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
126 resultados
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- Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis(2016) SPRAGUE, Stuart M.; BELLORIN-FONT, Ezequiel; JORGETTI, Vanda; CARVALHO, Aluizio B.; MALLUCHE, Hartmut H.; FERREIRA, Anibal; D'HAESE, Patrick C.; DRUEEKE, Tilman B.; DU, Hongyan; MANLEY, Thomas; ROJAS, Eudocia; MOE, Sharon M.Background: The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial. Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20 degrees C) serum. Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test: Bone histomorphometric assessment of turnover (bone formation rate/bone surface [BFR/BS]) and receiver operating characteristic curves for discriminating diagnostic ability. Results: The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve > 0.70 but < 0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was <103.8 pg/mL, and to discriminate high from nonhigh BFR/BS was >323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was <33.1 U/L, and for high from nonhigh BFR/BS, 42.1 U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively. Limitations: Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries. Conclusions: The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions. (C) 2016 by the National Kidney Foundation, Inc.
- 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.
- Increased bone resorption by long-term cigarette smoke exposure in animal model(2021) JUNQUEIRA, Jader Joel Machado; LOURENCO, Juliana Dias; SILVA, Kaique Rodrigues da; JORGETTI, Vanda; VIEIRA, Rodolfo P.; ARAUJO, Amanda Aparecida de; ANGELIS, Katia De; CORREIA, Aristides Tadeu; ALVES, Luan Henrique Vasconcelos; TIBERIO, Iolanda de Fatima Lopes Calvo; BARBOSA, Alexandre Povoa; LOPES, Fernanda Degobbi Tenorio Quirino dos SantosIntroduction: Clinical and experimental studies have been attesting the deleterious effects of smoking mainly due to the stimulation of osteoclastogenesis and inhibition of osteoblastogenesis. However the physiological mechanisms that can explain these changes are not fully understood. Aims: To evaluate the trabecular bone resorption effect caused by long-term exposure to cigarette smoke and the action of cytokines and reactive oxygen species involved in this process. Methods: Sixty young adult C57BL/6 mice were allocated to two groups: control, 30 animals exposed to filtered air for 1, 3 and 6 months; and smoke, 30 animals exposed to cigarette smoke for 1, 3 and 6 months. Femoral and tibial extraction was performed to evaluate the bone mineral matrix, bone cytokines (Receptor activator of nuclear factor-kappa B ligand -RANKL and Osteoprotegerin -OPG) and oxidative stress markers (Thiobarbituric acid reactive substances -Tbars). Results: Exposure to cigarette smoke (CS) generated changes in bone structural parameters in the 6th month of follow-up, demonstrating an evident bone loss; reduction in OPG/RANKL ratio from the 3rd month on and increase in Tbars in the first month, both closely related to the increase in osteoclastogenic activity and bone resorption. Conclusion: These findings reinforce the importance of CS-induced oxidative stress in bone compromising the bone cellular activities with a consequent impairment in bone turn over and changes in bone structure.
- HISTOMORPHOMETRIC ANALYSIS OF THE FEMORAL NECK IN PATIENTS WITH AND WITHOUT FEMORAL NECK FRACTURE(2015) SOUZA, Caio Goncalves De; JORGETTI, Vanda; REIS, Luciene Machado Dos; CROCI, Alberto TesconiObjective: To determine, through bone histomorphometry in femoral neck, whether there are differences in the cancellous bone of the proximal femur from female patients over 60 years old who had femoral neck fracture and similar patients who did not have such fracture. Methods: We analyzed the trabecular part of the femur of 13 female patients, aged over 60 years old, by the bone histomorphometry method. Seven of these patients had femoral neck fracture. All of them were subjected to hip arthroplasty. Results: Bone densitometry showed no significant difference. There was no significant difference on the average thickness of the trabecular bone (124.38 mu m versus 147.09 mu m). The number of bone trabeculae was lower (1.52, versus 1.88) and the separation between them was larger (541,19 mu m versus 391,14 mu m) in the fracture group. Conclusion: A difference in histomorphometric parameters of cancellous bone of the femur neck was observed among patients who had fractures as compared to patients who had not.
- Kidneys also ""speak Portuguese""(2021) SANTOS, Iara da Silva; ARAÚJO, Maria Júlia Correia Lima Nepomuceno; JORGETTI, Vanda; ELIAS, Rosilene Motta; BOVER, Jordi
- Digital radiography as an alternative method in the evaluation of bone density in uremic rats(2020) CASTRO, Bárbara Bruna Abreu de; CARMO, Wander Barros; OLIVEIRA, Roberto Sotto Maior Fortes; PETERS, Vera Maria; JORGETTI, Vanda; CUSTODIO, Melani Ribeiro; SANDERS-PINHEIRO, HeladyABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.
- 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.
- Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats(2022) CARMO, Wander Barros do; CASTRO, Barbara Bruna Abreu; MANSO, Luisa Cardoso; CARMO, Priscylla Aparecida Vieira do; RODRIGUES, Clovis Antonio; CUSTODIO, Melani Ribeiro; JORGETTI, Vanda; SANDERS-PINHEIRO, HeladyPhosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 +/- 18.6 vs. 41.5 +/- 22.1 mu mol/L; P = 0.001), phosphate (3.5 +/- 0.8 vs. 2.2 +/- 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 +/- 0.2 vs. 0.2 +/- 0.17; P = 0.0001), and FGF23 (81.36 +/- 37.16 pg/mL vs. 7.42 +/- 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 +/- 0.20; CKD/CH-FeCl: 0.40 +/- 0.16; CKD/CaCO3 0.34 +/- 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.
- Overview of renal osteodystrophy in Brazil: a cross-sectional study(2023) CARBONARA, Cinthia E. M.; ROZA, Noemi A. V.; REIS, Luciene M. dos; CARVALHO, Aluizio B.; JORGETTI, Vanda; OLIVEIRA, Rodrigo Bueno deIntroduction: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. Methods: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. Results: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. Conclusions: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.
- Persistence of Bone and Mineral Disorders 2 Years After Successful Kidney Transplantation(2013) NEVES, Carolina L.; REIS, Luciene M. dos; BATISTA, Daniella G.; CUSTODIO, Melani R.; GRACIOLLI, Fabiana G.; MARTIN, Rita de Cassia T.; NEVES, Katia R.; DOMINGUEZ, Wagner V.; MOYSES, Rosa M.; JORGETTI, VandaBackground. Studies that have conducted bone biopsies after kidney transplantation are scarce, and the results are conflicting. Methods. We evaluate the bone histomorphometry, in vitro proliferation, and alkaline phosphatase expression in osteoblasts isolated from bone biopsies from 27 kidney transplant patients. The patients had preserved renal function and were treated with the same immunosuppressive therapy, receiving a minimum dose of corticosteroids. Results. The biochemical analysis revealed that 41% of the patients presented with hypercalcemia, 26% presented with hypophosphatemia, and hypovitaminosis D was detected in 63%. The histomorphometric analysis showed a reduced trabecular number and increased trabecular separation, mineral apposition rate, and mineralization lag time, as well as higher osteoid surface, osteoblastic surface, resorption surface, and osteoclastic surface and a lower mineralizing surface, compared with the controls. Based on the TMV classification, bone turnover was normal in 48%, high in 26%, and low in 26% of patients. Bone mineralization was delayed in 48% of the patients, and 58% of the patients with hypovitaminosis D presented with delayed bone mineralization. Bone volume was low in 37% of the patients. The osteoblasts from patients exhibited a higher degree of proliferation compared with those from controls. Conclusion. Eight-two percent of our patients presented with alterations in at least one of the TMV parameters. Persistence of hyperparathyroidism, hypovitaminosis D, and immunosuppressive drugs may have influenced osteoblast function, which would explain many of the bone alterations found in these patients.