An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document

Abstract

Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Atypical HUS (aHUS) is a sub-type of HUS in which the TMA phenomena are the consequence of decreased regulation of the alternative complement pathway on cell surfaces due to a genetic cause. aHUS is an extremely rare disease that, despite the administration of standard treatment with plasma therapy, often progresses to terminal chronic renal failure with a high associated rate of mortality. In recent years, research has established the key role that the complement system plays in the induction of endothelial damage in patients with aHUS, through the characterisation of multiple mutations and polymorphisms in the genes that code for certain complement factors. Eculizumab is a monoclonal antibody that inhibits the terminal fraction of the complement protein, blocking the formation of a cell membrane attack complex. In prospective studies in patients with aHUS, administering eculizumab produces a rapid and sustained interruption in the TMA process, with significant improvements in long-term renal function and an important decrease in the need for dialysis or plasma therapy. In this document, we review and bring up to date the important aspects of this disease, with special emphasis on how recent advancements in diagnostic and therapeutic processes can modify the treatment of patients with aHUS.