Navegando por Palavras-chave "Hipercalciúria"
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- ItemSomente MetadadadosAnálise da expressão do sistema OPG/RANKL e outras citocinas em tecido ósseo de pacientes com litíase renal(Universidade Federal de São Paulo (UNIFESP), 2007) Gomes, Samirah Abreu [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]Os mecanismos envolvidos na doença óssea da Hipercalciúria Idiopática (HI) ainda permanecem desconhecidos. Citocinas tais como o receptor ativador do fator nuclear NF-kβ (RANK), seu ligante (RANKL) e a osteoprotegerina (OPG), dentre outras, são importantes reguladores da remodelação óssea. Até o momento, não existem estudos demonstrando a expressão óssea destas citocinas na Hipercalciúria Idiopática. O objetivo do presente estudo foi avaliar a expressão óssea de RANKL, OPG, interleucina 1α (IL-1α), fator de crescimento transformador β (TGF-β) e o fator de crescimento fibroblástico (bFGF) em pacientes com litiásicos com HI. Foram realizadas análises imunohistoquímicas de fragmentos ósseos calcificados obtidos de 36 biópsias ósseas previamente realizadas em pacientes litiásicos hipercalciúricos para estudo histomorfométrico no período de 1992 a 2005 nos Serviços de Nefrologia das Universidades Federal e Estadual de São Paulo (UNIFESP e USP). Para efeito de comparação utilizamos um grupo controle que constituiu de tecido ósseo posmortem obtido de 10 indivíduos saudáveis. Na análise histomorfométrica, os pacientes com HI apresentaram uma diminuição do volume ósseo (19,4 ± 7,0 vs 26,2 ± 8,3%, p=0,02), aumento da reabsorção óssea (8,3 ± 5,4 vs 2,6 ± 0,8%, p<0,001) e um aumento no tempo para a mineralização óssea (45,3 ± 31,4 vs 23,0 ± 2,4 dias, p<0,0001) quando comparados ao grupo controle. A imunohistoquímica revelou um aumento da expressão óssea para OPG e RANKL nos pacientes com Hipercalciúria Idiopática comparados aos controles (0,63 ± 0,60 vs 0,14 ± 0,15% e 0,90 ± 1,00 vs 0,27 ± 0,24%, p=0,03, respectivamente) enquanto que para IL-1α não se observou diferença estatística (1,0 ± 1,0 vs 0,7 ± 0,4%). A expressão óssea do RANKL foi significantemente maior em pacientes com HI que apresentaram elevada reabsorção óssea comparada aos com reabsorção óssea normal (1,10 ± 0,99 vs 0,50 ± 0,73%, p=0.03). A expressão óssea para o TGF-β mostrou-se reduzida nos pacientes HI em relação aos controles (0,54 ± 0,7 vs 1,48 ± 1,44%, p<0,003)diferentemente do bFGF que foi similar entre ambos. A expressão óssea do TGF-β se correlacionou diretamente com a superfície e volume osteóides e também com a superfície de mineralização óssea (r=0,36, r=0,50 e r=0,47, p<0,03) nos pacientes com HI. Concluímos que o aumento na expressão óssea do RANKL deve contribuir para a elevação na reabsorção óssea observada nos pacientes com HI. O aumento concomitante da expressão óssea da OPG deve ter sido secundário, na tentativa de antagonizar o efeito estimulante da reabsorção óssea induzida pelo RANKL. O achado da redução da expressão óssea do TGF-β sugere que esta citocina também tenha contribuído para o aumento da reabsorção óssea pela menor inibição do RANKL. Adicionalmente, a menor expressão do TGF-β pode estar relacionada ao retardo na mineralização óssea evidenciada nos pacientes com HI..
- ItemSomente MetadadadosAvaliação da densidade mineral, microarquitetura e resistência óssea de pacientes litiásicos por Tomografia Computadorizada Quantitativa Periférica de Alta Resolução (HR-pQCT) e suas relações com a calciúria(Universidade Federal de São Paulo (UNIFESP), 2020-07-30) Esper, Priscila Ligeiro Goncalves [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]; Universidade Federal de São PauloLow bone mineral density (BMD) at lumbar spine and femoral neck have been evidenced among nephrolithiasis patients. Histomorphometric analysis and quantitative computed tomography (qCT) have suggested the trabecular bone is most affected. The aim of the present study was to determine volumetric BMD (vBMD), bone microarchitecture, and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in stone formers (SF) in comparison with healthy subjects. In addition, the association of bone parameters with urinary calcium was investigated in the SF group. Fifty-eight (58) male SF (37.2 ±9.3 years old) and 49 premenopausal female SF (34.2 ±9.1 years old) underwent HR-pQCT/FEA, as well as areal BMD (aBMD) and trabecular bone score (TBS) by Dual-energy X-ray absorptiometry (DXA), whose results were compared to age-matched controls (186 females and 97 males). Urinary excretion of calcium, urea and sodium, serum biochemical, hormonal parameters and bone markers were determined in the SF group. Three-day dietary records were obtained from SF to determine calcium intake. Male and female SF presented significantly lower aBMD by DXA compared to controls at both sites. Male SF, but not female, exhibited significantly lower TBS than controls. HR-pQCT analysis revealed male and female SF had lower trabecular number (Tb.N) and increased trabecular separation (Tb.Sp). Female SF had also lower trabecular vBMD (Tb.vBMD) and increased cortical vBMD (Ct.vBMD). Parameters of bone strength were significantly lower only in male SF compared to controls. When SF were divided in tertiles, Tb.N was lower and Tb.Sp was higher in the 3rd versus the 1st tertile at the radius. Significant inverse correlations were detected at both skeletal sites between urinary calcium and HRpQCT parameters, such as Tb.vBMD, BV/TV and Tb.N as well as direct correlations with Tb.Sp. In conclusion, the pioneering use of HR-pQCT in stone formers revealed trabecular bone impairment, especially concerning microarchitecture, at both tibia and radius, when compared to healthy subjects. Trabecular vBMD and microarchitecture alterations were associated with urinary calcium excretion. A lower TBS by DXA and lower bone strength by FEA was also disclosed in male SF compared to controls, but not in female SF, which in turn exhibited higher cortical vBMD than their controls, what could have contributed to preserve bone strength in the latter. The findings of the present study suggest that nephrolithiasis represent a potential risk of bone fractures mainly among males, due to the reduction of bone strength.
- ItemAcesso aberto (Open Access)Avaliação da expressão do receptor de vitamina d (VDR) e das hidroxilases CYP27B1 e CYP24A1 e concentração sérica de 1,25-dihidroxivitamina D em pacientes litiásicos(Universidade Federal de São Paulo (UNIFESP), 2019-06-03) Melo, Thalita Lima [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]; http://lattes.cnpq.br/5039409992847018; http://lattes.cnpq.br/0399585291142239; Universidade Federal de São Paulo (UNIFESP)Introduction: The pathophysiological mechanisms for hypercalciuria comprise increased intestinal calcium absorption, reduced renal tubular reabsorption and increased bone resorption, which are influenced by calciotropic hormones such as PTH, FGF-23, 25OHD and 1,25(OH)D. The 1,25(OH)D is synthesized from 25(OH)D by the enzyme CYP27B1 (1α-hydroxylase), exerts its biological functions through binding to the vitamin D receptor (VDR) and is degraded by the enzyme CYP24A1. The expression of VDR and levels of 1,25(OH)D exceed the values of controls in some but not all hypercalciuric stone formers. Objective: We aimed to evaluate the expression of VDR, CYP27B1 and CYP24A1, and the serum 1,25(OH)D levels in hypercalciuric stone formers (HSF) in comparison with normocalciuric stone formers (NSF) and healthy subjects as controls (HS). Methods: Twenty-four-hour urine collections, blood samples for determination of biochemical and hormonal parameters including Klotho and FGF-23 and a 3-day dietary record were obtained from 30 participants from each of the groups. All participants were paired by gender, age and body mass index. VDR, CYP27B1 and CYP24A1 expression were measured by flow cytometry. Results: HSF compared to NSF and HS presented significantly higher urinary volume (2021±101 vs 1547±101 and 1488±101 ml/24h, p=0.000, mean ± standard error) and higher urinary excretion of calcium (345±12 vs 166±12 and 149±12 mg/24h, p=0.000), sodium (215±12 vs 168±10 and 179±10 mEq/24h, p=0.006), magnesium (108.5±6.8 vs 72.8±6.6 and 82.1±6.7 mg/24h, p=0.001), oxalate (25.3±1.6 vs 21.0±1.6 and 19.7±1.5 mg/24h, p=0.03), uric acid (690±26 vs 572±26 and 556±26 mg/24h, p=0.000) and phosphorus (979±49 vs 791±48 and 702±49 mg/24h, p=0.000). Calcium intake was lower in HSF versus NSF and HS (442±41 vs 594±42 and 559±41mg, respectively, p=0.027) and salt (NaCl) intake was higher in HSF versus NSF and HS (12.6±0.6 vs 9.8±0.6 e 10.5±0.6 g/day, p=0.006). Protein intake, assessed by protein equivalent of nitrogen appearance (PNA), was lower in HSF and NSF versus HS (1.1±0.0 and 1.0±0.0 vs 1.4±0.0 g/kg/day, p=0.006) with no differences in estimated potential renal acid load (PRAL), phosphorus and potassium intake among groups. Ionized calcium was significantly lower in HSF than NSF (1.29±0.0 vs 1.31±0.0 mmol/L, p<0.01). Serum 1,25(OH)D was significantly higher, even within normal ranges, in HSF and NSF than HS (22.5±1.2; 22.2±1.2 vs 17.4±1.2 pg/ml, p=0.007, respectively) but serum 25(OH)D, PTH, α-Klotho and plasma FGF-23 did not differ among groups. The VDR expression was higher in HSF and NSF than HS (80.8±3.2; 78.7±3.3 vs 68.6±3.2%, p=0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43±0.25 and 0.56±0.10 than 0.34±0.06, p=0.00). Conclusions: Stone-formers, regardless of urinary calcium levels, had higher VDR expression and 1,25(OH)D levels compared to controls. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.
- ItemSomente MetadadadosExpressão do fator de crescimento de fibroblasto 23 (FGF-23), do receptor de vitamina D (VDR) e de esclerostina (Sost) em tecido ósseo de pacientes litiásicos hipercalciúricos(Universidade Federal de São Paulo (UNIFESP), 2013) Menon, Viviane Barcellos [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]Alteracoes histomorfometricas representadas por reduzida formacao, elevada reabsorcao ossea e defeitos na mineralizacao ossea tem sido evidenciadas em pacientes litiasicos com hipercalciuria idiopatica (HI). O presente estudo teve como objetivo avaliar a expressao ossea do fator de crescimento de fibroblasto 23 (FGF-23), do receptor de vitamina D (VDR) e de esclerostina (Sost) em pacientes litiasicos HI. Analise imunohistoquimica foi realizada em 30 amostras de tecido osseo descalcificado obtidas de biopsias de litiasicos HI e em material post mortem de 33 controles sadios. Os valores dos parametros sericos foram obtidos dos prontuarios dos pacientes. A expressao ossea de FGF-23, VDR e Sost nao diferiu entre HI e controles. Quando os pacientes HI foram divididos de acordo com o nivel de reabsorcao ossea, elevada (n=21) ou normal (n=9), o subgrupo de HI com elevada reabsorcao ossea apresentou media maior de expressao de VDR, porem nao significante, e media significantemente maior de Sost versus reabsorcao ossea normal (18,3±12,8 vs 11,9±6,2%; p=0,12 & 11,2±12,6 vs 4,4±3,7%; p=0,03, respectivamente). A expressao ossea de FGF-23 nao se correlacionou com nenhum parametro histomorfometrico. No entanto, a superficie de reabsorcao (ES/BS) de pacientes HI correlacionou-se significantemente com a expressao de VDR nos osteoblastos (r=0,51; p=0,004) e com a expressao de Sost nos osteocitos (r=0,41; p=0,02). Essas correlacoes nao foram observadas entre os controles. Finalmente, observou-se correlacao positiva e significante entre a expressao de VDR e Sost com niveis sericos de 1,25(OH)2D3 (r=0,52; p=0,01 & r=0,53; p=0,02, respectivamente). Os presentes achados nao sugerem que o FGF-23 exerca influencia nas alteracoes osseas evidenciadas na HI. A expressao ossea de VDR e Sost foi fortemente correlacionada com o aumento de reabsorcao ossea em pacientes HI
- ItemSomente MetadadadosPrevalência de osteopenia em pacientes portadores de litíase renal(Universidade Federal de São Paulo (UNIFESP), 2007) Barros, Olivia Andrade [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]
- ItemAcesso aberto (Open Access)Renal stone disease: causes, evaluation and medical treatment(Sociedade Brasileira de Endocrinologia e Metabologia, 2006-08-01) Heilberg, Ita Pfeferman [UNIFESP]; Schor, Nestor [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The purpose of the present review is to provide an update about the most common risk factors or medical conditions associated with renal stone formation, the current methods available for metabolic investigation, dietary recommendations and medical treatment. Laboratory investigation of hypercalciuria, hyperuricosuria, hyperoxaluria, cystinuria, hypocitraturia, renal tubular acidosis, urinary tract infection and reduction of urinary volume is based on the results of 24-hr urine collection and a spot urine for urinary sediment, culture and pH. Blood analysis for creatinine, calcium and uric acid must be obtained. Bone mineral density has to be determined mainly among hypercalciurics and primary hyperparathyroidism has to be ruled out. Current knowledge does not support calcium restriction recommendation because it can lead to secondary hyperoxaluria and bone demineralization. Reduction of animal protein and salt intake, higher fluid intake and potassium consumption should be implemented. Medical treatments involve the use of thiazides, allopurinol, potassium citrate or other drugs according to the metabolic disturbances. The correction of those metabolic abnormalities is the basic tool for prevention or reduction of recurrent stone formation.