Serum zinc level in children with nephrotic syndrome

Abnormalities of zinc metabolism are well documented in patients with chronic renal disease. We aim to study changes in serum zinc level in children with nephrotic syndrome [NS]. A hospital based case control study conducted in pediatric nephrology clinic inAl-Kadhymia Teaching Hospital for the period between I January 2010 to 31 October 2010. Forty children with NS were studied. Patients were divided into two groups: 24 patients with relapse [with proteinuria] constitute group A, and 16 patients with remission [without proteinuria] were in group B. Both groups were further subdivided into subgroups according to treatment with or without corticosteroid. Control group consisted of 40 healthy children. Serum and urine albumin was measured for all children. Serum zinc level was estimated by atomic absorption spectrophotometry. Patients aged 2-14 years, girls were 23 and boys were 17. Patients maintained a significant low serum albumin level in group A which was normalized in group B. The mean serum zinc level in group A 57.2 +/- 15.286 microg/dl, was significantly lower than that of controls 96.2 +/- 7.501 microg/dl. An increase in the level was observed in group B, however still significantly lower from that of controls. Low serum zinc level was noted in all treatment groups with or without steroid therapy. The serum zinc-albumin ratio in group B, 1.6260 +/- 0.28864 microg/g was significantly lower than controls. These changes reflect actual lower zinc level in spite of normal serum albumin. Zinc deficiency is present in children with NS, both during relapse and remission. Both serum albumin and corticosteroid had no effect on low serum zinc levels in children with NS. Other probable factors for hypozincemia need to be highlighted in further studies

Pharmacokinetics of cyclosporin: a microemulsion in children with idiopathic nephrotic syndrome

OBJECTIVE: We present a prospective study of a microemulsion of cyclosporin to treat idiopathic nephrotic syndrome in ten children with normal renal function who presented cyclosporin trough levels between 50 and 150 ng/ml and achieved complete remission with cyclosporin. To compare the pharmacokinetic parameters of cyclosporin in idiopathic nephrotic syndrome during remission and relapse of the nephrotic state. METHOD: The pharmacokinetic profile of cyclosporin was evaluated with the 12-hour area under the timeconcentration curve (auc0-12) using seven time-point samples. This procedure was performed on each patient during remission and relapse with the same cyclosporin dose in mg/kg/day. The 12-hour area under the timeconcentration curve was calculated using the trapezoidal rule. All of the pharmacokinetic parameters and the resumed 4-hour area under the time-concentration curve were correlated with the 12-hour area under the timeconcentration curve. ClinicalTrials.gov:NCT01616446. RESULTS: There were no significant differences in any parameters of the pharmacokinetic of cyclosporin during remission and relapse, even when the data were normalized by dose. The best correlation with the 12-hour area under the time-concentration curve was the 4-hour area under the time-concentration curve on remission and relapse of the disease, followed by the 2-hour level after cyclosporin (c2) dosing in both disease states. CONCLUSIONS: These data indicate that the same parameters used for cyclosporin therapeutic monitoring estimated during the nephrotic state can also be used during remission. Larger controlled studies are needed to confirm these findings.

Insuficiência renal aguda em pacientes com doença glomerular: aspectos histológicos e papel da necrose tubular aguda / aspectos histológicos e papel da necrose tubular aguda / Acute renal failure in patients with glomerular diseases: histological and role of acute tubular necrosis

A insuficiência renal aguda é comum em pacientes com síndrome nefrótica, podendo requerer terapia de substituição renal e ser irreversível. A insuficiência renal aguda nesses pacientes pode ser precipitada por processos infecciosos, hipovolemia, drogas nefrotóxicas; entretanto na maioria dos casos a etiologia não é identificada e a insuficiência renal aguda é considerada idiopática. A necrose tubular aguda foi associada à insuficiência renal aguda em adultos com lesão mínima. O objetivo deste estudo é avaliar a correlação entre a necrose tubular aguda definida histologicamente com insuficiência renal aguda em pacientes com doença glomerular. Biópsias renais de pacientes com glomerulopatia foram analisadas quanto à intensidade da necrose tubular aguda e esses dados correlacionados com os dados clínicos e presença de insuficiência renal aguda. A análise foi realizada em duas amostras e a intensidade de necrose tubular aguda graduada de duas formas: na primeira amostra a intensidade de necrose tubular aguda foi graduada em cinco níveis de intensidade; na segunda amostra foi feita uma estimativa em percentual da área da cortical acometida. A acurácia da análise semiquantitativa na primeira amostra foi avaliada por meio da correlação com análise morfométrica relativa ao número de túbulos com características necróticas por área de cortical (Spearman r=0,88, P<0,0001) e ao percentual de área da cortical com necrose tubular aguda (Spearman r=0,93, P<0,0001). A reprodutibilidade da análise intraobservador foi regular (kappa=0,53, P<0,0001). A primeira amostra constou de 149 casos com idade média de 21±16 anos. A síndrome nefrótica esteve presente em 104 (72%) pacientes e os principais diagnósticos foram: doenças do espectro Lesão Mínima – Glomeruesclerose Segmentar e Focal (45%). Necrose tubular aguda foi observada em 114 (77%) pacientes. insuficiência renal aguda foi diagnosticada em 43 (42%) pacientes. Houve correlação positiva entre a intensidade da necrose tubular aguda e a presença de insuficiência renal (gamma=0,70, P<0,0001). A segunda amostra foi composta por 80 pacientes com idade média 32 ± 18 anos. Síndrome nefrótica foi diagnosticada em 72 (90%) casos e os principais diagnósticos foram as doenças do espectro lesão mínima-Glomeruloesclerose segmentar e focal (54, 68%). Necrose tubular aguda foi observada em 60 (75%) pacientes e insuficiência renal aguda foi diagnosticada em 28 (35%) casos. A intensidade de necrose tubular aguda foi maior nos pacientes com (29,1 ± 27,7) que nos pacientes sem insuficiência renal aguda (5.4 ± 5.1, P<0,0001). A presença de necrose tubular aguda apresentou alta especificidade para diagnóstico de insuficiência renal aguda quando estimada em 10% da cortical representada (especificidade 96,1%, curva ROC [AUC=0,832, P<0,0001]). Não houve diferença entre os grupos com e sem insuficiência renal aguda em relação ao sexo, proteinúria, doença renal e albumina sérica, colesterol e triglicérides. A freqüência de hipertensão arterial sistêmica foi maior no grupo com insuficiência renal aguda com idade mais elevada (P=0,015).

Crescimento e composição corporal em crianças e adolescentes com síndrome nefrótica córtico-dependente / Growth and body composition in children and adolescents with steroid-dependent nephrotic syndrome

Objetivo: Avaliar crescimento e composição corporal em crianças e adolescentes com Síndrome Nefrótica Córtico-Dependente (SNCD). Material e Métodos: Foram incluídos todos os pacientes de 5 a 18 anos, em acompanhamento por pelo menos dois anos, com diagnóstico de SNCD. Foram coletados dados referentes a: tempo de tratamento, valores consecutivos do colesterol, albuminemia, proteinemia total, dose de uso corticoide e peso, estatura e idade da primeira consulta. As avaliações antropométricas dobra cutãnea tricipital e subescapular, índice de massa corpórea, circunferência da cintura e z-escore de estatura/idade foram realizadas durante as consultas de rotina e realizadas somente quando se considerou a criança sem edema clinicamente visível. Estatística não paramétrica com p<0,05. Resultados: Foram estudados 18 pacientes, 11 do sexo masculino (61,1%), idade entre 6 e 16 anos (12,2 +-2,98), tempo médio de tratamento de 6,75 +- 3,75 anos. os valores iniciais do z-escore foram significativamente maiores do que os finais (-0,69 +- 0,80 e de -2,07 +- 1,61; p=0,003). A evolução individual do z-escore mostrou que houve diminuição em 14 (-1,37 +- 1,55) e manutenção dos valores em quatro pacientes. Comparando-se vários parâmetros que poderiam ser responsáveis pela diferença de evolução, somente a proteinúria residual foi significativamente diferente. A medida da circunferência muscular do braço foi significativamente menor no grupo com perda de z-escore. Conclusões: Foi observado na maioria dos pacientes, déficit de estatura e diminuição da massa magra, provavelmente associados à gravidade do quadro nefrótico, que necessitou de doses elevadas e prolongadas de corticóide.

Objective: To evaluate growth and body composition in children and adolescents with steroid-dependent nephrotic syndrome (SNCD). Methods: We included all patients 5-18 years, accompanied by at least two years, diagnosed with SNCD. Data were collected regarding the following: duration of treatment, consecutive values of cholesterol, albumin, total serum protein, dose of corticosteroid use and weight, height and age at first consultation. The anthropometric assessments triceps and subscapular, body mass index, waist circumference, and z-score height / age were performed during routine consultations and carried out only when they saw the child without edema clinically visible. Nonparametric statistical p <0.05. Results: We studied 18 patients, 11 male (61.1%), aged 6 to 16 years (12.2 + -2.98), mean treatment time of 6.75 + - 3.75 years. the initial values of z-scores were significantly higher than the final (-0.69 + - 0.80 and -2.07 + - 1.61, p = 0.003). The individual evolution of z-scores showed that there was a decrease in 14 (-1.37 + - 1.55) and maintenance of values in four patients. Comparing the various parameters that could account for the difference in evolution, only the residual proteinuria was significantly different. The measurement of arm muscle circumference was significantly lower in the group with loss of z-scores. Conclusions: We found in most patients, stunting and reduction in lean body mass, probably associated with the severity of the nephrotic, which required high doses and prolonged corticosteroid.

Pérdidas proteicas peritoneales en niños portadores de síndrome nefrótico en diálisis peritoneal / Peritoneal protein loss in children suffering from nephrotic syndrome undergoing peritoneal dialysis

Primary Nephrotic Syndrome (NS) responds favorably to steroids in 80-90 percent of cases. Most corticoresistant (CR) patients evolve into Chronic Renal Failure (CRF), Of unknown origin, a permeability factor in these patient's serum has been reported, with some known effects in membranes including the peritoneum. Objective: To evaluate peritoneal protein loss in CR children on Chronic Peritoneal Dialysis (CPD). Patients and Methods: Four year retrospective analysis. Group 1 included 9 CR children, Group 2 was a control group of 10 children with CRF of other causes on CPD. Children in both groups were comparable in age, gender, weight, body surface, duration of CPD, concentration of solution, modality and dose of dialysis. Both groups were evaluated at 1, 6 and 12 months after admission. Results: No differences were observes in biochemical parameters: creatinine, urea nitrogen, calcium, phosphorus. PTH (Parathyroid hormone) was significantly higher in the control group (164 +/- 144 vs 564 +/- 454 pg/dl p < 0,05), albumin was lower in NS patients at the beginning (2.27 +/- 0.63 gr/dl vs 3.62 +/- 1.45 gr/dl p < 0,05) and end (2.8 +/- 0.5 gr/ dl vs 3.9 +/- 0.86 gr/dl, p < 0,05) of the evaluation. Peritoneal protein loss was significantly larger in the index group at the beginning (3,41 +/- 2,01 vs 1,76 +/- 1,45 gr/m7dia), and end (4,27 +/- 3,47 vs 1,66 +/-1,31 gr/m7dia, (p < 0.05) of the evaluation. The same happened with urinary loss: while there was no difference in protein intake, peritoneal KtV or total KtV between groups, residual KtV was significantly lower among NS patients at the end of the study, suggesting an earlier drop in residual renal function. No differences were observed in rates of peritonitis between groups in the study period. Conclusion: Peritoneal protein loss in CPD children with NS are significantly larger than other patients in CPD, suggesting a possible systemic permeability factor in these patients.

El Síndrome Nefrótico primario (SN) responde favorablemente a corticoides en un 80-90 por ciento de los casos. Los pacientes cortico resistentes (SNCR) evolucionan, en su gran mayoría, a insuficiencia renal crónica (IRC). De etiología desconocida, se ha reportado la presencia de un factor de permeabilidad (FP) en el suero de estos pacientes, con algunos efectos conocidos a nivel de otras membranas biológicas, incluyendo el peritoneo. Objetivo: Evaluar las pérdidas proteicas vía peritoneo en niños con SNCR en diálisis peritoneal crónica (DP). Pacientes y Método: Análisis retrospectivo de 4 años (2003-2007), Se incluyeron 9 pacientes portadores de SNCR (grupo 1), y un grupo control de 10 niños en DP portadores de IRC por otra etiología (grupo 2). Se evaluó a los 2 grupos al mes 1 y 6 ó 12 de su ingreso. Los grupos fueron comparables respecto a edad, sexo, peso, superficie corporal, tiempo en DP, concentración de dextrosa utilizada, modalidad dialítica y dosis de diálisis. Resultados: No se observó diferencias de los parámetros bioquímicos (creatinina, nitrógeno ureico, calcio, fósforo). La hormona paratiroidea (PTH) fue significativamente mayor en el grupo control (164 +/- 144 vs 564 +/- 454 pg/dl p < 0,05), y la albúmina fue menor en los pacientes con SN al inicio (2,27 +/- 0,63 gr/dl vs 3,62 +/- 1,45 gr/dl p < 0,05) y al final de la evaluación (2,8 +/- 0,5 gr/dl vs 3,9 +/- 0,86 gr/dl, p < 0,05). Las pérdidas proteicas peritoneales fueron significativamente mayores en el grupo 1 vs el grupo 2 al ingreso: 3,41 +/- 2,01 vs 1,76 +/- 1,45 gr/m²/día, y al final de la evaluación: 4,27 +/- 3,47 vs 1,66 +/-1,31 gr/m²/día, (p < 0,05) respectivamente. Lo mismo ocurrió con las pérdidas urinarias. No hubo diferencias en la ingesta proteica, KtV peritoneal ni KtV total entre los grupos, mientras que el KtV residual fue significativamente menor en los pacientes nefróticos al término del estudio, sugiriendo una caída más precoz de la función renal residual. Tampoco...

Regulación del metabolismo del colesterol y ácidos grasos en el síndrome nefrótico experimental por las proteínas que se unen a los elementos regulatorios de esteroles (SREBP's): efecto de la soya / Metabolism of cholesterol and fatty acids in nephrotic syndrome and its regulation by sterol regulatory element brinding proteins (SREBP's): Effect of soy protein consumption

El síndrome nefrótico (SN) cursa con hiperlipidemia. Se conoce que la biosíntesis del colesterol y de los ácidos grasos es regulada por los factores transcripcionales que se unen a los elementos de respuesta a esteroles (SREBP's). El consumo de proteína de soya disminuye la concentración de estos lípidos, aunque su mecanismo de acción no es del todo conocido. El objetivo de este estudio fue conocer si el consumo de la proteína de soya reduce los niveles de colesterol y triglicéridos a través de una regulación de las SREBP 's. Se estudiaron ratas Wistar macho con SN experimental por 64 días. Se observó que las concentraciones plasmáticos de colesterol y triglicéridos plasmáticos, así como de la proteinuria eran significativamente menores en las ratas alimentadas con proteína de soya que aquellas que consumían caseína. Estos cambios se asociaron con disminución de la expresión del ARNm SREBP 1 y de las enzimas de la síntesis de ácidos grasos. Los análisis por Western Blot revelaron que en los núcleos de hepatocitos obtenidos de ratas alimentadas con proteína de soya hubo menor presencia del factor transcripcional SREBP 1. Los resultados de este estudio indican que el consumo de proteína de soya produce efectos benéficos durante el síndrome nefrótico.

Hyperlipidemia occurs during nephrotic syndrome (NS). It is known that cholesterol and fatty acid biosynthesis is controlled by the transcription factors sterol regulatory element binding proteins (SREBPs). Soy protein consumption reduces the concentration of these lipids, although its mechanism of action is not well known. The aim of the present study was to establish whether soy protein consumption reduces cholesterol and triglycerides levels by regulating of SREBPs. Male Wistar rats with experimental NS were studied for 64 days. The results showed that rats fed with soy protein had significantly lower plasma cholesterol and triglyceride concentrations as well as proteinuria than rats fed with casein diet. These decrements were associated with a decrease in the expression of SREBP 1 and fatty acid biosynthetic enzymes. In addition, Western blot analysis revealed that in nuclear extracts from hepatocytes of rats fed with soy protein, there was a lower concentration of SREBP 1 than in rats fed with casein. The results of this study indicate that consumption of a soy protein diet has beneficial effects on nephrotic syndrome.

Dislipidemias en enfermedades renales: etiopatogenia y tratamiento / Dyslipidemias in renal diseases: pathogenesis and treatment

Patients with renal diseases like nephorotic syndrome, chronic renal failure (uremia) and renal transplantation frequently present disturbances of lipid metabolisms, howerer their pathogenesis is partially understood. Moreover, cardiovascular diseases are responsible for many deaths in these patients. Although the effect of the dyslipidemias in the development of atherosclerosis in renal diseases is not clear, they probably play a role. Since actually the survival of these patients is substantial, it is important to manage them appropriately with regard to their dyslipidemias. this review will examine the pathogenesis and treatment of dyslipidemias in patients with nephrotic syndrome, chronic renal failure and renal transplantation