Atypical hemolytic uremic syndrome (aHUS) is a rare form of
thrombotic microangiopathy (TMA). It has an unfavorable outcome with death rates as high as 25% during the acute phase and up to 50% of cases progressing to
end-stage renal failure. Uncontrolled complement activation through the alternative pathway is thought to be the main underlying pathopysiology of aHUS and corresponds to all the deleterious findings of the disease.
Thrombotic thrombocytopenic purpura (
TTP) and
Shiga toxin-associated HUS are the 2 other important TMA diseases. Although differentiating HUS from
TTP is relatively easy in children with a preceding diarrheal illness or invasive S. pneumoniae, differentiating aHUS from
TTP or other microangiopathic disorders can present a major diagnostic challenge in adults. ADAMTS13 analysis is currently the most informative diagnostic test for differentiating
TTP, congenital
TTP, and aHUS. Today empiric plasma
therapy still is recommended by expert opinion to be used as early as possible in any patient with symptoms of aHUS. The overall treatment goal remains restoration of a physiological balance between activation and control of the alternative complement pathway. So it is a reasonable approach to block the
terminal complement complex with
eculizumab in order to prevent further organ injury and increase the likelihood organ recovery. Persistence of
hemolysis or lack of improvement of renal function after 3-5 daily
plasmaphereses have to be regarded as the major criteria for uncontrolled TMA even if platelet count has normalized and as an indication to switch the treatment to
eculizumab.
Eculizumab has changed the future perspectives of patients with aHUS and both the FDA and the EMA have approved it as life-long treatment. However, there are still some unresolved issues about the follow-up such as the optimal duration of
eculizumab treatment and whether it can be stopped or how to stop the
therapy.