Personalised management of atypical haemolytic uraemic syndrome

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Haemolytic Uraemic Syndrome (HUS) is a severe complication of infection with the bacteria E.Coli O157. In ~10% of patients kidney failure occurs due to a toxin released by the bacteria. Atypical HUS is a rarer form of the disease which is not associated with these bacteria and in many cases there is a genetic predisposition to the disease. Work in Newcastle funded by the MRC previously identified that abnormalities in genes for complement proteins predispose to disease in around 50% of cases. The complement system plays an important role in protecting the body from infection by killing micro-organisms. If these complement proteins are faulty then the body's own kidney cells can be damaged by these same mechanisms. This key discovery ultimately resulted in the introduction of a drug which prevents complement activation, Eculizumab. This revolutionised treatment for patients with this condition and prevented them from developing kidney failure.More recently we have identified a subgroup of aHUS patients who do not respond to this drug. In these families we are undertaking genetic analysis to identify the underlying cause and are identifying genes that do not appear to be involved in the complement pathway. By identifying these novel genetic causes of aHUS and by defining simple blood tests that will quickly identify these patients we will prevent ineffective use of complement inhibitory therapy, avoiding the infectious side effects of this medication. Additionally, by identifying new pathways responsible for disease, new drugs can be developed to target these pathway resulting in the same translational benefits seen following our original discover. Ultimately this work will allow personalised treatment for our patients with aHUS.