Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome
Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children, a randomized controlled trial. Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DWK, Weiss R, Kaskel FJ, et al. JAMA 2003;290(10):1337-1344.
A study of 145 children with diarrhea-associated hemolytic uremic syndrome (HUS) was undertaken in the U.S. and Canada to determine if administration of an oral agent that binds Shiga toxin could diminish the severity of HUS. The children were randomized into two groups, one receiving the binding agent and the other receiving a placebo. Death and other serious nonrenal complications were similar between the two groups, as was the need for dialysis. Likewise, secondary outcomes, such as the need for transfusion, hypertension, and length of hospital stay were similar in the two groups. Thus, oral treatment with a Shiga toxin-binding agent was ineffective at reducing the severity of diarrhea-associated HUS in pediatric patients. It is possible that therapy failed because treatment may have been initiated too late in the course of the disease or that only 23 % of patients had viable Shiga toxin-producing E. coli (STEC) or free Shiga toxin in their stool samples at the initiation of therapy. Impaired gastrointestinal motility may have limited delivery of the drug or the interaction between STEC and the gastrointestinal epithelium may hinder the capacity of the drug to bind Shiga toxin in the body. Although other toxin-binding products are under development, the authors suggest that novel agents that inhibit the action of circulating toxins, such as monoclonal antibodies, should be evaluated.