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| .:: FACTS ::. |
Haemolytic Uraemic Syndrome (HUS)
Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and renal replacement treatment in children.
It is defined by the triad:
- acute hemolytic anemia
- thrombocytopenia
- acute renal failure
The most frequent cause of HUS is a food-borne infection by Shiga toxin (also termed verotoxin) producing Escherichia coli (STEC, synonym VTEC). The infection presents with diarrhea which often turns bloody and may progress with severe extra intestinal manifestations like acute renal failure, neurological abnormalities and heart failure. About 10% of these severe courses are fatal.
The main source of infections with STEC is cattle, in which these bacteria are non-pathogenic. STEC reside in the gastrointestinal tract of healthy ruminants and are shed with the feces. Meat is one important source of transmission. Outbreaks caused by contaminated lettuce, alfalfa sprouts, unpasteurized milk, and apple cider have also been reported.
Although HUS most commonly appears as a complication of an infection with Shiga toxin-producing E. coli, it can also be caused by other infections (such as S. pneumoniae) or by inherited or acquired abnormalities, mostly in the regulatory proteins of the complement system. This group of patients is referred to as atypical HUS.
Atypical HUS (aHUS)
5% of all HUS cases show an atypical or recurrent course, not associated with E. coli. Patients with HUS and no evidence of EHEC infection should be fully investigated for the known complement disorders and for autoantibodies against factor H. An accurate diagnostic evaluation of HUS based on the latest knowledge of dysfunction of the alternative pathway of the complement cascade should help predicting the risk of renal failure.
Predisposing factors for development of aHUS are:
- mutations in the complement regulatory proteins: FH, MCP (also known as CD46) and FI.
- mutations in activating components of the alternative pathway, FB and C3
- acquired factor H dysfunction, due to anti-factor H antibodies.
Nevertheless, there is strong evidence that mutations have incomplete penetrance and are just a predisposing factor for the disease. Further knowledge on genetic factors and familiar predispositions are of utmost importance for the quick diagnosis and treatment of the disease. Evidence based treatment guidelines are missing. Thus, current first line treatment is plasma exchange and/or infusion. Eculizumab, a monoclonal antibody against C5, has shown encouraging results in aHUS patients. Clinical trials evaluating the security and efficacy of this novel drug are ongoing.
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