Atypical hemolytic uremic syndrome

Abstract

Atypical (or complement mediated) hemolytic uremic syndrome (aHUS) is a rare disease with high risk of severe organ damage and death. As a representative of thrombotic microangiopathies it is defined by microangiopathic hemolytic anemia, thrombocytopenia and endothelial cell damage resulting in ischemic target organ injury, especially kidney failure.

A variety of clinical scenarios can have the features of thrombotic microangiopathies thus impeding the differential diagnosis of the underlying condition. aHUS is caused by a genetic or acquired defect in regulation of the alternative complement pathway resulting in its persistent activation, formation of terminal membrane attacking complexes, microvascular endothelial damage and ischemic organ injury. Roughly 50 % of patients have rare germline variants in complement genes, detection of antibodies againist complement factors (CFH) is much less common. In carriers of these genetic mutations, due to the incomplete genetic penetrance of aHUS, clinically significant disease often requires a complement amplifying trigger such as infection, surgery or pregnancy. Identification of germline variant is not necessary for the diagnosis of aHUS, however it is important for estimation of the prognosis and the risk of relapse after treatment cessation or kidney transplant. Thanks to the new specific treatment options represented by complement inhibitors, the prognosis of patients with aHUS improved rapidly, however remains dependent on fast and correct diagnostics and rapid treatment initiation. Further discussed and unsolved questions relate to duration and posibility of cessation of the treatment and further management and follow up of patients after the episode of aHUS.