Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome.

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

[Update on the treatment of endemic hemolytic uremic syndrome. Pathogenesis and treatment of the most severe systemic complication of infections by Shiga toxin-producing Escherichia coli]. / Actualización en el tratamiento del síndrome urémico hemolítico endémico. Patogénesis y tratamiento de la complicación sistémica más grave de las infecciones por Escherichia coli productor de toxina Shiga.

The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli (STEC) infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, giving account for 20% of renal transplants in children and adolescents in our country. In spite of the extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in national status and contributions made by Argentinean groups.

Actualización en el tratamiento del síndrome urémico hemolítico endémico: Patogénesis y tratamiento de la complicación sistémica más grave de las infecciones por Escherichia coli productor de toxina Shiga / Update on the treatment of endemic hemolytic uremic syndrome: Pathogenesis and treatment of the most severe systemic complication of infections by Shiga toxin-producing Escherichia coli

La forma típica o post-diarreica del síndrome urémico hemolítico (SUH) es la complicación más grave de las infecciones por cepas de Escherichia coli productoras de toxina Shiga (STEC). En la Argentina el SUH es un problema crítico de salud pública, ya que representa la principal causa de falla renal aguda en la infancia, la segunda causa de falla renal crónica, y aporta el 20% de los casos de transplante renal durante la infancia y la adolescencia. A pesar de los avances en el conocimiento de su patogénesis, el único tratamiento actual de los pacientes con SUH es de sostén, y no existen terapias específicas ni preventivas. En la presente revisión expondremos los conocimientos básicos de los mecanismos patogénicos y discutiremos los enfoques terapéuticos tradicionales e innovadores, con especial foco en la situación nacional y los aportes hechos por grupos de la Argentina.

The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli (STEC) infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, giving account for 20% of renal transplants in children and adolescents in our country. In spite of the extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in national status and contributions made by Argentinean groups.

Hemolytic uremic syndrome: pathogenesis and update of interventions.

The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, accounting for 20% of renal transplants in children and adolescents in Argentina. Despite extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in Argentinean contribution. The hope that a better understanding of transmission dynamics and pathogenesis of this disease will produce better therapies to prevent the acute mortality and the long-term morbidity of HUS is the driving force for intensified research.

[Body composition by simple anthropometry, bioimpedance and DXA in preschool children: interrelationships among methods]. / Composición corporal en niños preescolares: comparación entre métodos antropométricos simples, bioimpedancia y absorciometría de doble haz de rayos X.

OBJECTIVE: To examine the interrelationships of body composition variables derived from simple anthropometry, bioelectrical impedance (BIA) and dualenergy X-ray absorptiometry (DXA). POPULATION, MATERIAL AND METHODS: A total of 230 healthy preschool children (118 males and 112 females) age 4-6 years, attending a day care center, were examined to determine body mass index (BMI) and waist circumference (WC). Percentage of body fat content (%BF) was predicted by BIA (Maltron BF- 900) and DXA (Lunar DPX-L, pediatric software). RESULTS: BMI and WC did not show significant differences among sex, while %BF by BIA or DXA did. BIA measures were lower than DXA s (p <0.0001). Correlation between BIA vs. anthropometric methods and WC vs. DXA were moderate (Pearson r= 0.43 to 0.53), whereas the other correlations were strong (r= 0.71 to 0.83). However Bland Altman comparison showed wide limits of agreement between BIA and DXA; BIA significantly underestimated %BF as determined by DXA (p <0.0001). CONCLUSION: The methods used to estimate body composition in healthy preschool children highly correlated. However, the Bland Altman procedure suggests that BIA and DXA should not be used interchangeably.

Composición corporal en niños preescolares: comparación entre métodos antropométricos simples, bioimpedancia y absorciometría de Doble Haz de Rayos X / Body composition by simple anthropometry, bioimpedance and DXA in Preschool Children: interrelationships among methods

Objetivo. Comparar la composición corporal estimadapor dos métodos antropométricos simples ypor impedanciometría (BIA, por sus siglas en inglés)y absorciometría de doble haz de rayos X(DXA, por sus siglas en inglés) y estudiar las correlacionesexistentes entre ellos, en una poblaciónpreescolar de Argentina.Población, material y métodos. Se estudió transversalmenteuna población clínicamente sana, deedad comprendida entre 4 y 6 años, de 230 niños(118 varones y 112 niñas), que concurrían a JardinesIntegrales de La Matanza, Argentina. Se determinóel índice de masa corporal (IMC), la circunferenciade cintura (Cci) y el contenido de grasa corporal,expresado como porcentaje, por BIA (Maltron BF-900) y por DXA (densitómetro Lunar DPX-L, softwarepediátrico).Resultados. En IMC y Cci no se observaron diferenciasestadísticamente significativas entre ambossexos, pero sí en el porcentaje de grasa corporal porBIA o DXA. La correlación entre BIA y ambos métodosantropométricos fue moderada (r de Pearson=0,43-0,53), al igual que entre DXA y Cci (r= 0,66),mientras que las demás correlaciones fueron fuertes(r= 0,71-0,83). Las medidas obtenidas por BIA yDXA no concordaron (prueba de Bland Altman); sinembargo, las diferencias se distribuyeron en formahomogénea a lo largo del eje horizontal e independientementede las medias. BIA reprodujo valoresmás bajos de porcentaje de grasa corporal que DXA(p <0,0001).Conclusiones. Existe buena correlación entre losmétodos antropométricos sencillos y la bioimpedanciay DXA. Sin embargo, los resultados no sonintercambiables, incluso entre BIA y DXA (AU)

Objective. To examine the interrelationships of body composition variables derived from simple anthropometry, bioelectrical impedance (BIA) and dualenergy X-ray absorptiometry (DXA). Population, material and methods. A total of 230 healthy preschool children (118 males and 112 females) age 4-6 years, attending a day care center, were examined to determine body mass index (BMI) and waist circumference (WC). Percentage of body fat content (%BF) was predicted by BIA (Maltron BF- 900) and DXA (Lunar DPX-L, pediatric software). Results. BMI and WC did not show significant differences among sex, while %BF by BIA or DXA did. BIA measures were lower than DXA´s (p <0.0001). Correlation between BIA vs. anthropometric methods and WC vs. DXA were moderate (Pearson r= 0.43 to 0.53), whereas the other correlations were strong (r= 0.71 to 0.83). However Bland Altman comparison showed wide limits of agreementbetween BIA and DXA; BIA significantly underestimated %BF as determined by DXA (p <0.0001). Conclusion. The methods used to estimate body composition in healthy preschool children highly correlated. However, the Bland Altman procedure suggests that BIA and DXA should not be used interchangeably.(AU)

Composición corporal en niños preescolares: comparación entre métodos antropométricos simples, bioimpedancia y absorciometría de Doble Haz de Rayos X / Body composition by simple anthropometry, bioimpedance and DXA in Preschool Children: interrelationships among methods

Objetivo. Comparar la composición corporal estimadapor dos métodos antropométricos simples ypor impedanciometría (BIA, por sus siglas en inglés)y absorciometría de doble haz de rayos X(DXA, por sus siglas en inglés) y estudiar las correlacionesexistentes entre ellos, en una poblaciónpreescolar de Argentina.Población, material y métodos. Se estudió transversalmenteuna población clínicamente sana, deedad comprendida entre 4 y 6 años, de 230 niños(118 varones y 112 niñas), que concurrían a JardinesIntegrales de La Matanza, Argentina. Se determinóel índice de masa corporal (IMC), la circunferenciade cintura (Cci) y el contenido de grasa corporal,expresado como porcentaje, por BIA (Maltron BF-900) y por DXA (densitómetro Lunar DPX-L, softwarepediátrico).Resultados. En IMC y Cci no se observaron diferenciasestadísticamente significativas entre ambossexos, pero sí en el porcentaje de grasa corporal porBIA o DXA. La correlación entre BIA y ambos métodosantropométricos fue moderada (r de Pearson=0,43-0,53), al igual que entre DXA y Cci (r= 0,66),mientras que las demás correlaciones fueron fuertes(r= 0,71-0,83). Las medidas obtenidas por BIA yDXA no concordaron (prueba de Bland Altman); sinembargo, las diferencias se distribuyeron en formahomogénea a lo largo del eje horizontal e independientementede las medias. BIA reprodujo valoresmás bajos de porcentaje de grasa corporal que DXA(p <0,0001).Conclusiones. Existe buena correlación entre losmétodos antropométricos sencillos y la bioimpedanciay DXA. Sin embargo, los resultados no sonintercambiables, incluso entre BIA y DXA

Objective. To examine the interrelationships of body composition variables derived from simple anthropometry, bioelectrical impedance (BIA) and dualenergy X-ray absorptiometry (DXA). Population, material and methods. A total of 230 healthy preschool children (118 males and 112 females) age 4-6 years, attending a day care center, were examined to determine body mass index (BMI) and waist circumference (WC). Percentage of body fat content (%BF) was predicted by BIA (Maltron BF- 900) and DXA (Lunar DPX-L, pediatric software). Results. BMI and WC did not show significant differences among sex, while %BF by BIA or DXA did. BIA measures were lower than DXA´s (p <0.0001). Correlation between BIA vs. anthropometric methods and WC vs. DXA were moderate (Pearson r= 0.43 to 0.53), whereas the other correlations were strong (r= 0.71 to 0.83). However Bland Altman comparison showed wide limits of agreementbetween BIA and DXA; BIA significantly underestimated %BF as determined by DXA (p <0.0001). Conclusion. The methods used to estimate body composition in healthy preschool children highly correlated. However, the Bland Altman procedure suggests that BIA and DXA should not be used interchangeably.

Role of polymorphonuclear leukocytes in the pathophysiology of typical hemolytic uremic syndrome.

Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx), through an interaction with its globotriaosylceramide (Gb3) receptor. Although, Stx is the main pathogenic factor and necessary for HUS development, clinical and experimental evidence suggest that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS) and neutrophils (PMN) represent two central components of inflammation during a Gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. In the present review, we discuss the contribution of experimental models and patient's studies in an attempt to elucidate the pathogenic mechanisms of HUS.

[Hemolytic uremic syndrome. Clinical manifestations. Treatment]. / Síndrome urémico hemolítico. Manifestaciones clínicas. Tratamiento.

Clinical manifestation are described in children with epidemic HUS. The intestinal involvement in the prodromic period, is outlined and the most common disturbances such acute renal failure, thrombocytopenia, hemolytic anemia, leucocitosis hypertension, neurological, pancreatic and cardiac manifestations are described. We discuss the acid-base and electrolyte disturbances, metabolic acidosis, hyponatremia, hyperkalemia. The etiopathogenic treatment and the control of renal sequelae are also discussed.

Síndrome Urémico Hemolítico: manifestaciones clínicas: tratamento / Hemolytic uremic syndrome: clinical manifestations: Treatment

Clinical manifestation are described in children with epidemic HUS. The intestinal involvement in the prodromic period, is outlined and the most common disturbances such acute renal failure, thrombocytopenia, hemolytic anemia, leucocitosis hypertension, neurological, pancreatic and cardiac manifestations are described. We discuss the acid-base and electrolyte disturbances, metabolic acidosis, hyponatremia, hyperkalemia. The etiopathogenic treatment and the control of renal sequelae are also discussed.(AU)

Síndrome Urémico Hemolítico: manifestaciones clínicas: tratamento / Hemolytic uremic syndrome: clinical manifestations: Treatment

Clinical manifestation are described in children with epidemic HUS. The intestinal involvement in the prodromic period, is outlined and the most common disturbances such acute renal failure, thrombocytopenia, hemolytic anemia, leucocitosis hypertension, neurological, pancreatic and cardiac manifestations are described. We discuss the acid-base and electrolyte disturbances, metabolic acidosis, hyponatremia, hyperkalemia. The etiopathogenic treatment and the control of renal sequelae are also discussed.