RESUMO
INTRODUCTION: Children with chronic kidney disease (CKD) and receiving peritoneal dialysis (PD) have disorders of mineral metabolism that impact their growth, survival and cardiovascular functions. New molecular markers offer a better understanding of the pathophysiology of this disease. OBJECTIVE: To characterize some components of mineral metabolism, with emphasis on FGF23/Klotho and cardiovascular functions (CV) of these patients. PATIENTS AND METHOD: Prospective observational cohort study. EXCLUSION CRITERIA: serum 25 (OH) vitamin D < 20 ng/ml, peritonitis within the last two months and active nephrotic syndrome. Calcemia, phosphemia, parathyroid hormone (PTH), 25 (OH) vitD3, 1.25 (OH) vitD3, FGF23 and Klotho in plasma were measured. FGF23 and Klotho were quantified in healthy children as a control group. Echocardiography was performed calculating the left ventricular mass index (LVMI). Descriptive statistics analysis, Pearson correlation coefficient for association among variables and multivariate analysis were conducted. RESULTS: 33 patients, 16 males, aged between 1.2 and 13.4 years were included. Age of onset for PD: 7.3 ± 5.0 years, time receiving PD: 13.5 ± 14.5 months. The plasma concentration of 25 (OH) vitD3 was 34.2 ± 6.3 pg/ml. Calcemia and phosphemia values were 9.8 ± 0.71 and 5.4 ± 1.0 mg/dl respectively. PTH was 333 ± 287 pg/ml. FGF23 in plasma was 225.7 ± 354.3 pg/ml and Klotho 131.6 ± 72 pg/ml, and in the controls ( n = 16 ), it was 11.9 ± 7.2 pg/ml and 320 ± 119 pg/ml, respectively. The residual and total dose of dialysis (KtV) was 1.6 ± 1.3 and 2.9 ± 1.6, respectively. FGF23 levels significantly correlated with calcium (p < 0.001, r = 0.85), and inversely with residual KtV, showing no relationship with phosphemia. Klotho level correlated negatively with residual KtV and also, it showed a negative association with chronological age and age at onset of PD. LVMI > 38 g/m² was confirmed in 20/28 patients. CONCLUSIONS: The values of FGF23, and PTH are elevated in children with CKD on PD. Klotho levels in CKD patients are lower than control children. A strong association of calcemia with FGF23 and PTH is reported. Residual renal function is inversely associated with FGF23 and Klotho. A high incidence of left ventricular hypertrophy was found evidencing a cardiovascular compromise in these patients.
Assuntos
Hipertrofia Ventricular Esquerda/epidemiologia , Minerais/metabolismo , Diálise Peritoneal/métodos , Insuficiência Renal Crônica/terapia , Adolescente , Idade de Início , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Ecocardiografia , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/sangue , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Lactente , Proteínas Klotho , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/fisiopatologiaRESUMO
Introduction: Children with chronic kidney disease (CKD) and receiving peritoneal dialysis (PD) have disorders of mineral metabolism that impact their growth, survival and cardiovascular functions. New molecular markers offer a better understanding of the pathophysiology of this disease. Objective: To characterize some components of mineral metabolism, with emphasis on FGF23/Klotho and cardiovascular functions (CV) of these patients. Patients and Method: Prospective observational cohort study. Exclusion criteria: serum 25 (OH) vitamin D < 20 ng/ml, peritonitis within the last two months and active nephrotic syndrome. Calcemia, phosphemia, parathyroid hormone (PTH), 25 (OH) vitD3, 1.25 (OH) vitD3, FGF23 and Klotho in plasma were measured. FGF23 and Klotho were quantified in healthy children as a control group. Echocardiography was performed calculating the left ventricular mass index (LVMI). Descriptive statistics analysis, Pearson correlation coefficient for association among variables and multivariate analysis were conducted. Results: 33 patients, 16 males, aged between 1.2 and 13.4 years were included. Age of onset for PD: 7.3 +/- 5.0 years, time receiving PD: 13.5 +/- 14.5 months. The plasma concentration of 25 (OH) vitD3 was 34.2 +/- 6.3 pg/ml. Calcemia and phosphemia values were 9.8 ± 0.71 and 5.4 +/- 1.0 mg/dl respectively. PTH was 333 +/- 287 pg/ml. FGF23 in plasma was 225.7 +/- 354.3 pg/ml and Klotho 131.6 +/- 72 pg/ml, and in the controls ( n = 16 ), it was 11.9 +/- 7.2 pg/ml and 320 +/- 119 pg/ml, respectively. The residual and total dose of dialysis (KtV) was 1.6 +/- 1.3 and 2.9 +/- 1.6, respectively. FGF23 levels significantly correlated with calcium (p < 0.001, r = 0.85), and inversely with residual KtV, showing no relationship with phosphemia. Klotho level correlated negatively with residual KtV and also, it showed a negative association with chronological age and age at onset of PD. LVMI > 38 g/m² was confirmed in 20/28 patients...
Introducción: Los niños portadores de Enfermedad renal crónica (ERC) en diálisis peritoneal (DP) presentan alteraciones del metabolismo mineral que afectan su crecimiento, estado cardiovascular y sobrevida. Nuevos marcadores moleculares representan una mejor comprensión de la fisiopatología de esta enfermedad. Objetivo: Caracterizar componentes del metabolismo mineral, con énfasis en FGF23/Klotho, y estado cardiovascular (CV) en este grupo de pacientes. Pacientes y Método: Estudio prospectivo observacional. Criterios de exclusión: niveles de 25 (OH) vitamina D < 20 ng/ml, peritonitis hasta 2 meses previos y síndrome nefrótico activo. Se midió calcemia, fosfemia, paratohormona (PTH), 25 (OH) vitD3, 1,25 (OH) vitD3, FGF23 y Klotho en plasma. Se cuantificó FGF23 y Klotho en niños sanos como grupo control. Se efectuó ecocardiografía, calculándose el índice de masa ventricular izquierda (IMVI). Se realizó análisis estadístico descriptivo, coeficiente de correlación de Pearson para asociación entre variables y análisis multivariado. Resultados: Se incluyeron 33 pacientes, 16 varones, edad 1,2 a 13,4 años. Edad de inicio de DP: 7,3 +/- 5,0 años, tiempo en DP: 13,5 +/- 14,5 meses. El nivel plasmático de 25 (OH) vitD3 fue 34,2 +/- 6,3 pg/ml. Los valores de calcemia y fosfemia fueron 9,8 +/- 0,71 y 5,4 +/- 1,0 mg/dl respectivamente. La PTH fue de 333 +/- 287 pg/ml. El FGF23 en plasma fue de 225,7 +/- 354,3 pg/ml y Klotho 131,6 +/- 72 pg/ml, y en los controles (n = 16) fue de 11,9 +/- 7,2 pg/ ml y 320 +/- 119 pg/ml, respectivamente. La dosis de diálisis (KtV) residual y total fue de 1,6 +/- 1,3 y 2,9 +/- 1.6, respectivamente. El nivel de FGF23 se correlacionó significativamente con la calcemia (p < 0,001, r = 0,85), e inversamente con el KtV residual, sin mostrar relación con la fosfemia. El nivel de Klotho...
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Humanos , Masculino , Feminino , Pré-Escolar , Criança , Nefropatias/metabolismo , Nefropatias/terapia , Diálise Renal , Doença Crônica , Cálcio/sangue , Nefropatias/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Fósforo/sangue , Glucuronidase/metabolismo , Biomarcadores , Minerais/metabolismo , Hormônio Paratireóideo , Estudos ProspectivosRESUMO
Congenital Nephrotic Syndrome (CNS) is defined as a corticoresistant nephrotic syndrome which appears in the first 90 days of life. NPHS1 gene mutations, codifying nephrine cause nearly 40 percent of the cases. Such a clinical case has not yet been described in Chile. Objective: Describe a patient with CNS and his genetic study. Clinical case: Full-term 38 week male newborn, birth weight 2620 gr, height 48,5 cm, ALPGAR 9/10. Head circumf: 33 cm. First child, well controlled pregnancy. 16 days after birth, he develops edema, massive proteinuria (3,2 gr/ dl), hypoalbuminemia (0,79 mg/dl) and hypercholesterolemia ( total cholesterol: 318 mg/dl). Renal sonogram showed increase in size and echogenicity in both kidneys, and loss of corticomedullar differentiation. Renal biopsy showed diffuse mesangial glomeruloesclerosis. Genetic study for NPHS1 was performed through direct sequencing of 29 exons and adjacent regions of introns chromosome 19q13.1. Analysis disclosed C567X, ho-mozygote mutation. Conclusions: The first case of Nephrine mutation causing CNSis described in Chile. The importance of genetic studies in these patients is highlighted for clinical decision making.
El síndrome nefrótico congénito (SNC) se define como un síndrome nefrótico córticoresistente que aparece en los primeros 90 días de vida. Mutaciones en el gen NPHS1 que codifica a la nefrina son causantes de aproximadamente del 40 por ciento de los niños con SNC. En Chile no se ha descrito hasta ahora esta mutación asociada al cuadro clínico. Objetivo: Describir el caso de un paciente con SNC y su estudio genético. Caso clínico: Paciente de sexo masculino, RNT 38 semanas, PRN 2620 gr, TN 48,5 cm APGAR 9/10. CC: 33 cm. Embarazo controlado primer hijo. A los 16 días comienza con edema, proteinuria masiva (3,2 gr/dl), hipoalbuminemia (0,79 mg/dl) e hipercolesterolemia (colesterol total: 318 mg/dl). Se descarta TORCH (-). La ecografía renal mostró un aumento de tamaño y de ecogenicidad de ambos riñones, pérdida de diferenciación corticomedular. La biopsia renal se informó como glomeruloesclerosis mesangial difusa. El estudio genético para NPHS1 se realizó por secuenciación directa de los 29 exones y las regiones adyacentes de los intrones en el cromosoma 19q13.1 El análisis demostró una mutación C567X, homocigoto. Conclusiones: Se describe el primer caso de mutación para Nefrina en un SNC chileno. Se destaca la importancia del estudio genético en estos pacientes debido a las implicancias en las decisiones clínicas y terapéuticas.
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Humanos , Masculino , Lactente , Síndrome Nefrótica/cirurgia , Síndrome Nefrótica/congênito , Síndrome Nefrótica/genética , Transplante de Rim , Mutação , Nefrectomia , Proteínas de Membrana/genéticaRESUMO
Steroid-Resistant Nephrotic Syndrome (SRNS) is found in approximately 20 percent of patients with Nephrotic Syndrome (NS). Podocyte-gen mutations are diagnosed in a half of these children. Nephrin (NPHS1), podocin (NPHS2) and Wilms tumor suppressor gene (WT1) are the most frequently founded mutations. These patients usually progress to End Stage Renal Disease (ESRD). Objective: Current concepts in genetic diagnostic of NS in pediatrics are presented. A local experience is analyzed. In Chilean pediatric patients with SRNS, a mutational analysis of the NPHSl and NPHS2 gene was carried out by direct sequencing of the coding regions following polymerase chain reaction (PCR) amplification of genomic leukocyte DNA with flanking intronic primers. For WTl (exon 8 and exon 9), PCR of these fragments were done. Thirty-three patients were included, 17 males, 11,1 +/- 6.8 years. 54 percent of them developed ESRD, 12 patients were transplanted at the time of the analysis, 5 were under dialysis therapy, and 16 children correspond to ESRD Stage 3 and 4. Genetic analysis showed a gen mutation in 9 patients, NPHSl in 3 and NPHS2 in 6 of them. All genetic NS patients were cyclosporine-resistant. Post transplant relapse of NS was lower in genetic patients (p < 0.05). Conclusion: SRNS in children should be always evaluated from a genetic approach in order to avoid long-term immunosuppression, and to anticipate a clinical evolution after kidney transplantation.
En pediatría, el 20 por ciento de los pacientes portadores de Síndrome Nefrótico Idiopático son corticoresistentes (SNCR). Aproximadamente la mitad de ellos corresponden a mutaciones de genes que codifican proteínas del podocito. Las mutaciones más frecuentes corresponden al gen de la nefrina (NPHS1), la podocina (NPHS2) y del gen supresor del tumos de Wilms (WT1). Estas formas hereditarias no responden a tratamientos inmu-nosupresores y pueden progresar a enfermedad renal terminal (ERT). Objetivo: Revisar el estado actual del diagnóstico genético en Síndrome Nefrótico en niños, y presentar esta experiencia nacional de esta patología. Para el estudio de pacientes pediátricos chilenos, se realizó análisis de mutación del gen NPH2 por secuen-ciación directa de la regiones codificantes por PCR para la amplificación del DNA genómico leucocitario con partidores de acompañamiento intrónico. Para nefrina se procedió a extraer el DNA genómico, y se realizó la búsqueda de mutaciones de NPHSl por secuenciación directa de los 29 exones codificantes y las uniones intrónicas adyacentes, mientras que para el estudio de WTl se practicó el análisis mutacional de los exones 8 y 9, realizado por secuenciación directa del producto amplificado de WT1-PCR. Se han estudiado 33 pacientes provenientes de 29 familias, 17 varones, edad 11,1 +6,8 años. Dieciocho pacientes (54 por ciento) evolucionaron a ERT. Doce pacientes estaban trasplantados, 5 en diálisis, y 16 estaban en etapas 3-4 de enfermedad renal crónica. El estudio genético identificó mutaciones en 9 pacientes (27 por ciento), 3 correspondieron a NPHS1, 6 a NPHS2. Ningún caso con mutación respondió a tratamiento de Ciclosporina A (CsA), y las recaídas posttrasplante fueron significativamente menores en el grupo con mutación (+). Conclusión: Las mutaciones en estos genes deben ser estudiadas en cada niño con SNCR con el fin de evitar tratamientos prolongados e inefectivos, y anticipar la evolución después del trasplante renal.
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Humanos , Mutação , Proteínas de Membrana/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Análise Mutacional de DNA , Membrana Basal Glomerular , Taxa de Filtração Glomerular , Reação em Cadeia da PolimeraseRESUMO
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...
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Diálise Peritoneal , Peritônio/metabolismo , Proteínas/metabolismo , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/terapia , Estudos de Casos e Controles , Permeabilidade , Proteínas Sanguíneas/análise , Estudos RetrospectivosRESUMO
Background: Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Aim: To describe the characteñstics ofpatients with the diagnosis ofHUS in Chile, and to identify the most reliable early predictors oímorbidity and moñality. Material and methods: The clinical records ofpatients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. Results: A cohort of 587 patients aged 2 to 8 years, 48 percent males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39 percent of the patients, hypertension in 45 percent and seizures in 17 percent. Forty two percent required renal replacement therapy (RRT) and perítoneal dialysis was used in the majoríty of cases (78 percent). The most frequently isolated etiological agentwas Escherichia coli. Mortality rate was 2.9 percent in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC) >20.000/mm³ and requirements of renal replacement therapy (p <0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC >20.000/mm³, seizures and hypertension. Conclusions: The present study emphasizes important clinical and epidemiological aspeets ofHUSin a Chilean pediatricpopulation.
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Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Injúria Renal Aguda , Anuria/etiologia , Síndrome Hemolítico-Urêmica/complicações , Injúria Renal Aguda , Anuria/epidemiologia , Anuria/terapia , Serviços de Saúde da Criança/estatística & dados numéricos , Chile/epidemiologia , Seguimentos , Síndrome Hemolítico-Urêmica/mortalidade , Síndrome Hemolítico-Urêmica/terapia , Hospitalização , Modelos Logísticos , Prognóstico , Diálise Renal , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. AIM: To describe the characteristics of patients with the diagnosis of HUS in Chile, and to identify the most reliable early predictors of morbidity and mortality. MATERIAL AND METHODS: The clinical records of patients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. RESULTS: A cohort of 587 patients aged 2 to 8 years, 48% males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39% of the patients, hypertension in 45% and seizures in 17%. Forty two percent required renal replacement therapy (RRT) and peritoneal dialysis was used in the majority of cases (78%). The most frequently isolated etiological agent was Escherichia coli. Mortality rate was 2.9% in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC)>20.000/mm3 and requirements of renal replacement therapy (p<0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC>20.000/mm3, seizures and hypertension. CONCLUSIONS: The present study emphasizes important clinical and epidemiological aspects of HUS in a Chilean pediatric population.
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Injúria Renal Aguda/etiologia , Anuria/etiologia , Síndrome Hemolítico-Urêmica/complicações , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Anuria/epidemiologia , Anuria/terapia , Criança , Serviços de Saúde da Criança/estatística & dados numéricos , Pré-Escolar , Chile/epidemiologia , Feminino , Seguimentos , Síndrome Hemolítico-Urêmica/mortalidade , Síndrome Hemolítico-Urêmica/terapia , Hospitalização , Humanos , Lactente , Modelos Logísticos , Masculino , Prognóstico , Diálise Renal , Estudos Retrospectivos , Fatores de RiscoRESUMO
El modelo de la Cinética de Urea se ha usado rutinariamente para ajustar la terapia de hemodiálisis y diálisis peritoneal desde los estudios del Nacional Cooperative Dialysis Study (NCDS) a comienzos de la década del 70, derivando en lo que actualmente se conoce como la medición de la Dosis de Diálisis (Kt/V), la Depuración de Creatinina (CrCl), la Velocidad de Catabolismo Proteico (VCP), y elequivalente proteico de la Aparición de Nitrógeno Ureico (PNA), todos ellos parámetros que requieren una monitorización periódica de acuerdo a las recomendaciones DOQI (Dialysis Outcome Quality Initiative).