Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, 
thrombocytopenia, and acute renal failure. HUS is classified as either diarrhea 
associated, most commonly caused by infection with Escherichia coli O157, or the 
less common atypical HUS (aHUS), which may be familial or sporadic. 
Approximately 50% of patients with aHUS have mutations in one of the complement 
control proteins: factor H, factor I, or membrane cofactor protein (MCP). These 
proteins regulate complement activation through cofactor activity, the 
inactivation of C3b by limited proteolytic cleavage, a desirable event in the 
fluid phase (no target) or on healthy self-tissue (wrong target). Complement 
activation follows the endothelial cell injury that characterizes HUS. This 
disease represents a model of what takes place when inappropriate complement 
activation occurs on self-tissues due to the presence of mutated complement 
regulatory proteins. Screening for mutations in factor H, factor I, or MCP is 
expensive and time consuming. One approach is to perform antigenic screening for 
factor H and factor I deficiency and to look for low levels of MCP (CD46) 
expression by flow cytometry. Complement regulatory protein deficiency impacts 
treatment decisions as patients with aHUS have a recurrence rate in renal 
transplants of approximately 50%, whereas those with factor H mutations have an 
even higher risk (approximately 80%). By contrast, MCP deficiency can be 
corrected in part by a renal allograft. However, caution in the use of 
live-related donations is needed because of the high rates of incomplete 
penetrance of the described mutations.