Navegando por Palavras-chave "Diabetic nephropathy"
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- ItemAcesso aberto (Open Access)Bases moleculares da glomerulopatia diabética(Sociedade Brasileira de Endocrinologia e Metabologia, 2007-08-01) Lagranha, Claudia J.; Fiorino, Patricia; Casarini, Dulce Elena [UNIFESP]; Schaan, Beatriz D'Agord; Irigoyen, Maria Claudia [UNIFESP]; HC Instituto do Coração Unidade de Hipertensão; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Fundação Universitária de Cardiologia Instituto de Cardiologia Laboratório de Cardiologia Molecular e CelularThe determinant of the diabetic nephropathy is hyperglycemia, but hypertension and other genetic factors are also involved. Glomerulus is the focus of the injury, where mesangial cell proliferation and extracellular matrix occur because of the increase of the intra- and extracellular glucose concentration and overexpression of GLUT1. Sequentially, there are increases in the flow by the poliol pathway, oxidative stress, increased intracellular production of advanced glycation end products (AGEs), activation of the PKC pathway, increase of the activity of the hexosamine pathway, and activation of TGF-beta1. High glucose concentrations also increase angiotensin II (AII) levels. Therefore, glucose and AII exert similar effects in inducing extracellular matrix formation in the mesangial cells, using similar transductional signal, which increases TGF-beta1 levels. In this review we focus in the effect of glucose and AII in the mesangial cells in causing the events related to the genesis of diabetic nephropathy. The alterations in the signal pathways discussed in this review give support to the observational studies and clinical assays, where metabolic and antihypertensive controls obtained with angiotensin-converting inhibitors have shown important and additive effect in the prevention of the beginning and progression of diabetic nephropathy. New therapeutic strategies directed to the described intracellular events may give future additional benefits.
- ItemAcesso aberto (Open Access)Comparação das características clínicas e laboratoriais entre pacientes portadores de diabetes mellitus tipo 2 há mais de 20 anos, com ou sem nefropatia diabética(Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Albuquerque, Marcelo Nonato Cavalcanti de [UNIFESP]; Sesso, Ricardo de Castro Cintra [UNIFESP]; http://lattes.cnpq.br/1182565752545891; http://lattes.cnpq.br/5349079867856649; Universidade Federal de São Paulo (UNIFESP)Introdução: A nefropatia diabética é a causa mais comum de doença renal crônica (DRC) em estágio terminal nos EUA e na Europa e sua incidência e prevalência continuam a subir, levando a um grande custo humano e econômico. Aproximadamente, 40% das pessoas com diabetes desenvolvem nefropatia diabética, que se manifesta como albuminúria e / ou diminuição da taxa de filtração glomerular (TFG). Objetivo: Avaliar em um centro de referência universitário a prevalência de nefropatia diabética em pacientes portadores de diabetes tipo 2 com mais de 20 anos de doença e comparar as características clínicas e laboratoriais dos portadores e não portadores de nefropatia diabética. Descrever clínica e laboratorialmente o grupo de pacientes que apresentam TFGe< 60 mL/min/1,73m2 sem microalbuminúria. Comparar dados clínicos e laboratoriais dos seguintes grupos de portadores de nefropatia diabética:1- TFGe <60 ml/min/1,73m2 e presença de micro ou macroalbuminúria; 2- TFGe<60 ml/min/1,73m2 sem micro ou macroalbuminúria; 3- TFGe ≥60 ml/min/1,73m2 e com micro ou macroalbuminúria. Metodologia:Realizado estudo transversal envolvendo pacientes portadores de DM2 com mais de 20 anos do diagnóstico da doença companhados no Centro de diabetes da disciplina de Endocrinologia da Universidade Federal de São Paulo (Unifesp). Resultados: Foi encontrada uma prevalência de 64% de portadores de nefropatia diabética e classificação de albuminúria nos estágios A1, A2 e A3 de 52,1%, 26,8% e 21,1%, respectivamente. Os portadores de nefropatia diabética apresentaram uma prevalência maior de retinopatia diabética, acidente vascular cerebral, hipotireoidismo e hiperuricemia, um menor uso de estatinas, uma maior prevalência no uso de insulina, maiores níveis de PAS, PAD, colesterol total, triglicerídios e hemoglobina glicada quando comparados aos não portadores. Na análise multivariada por regressão logística múltipla, idade, sexo, tempo de diagnóstico, história prévia de AVC, hipotireoidismo, retinopatia diabética, PAD, circunferência do quadril, níveis de colesterol total, triglicerídios e hemoglobina mostraram associação significante com a presença da nefropatia diabética. O grupo com TFG <60mL/min/1.73m2 e albuminúria no estágio 2 e 3 apresentou maior prevalência de retinopatia diabética, AVC e uso de insulina. Esse grupo de pacientes também apresentou maiores níveis de PAS, PAD, Hb1Ac e ácido úrico sérico. Pacientes com TFGe <60 ml/min/1,73m2 sem microalbiminúria foi encontrado em 25% dos portadores de nefropatia diabética e esse grupo é formado por 87% de pacientes do sexo feminino. Conclusão: Uma elevada prevalência de nefropatia diabética foi encontrada em portadores de DM2 com mais de 20 anos do diagnóstico. Diferenças clínicas e laboratoriais foram encontradas entre os grupos
- ItemAcesso aberto (Open Access)Comparison of methods for urinary albumin determination in patients with type 1 diabetes(Associação Brasileira de Divulgação Científica, 2002-03-01) Khawali, Cristina [UNIFESP]; Andriolo, Adagmar [UNIFESP]; Ferreira, Sandra Roberta Gouvea [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)We tested the correlation of the albumin-to-creatinine ratio (A/C) in an early-morning urine sample, measured with a commercial kit (DCA 2000®), with the conventional immunoturbidimetric determination in the laboratory and with overnight albumin excretion rate (reference method). Fifty-five type 1 diabetic adolescents had their first-morning urine collected on the 1st and 8th day of the period. Urinary albumin and creatinine were determined immediately using the DCA 2000® kit. Samples were also stored for laboratory analysis. To evaluate the correlation between early-morning urinary A/C ratio and overnight albumin excretion rate, 16 subjects had a timed overnight urine collection. A/C ratios determined with the DCA 2000® kit and by the laboratory method were 13.1 ± 20.5 and 20.4 ± 46.3 mg/g, respectively. A/C results by both methods proved to be strongly correlated (r = 0.98, P<0.001). DCA 2000®-determined A/C showed 50% sensitivity and 100% specificity when compared to the reference method. Spot urinary A/C of the subset of 16 subjects significantly correlated with their overnight albumin excretion rate (r = 0.98, P<0.001). Intraindividual variation ranged from 17 to 32% and from 9 to 63% for A/C and overnight albumin excretion rate, respectively. In conclusion, an early-morning specimen should be used instead of timed overnight urine and the A/C ratio is an accurate, reliable and easily determined parameter for the screening of diabetic nephropathy. Immediate measurement of the A/C ratio is feasible using the DCA 2000® kit. Intraindividual variability indicates the need for repeated determinations to confirm microalbuminuria and the diagnosis of incipient diabetic nephropathy.
- ItemSomente MetadadadosEffects of Glucose Deprivation or Glucose Instability on Mesangial Cells in Culture(Karger, 2009-01-01) Santos, Carla de Lima e [UNIFESP]; Arnoni, Carine P. [UNIFESP]; Schor, Nestor [UNIFESP]; Boim, Mirian A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Mesangial cell ( MC) abnormalities play a central role in diabetic nephropathy. Variations in plasma glucose levels may contribute to MC dysfunction. This study evaluated the effects of glucose deprivation or fluctuations on MC viability, glucose uptake, and mesangial matrix production. the expression levels of fibronectin and glucose transporters (GLUT-1 and GLUT-4) were determined. MCs were exposed to normal (NG, 10 m M), low (LG, 1 m M) or high (HG, 30 m M) glucose concentrations for 1, 4, 12, 24 and 72 h. Glucose oscillation was achieved by alternating the glucose concentration (LG, NG or HG) in the medium every 8, 12, and 4 h over a total of 24 h. LG induced a significant increase (90%) in glucose uptake dependent of GLUT-1, which was not followed by alteration in fibronectin expression. Fluctuations in glucose levels induced a rise in glucose uptake also mediated by GLUT-1. Fibronectin did not change in any oscillation group. Results suggest that, in spite of a rise in glucose uptake by MCs under low glucose availability, or exposed to glucose fluctuations, mesangial matrix overproduction did not occur. Thus, neither glucose deprivation nor glucose instability, at least during short periods, is involved in the mesangial matrix overproduction observed in diabetes. Copyright (c) 2008 S. Karger AG, Basel
- ItemAcesso aberto (Open Access)Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats(Biomed Central Ltd, 2013-01-16) Ptilovanciv, Ellen O. N. [UNIFESP]; Fernandes, Gabryelle S. [UNIFESP]; Teixeira, Luciana C. [UNIFESP]; Reis, Luciana A. [UNIFESP]; Pessoa, Edson A. [UNIFESP]; Convento, Marcia B. [UNIFESP]; Simoes, Manuel J. [UNIFESP]; Albertoni, Guilherme A. [UNIFESP]; Schor, Nestor [UNIFESP]; Borges, Fernanda T. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1) is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. the goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. the hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME). A group of normoglycemic, untreated rats was used as the control (CTL).Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS) were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. in the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group.There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. in the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. in conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant activity of HO-1.
- ItemAcesso aberto (Open Access)Influência do treinamento físico combinado nas vias de sinalização da mTOR e da PGC-1α renal em ratos com diabetes experimental(Universidade Federal de São Paulo (UNIFESP), 2016-06-30) Jorge, Luciana [UNIFESP]; Schor, Nestor [UNIFESP]; http://lattes.cnpq.br/8276708741672261; http://lattes.cnpq.br/0873489026647730; Universidade Federal de São Paulo (UNIFESP)Diabetes Mellitus (DM) is a multifactorial disease resulting from either failure in the secretion of insulin, and in the commitment of its action, leading to hyperglycemia and producing changes in the metabolism of carbohydrates, fats and proteins. These changes induce complications, among which stands out the diabetic nephropathy (DN). In these cases, the activation of molecular pathways plays an important role in the pathophysiological process. Studies indicated that regular physical exercise is an effective tool to decrease the progression of DN being indicated as a non-? pharmacological treatment. The aim of this study was to evaluate the benefits of aerobic and resistance exercise in the pathophysiology of ND with subsequent possibility of prescription of this type of training for both healthy subjects and diabetic, aimed to minimize the deterioration of renal function. In this study, Wistar rats were submitted to three different exercise training (ET) protocols, which were prescribed with intensity of 40 to 60%, based on the results of stress tests specific to each modality. Streptozotocin (STZ) was used to diabetes induction (50 mg / kg IV). Animals were separated into eight groups: four controls (non-?trained, trained resisted, trained aerobic and combined trained) and four diabetics (non-?trained, trained resisted, trained aerobic and combined trained), with 6 to 8 rats / group. Were analyzed blood glucose, response to the maximum test effort, weight and kidney function, renal histology and proteins expression in dynamic mitochondrial pathway (AMPK/Mfn2/DRP-?1) and renal hyperthrophy pathway (AKT/mTOR) (assessed by Western blot). Ours results showed that all ET modality can modulate the in dynamic mitochondrial pathway (p<0,05) and renal hyperthrophy pathway (p<0,05) when compared with the diabetics non trained, in addition the progression of diabetic nephropathy,atenued the proteinuria and renal dysfunction (p<0,05). This results showed that the associated the aerobic and resistance can be control/prevent the diabetic nephropathy, may be a non pharmacological treatments in a significant way.
- ItemSomente MetadadadosIs Cystatin C a Useful Marker in the Detection of Diabetic Kidney Disease?(Karger, 2010-01-01) Borges, Rodolfo L. [UNIFESP]; Hirota, Andrea H.; Quinto, Beata M. R. [UNIFESP]; Ribeiro, Arthur B. [UNIFESP]; Zanella, Maria T.; Batista, Marcelo C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background/Aims: To evaluate cystatin C as a marker of diabetic kidney disease in normoalbuminuric diabetic patients without chronic kidney disease (CKD). Methods: A cross-sectional study was carried out comprising 243 hypertensive patients, 61 of them with type 2 diabetes, presenting normoalbuminuria and an estimated glomerular filtration rate (eGFR) >= 60 ml/min/1.73 m(2). Renal function assessment included determinations of serum creatinine and cystatin C levels, microalbuminuria, as well as eGFR through Cockcroft-Gault and Modification of Diet in Renal Disease equations. Results: Diabetic patients presented higher cystatin C levels than nondiabetic patients (0.95 +/- 0.19 vs. 0.89 +/- 0.17 mg/l; p < 0.05). in the binary logistic regression, the presence of diabetes and metabolic syndrome was significantly associated with elevated cystatin C levels. Diabetic patients also presented a slightly greater albuminuria (6.72 +/- 4.43 vs. 5.07 +/- 3.59 mu g/min; p < 0.05). Conclusions: Our results suggest that elevated cystatin C levels in diabetic patients may identify a certain degree of renal dysfunction even when albuminuria and eGFR do not mirror CKD. Longitudinal studies with direct GFR measures need to be done in order to confirm the value of cystatin C as an indicative of worse renal outcomes in the diabetic population. Copyright (C) 2009 S. Karger AG, Basel
- ItemSomente MetadadadosUrinary MCP-1 and RBP: Independent predictors of renal outcome in macroalbuminuric diabetic nephropathy(Elsevier B.V., 2012-11-01) Titan, S. M.; Vieira, J. M.; Dominguez, W. V.; Moreira, S. R. S. [UNIFESP]; Pereira, A. B. [UNIFESP]; Barros, R. T.; Zatz, R.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense.Methods: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis. doubling of serum creatinine or death (primary outcome. PO) in 56 type 2 diabetic patients with macroalbuminuric DN.Results: Mean follow-up time was 30.7 +/- 10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-beta or VEGF. in the Cox regression, urinary RBP. MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p = 0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p = 0.02 for log MCP-1) remained as significant independent predictors of the PO.Conclusion: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated. (C) 2012 Elsevier Inc. All rights reserved.