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Pathogenesis, treatment, and therapeutic trials in hemolytic uremic syndrome

Pathogenesis, treatment, and therapeutic trials in hemolytic uremic syndrome. Trachtman H, Christen E. Current Opinion in Pediatrics 1999;11(2):162-168.

ABSTRACT:

This review article focuses on recent advances in our understanding of diarrhea-associated hemolytic uremic syndrome (D+HUS). Of particular relevance is the section on clinical prognosis and treatment of HUS. The long-term prognosis of children who recover from D+HUS but who have persistent proteinuria one year later is guarded. In one study cited, reduced glomerular filtration rate (GFR) was found in six of seven children with D+HUS. Histological changes (examined at five years on average after illness) in six patients did not correlate with GFR or urinary protein excretion. These findings indicate that extended follow-up of these patients by nephrologists is fully justified. There is considerable controversy about whether antibiotic treatment prevents or ameliorates D+HUS. For example, the attack rate of D+HUS during the 1993 Jack-in-the-Box outbreak failed to demonstrate a difference in the occurrence of HUS among those who had been given antibiotics versus those given no treatment for the enteritis. In contrast, during the 1996 outbreak in Sakai, Osaka, Japan antibiotic treatment within three days of the onset of diarrhea reduced the risk of HUS by three-fold and caused more rapid recovery than in children with no antibiotic treatment. The authors conclude that in the absence of a controlled clinical trial, the efficacy of antibiotic treatment on the prevention and amelioration of HUS should be considered unproven. Caution is advised in routinely prescribing antibiotics to children with bloody diarrhea. SYNSORB Pk, which binds Shiga toxin to protect cells against the toxin, has been tested in a trial in children with bloody diarrhea in Canada. That study found a 54% reduction in the risk of developing HUS. A follow-up trial is in progress. Gabexate mesilate, used as an anticoagulant, ameliorated disease in a preliminary study but the findings must be confirmed in a controlled study. Intravenous gamma-globulin has not been found to be beneficial. D+HUS can be eradicated with the proper combination of prevention and treatment strategies; perhaps in the coming years the gap between basic science and medical therapy will see a rapid close.