globotriaosylceramide and Hepatorenal-Syndrome

Gastrointestinal infection with verotoxin-producing Escherichia coli (VTEC) has been strongly implicated in the etiology of the hemolytic uremic syndrome (HUS), the leading cause of pediatric acute renal failure. The binding of fluorescein-conjugated VT1 overlaid on to frozen human renal sections has been examined. Sections from biopsies of infants aged < 2 years were compared with those from adult autopsies. VT primarily stained distal convoluted tubules, particularly those adjacent to glomeruli, and collecting ducts. VT-binding was detected within the infant glomerulus but not the adult. Binding of the toxin was removed when the section was pretreated with alpha-galactosidase, confirming the receptor-binding specificity for globotriaosyl ceramide (gal alpha 1-4gal beta 1-4 glucosylceramide), the glycolipid receptor for VT. These studies may suggest that differential localization of this glycolipid in the pediatric renal glomerulus is a risk factor for the development of HUS following infection with VTEC.

Topics: Adult; Age Factors; alpha-Galactosidase; Bacterial Toxins; Carbohydrate Sequence; Child; Child, Preschool; Escherichia coli Infections; Gastrointestinal Diseases; Glycolipids; Hemolytic-Uremic Syndrome; Hepatorenal Syndrome; Histocytochemistry; Humans; In Vitro Techniques; Infant; Kidney; Molecular Sequence Data; Nephrosis, Lipoid; Receptors, Cell Surface; Shiga Toxin 1; Trihexosylceramides