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INTRODUCTION: Urinary CD80 has been shown to have good specificity for minimal change disease (MCD) in children. However, the investigation of circulating factors such as soluble urokinase plasminogen activator receptor (suPAR) as biomarkers of focal segmental glomerulosclerosis (FSGS) is quite controversial. The objective of this study was to determine whether urinary CD80 and serum suPAR can be used for the diagnosis of MCD and FSGS, respectively, in the adult population of Brazil. We also attempted to determine whether those biomarkers assess the response to immunosuppressive treatment. METHODS: This was a prospective study in which urine and blood samples were collected for analysis of CD80 and suPAR, respectively, only in the moment of renal biopsy, from patients undergoing to diagnostic renal biopsy. At and six months after biopsy, we analyzed serum creatinine, serum albumin, and proteinuria in order to evaluate the use of the CD80 and suPAR collected in diagnosis as markers of response to immunosuppressive treatment. In healthy controls were collected urinary CD80 and proteinuria, serum suPAR, and creatinine. RESULTS: The results of 70 renal biopsies were grouped, by diagnosis, as follows: FSGS (n = 18); membranous nephropathy (n = 14); MCD (n = 5); and other glomerulopathies (n = 33). There was no significant difference among the groups in terms of the urinary CD80 levels, and serum suPAR was not significantly higher in the FSGS group, as would have been expected. Urinary CD80 correlated positively with nephrotic syndrome, regardless of the type of glomerular disease. Neither biomarker correlated with proteinuria at six months after biopsy. CONCLUSION: In adults, urinary CD80 can serve as a marker of nephrotic syndrome but is not specific for MCD, whereas serum suPAR does not appear to be useful as a diagnostic or treatment response marker.
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Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.
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Fosfatos/metabolismo , Insuficiência Renal Crônica/metabolismo , Animais , Fatores de Crescimento de Fibroblastos/metabolismo , Fibrose , Humanos , Rim/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
BACKGROUND/OBJECTIVE: Loss of renal function may induce secondary hyperparathyroidism (s-HPT), which triggers several complications leading to an extreme decline in quality of life and increased mortality in affected patients. We evaluated whether parathyroidectomy (PTx), as surgical treatment for s-HPT, modifies body composition, and hormones involved in the protein-energy metabolism of affected patients. SUBJECTS/METHODS: Overall, 30 s-HPT patients were evaluated at two times, before PTx (pre PTx) and 6 months after PTx (post PTx). Patients were evaluated by biochemistry analysis, anthropometry, electrical bioimpedance (BIA), food intake diary, handgrip strength, and modified global subjective nutritional assessment (SGA). RESULTS: After PTx, patients showed decreased serum levels of total and ionic calcium, as well as decreased alkaline phosphatase and PTH, and increased 25 (OH) vitamin D. These results demonstrate that PTx was efficient to correct part of the mineral disorder. We also observed an increase in caloric intake, body weight, body mass index (BMI), phase angle, handgrip strength, SGA score, and a decreasing in the percentage of weight loss. The osteocalcin concentration of both carboxylated (cOC) and undercarboxylated form was diminished post PTx. The cOC correlated with bone metabolism markers and SGA score. CONCLUSIONS: PTx modified body composition improving nutritional status and preventing the progression of weight loss with increased of energy intake, BMI, handgrip strength, phase angle of BIA, and SGA score. The present study also suggests an association of cOC with bone markers and SGA score. Further studies are needed to better clarify these associations with larger sample size.
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Hiperparatireoidismo Secundário , Insuficiência Renal Crônica , Biomarcadores , Composição Corporal , Osso e Ossos , Força da Mão , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Hormônio Paratireóideo , Paratireoidectomia , Qualidade de VidaRESUMO
BACKGROUND: 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.
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Osso e Ossos/metabolismo , Cálcio/metabolismo , Hiperparatireoidismo Secundário/sangue , Paratireoidectomia , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Proteínas Morfogenéticas Ósseas/sangue , Proteínas Morfogenéticas Ósseas/genética , Osso e Ossos/patologia , Sinalização do Cálcio , Estudos Transversais , Feminino , Regulação da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Hiperparatireoidismo Secundário/genética , Hiperparatireoidismo Secundário/patologia , Hiperparatireoidismo Secundário/cirurgia , Transporte de Íons , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteocalcina/genética , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/genética , Estudos Prospectivos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/terapiaRESUMO
Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (Pi) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent Pi absorption is modulated by dietary Pi. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary Pi concentration over 2 days would alter hormones involved in Pi metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LPi), normal (Nx/NPi), and high (Nx/HPi). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HPi group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LPi group compared with the Nx/HPi group. Modification of Pi concentration in the diet affected the apoptosis of enterocytes, particularly with Pi overload. MEPE expression was higher in the Nx/HPi group than in the Nx/NPi. These data reveal the importance of early control of Pi in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.
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Fatores de Crescimento de Fibroblastos/metabolismo , Intestinos/fisiologia , Hormônio Paratireóideo/metabolismo , Fosfatos/metabolismo , Fósforo na Dieta/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Animais , Fator de Crescimento de Fibroblastos 23 , Homeostase/fisiologia , Masculino , Ratos , Ratos Wistar , Insuficiência Renal Crônica/metabolismo , Uremia/metabolismoRESUMO
BACKGROUND: Observational studies have shown a beneficial effect of obesity on bone health; however, most of those studies were not based on bone biopsies. Metabolic syndrome (MetS) could have an effect on bone remodeling. However, there are no data on the effects of MetS in the presence of renal osteodystrophy. OBJECTIVE: The aim of this study was to investigate associations between MetS and renal osteodystrophy using the bone histomorphometric turnover-mineralization-volume (TMV) classification. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This observational cross-sectional study included 55 hemodialysis patients (28 women/27 men) who were evaluated for MetS and bone histomorphometry. Biochemical parameters included calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, free serum leptin, fibroblast growth factor 23 (FGF23), intact osteocalcin, sclerostin (Scl), glucose, insulin, and thyroid hormones. Robust models of multivariate linear regressions were used for the statistical analyses. RESULTS: Females had higher iPTH levels (1,143 vs. 358, p = 0.02). Patients with normal bone volume (BV/TV) had a higher prevalence of MetS (73.6% vs. 41.7%, p = 0.02) and higher serum phosphorus, C-terminal FGF23 and insulin levels. The multivariate regression analysis showed that low-density lipoprotein cholesterol (LDL) was positively correlated with bone formation rate (BFR/BS) and negatively associated with mineralization lag time. Bone volume was negatively associated with age but positively associated with MetS. Body mass index (BMI) was not correlated with any of the bone histomorphometric parameters. CONCLUSION: Our results suggest that MetS is not a risk factor for low bone volume in hemodialysis patients. Furthermore, BMI alone was not related to bone volume in this population.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Síndrome Metabólica/complicações , Obesidade/complicações , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Densidade Óssea , Proteínas Morfogenéticas Ósseas/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Marcadores Genéticos , Humanos , Resistência à Insulina , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangueRESUMO
OBJECTIVE: 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 (124.38µm versus 147.09µm). The number of bone trabeculae was lower (1.52, versus 1.88) and the separation between them was larger (541,19µm versus 391,14µm) 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.
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OBJECTIVE: To determine whether there is a difference on the bone architecture in patients with femoral neck fracture compared to patients with intertrochanteric fractures and assess the importance of aging on bone microarchitecture in patients with proximal femoral fracture. METHODS: Biopsy of the iliac crest was made in seventeen patients between 55 and 90 years old who were admitted to the emergency room with fractures of the proximal end of the femur. After a small fragment was removed, we made a histomorphometric analysis of it. RESULTS: There was no significant difference between patients with femoral neck fracture and trochanteric fracture in structural parameters, formation and resorption. Comparing age groups we also did not find any significant change between the groups in the parameters volume and trabecular separation. CONCLUSION: There are no difference in the morphometric parameters analyzed between the different types of fracture and age is not a significant factor in the alteration of these parameters.
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INTRODUCTION: 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 D3 [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 m2. 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 (râ=â-0.53, pâ=â0.003) and positively with serum deoxypyridinoline (râ=â0.53, pâ=â0.004). 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, pâ=â0.01). 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%, pâ=â0.003), and an increased expression of Receptor Activator of NF-κB 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.
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Doenças Ósseas/sangue , Nefrite Lúpica/sangue , Adulto , Aminoácidos/sangue , Doenças Ósseas/diagnóstico , Células Cultivadas , Quimiocina CCL2/sangue , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Masculino , Osteoblastos/metabolismo , Ligante RANK/sangue , Vitamina D/sangue , Adulto JovemRESUMO
BACKGROUND: Extensive bone defects are still a challenge for reconstructive surgery. Allogenic bones can be an alternative with no donor area morbidity and unlimited amount of tissue. Better results can be achieved after allogenic bone preparation and adding a vascular supply, which can be done along with flap prefabrication. The purpose of this study was to evaluate demineralized/lyophilized and deep-frozen allogenic bones used for flap prefabrication and the tissue expression of transforming growth factor ß (TGF-ß) in these bone fragments. METHODS: Fifty-six Wistar rat bone diaphyses were prepared and distributed in 4 groups: demineralized/lyophilized (experimental group 1 and control group 2) and deep freezing (experimental group 3 and control group 4). Two bone segments (one of each group) were implanted in rats to prefabricate flaps using superficial epigastric vessels (experimental groups) or only transferred as grafts (control groups). These fragments remained in their respective inguinal regions until the death that occurred at 2, 4, and 6 weeks after the operation. Semiquantitative histologic (tetracycline marking, cortical resorption, number of giant cells, and vascularization) and histomorphometrical quantitative (osteoid thickness, cortical thickness, and fibrosis thickness) analyses were performed. Transforming growth factor ß immunohistochemistry staining was also performed. RESULTS: Group 1 fragments presented an osteoid matrix on their external surface in all periods. Cartilage formation and mineralization areas were also noticed. These findings were not observed in group 3 fragments. Group 1 had more mineralization and double tetracycline marks, which were almost not seen in group 3. Cortical resorption and the number of giant cells were greater in group 3 in all periods. Vascularization and fibrosis thickness were similar in both experimental groups. Group 1 had more intense TGF-ß staining within 2 weeks of study. Nevertheless, from 4 weeks onward, group 3 presented statistically significant stronger staining. CONCLUSIONS: Although there are some differences between the preparation methods of allogenic bone, it is possible to prefabricate flaps with demineralized/lyophilized and deep-frozen bones.