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
7 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.
conferenceObject Cigarette smoke exposure leads to bone resorption, matrix remodeling and a worsening in bone mineralization(2016) TEODORO, W. Rosolia; BARHOSA, A. Povoa; LOURENCO, J. Dias; VELOSA, A. P. Pereira; MARTINS, J.; OLIVO, C. Rosa; JORGETTI, V.; LOPES, F. D. T. Q. S.- 1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression(2016) LIU, Eva S.; MARTINS, Janaina S.; RAIMANN, Adalbert; CHAE, Byongsoo Timothy; BROOKS, Daniel J.; JORGETTI, Vanda; BOUXSEIN, Mary L.; DEMAY, Marie B.X-linked hypophosphatemia (XLH) is characterized by impaired renal tubular reabsorption of phosphate owing to increased circulating FGF23 levels, resulting in rickets in growing children and impaired bone mineralization. Increased FGF23 decreases renal brush border membrane sodium-dependent phosphate transporter IIa (Npt2a) causing renal phosphate wasting, impairs 1-alpha hydroxylation of 25-hydroxyvitamin D, and induces the vitamin D 24-hydroxylase, leading to inappropriately low circulating levels of 1,25-dihydroxyvitamin D (1,25D). The goal of therapy is prevention of rickets and improvement of growth in children by phosphate and 1,25D supplementation. However, this therapy is often complicated by hypercalcemia and nephrocalcinosis and does not always prevent hyperparathyroidism. To determine if 1,25D or blocking FGF23 action can improve the skeletal phenotype without phosphate supplementation, mice with XLH (Hyp) were treated with daily 1,25D repletion, FGF23 antibodies (FGF23Ab), or biweekly high-dose 1,25D from d2 to d75 without supplemental phosphate. All treatments maintained normocalcemia, increased serum phosphate, and normalized parathyroid hormone levels. They also prevented the loss of Npt2a, alpha-Klotho, and pERK1/2 immunoreactivity observed in the kidneys of untreated Hyp mice. Daily treatment with 1,25D decreased urine phosphate losses despite a marked increase in bone FGF23 mRNA and in circulating FGF23 levels. Daily 1,25D was more effective than other treatments in normalizing the growth plate and metaphyseal organization. In addition to being the only therapy that normalized lumbar vertebral height and body weight, daily 1,25D therapy normalized bone geometry and was more effective than FGF23Ab in improving trabecular bone structure. Daily 1,25D and FGF23Ab improved cortical microarchitecture and whole-bone biomechanical properties more so than biweekly 1,25D. Thus, monotherapy with 1,25D improves growth, skeletal microarchitecture, and bone strength in the absence of phosphate supplementation despite enhancing FGF23 expression, demonstrating that 1,25D has direct beneficial effects on the skeleton in XLH, independent of its role in phosphate homeostasis. (C) 2016 American Society for Bone and Mineral Research.
- Role of proton receptor OGR1 in bone response to metabolic acidosis?(2016) JORGETTI, Vanda; DRUEEKE, Tilman B.; OTT, Susan M.Chronic metabolic acidosis stimulates bone resorption, resulting in loss of calcium and bicarbonate from bone. Both osteoblasts and osteoclasts sense extracellular H+ by the G-protein coupled receptor, OGR1, whose activation leads to increased bone resorption as well as decreased bone formation. Krieger et al. examined the effect of OGR1 knockout in mice. They found an unexpected increase in bone resorption, but nevertheless an increase in bone volume linked to enhanced bone formation. This discovery opens a window of opportunity to explore potential new anabolic treatments for patients with low bone mass. (C) 2016 International Society of Nephrology
- The deceptive concept of hypoparathyroidism and recurrence after parathyroidectomy in dialysis patients: are we offering a Procrustean bed to some patients?(2016) MONTENEGRO, FABIO LUIZ DE MENEZES; BRESCIA, MARILIA D'ELBOUX GUIMARAES; NASCIMENTO JÚNIOR, CLIMÉRIO PEREIRA; MASSONI NETO, LEDO MAZZEI; ARAP, SÉRGIO SAMIR; SANTOS, STÊNIO ROBERTO CASTRO LIMA; GOLDENSTEIN, PATRÍCIA TASCHNER; BUENO, RODRIGO OLIVEIRA; CUSTODIO, MELANI RIBEIRO; JORGETTI, VANDA; MOYSES, ROSA MARIA AFFONSOABSTRACT Objective: to analyze the frequency of hypoparathyroidism and of its recurrence after parathyroidectomy in dialysis patients according to different existing classifications. Methods: we conducted a retrospective study of 107 consecutive dialysis patients undergoing total parathyroidectomy with immediate autograft in a tertiary hospital from 2006 to 2010. We studied the changes in PTH levels in the postoperative period over time. Were grouped patients according to different PTH levels targets recommended according to the dosage method and by the American and Japanese Nephrology Societies, and by an International Experts Consortium. Results: after parathyroidectomy, there was sustained reduction in serum calcium and phosphatemia. The median value of PTH decreased from 1904pg/ml to 55pg/ml in 12 months. Depending on the considered target level, the proportion of patients below the target ranged between 17% and 87%. On the other hand, the proportion of patients with levels above the target ranged from 3% to 37%. Conclusion: the application of different recommendations for PTH levels after parathyroidectomy in dialysis patients may lead to incorrect classifications of hypoparathyroidism or recurrent hyperparathyroidism and resultin discordant therapeutic conducts.
- The pitfall of treating low bone turnover: Effects on cortical porosity(2016) ARAUJO, Maria Julia C. L. N.; KAROHL, Cristina; ELIAS, Rosilene M.; BARRETO, Fellype C.; BARRETO, Daniela Veit; CANZIANI, Maria Eugenia F.; CARVALHO, Aluizio B.; JORGETTI, Vanda; MOYSES, Rosa M. A.Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46 +/- 13 years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)1 and correlated with PTH (p = 0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p = 0.015) and the delta of PTH (p = 0.03); it was also higher among non-white patients than in white patients (p = 0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2) = 0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.