Abstract
Atypical hemolytic uremic syndrome (aHUS) is one of many causes of thrombotic microangiopathies (TMA) and represents about 5-10% of all HUS. aHUS is a very rare life-threatening disease with can impair many body systems and untreated disease can have a very poor prognosis with high morbidity and also mortality. More than 40% of patients are older than 18 years of age.
Permanent activation of alternative complement pathway due to the defective function of some complement factors is a leading cause of the disease. Alteration in some complement factors function is caused by loss of function mutations in responsible genes or in formation of specific autoantibodies against these factors.
The most frequent mutations are in complement factor H (CFH), I (CFI) and B (CFB), which are associated with worse course of the disease. Mutations in genes for membrane cofactor protein (MCP) or thrombomodulin (THBD) are associated with better outcomes by contrast.
Treatment with plasma infusions (PI) or plasma exchanges (PE) remains still the first therapeutic step during treatment of adults while eculizumab represents the first line of treatment in children and is also a drug of choice in adult patients who are refractory to or dependent on PI/PE. Eculizumab is humanized monoclonal antibody against complement factor C5 which very effectively blocks alternative pathway activation and leads to normalization of parameters of haemolysis and also to normalization of renal function.
Prognosis of patients treated by eculizumab is currently significantly better but the treatment generates many questions which need to be answered. For example, how long should be patients treated, when we can stop the treatment, how to manage patients with terminal renal failure who are indicated to renal transplantation, and many others.
We try to find some answers in this article.