Uso de ibuprofeno en el tratamiento de pacientes pediátricos con poliuria y disnatremia. Reporte de una serie de casos / Ibuprofen use for the treatment of pediatric patients with polyuria and dysnatremia. A case series report

Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.

Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/ kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.

Ibuprofen use for the treatment of pediatric patients with polyuria and dysnatremia. A case series report. / Uso de ibuprofeno en el tratamiento de pacientes pediátricos con poliuria y disnatremia. Reporte de una serie de casos.

Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.

Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.

[Antiproteinuric action of amiloride in paediatric patient with corticoresistant nephrotic syndrome]. / Acción antiproteinúrica del amiloride en el paciente pediátrico con síndrome nefrótico corticorresistente.

INTRODUCCION: In nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both variables. OBJETIVES: Evaluate the anti-proteinuric effect of 2 non-immunological therapeutic regimens, the quantitative relationship between podocyturia and proteinuria. MATERIAL AND METHODS: We included children aged 4 to 12 years with corticoresistant nephrotic syndrome, using 2 different schemes: group A, enalapril+losartan, and group B, enalapril+losartan+amiloride. RESULTS: In group A, 17 patients completed the study, the initial mean proteinuria was 39mg/m2/h and mean proteinuria at the end was 24mg/m2/h, while in group B 14 patients were treated and the initial average proteinuria was 36mg/m2/h and the end average proteinuria was 13mg/m2/h. The paired T test showed significant differences in the decrease in proteinuria, for patients in group B without variation in podocyturia. The 2 factors associated with an increase in proteinuria were podocyturia and the time elapsed from the diagnosis of cortico-resistant nephrotic syndrome to the start of treatment anti-proteinuric. CONCLUSIONS: The use of amiloride decreased proteinuria, without significantly modifying podocyturia; we did not observe a positive relationship between both variables.

Hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli infection in Argentina: update of serotypes and genotypes and their relationship with severity of the disease.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS). Only few studies correlated serotypes and stx genotypes with disease severity. This study aimed to update STEC serotypes, stx genotypes, and virulence factors (eae and ehxA) in a cohort of patients with STEC-HUS and investigate whether they influence the severity of disease. METHODS: In this multicentric study, children hospitalized between 2005 and 2016 with STEC-HUS confirmed by the National Reference Laboratory were included. Serotypes (O157, O145, O121, and others), stx genotypes (stx1a, stx2a, stx2c, stx2d, and others), and virulence factors were analyzed, and their association with dialysis requirement (>10 days); severe neurological, cardiovascular, and/or bowel involvement; and death was assessed. RESULTS: The records of 280 patients were reviewed; 160 females, median age 21 months (IQR18m). STEC O157 was isolated in 206 (73.6%) patients, O145 in 47 (16.8%), O121 in 15 (5.4%), and other serotypes in 12 (4.2%). The stx2a/2c genotype was carried by 179 (63.9%) strains, stx2a by 94 (33.6%), stx1a/stx2a by five (1.8%), and stx1a only by two (0.7%). All strains except six harbored eae and ehxA genes. Fifty-nine (21.1%) patients had severe neurological involvement, 29 (10.4%) severe bowel injury, 14 (5%) cardiovascular involvement, 53 (18.9%) required > 10 days of dialysis, and 12 (4.3%) died. Neither serotypes nor stx genotypes detected were significantly linked to severity. CONCLUSIONS: Serotype O157 and virulence stx2a/2c, eae, ehxA genotype are prevalent in Argentina, and no relationship was found between severity and serotypes and genotypes of STEC detected.

Antiproteinuric action of amiloride in paediatric patient with corticoresistant nephrotic syndrome.

INTRODUCCION: In nephrotic syndrome, increased podocyturia accompanies pathologic proteinuria. The therapeutic regimen with enalapril, losartan and amiloride could reduce both variables. OBJETIVES: Evaluate the anti-proteinuric effect of 2 non-immunological therapeutic regimens, the quantitative relationship between podocyturia and proteinuria. MATERIAL AND METHODS: We included children aged 4-12 years with corticoresistant nephrotic syndrome, using 2 different schemes: group A, enalapril + losartan, and group B, enalapril + losartan + amiloride. RESULTS: In group A, 17 patients completed the study, the initial mean proteinuria was 39 mg/m2/h and mean proteinuria at the end was 24 mg/m2/h, while in group B 14 patients were treated and the initial average proteinuria was 36 mg/m2/h and the end average proteinuria was 13 mg/m2/h. The paired T test showed significant differences in the decrease in proteinuria, for patients in group B without variation in podocyturia. The 2 factors associated with an increase in proteinuria were podocyturia and the time elapsed from the diagnosis of cortico-resistant nephrotic syndrome to the start of treatment anti-proteinuric. CONCLUSIONS: The use of amiloride decreased proteinuria, without significantly modifying podocyturia; we did not observe a positive relationship between both variables.

Gangrena de Fournier en un niño con síndrome nefrótico corticorresistente. A propósito de un caso / Fournier gangrene in a child with steroid-resistant nephrotic syndrome. Report of one case

La gangrena de Fournier es una fascitis necrotizante que afecta las regiones genital, perineal y perianal, de inicio súbito y diseminación rápidamente progresiva. Su diagnóstico obliga a una urgente intervención interdisciplinaria. La asociación con enfermedades nefrológicas es rara.Se presenta un caso de gangrena de Fournier en un niño con síndrome nefrótico corticorresistente y anasarca con edema escrotal grave. Recibió un esquema antibiótico de amplio espectro y se realizó un desbridamiento quirúrgico extenso e inmediato de la lesión necrótica. Posteriormente, requirió reparación por parte de Cirugía Plástica. Presentó una respuesta clínica favorable a la terapéutica instaurada.

Fournier gangrene is a necrotizing fasciitis that affects the genital, perineal and perianal regions, of sudden onset and rapidly progressive dissemination. Its diagnosis requires an urgent and interdisciplinary intervention. The association with nephrologic diseases is rare.We present a case of Fournier gangrene in a child with steroid-resistant nephrotic syndrome and anasarca with severe scrotal edema. He received a broad-spectrum antibiotic scheme and extensive an immediate surgical debridement of the necrotic lesion was carried out. Subsequently, it was repaired by Plastic Surgery. He presented a favourable clinical response

[Fournier gangrene in a child with steroid-resistant nephrotic syndrome. Report of one case]. / Gangrena de Fournier en un niño con síndrome nefrótico corticorresistente. A propósito de un caso.

Fournier gangrene is a necrotizing fasciitis that affects the genital, perineal and perianal regions, of sudden onset and rapidly progressive dissemination. Its diagnosis requires an urgent and interdisciplinary intervention. The association with nephrologic diseases is rare. We present a case of Fournier gangrene in a child with steroidresistant nephrotic syndrome and anasarca with severe scrotal edema. He received a broad-spectrum antibiotic scheme and extensive an immediate surgical debridement of the necrotic lesion was carried out. Subsequently, it was repaired by Plastic Surgery. He presented a favourable clinical response.

La gangrena de Fournier es una fascitis necrotizante que afecta las regiones genital, perineal y perianal, de inicio súbito y diseminación rápidamente progresiva. Su diagnóstico obliga a una urgente intervención interdisciplinaria. La asociación con enfermedades nefrológicas es rara. Se presenta un caso de gangrena de Fournier en un niño con síndrome nefrótico corticorresistente y anasarca con edema escrotal grave. Recibió un esquema antibiótico de amplio espectro y se realizó un desbridamiento quirúrgico extenso e inmediato de la lesión necrótica. Posteriormente, requirió reparación por parte de Cirugía Plástica. Presentó una respuesta clínica favorable a la terapéutica instaurada.

Podocituria en pacientes pediátricos con enfermedad de Fabry / Podocyturia in paediatric patients with Fabry disease

Introducción: La enfermedad de Fabry (EF) es un trastorno hereditario causado por una deficiencia de la actividad de la enzima alfa-galactosidasa A, cuya transmisión está relacionada con el cromosoma X. Objetivos: Los objetivos del estudio fueron: 1. Cuantificar la presencia de podocitos en pacientes pediátricos con EF y compararla con el valor de la podocituria medida en controles sanos. 2. Determinar en pacientes con EF si una mayor podocituria está relacionada con la albuminuria patológica. 3. Determinar los factores de riesgo asociados con la albuminuria patológica. Métodos: Implementamos un estudio analítico observacional de casos y controles, separados en 2 grupos de acuerdo con la ausencia de enfermedad (grupo control) o con la presencia de enfermedad (grupo Fabry). Resultados: Estudiamos a 31 pacientes, 11 con EF y 20 controles, con una media de edad de 11,6 años. La diferencia entre el tiempo medio transcurrido desde el diagnóstico de EF hasta la medición de la podocituria (40 meses) y la aparición de la albuminuria patológica (34 meses) no fue significativa (p: 0,09). Los podocitos se identificaron mediante tinción para sinaptopodina y las diferencias medias cuantitativas entre ambas podociturias fueron estadísticamente significativas (p: 0,001). La albuminuria fue fisiológica en 4 de las pacientes Fabry y el riesgo relativo para desarrollar albuminuria patológica de acuerdo con la podocituria fue en el grupo control 1,1 y en el grupo Fabry 3,9, con un coeficiente de correlación entre la podocituria y la albuminuria en el grupo Fabry de 0,8354. Finalmente los 2 factores de riesgo asociados al desarrollo de albuminuria patológica fueron la podocituria (OR 14) y la edad mayor a 10 años (OR 18). No encontramos riesgo significativo ni en el filtrado glomerular (FG) (OR 0,5), ni en el género (OR 1,3). El FG medio se mantuvo dentro de valores normales. Conclusión: La detección de podocituria en pacientes pediátricos con EF podría utilizarse como un marcador temprano de daño renal previo y relacionado con la albuminuria patológica

Introduction: Fabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome. Objectives: The objectives of the study were: 1. To quantify the presence of podocytes in paediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria. Methods: We performed an analytical, observational study of Fabry and control subjects, which were separated into 2groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group). Results: We studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years. The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p = 0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p = 0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values. Conclusion: The detection of podocyturia in paediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria

Podocyturia in paediatric patients with Fabry disease. / Podocituria en pacientes pediátricos con enfermedad de Fabry.

INTRODUCTION: Fabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome. OBJECTIVES: The objectives of the study were: 1. To quantify the presence of podocytes in paediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria. METHODS: We performed an analytical, observational study of Fabry and control subjects, which were separated into 2groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group). RESULTS: We studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years. The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p=0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p=0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values. CONCLUSION: The detection of podocyturia in paediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria.

Clinical parameters, LysoGb3, podocyturia, and kidney biopsy in children with Fabry disease: is a correlation possible?

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase enzyme deficiency. We present clinical, biochemical, and histologic findings in children with classical phenotypic presentation of Fabry disease. METHODS: A retrospective analysis was performed using charts from 14 children with confirmed diagnosis. Clinical parameters were evaluated. Globotriaosylsphingosine -lysoGb3- detection in plasma, podocyturia, and kidney biopsy were carried out in all cases. RESULTS: All patients except one demonstrated at least one symptom of Fabry disease. LysoGb3 levels were above the normal range in all patients. Podocyturia was documented in all patients. Kidney biopsy revealed glomerular, interstitial, vascular, and tubular changes on light microscopy in nearly all patients. Electron microscopy showed podocyte inclusions in all patients. CONCLUSIONS: No difference in symptomatology was discernible between boys and girls. Podocyturia was detectable in children serving as a possible early marker of kidney injury. LysoGb3 was elevated in all cases, emphasizing the importance for diagnosis especially in female patients with normal αGal A activity. A possible association between lysoGb3 and symptom severity and histological involvement in kidney biopsy should be assessed in prospective studies with enough statistical power to determine if lysoGb3 can be used to predict nephropathy in children with Fabry disease.

Hyponatremia: a new predictor of mortality in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome.

OBJECTIVES: (1) Evaluate mortality rate in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, (2) determine the leading causes of death, and (3) identify predictors of mortality at hospital admission. METHODS: We conducted a multicentric, observational, retrospective, cross-sectional study. It included patients under 18 years old with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome hospitalized between January 2005 and June 2016. Clinical and laboratory data were obtained from the Argentine National Epidemiological Surveillance System of Hemolytic Uremic Syndrome. Clinical and laboratory variables were compared between deceased and non-deceased patients. Univariate and multivariate analyses were performed. ROC curves and area under the curve were obtained. RESULTS: Seventeen (3.65%) out of the 466 patients died, being central nervous system involvement the main cause of death. Predictors of death were central nervous system involvement, the number of days since the beginning of diarrhea to hospitalization, hyponatremia, high hemoglobin, high leukocyte counts, and low bicarbonate concentration on admission. In the multivariate analysis, central nervous system involvement, sodium concentration, and hemoglobin were independent predictors. The best cut off for sodium was ≤ 128 meq/l and for hemoglobin ≥ 10.8 g/dl. CONCLUSIONS: Mortality was low in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, being central nervous system involvement the main cause of death. The best mortality predictors found were central nervous system involvement, hemoglobin, and sodium concentration. Hyponatremia may be a new Shiga toxin-producing Escherichia coli hemolytic uremic syndrome mortality predictor.

Estudio comparativo entre el esquema convencional y el tratamiento prolongado con esteroides en el síndrome nefrótico cortico-sensible primario en Pediatría / Comparative study of the conventional scheme and prolonged treatment with steroids on primary steroid-sensitive nephrotic syndrome in children

Resumen: Introducción: En el síndrome nefrótico cortico-sensible (SNCS), la corticoterapia prolongada podría reducir la frecuencia de recaídas. El objetivo de este trabajo fue la comparación de un esquema corticoide prolongado frente al tratamiento habitual del SNCS primario, evaluando los siguientes parámetros: el número de pacientes con recaídas, el número total de recaídas, el tiempo medio transcurrido al iniciar el tratamiento, hasta la remisión y hasta la primera recaída, la dosis acumulada de corticosteroides y la toxicidad esteroide. Métodos: La población se dividió en dos grupos: el grupo A (27 pacientes) recibió 16-β-metilprednisona durante 12 semanas, reduciendo la dosis hasta la semana 24; y el grupo B (29 pacientes) recibió 16-β-metilprednisona durante 12 semanas, y placebo hasta la semana 24. Resultados: La tasa de incidencia acumulada de recaídas (persona/año) fue en el grupo A 36/100, y en el grupo B 66/100 (p = 0.04). El tiempo medio transcurrido (días) hasta la primera recaída fue de 114 en el grupo A y 75 en el grupo B (p = 0.01). Las diferencias de tiempo transcurrido al iniciar tratamiento y hasta la remisión entre ambos grupos no fueron significativas. El total acumulado de recaídas fue de 9 en el grupo A y 17 en el grupo B (p = 0.04), y el total de pacientes con recaídas fue de 3 (grupo A) y 7 (grupo B) (p = 0.17). La dosis media acumulada (mg/m2) por paciente fue de 5,243 en el grupo A y de 4,306 en el grupo B (p = 0.3), y el cortisol sérico (μg/dl) final fue de 14 en el grupo A y 16 en el grupo B (p = 0.4). La toxicidad esteroide fue similar entre ambos grupos. Conclusiones: La duración del tratamiento disminuyó el número de recaídas, sin incrementar la toxicidad esteroide.

Abstract: Background: In the steroid-sensitive nephrotic syndrome (SSNS) the prolonged treatment with steroids could decrease the frequency of relapses. We conducted a comparative study of prolonged steroid scheme and the usual treatment of primary SSNS to assess: the number of patients with relapses, mean time to treatment initiation, to remission and to first relapse, total number of relapses, total cumulative dose of steroids, and the steroid toxicity. Methods: Patients were divided into two groups: group A (27 patients) received 16-β-methylprednisolone for 12 weeks, reducing the steroid until week 24. Group B (29 patients) received 16-β-methylprednisolone for 12 weeks and placebo until week 24. Results: Cumulative incidence rate of relapse (person/years) for group A was of 36/100 and 66/100 for group B (p = 0.04). Average elapsed time to first relapse was of 114 days for group A and of 75 days to for group B (p = 0.01). The difference in time for initial response to treatment and up to achieve remission between both groups was not significant. Total cumulative relapses were 9 for group A and 17 for group B (p = 0.04). Total patients with relapses were 3 for group A and 7 for group B (p = 0.17). Cumulative average dose per patient was 5,243 mg/m2 for group A and 4,306 mg/m2 for group B (p = 0.3), and serum cortisol was 14 μg/dl for group A and 16 μg/dl for group B (p = 0.4). There were no steroid toxicity differences between groups. Conclusions: The duration of the treatment had an impact on the number of relapses without increasing steroid toxicity.

[Comparative study of the conventional scheme and prolonged treatment with steroids on primary steroid-sensitive nephrotic syndrome in children]. / Estudio comparativo entre el esquema convencional y el tratamiento prolongado con esteroides en el síndrome nefrótico cortico-sensible primario en Pediatría.

BACKGROUND: In the steroid-sensitive nephrotic syndrome (SSNS) the prolonged treatment with steroids could decrease the frequency of relapses. We conducted a comparative study of prolonged steroid scheme and the usual treatment of primary SSNS to assess: the number of patients with relapses, mean time to treatment initiation, to remission and to first relapse, total number of relapses, total cumulative dose of steroids, and the steroid toxicity. METHODS: Patients were divided into two groups: group A (27 patients) received 16-ß-methylprednisolone for 12 weeks, reducing the steroid until week 24. Group B (29 patients) received 16-ß-methylprednisolone for 12 weeks and placebo until week 24. RESULTS: Cumulative incidence rate of relapse (person/years) for group A was of 36/100 and 66/100 for group B (p=0.04). Average elapsed time to first relapse was of 114 days for group A and of 75 days to for group B (p=0.01). The difference in time for initial response to treatment and up to achieve remission between both groups was not significant. Total cumulative relapses were 9 for group A and 17 for group B (p=0.04). Total patients with relapses were 3 for group A and 7 for group B (p=0.17). Cumulative average dose per patient was 5,243mg/m2 for group A and 4,306mg/m2 for group B (p=0.3), and serum cortisol was 14µg/dl for group A and 16µg/dl for group B (p=0.4). There were no steroid toxicity differences between groups. CONCLUSIONS: The duration of the treatment had an impact on the number of relapses without increasing steroid toxicity.

Evaluación del metabolismo fosfo-cálcico en el síndrome nefrófico córtico-sensible primario en pediatría / Evaluation of bone and mineral metabolism in primary corticosteroid-sensitive pediatric nephrotic syndrome

Introducción: el tratamiento esteroide del síndrome nefrótico cortico sensible (SNCS) puede causar alteraciones del metabolismo mineral, prevenibles con calcio y vitamina D. Se llevó a cabo un estudio de cohortes de tipo retrospectivo longitudinal a lo largo de 36 meses. Objetivos: 1) evaluar la relación entre la Dosis Acumulativa de corticoides (DAC) con la concentración sérica de 25-OH Vitamina D y con el Contenido Mineral Ëseo (CMO); 2) evaluar la relación entre la DAC y el CMO en la Densitometría Mineral Ësea (DMO). Material y métodos: Incluimos a pacientes entre 2 años y 12 años con síndrome nefrótico primario cortico-sensible (SNCS) (primer episodio o síndrome nefrótico recaedor o síndrome nefrótico cortico-dependiente), normotensos, eutróficos y con FG>90ml/min/1.73m2, los cuales se separaron en 3 grupos: GRUPO A: 3 o 6 años (puntaje Z y CMO), edad ósea, PTHi. Resultados: Evaluamos a 29 pacientes, con una edad media de 4,4 años. La DMO se realizó en 11 pacientes y no hubo diferencias significativas entre los grupos (p=0,08). Tampoco hubo diferencias significativas entre la media de la edad cronológica y la edad ósea media media (p 0,3). La prueba T para evaluar la dosis de 25-OH colecalciferol al aumentar la dosis de Ergocalciferol fue significativa (T:32.4 Q: <0.001). Hubo una correlación significativa entre los tres grupos: entre la dosis de Vitamina D y el dosaje sérico de Vitamina D de 0,9; entre el DAC y la dosis de 25 OH colecalciferol de 0,62 y entre el DAC y el CMO de 0.44. Por último, el aumento promedio en los tres grupos de dosis de vitamina D fue de 1833UI. Conclusiones: Observamos una relación entre la DAC e hipovitaminosis D, corregible al aumentar la dosis de Vitamina D.

Introduction: steroid treatment for corticosteroid-sensitive nephrotic syndrome (CSNS) could cause bone and mineral metabolism alterations, preventable with calcium and Vitamin D. Objectives: We carried out a preliminary retrospective study along 36 months with the following objectives. 1) To evaluate the relationship between Cumulative Corticosteroid Doses (CCD) and 25-0 Vitamin D serum concentration and with Bone Mineral Content (BMC); 2) To evaluate the relationship between CCD and Bone Mineral Densitomety (BMD). Methods: We included patients between 2 and 12 years of age with corticosteroid sensitive primary nephrotic syndrome (CSNS) (first episode, relapsing nephrotic syndrome, corticosteroid dependent nephrotic syndrome) normotensive, eutrophic and FG>:90ml/min/1.73 m2, who were divided into three groups: GROUP A: =3 or 4 relapses/year, GROUP C: CSNS, we measured: a) Quarterly: calcemia, phosphatemia, alkaline phosphatase; b) half-yearly: 25-OH cholecalcipherol levels, CCD; c) annually BMD in children >6 years (score Z and BMC), bone age, PTHi. Results: We evaluated 29 patients, average age: 4.4 years. The BMD was performed on 11 patients and there were no significant differences among the groups (p=0.08). No significant differences were seen between chronologic age and average bone age (p=0.3). Change in 25-OH cholecalcipherol levels due to the increase of ergocalcipherol dose was significant (T:32.4 Q:<0.001). There were significant correlation in the three groups, between Vitamin D dose and Vitamin D serum levels (Pearson correlation R=0.9), between CCD and 25 OH cholecalcipherol dose: (Pearson correlation R=0.62) and between CCD and BMC (Pearson correlation R=0.44). Finally, in these three groups the average increase of vitamin D was: 1833IU. Conclusions: We found a relationship between CCD and hypovitaminosis D, which could be corrected increasing Vitamin D dose.

Treatment of idiopathic hypercalciuria and its impact on associated diseases.

UNLABELLED: Idiopathic hypercalciuria may be associated with urinary tract infection, hematuria, nephrolithiasis and osteopenia. In order to describe the occurrence of these concurrent conditions related to the variation in urinary calcium and hypercalciuria response to sequential therapy, with a normal protein and low sodium diet, potassium citrate and hydrochlorothiazide; 46 patients older than 4 years, with no urinary tract diseases, sphincter control and normal blood creatinine values were followed-up during 43 months. Hypercalciuria was seen to be associated with kidney stones (EAR 47%; RR 3.3), hematuria (EAR 71%; RR 2.5), urinary tract infections (EAR 57%; RR 3), and osteopenia (EAR 33%; RR 3). A normal value of urinary calcium was achieved with sequential therapy in 43 patients, but during follow-up 32 patients discontinued treatment and hypercalciuria recurred in 44% of them, in association with hematuria and urinary tract infection. CONCLUSIONS: Sequential therapy reduced hypercalciuria and the incidence of associated diseases.

Treatment of idiopathic hypercalciuria and its impact on associated diseases / Tratamiento de la hipercalciuria idiopática y su incidencia sobre las patologías asociadas

Idiopathic hypercalciuria may be associated with urinary tract infection, hematuria, nephrolithiasis and osteopenia. In order to describe the occurrence of these concurrent conditions related to the variation in urinary calcium and hypercalciuria response to sequential therapy, with a normal protein and low sodium diet, potassium citrate and hydrochlorothiazide; 46 patients older than 4 years, with no urinary tract diseases, sphincter control and normal blood creatinine values were followed-up during 43 months. Hypercalciuria was seen to be associated with kidney stones (EAR 47%; RR 3.3), hematuria (EAR 71%; RR 2.5), urinary tract infections (EAR 57%; RR 3), and osteopenia (EAR 33%; RR 3). A normal value of urinary calcium was achieved with sequential therapy in 43 patients, but during follow-up 32 patients discontinued treatment and hypercalciuria recurred in 44% of them, in association with hematuria and urinary tract infection. Conclusions. Sequential therapy reduced hypercalciuria and the incidence of associated diseases.

La hipercalciuria idiopática puede asociarse con infección urinaria, hematuria, nefrolitiasis y osteopenia; con los objetivos de describir la aparición de estas patologías concurrentes, relacionadas con la variación del calcio urinario y la respuesta al tratamiento secuencial de la hipercalciuria, con dieta normoproteica-hiposódica, citrato de potasio e hidroclorotiazida, controlamos durante 43 meses a 46 pacientes mayores de 4 años, sin uropatías, con control esfinteriano y creatininemias normales. Observamos que la hipercalciuria se asoció con litiasis renal (RAE 47%; RR 3,3); hematuria (RAE 71%; RR 2,5); infecciones urinarias (RAE 57%; RR 3) y osteopenia (RAE 33%; RR 3). La terapéutica secuencial normalizó el calcio urinario en 43 pacientes, pero durante el seguimiento, 32 interrumpieron el tratamiento y la hipercalciuria reapareció en 44% de ellos, asociada a hematuria e infección urinaria. Conclusiones. El tratamiento secuencial redujo la hipercalciuria y disminuyó la incidencia de patologías asociadas.

Treatment of idiopathic hypercalciuria and its impact on associated diseases / Tratamiento de la hipercalciuria idiopática y su incidencia sobre las patologías asociadas

Idiopathic hypercalciuria may be associated with urinary tract infection, hematuria, nephrolithiasis and osteopenia. In order to describe the occurrence of these concurrent conditions related to the variation in urinary calcium and hypercalciuria response to sequential therapy, with a normal protein and low sodium diet, potassium citrate and hydrochlorothiazide; 46 patients older than 4 years, with no urinary tract diseases, sphincter control and normal blood creatinine values were followed-up during 43 months. Hypercalciuria was seen to be associated with kidney stones (EAR 47%; RR 3.3), hematuria (EAR 71%; RR 2.5), urinary tract infections (EAR 57%; RR 3), and osteopenia (EAR 33%; RR 3). A normal value of urinary calcium was achieved with sequential therapy in 43 patients, but during follow-up 32 patients discontinued treatment and hypercalciuria recurred in 44% of them, in association with hematuria and urinary tract infection. Conclusions. Sequential therapy reduced hypercalciuria and the incidence of associated diseases.(AU)

La hipercalciuria idiopática puede asociarse con infección urinaria, hematuria, nefrolitiasis y osteopenia; con los objetivos de describir la aparición de estas patologías concurrentes, relacionadas con la variación del calcio urinario y la respuesta al tratamiento secuencial de la hipercalciuria, con dieta normoproteica-hiposódica, citrato de potasio e hidroclorotiazida, controlamos durante 43 meses a 46 pacientes mayores de 4 años, sin uropatías, con control esfinteriano y creatininemias normales. Observamos que la hipercalciuria se asoció con litiasis renal (RAE 47%; RR 3,3); hematuria (RAE 71%; RR 2,5); infecciones urinarias (RAE 57%; RR 3) y osteopenia (RAE 33%; RR 3). La terapéutica secuencial normalizó el calcio urinario en 43 pacientes, pero durante el seguimiento, 32 interrumpieron el tratamiento y la hipercalciuria reapareció en 44% de ellos, asociada a hematuria e infección urinaria. Conclusiones. El tratamiento secuencial redujo la hipercalciuria y disminuyó la incidencia de patologías asociadas.(AU)

Treatment of idiopathic hypercalciuria and its impact on associated diseases. / Treatment of idiopathic hypercalciuria and its impact on associated diseases.

UNLABELLED: Idiopathic hypercalciuria may be associated with urinary tract infection, hematuria, nephrolithiasis and osteopenia. In order to describe the occurrence of these concurrent conditions related to the variation in urinary calcium and hypercalciuria response to sequential therapy, with a normal protein and low sodium diet, potassium citrate and hydrochlorothiazide; 46 patients older than 4 years, with no urinary tract diseases, sphincter control and normal blood creatinine values were followed-up during 43 months. Hypercalciuria was seen to be associated with kidney stones (EAR 47

; RR 3.3), hematuria (EAR 71

; RR 2.5), urinary tract infections (EAR 57

; RR 3), and osteopenia (EAR 33

; RR 3). A normal value of urinary calcium was achieved with sequential therapy in 43 patients, but during follow-up 32 patients discontinued treatment and hypercalciuria recurred in 44

of them, in association with hematuria and urinary tract infection. CONCLUSIONS: Sequential therapy reduced hypercalciuria and the incidence of associated diseases.

Uso del sirolimus en pacientes con síndrome nefrótico córtico-resistente primario / Use of sirolimus in patients with primary steroid-resistant nephrotic syndrome

La persistencia de la proteinuria nefrótica favorece la progresión hacia la insuficiencia renal. Hemos diseñado un protocolo terapéutico con sirolimus para ese grupo de pacientes implementando un estudio clínico prospectivo, intervencionista y no aleatorizado, sobre una cohorte de 13 pacientes con una edad media de 10 años; todos con síndrome nefrótico córtico-resistente primario y glomerulosclerosis focal y segmentaria; resistentes también a la ciclofosfamida, a los inhibidores de la calcineurina y al empleo de enalapril y losartán. La dosis media empleada de sirolimus fue de 3,6 mg/m2/día y el tratamiento duró 12 meses. Evaluamos la eficacia terapéutica acorde a la reducción de la proteinuria (respuesta total, parcial y ausente), y también fueron evaluadas la severidad del daño histológico pretratamiento y el tiempo previo transcurrido hasta recibir el sirolimus. Nueve de los trece pacientes tuvieron remisión parcial o total del síndrome nefrótico, y el tiempo medio previo transcurrido y la severidad del daño histológico influyeron en el tipo de respuesta. Consideramos que el sirolimus es una opción válida de tratamiento para los pacientes con síndrome nefrótico córtico-resistente, aunque probablemente sea necesario un inicio terapéutico más precoz (AU)

Persistent nephrotic syndrome that does not respond to treatment may cause progression to kidney failure. We designed a therapeutic protocol with sirolimus for this group of patients. We conducted a prospective, interventional, time series, cohort study lasting 20 months. Thirteen patients were enrolled, with a mean age of 10 years (range: 8-18 years old) with steroid-resistant primary nephrotic syndrome and a histological diagnosis of focal and segmental glomerulosclerosis. We administered sirolimus 3.6mg/m2/day. The duration of this regimen was 12 months in responsive patients. The protocol's efficacy was assessed according to reduction of proteinuria (3 response levels: total, partial, or no response). Severity of histological renal damage and mean time from clinical diagnosis to protocol initiation were also assessed. Nine of 13 patients responded to the treatment with sirolimus, and mean progression time and the severity of histological renal damage influenced response to therapy. We believe that sirolimus is a valid treatment option in patients with steroid-resistant nephrotic syndrome, even though this regimen probably requires an earlier treatment (AU)

Use of sirolimus in patients with primary steroid-resistant nephrotic syndrome.

Persistent nephrotic syndrome that does not respond to treatment may cause progression to kidney failure. We designed a therapeutic protocol with sirolimus for this group of patients. We conducted a prospective, interventional, time series, cohort study lasting 20 months. Thirteen patients were enrolled, with a mean age of 10 years (range: 8-18 years old) with steroid-resistant primary nephrotic syndrome and a histological diagnosis of focal and segmental glomerulosclerosis. We administered sirolimus 3.6mg/m2/day. The duration of this regimen was 12 months in responsive patients. The protocol's efficacy was assessed according to reduction of proteinuria (3 response levels: total, partial, or no response). Severity of histological renal damage and mean time from clinical diagnosis to protocol initiation were also assessed. Nine of 13 patients responded to the treatment with sirolimus, and mean progression time and the severity of histological renal damage influenced response to therapy. We believe that sirolimus is a valid treatment option in patients with steroid-resistant nephrotic syndrome, even though this regimen probably requires an earlier treatment.