Despite the use of supportive care, an estimated 33–40% of patients will die or have end-stage renal disease (ESRD) with the first clinical manifestation of aHUS, and 65% of patients will die, require dialysis, or have permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI) therapy. Patients who survive the presenting signs and symptoms of aHUS endure a chronic thrombotic and inflammatory state, which puts them at lifelong elevated risk of sudden blood clotting, kidney  failure, other severe complications and premature death.Historically, treatment options for aHUS were limited to plasma exchange or plasma infusion (PE/PI) therapy, which carries significant risks and has not been proven effective in any controlled trials. People with aHUS and ESRD have also had to undergo lifelong dialysis, which has a 5-year survival rate of 34–38%. Pathogenesis
HUS is one of the thrombotic microangiopathies, a category of disorders that includes STEC-HUS, aHUS, and thrombotic thrombocytopenic purpura (TTP). STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin(s), usually types of E. coli, that expresses verotoxin (also called Shiga-like toxin). E. coli can produce stx1 and/or stx2 Shiga toxins, the latter being more dangerous. A combination of both toxins in certain ratios is usually associated with HUS. These Shiga toxins bind GB3 receptors, globotriaosylceramide, which are present in renal tissue more than any other tissue and are also found in central nervous system neurons and other tissue. Children have more GB3 receptors than adults which may be why children are more susceptible to HUS.
Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.Most cases occur after infectious diarrhea due to a specific type of E. coli called O157:H7. Other causes include S. pneumoniae, Shigella, Salmonella, and certain medications. The underlying mechanism typically involves the production of Shiga toxin by the bacteria. Atypical hemolytic uremic syndrome (aHUS) is often due to a genetic mutation and presents differently. However, both can lead to widespread inflammation and multiple blood clots in small blood vessels, a condition known as thrombotic microangiopathy.Treatment involves supportive care and may include dialysis, steroids, blood transfusions, or plasmapheresis. About 1.5 per 100,000 people are affected per year. Less than 5% of those with the condition die. Of the remainder, up to 25% have ongoing kidney problems. HUS was first defined as a syndrome in 1955. Signs and symptoms
After eating contaminated food, the first symptoms of infection can emerge anywhere from 1 to 10 days later, but usually after 3 to 4 days.