Padrões morfológicos de lesão glomerular e correlação com achados clinicolaboratoriais de 43 crianças com síndrome nefrótica Morphologic patterns of glomerular lesion and correlation with clinical and laboratory findings of 43 children with nephrotic syndrome

OBJETIVOS: Avaliar a associação entre os parâmetros clinicolaboratoriais e alteração morfológica de biópsias renais em crianças com síndrome nefrótica. MÉTODOS: Os dados foram obtidos dos prontuários médicos de 43 crianças com síndrome nefrótica submetidas a biópsia renal. RESULTADOS: Vinte e oito pacientes eram do sexo masculino (65,1%), idades entre 1,4 a 12 anos (média de 4,7±3,2). Quarenta e dois pacientes (97,7%) apresentaram edema; 83,7%, oligúria e 32,5%, hipertensão arterial. A média de proteinúria foi 15,3g/1,73m²SC/dia e 55,8% apresentaram hematúria microscópica. As biópsias renais mostraram: glomerulonefrite proliferativa mesangial (GNPM) em 37,2%, glomeruloesclerose segmentar e focal (GESF) em 27,9%, alterações glomerulares mínimas (LM) em 25,6%, glomerulonefrite membranoproliferativa (GNMP) em 7% e glomerulonefrite membranosa (GNM) em 2,3%. Vinte e seis pacientes (60,5%) apresentaram resistência ao corticosteróide. Idade, sexo, hipertensão arterial, oligúria, uréia e creatinina séricas não mostraram diferenças estatísticas significativas entre os pacientes com GNPM, GESF e LM. Os pacientes com GNPM e GESF apresentaram maior freqüência de hematúria microscópica (p < 0,003 e p < 0,03; respectivamente). Os pacientes com GESF apresentaram maiores níveis de proteinúria (p < 0,01 versus LM e p < 0,05 versus GNPM). Os pacientes com LM apresentaram sensibilidade ao corticosteróide (p < 0,001 versus GESF e p = 0,047 versus GNPM). CONCLUSÕES: Sexo, idade, presença de hipertensão arterial ou oligúria e níveis séricos de uréia e creatinina não auxiliaram na diferenciação entre pacientes com GNPM, GESF e LM. Os pacientes com LM apresentaram sensibilidade a corticosteróides e menos probabilidade de apresentar hematúria microscópica. Pacientes com GESF apresentaram maiores níveis de proteinúria.<br>OBJECTIVES: To evaluate the association between clinical features and laboratory findings with the morphological changes in children with nephrotic syndrome. METHODS: The data were obtained from medical records of 43 children with nephrotic syndrome submitted to renal biopsy. RESULTS: Twenty-eight patients were male (65.1%), aged 1.4-12 years (mean 4.7 ± 3,2). Forty-two patients (97,7%) presented edema, 83.7% oliguria and 32.5% hypertension. The mean of proteinuria was 15.3g/1.73m² BSA per day and 55.8% presented microscopic hematuria. Renal biopsies showed: proliferative mesangial glomerulonephritis (PMGN) in 37.2%, focal segmental glomerulosclerosis (FSGS) in 27.9%, minimal change disease (MCD) in 25.6%, membranoproliferative glomerulonephritis (MPGN) in 7% and membranous glomerulonephropathy (MGN) in 2.3%. Twenty-six patients (60.5%) were steroid-resistant. Age, sex, hypertension, oliguria, serum urea and creatinine showed no statistically significant change between the patients with PMGN, FSGS and MCD. The patients with PMGN and FSGS showed higher frequency of microscopic hematuria (p < 0.003 and p < 0.03, respectively) and those with FSGS higher level of proteinuria. The patients with MCD were steroid responsive (p < 0.001 versus FSGS and p = 0.047 versus PMGN). CONCLUSION: Age, sex, hypertension, oliguria, serum urea and creatinine did not help to distinguish between the patients with PMGN, FSGS and MCD. The patients with MCD were steroid responsive and less likely to have microscopic hematuria. Patients with FSGS presented higher level of proteinuria

Islet of Langerhans transplantation. A comparative study of two different methods for isolating islet cells from rat pancreas

Two different methods for isolation of islet of Langerhans on control of metabolic abnormalities of alloxan-induced diabetic rat were tested. Sixty rats were randomly assigned to four experimental groups: GI included 10 non-diabetic control rats, GII included 10 diabetic control rats, without treatment, GIII included 20 diabetic rats (10 inbred and 10 outbred rats) that received islet of Langerhans transplantation (ILT) using islet cells prepared by collagenase, and GIV included 20 diabetic rats (10 inbred and 10 outbred rats) submitted to ILT using islet cells prepared by nonenzymatic method. Clinical and laboratory parameters at beginning and 4, 7, 14, 21 and 30 days of follow-up were recorded. Outbred rats were immunosuppressed with cyclosporin A, diabetes was induced by e.v. alloxan administration, and islet cells were isolated from normal donor Lewis rats and injected into the portal vein. ILT corrected the body weight gain, polyuria, polydipsia, polyphagia, and the high levels of blood and urine glucose in 73.7% of rats treated by enzymatic method and in 64.7% of those ones treated by nonenzymatic method. However, there was no significantly difference between the two methods (P > 0.50). We did not also observe significantly difference between the two methods when ILT was performed either in inbred or outbred rats. We concluded that ILT performed by nonenzymatic method may be an alternative treatment for diabetes due to be less expensive and to have possible advantages in the isolation process

Estudo comparativo entre cinco diferentes tratamentos sobre as alterações clínicas e laboratoriais do rato diabético induzido pela aloxana Comparative study among five different treatments on the clinical and laboratory changes of the alloxan-induced diabetic rats

OBJETIVOS: Este estudo visa a analisar os efeitos, a longo prazo, de cinco diferentes tratamentos sobre o controle metabólico de ratos diabéticos aloxânicos. MÉTODOS: Foram analisados 7 grupos experimentais, com 50 ratos cada um, sendo: GN o grupo controle normal; GD o grupo controle diabético, sem tratamento; GI, GA e GIA os grupos tratados, respectivamente, com insulina, acarbose e associação insulina + acarbose; GTIL o grupo tratado com transplante de ilhotas de Langerhans; e o GTPD o grupo tratado com transplante pancreatoduodenal heterotópico. Parâmetros clínicos (peso, ingestão hídrica, ingestão alimentar e diurese) e laboratoriais (glicemia, glicose urinária e insulina plasmática) foram avaliados em todos os animais, no início do experimento, e após 1, 3, 6, 9 e 12 meses de seguimento. RESULTADOS: À exceção do GN, mortalidade foi observada em todos os grupos experimentais no seguimento de 12 meses (GD= 50%; GI= 20%; GA= 26%; GIA= 18%; GTIL= 4%; GTPD= 20%). Em GD, GI, GA e GIA os óbitos ocorreram por distúrbios metabólicos ou hidroeletrolíticos e/ou pneumonia, diarréia e caquexia; em GTIL e GTPD todos os óbitos ocorreram por falhas técnicas no pós-operatório até 72h. Animais dos grupos GI, GA e GIA tiveram melhora significativa (p < 0,05) de todos os parâmetros clínicos e laboratoriais observados em ratos diabéticos, sem diferença de efetividade entre os tratamentos. Porém, os resultados observados nestes grupos, biologicamente não foram comparáveis aos observados em GTIL e GTPD, onde observou-se correção completa, aos níveis normais, de todas as variáveis analisadas (p<0,01). CONCLUSÕES: Os tratamentos convencionais com insulina, acarbose e insulina + acarbose melhoraram o estado diabético grave dos ratos tratados, contudo, a eficácia dos tratamentos foi significativamente inferior à oferecida pelo GTIL e GTPD.<br>PURPOSE: The long-term effects of five different treatments of diabetes were evaluated in alloxan-induced diabetic rats. METHODS: Seven experimental groups, with 50 rats each (GN normal control; GD untreated diabetic control; GI, GA, GIA treated groups with insulin, acarbose, and insulin plus acarbose, respectively; GTIL, GTPD treated groups with islet of Langerhans and pancreas transplantation) were studied. Clinical (body weight, water intake, food intake and urine output) and laboratory (blood and urinary glucose, and plasma insulin) parameters were analyzed at the beginning of the study, and after 1, 3, 6, 9 and 12 months of follow-up. RESULTS: Mortality was observed in all groups, except GN, during 12 months (GD= 50%; GI= 20%; GA= 26%; GIA= 18%; GTIL= 4%; GTPD= 20%). Rats from the GD, GI, and GIA groups died due to metabolic or hydrossaline disbalance, and/or pneumonia, diarrhoea, and cachexy. All deaths observed in GTIL and GTPD groups were in decorrence of technical failure at the immediate postoperative, until 72h. Animals from the GI, GA and GIA had significative improving of the clinical and laboratory parameters (p < 0,05) observed in diabetic rats, being the efficacy of theses treatments equal. However, rats from the GTIL and GTPD groups had better control of these parameters than GI, GA, and GIA groups. Transplanted rats had complete restoration, at the normal levels, of all analyzed variables (p<0,01). CONCLUSIONS: Conventional treatments with insulin, acarbose, and insulin plus acarbose improved the severe diabetic state of the alloxan-diabetic rats, but pancreas and islet transplantation have a better performance for treatment of diabetes

The number of podocyte and slit diaphragm is decreased in experimental diabetic nephropathy O número de podócitos e fendas diafragmáticas estão alterados na nefropatia diabética

PURPOSE: To determine the number of podocyte, slit diaphragms, slit diaphragm extensions and GBM thickness in diabetic nephropathy. METHODS: Sixty "Rattus Wistar"of both sexes weighing 200-300g were divided in two experimental groups: normal group 10 animals, and alloxan diabetic rats - 50 animals. Alloxan was administered in a single IV dose of 42mg/kg body weight. Body weight, water and food intake, diuresis, and blood and urine glucose were determined in both groups before alloxan injection and two weeks, six and twelve months after alloxan injection. Proteinuria was measured at 12 months in both groups. After 12 months animals were sacrificed, and the right kidney processed for electron microscopy. RESULTS: Clear clinical and laboratory signs of severe diabetes were seen, in all alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM) thickening, podocyte number, and slit diaphragm number and extension were determined. GBM of all diabetic rats was significantly thicker (median=0.29µm; semi-interquartile range=0.065µm) than in the normal rats (0.23µm; 0.035µm). Diabetic rat podocyte number (8; 1), slit diaphragm number (4; 1), and slit diaphragm extension (0.021µm; 0.00435µm) were significantly lower than in normal rats (11; 1) and (7; 1.5), and (0.031µm; 0.0058µm). Diabetic rat proteinuria (0.060mg/24h; 0.037mg/24h) was higher than in normal rats (0.00185mg/24h; 0.00055mg/24h). CONCLUSION: Experimental diabetes is associated with significant (p<0.05) changes in podocyte foot process, slit number, slit diaphragm extension, and GBM thickness.<br>OBJETIVO: Determinar o número de podocitos e fendas diafragmáticas, a extensão das fendas diafragmáticas e a espessura da Membrana Basal Glomerular (MBG) na nefropatia diabética. MÉTODOS: Sessenta "Rattus Wistar" de ambos os sexos, pesando entre 200-300g, foi dividido em dois grupos experimentais: grupo normal 10 animais, e grupo diabético induzido por aloxana - 50 animais. A Aloxana foi administrada em dose única endovenosa de 42mg/kg de peso. Medimos o peso, ingestão de água e comida, diurese e glucose sérica e urinária em ambos os grupos antes da injeção de aloxana e 2 (duas) semanas, seis e dose meses após a injeção. A proteinúria foi mensurada aos dose meses em ambos os grupos, no momento do sacrifício, onde removemos o rim direito para estudo ultraestrutural. RESULTADOS: Observamos sinais clínicos e laboratoriais de diabetes severo, nos animais diabéticos aloxânicos em todos os períodos de seguimento. Foi determinado o espessamento da membrana basal glomerular (MBG), número de podocitos, número de fendas diafragmáticas e sua extensão. A membrana basal glomerular do rato diabético mostrou espessamento significativo (mediana=0.29µm; amplitude semi-interquartilica = 0,065µm) em relação ao animal normal (0,23µm; 0,035µm). O número de podocitos do animal diabético (8; 1), número de fenda diafragmática (4; 1), e extensão das fendas diafragmáticas (0,021µm; 0,00435µm) foi significativamente menor em relação aos animais normais (11; 1) e (7; 1.5), e (0,031µm; 0,0058µm). A taxa da proteinúria (0,060mg/24h; 0,037mg/24h) foi maior que nos animais normais (0,00185mg/24h; 0,00055mg/24h). CONCLUSÃO: O diabetes experimental está associado com significativas alterações (p< 0,05) no número de processos podálicos e fendas diafragmáticas e extensão das fendas diafragmáticas e espessamento da membrana basal glomerular (MBG)

Role of metabolic control on diabetic nephropathy

OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N), non-treated alloxan-diabetic rats (D), alloxan-diabetic rats treated with acarbose (AD), alloxan-diabetic rats treated with insulin (ID), and alloxan-diabetic rats treated with insulin plus acarbose (IAD). The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy

Progression of nephropathy after islet of langerhans transplantation in alloxan-induced diabetic rats

We studied the effects of islet of Langerhans transplantation (IT) on the kidney lesions of rats with alloxan-induced diabetes. Forty-five inbred male Lewis rats were randomly assigned to 3 experimental groups: group Gl included 15 non-diabetic control rats (NC), group GIT included 15 alloxan-induced diabetic rats (DC), and group III included 15 alloxan-induced diabetic rats that received pancreatic islet transplantation prepared by nonenzymatic method from normal donor Lewis rats and injected into the portal vein (IT). Each group was further divided into 3 subgroups of 5 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratorial parameters were recorded in the mentioned periods in the 3 experimental groups. For histology, the kidneys of all rats of each subgroup were studied and 50 glomeruli and 50 tubules of each kidney were analyzed using light microscopy by two different investigators in a double blind study. The results showed progressive glomerular basement membrane thickening (GBMT), mesangial enlargement (ME), and Bowman's capsule thickening (BCT) in the 3 experimental groups throughout the follow-up. These alterations were significantly more severe in DC rats at 6 months when compared to NC rats (p < 0.01). However, the degree of GBMT, ME, and BCT observed in DC rats was not statistically different from IT rats at 1, 3, and 6 months. In addition, Armanni-Ebstein lesions of the tubules (AE) and tubular lumen protein (PRO) observed in DC rats were also observed in IT rats all over the study. These lesions were never present in NC rats. We conclude that IT did not prevent progression of kidney lesions in alloxan-induced diabetic rats within 6 months after transplantation

Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control Redução do número de podócitos na fase tardia da nefropatia diabética aloxânica: prevenção pelo controle glicêmico

PURPOSE: To determine podocyte number and GBM thickness in diabetic rats either under glycemic control or without glycemic control at 6 and 12 months after diabetes induction. METHODS: 100 wistar rats weighing 200-300g were divided into 6 groups: Normal group (N6 and N12- 25 rats); Diabetic group (D6 and D12- 25 rats), diabetic treated group ( DT 6 and DT 12- 25 rats) on insulin 1,8- 3,0 IU/Kg associated with acarbose (50mg to 100g of food) daily mixed in chow. Alloxan was injected intravenously in a dose of 42 mg/Kg of weight. Body weight, waterintake, 24-h diuresis, glycemia and glucosuria were determined before induction, 7 and 14 days after induction and monthly thereafter. Treatment started at day 14. Three groups were sacrificed at 6 months (N6,D6, DT6) and 3 groups at 12 months (N12, D12, DT12) with the renal tissue being prepared for electron microscopy. RESULTS: Glycemia in DT6&uml;and in DT12 was significantly different from that in D6 and D12 rats and similar to that in N6 and N12 animals. The number of podocytes in DT6 was not different from that in N6 and D6 (median = 11); the number of podocytes in DT12 (median = 11) differed from that in D12 (median = 8), but not from that in N12 (median = 11). GBM thickness in D6 (0.18 micrometers) was lower than in D12 (0.29 micrometers); while in DT6 (0.16 micrometers) it was lower than in D6 (0.18 micrometers). In DT12 (0.26 micrometers), it was lower than in D12 (0.29 micrometers). CONCLUSION: The control of hyperglycemia prevented GBM thickening in early and late (12 mo) alloxan diabetic nephropathy and podocyte number reduction.<br>OBJETIVO: Avaliar o número de podócitos e espessamento da membrana basal glomerular (MBG) em ratos diabéticos com e sem controle glicêmico com 6 e 12 meses da indução. MÉTODOS: 100 ratos Wistar com 200-300g compuseram 6 grupos: Normal (N6, N12 - 25 animais) Diabético (D6,D12 - 25 animais) e diabético tratado com insulina 1,8 a 3,0 U/Kg e acarbose misturada a ração (50g para cada 100g de ração) (DT6 e DT12 - 25 animais). Aloxana foi ministrada via endovenosa na dose de 42mg/Kg. Peso, ingestão hídrica e diurese de 24 horas e glicemia e glicosúria foram determinados antes da inoculação, 7 e 14 dias após e mensalmente. No 14ª dia foi iniciado o tratamento. Três grupos de animais (N6, D6 e DT6) foram sacrificados no 6&deg; mês e três grupos (N12, D12 e DT12), no 12ª mês sendo o tecido renal processado para estudo à microscopia eletrônica. RESULTADOS: A glicemia dos animais DT6 e DT12 diferiram significativamente, dos ratos D6 e D12, e não diferiram dos grupos N6 e N12. O número de podócitos do grupo DT6 não diferiu de N6 e D6 (mediana=11); o número de podócitos de DT12 (mediana=11) diferiu de D12 (mediana=8) e não diferiu de N12 (mediana=11). O espessamento da MBG de D6 (0,18 micrômetros) foi menor que D12 (0,29 micrômetros); de DT6 (0,16 micrômetros) foi menor que D6 (0,18 micrômetros) e de DT12 (0,26 micrômetros) foi menor que D12 (0,29 micrômetros). CONCLUSÃO: O controle da hiperglicemia preveniu o espessamento da MBG na nefropatia diabética aloxânica precoce (6 meses) e tardia (12 meses), e a diminuição do número de podócitos

Prevalência de pressão arterial elevada em crianças e adolescentes do ensino fundamental Prevalencia de presión arterial elevada en niños y adolescentes de la enseñanza fundamental Prevalence of elevated blood pressure in children and adolescents attending highschool

OBJETIVO: Verificar a prevalência de pressão arterial elevada em crianças e adolescentes e sua associação com indicadores antropométricos. MÉTODOS: Estudo transversal de estudantes de três instituições de ensino em Botucatu (SP). As variáveis avaliadas foram: pressão arterial (PA) (obtida em três ocasiões diferentes), peso, estatura, índice de massa corporal (IMC), circunferência braquial, circunferência abdominal (CA), dobras cutâneas tricipital e subescapular. A PA foi aferida por método auscultatório e classificada em pré-hipertensão (PH) e hipertensão arterial (HAS), para os valores entre os percentis 90 e 95 e maior que o percentil 95, respectivamente. Os dados antropométricos foram comparados, segundo o sexo, pelo teste t de Student. A correlação de Pearson foi utilizada para verificar a variação das PA sistólica (PAS) e diastólica (PAD) segundo dados antropométricos. A variação do escore Z da PA segundo percentil de IMC foi avaliada pela análise de variância seguida do teste de Tukey. RESULTADOS: Foram avaliadas 903 crianças (51,7% meninos), com idade de 9,3±2,5 anos para ambos os sexos. A prevalência de PH foi de 9,1% e de HAS foi de 2,9%. Houve correlação positiva significativa entre os níveis de PAS e PAD elevados e as variáveis antropométricas, com valores maiores para peso (r=0,53 e r=0,45, p<0,05, respectivamente) e CA (r=0,50 e r=0,38, p<0,05, respectivamente). CONCLUSÕES: A prevalência de níveis pressóricos elevados nesta casuística foi compatível com outros estudos brasileiros e internacionais, correlacionando-se positivamente com indicadores antropométricos elevados, o que sinaliza a influência do excesso de peso na PA já na infância.<br>OBJETIVO: Verificar la prevalencia de presión arterial elevada en niños y adolescentes y su asociación con indicadores antropométricos. MÉTODOS: Estudio transversal incluyendo a estudiantes de tres instituciones de enseñanza de Botucatu (São Paulo, Brasil). Las variables evaluadas fueron: presión arterial (PA) (obtenida en tres ocasiones distintas), peso, estatura, índice de masa corporal (IMC), circunferencia braquial, circunferencia abdominal (CA), pliegues cutáneos tricipital y subescapular. La PA fue verificada por método auscultatorio, siendo posteriormente clasificada como pre-hipertensión (PH) e hipertensión arterial (HAS) para los valores entre los percentiles 90 y 95 y superior al percentil 95, respectivamente. Los datos antropométricos fueron comparados, conforme al sexo, por la prueba t de Student. La correlación de Pearson fue utilizada para verificar la variación de las PA sistólica (PAS) y diastólica (PAD) según datos antropométricos. La variación del escore Z de la PA según percentil de IMC fue evaluada por el análisis de variancia seguida por la prueba de Tukey. RESULTADOS: Se evaluaron 903 niños (51,7% niños), con edad de 9,3±2,5 años para ambos sexos. La prevalencia de PH fue de 9,1% y de HAS fue de 2,9%. Hubo correlación positiva significativa entre los niveles presóricos elevados (PAS/PAD > percentil 90) y las variables antropométricas, con valores mayores para peso (r=0,53 y r=0,45, p<0,05, respectivamente) y CA (r=0,50 y r=0,38, p<0,05, respectivamente). CONCLUSIONES: La prevalencia de niveles presóricos elevados en esta casuística fue compatible con otros estudios brasileños e internacionales, correlacionándose positivamente con indicadores antropométricos elevados, lo que señaliza la influencia del exceso de peso en la PA ya en la infancia.<br>OBJECTIVE: To assess the prevalence of elevated blood pressure in schoolchildren and adolescents and the association of blood pressure with anthropometric measures. METHODS: This cross-sectional study, conducted in three schools in Botucatu, Brazil, collected blood pressure (BP) measurements taken at three different time points and anthropometric data: weight, height, body mass index (BMI), arm circumference, waist circumference, triceps and subscapular skinfolds. Blood pressure was measured using the auscultation method, and children were classified into two groups: pre-hypertension or hypertension for values between the 90th and 95th percentiles or above the 95th percentile. Data were compared according to sex using the Student's t test. The Pearson correlation coefficient was used to evaluate the association between blood pressure and anthropometric data. To evaluate blood pressure, the Z score according to BMI percentile categories, one-factor analysis of variance (ANOVA) and the Tukey post hoc test were used. RESULTS: This study evaluated 903 children and adolescents (51.7% boys) whose mean age was 9.3±2.5 years. The prevalence of pre-hypertension and hypertension was 9.1% and 2.9%. There was a positive correlation between both systolic and diastolic blood pressure and anthropometric variables, especially for weight (r=0.53 and r=0.45, p<0.05) and waist circumference (r=0.50 and r=0.38, p<0.05). CONCLUSIONS: The prevalence of elevated blood pressure in this study was similar to what has been reported in international and national studies. A positive correlation with abnormal anthropometric measures was found. These results suggest that overweight affects blood pressure already in childhood