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Pathophysiology of Childhood Hemolytic Uremic Syndrome

Investigators
Tarr, Phillip
Institutions
Children's Hospital and Regional Medical Center - Seattle
Start date
1996
End date
2001
Objective
Escherichia coli 0157:H7 infection remains frequently diagnosed in western Washington children before HUS ensues, thereby identifying a population of children at high risk of developing microangiopathic sequelae within a week. This study will examine such children, and assay a selected variety of circulating, urinary and fecal inflammatory, prothrombotic, vasoactive, genetic, and microbial factors which could plausibly play, initiate and/or perpetuate microangiopathic abnormalities leading to HUS.
More information
Approximately 10% of children with Escherichia coli 0157:H7 infection develop the hemolytic uremic syndrome (HUS). The pathophysiologic cascade leading from gastrointestinal infection with this Shiga-toxigenic organism to systemic vascular injury is incompletely understood. There are no suitable animal models in which glomerular thrombotic lesions result from enteral or parenteral challenge with Shiga-toxin, or enteral challenge with E. coli 0157:H7 or other Shiga-toxigenic E. Coli. Escherichia coli 0157:H7 infection remains frequently diagnosed in western Washington children before HUS ensues, thereby identifying a population of children at high risk of developing microangiopathic sequelae within a week. This study will examine such children, and assay a selected variety of circulating, urinary and fecal inflammatory, prothrombotic, vasoactive, genetic, and microbial factors which could plausibly play, initiate and/or perpetuate microangiopathic abnormalities leading to HUS. These include cytokines, thrombogenic factors, fibrinolytic factors, markers of endothelial cell injury/activation, arachidonic acid metabolites, circulating endotoxin levels, platelet activating factor concentrations, expression of host cell antigens, concentrations of E. coli 0157:H7 and of fecal free toxin, and toxin genotype. In addition to defining the elements of the cascade leading to kidney failure in children with E. coli 0157:H7 infection, this research could also identify the group at highest risk of developing HUS following enteric infection E. coli 0157:H7, thereby suggesting children most likely to benefit from novel therapeutic strategies.
Funding Source
Nat'l. Inst. of Diabetes and Digestive and Kidney Diseases
Project number
5R01DK052081-05
Categories
Natural Toxins
Bacterial Pathogens
Escherichia coli