Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

“…Age of initial onset of aHUS is approximately equal in adults and children [28,29] and distribution is similar between males and females, although there is a slight predominance in females among adult onset patients [28]. Prognosis is poor with a mortality up to 25% and over half of patients developing ESRD after the first presentation of aHUS [12,17,25,46,47].…”

Section: Hus: Stec-hus and Ahusmentioning

confidence: 99%

“…Therefore, to confirm a diagnosis of aHUS, it is necessary that tests for STEC (Shiga toxin) and pneumococcus infections are negative and ADAMTS13 activity is normal ( > 5%-10%). Measurement of serum levels of C3, C4, CFH and CFI, and complement antibody and genetic mutation screening can give an indication [13,54], although it should be noted that normal complement protein levels or the absence of a mutation does not exclude a diagnosis of aHUS as serum activity does not correlate with complement activity on the endothelial surface [46,55,56].…”

Section: Diagnosismentioning

confidence: 99%

“…While PE initially manages haematological symptoms in some patients, up to 65% of aHUS patients require dialysis, develop permanent kidney damage or die within 1 year despite PE or plasma infusion (PI) [25]. However, haematologic improvement does not mean that TMA is not ongoing in organs, and unlike in the treatment of TTP, it has been demonstrated that the use of PE in aHUS is mostly ineffective [46].…”

Section: Treatment Treatment Of Ahusmentioning

confidence: 99%

“…For this group, eculizumab prophylactic therapy has been proposed as preferable to PE for several reasons, including failure of PE to prevent TMA, the unpredictable risk of TMA when PE is tapered and subclinical progression of disease [46,48,66,68].…”

Section: Kidney Transplantationmentioning

confidence: 99%

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Atypical hemolytic uremic syndrome: from diagnosis to treatment

Franchini¹

2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Thrombotic microangiopathy (TMA) is a relatively rare condition but a medical urgency requiring immediate intervention to avoid irreversible organ damage or death. Symptoms on presentation include microangiopathic haemolytic anaemia, thrombocytopenia and organ damage. The most frequent direct causes of TMA are thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS). The most common form of HUS is related to Shiga toxin producing Escherichia coli (STEC) infection while approximately 10% of cases are due to dysregulation of the complement pathway (atypical haemolytic uremic syndrome, aHUS). Optimal treatment regimens differ depending on the underlying cause; however, differential diagnosis may be difficult. The most accurate method of diagnosis is based on exclusion and should consider, beyond the symptoms common to TMA, ADAMTS13 activity levels and STEC infection status. For the management of TTP, plasma exchange (PE) is the most important acute intervention and is associated with lower mortality and better outcomes than plasma infusion. In most patients with STEC-HUS, the course of disease is selflimiting although management of acute kidney injury is often required. Until recently, the management of aHUS consisted of early and intensive PE, although this was mostly ineffective in protecting from subsequent organ damage. Eculizumab, an inhibitor of the alternative complement pathway, produces a rapid and sustained inhibition of the TMA process, with significant improvements in long-term clinical outcomes. Due to the significant improvement achieved, eculizumab has subsequently been approved as first-line therapy when an unequivocal diagnosis of aHUS has been made.

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