Pathogenesis, treatment, and therapeutic trials in hemolytic uremic syndrome

Diarrhea-associated hemolytic uremic syndrome is one of the most common causes of acute renal failure in childhood. Nearly all cases are the result of an antecedent infection by Shiga toxin--producing strains of Escherichia coli, especially the O157:H7 serotype. Most cases occur after ingestion of contaminated meat; however, new food sources such as leaf lettuce, alfalfa sprouts, and goat's milk have been identified, and diarrhea-associated hemolytic uremic syndrome can occur after exposure to contaminated water in recreational swimming sites. Diarrhea-associated hemolytic uremic syndrome is a systemic disease with activation of a variety of inflammatory cytokines. Kidney injury may result from direct effects of the Shiga toxin on renal tubular epithelial cells as well as endothelial cells. Early diagnosis of diarrhea-associated hemolytic uremic syndrome may be expedited by the introduction of new techniques to rapidly detect toxin and microorganism in stool samples. Optimal therapy of diarrhea-associated hemolytic uremic syndrome includes intensive management of the renal failure and serious extrarenal complications that may occur during the course of disease. The role of antibiotics in prevention and amelioration of diarrhea-associated hemolytic uremic syndrome remains controversial. Experimental therapies that are undergoing evaluation in clinical trials include SYNSORB Pk (SYNSORB Biotech, Inc., Calgary, Alberta, Canada), a drug designed to bind Shiga toxin in the lumen of gastrointestinal tract. Immunization strategies are also being developed and tested. It is hoped that with continued progress in this field the incidence of diarrhea-associated hemolytic uremic syndrome in children will be substantially reduced in the coming years.