Complement in Typical Hemolytic Uremic Syndrome

Hemolytic uremic syndrome (HUS) is a severe disease characterized by the clinical triad of hemolytic anemia, thrombocytopenia, and acute renal failure. HUS exists in two forms: the atypical diarrhea-negative HUS, which is often associated with complement disorders, and the more frequent diarrheal-associated typical HUS, which is caused by infections with enterohemorrhagic Escherichia coli. The virulence factors of the latter have been studied well, and Shiga toxin (Stx)2 is reported to represent the most important one. In contrast, risk factors on the host side have not been intensively studied until recently: Complement activation products have been detected in the serum and plasma of HUS patients, and an in vitro study could show that Stx2 not only damages the kidney directly but also indirectly via complement, in two ways. First, it activates complement, and second, it delays the functions of its control protein factor H on the cell surface, both known to damage the kidney.