESENDE, Aline Lazara; REIS, Luciene Machado dos; DIAS, Cristiane Bitencourt; CUSTODIO, Melani Ribeiro; JORGETTI, Vanda; WORONIK, ViktoriaIntroduction: Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology. Methods: We studied 15 pre-menopausal patients with <= 2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D-3 [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis. Results: LN patients presented a mean age of 29.5 +/- 10 years, a proteinuria of 4.7 +/- 2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31-87) ml/min/1,73 m(2). They were on glucocorticoid therapy for 34 +/- 12 days. All patients presented vitamin D insufficiency (9.9 +/- 4.4 ng/ml, range 4-20). Urinary MCP1 correlated negatively with 25(OH)D (r = -0.53, p = 0.003) and positively with serum deoxypyridinoline (r = -0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0 +/- 9.1 vs. 22.9 +/- 5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient's bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61 +/- 0.82 vs. 1.08 +/- 0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-kappa B ligand (RANKL) (1.76 +/- 0.92 vs. 0.41 +/- 0.28%, p<0.001) when compared to controls. Discussion: Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters. Glucocorticoid use, vitamin D insufficiency and inflammation might be involved in the physiopathology of bone metabolism disturbance.
- Predictive Factors of One-Year Mortality in a Cohort of Patients Undergoing Urgent-Start Hemodialysis(2017) MAGALHAES, Luciene P.; REIS, Luciene M. dos; GRACIOLLI, Fabiana G.; PEREIRA, Benedito J.; OLIVEIRA, Rodrigo B. de; SOUZA, Altay A. L. de; MOYSES, Rosa M.; ELIAS, Rosilene M.; JORGETTI, VandaBackground Chronic kidney disease (CKD) affects 10-15% of adult population worldwide. Incident patients on hemodialysis, mainly those on urgent-start dialysis at the emergency room, have a high mortality risk, which may reflect the absence of nephrology care. A lack of data exists regarding the influence of baseline factors on the mortality of these patients. The aim of this study was to evaluate the clinical and laboratory characteristics of this population and identify risk factors that contribute to their mortality. Patients and methods We studied 424 patients who were admitted to our service between 01/2006 and 12/2012 and were followed for 1 year. We analyzed vascular access, risk factors linked to cardiovascular disease (CVD) and mineral and bone disease associated with CKD (CKD-MBD), and clinical events that occurred during the follow-up period. Factors that influenced patient survival were evaluated by Cox regression analysis. Results The patient mean age was 50 18 years, and 58.7% of them were male. Hypertension was the main cause of primary CKD (31.8%). Major risk factors were smoking (19.6%), dyslipidemia (48.8%), and CVD (41%). Upon admission, most patients had no vascular access for hemodialysis (89.4%). Biochemical results showed that most patients were anemic with high C-reactive protein levels, hypocalcemia, hyperphosphatemia, elevated parathyroid hormone and decreased 25-hydroxy vitamin D. At the end of one year, 60 patients died (14.1%). These patients were significantly older, had a lower percentage of arteriovenous fistula in one year, and low levels of 25-hydroxy vitamin D. Conclusions The combined evaluation of clinical and biochemical parameters and risk factors revealed that the mortality in urgent-start dialysis is associated with older age and low levels of vitamin D deficiency. A lack of a permanent hemodialysis access after one year was also a risk factor for mortality in this population.