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

Campistol, Josep M.; Arias, Manuel; Ariceta, Gema; Blasco, Miguel; Espinosa, Laura; Espinosa, Mario; Grinyó, Josep M.; Macía, Manuel; Mendizábal, Santiago; Praga, Manuel; Román, Elena; Torrá, Roser; Valdés, Francisco; Vilalta, R.; Córdoba, Santiago Rodrı́guez de

doi:10.1016/j.nefroe.2015.11.006

Cited by 118 publications

(250 citation statements)

References 134 publications

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“…In aHUS, the pathophysiological consequences result directly from damage caused by the uncontrolled activation of the alternative complement pathway leading to excessive complement activation on cell membranes [13,14]. A link between complement and aHUS was first reported in 1981 in two brothers who had a deficiency of CFH and mutations in the gene encoding CFH were recognised to be associated with aHUS in 1998 [15,16].…”

Section: Atypical Haemolytic Uraemic Syndromementioning

confidence: 99%

“…The different roles of cleavage products in microbial defence and removal of dead or damaged cells is also shown. Mutations in complement system genes have been identified in 50%-60% of patients with aHUS [13,14]. The mutations identified impair regulation in the alternative pathway at the level of the C3 convertase and Figure 2 describes these mechanisms.…”

Section: Atypical Haemolytic Uraemic Syndromementioning

confidence: 99%

“…In the US, aHUS is estimated to have an annual incidence rate of ∼1-2 cases/million inhabitants [45] and in Europe, a recent international, multicentre study reported an incidence of 0.11 cases/million inhabitants between the ages of 0 and 18 years [13]. 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].…”

Section: Hus: Stec-hus and Ahusmentioning

confidence: 99%

“…As discussed, TMA can be due to several causes and may be further precipitated by other underlying diseases, drugs, bone marrow transplant, or pregnancy [13]. In these cases, intervention to discontinue the event which initiated the onset of symptoms (if possible, e.g., stopping a drug treatment) may lead to resolution of TMA.…”

Section: Diagnosismentioning

confidence: 99%

“…TTP may potentially be accurately differentiated from aHUS by severe deficiency of the ADAMTS13 protease [13,50] and, if the facilities are available, ADAMTS13 activity can be assessed within 2 days. It is important to take samples for analysis before any plasma has been given.…”

Section: Diagnosismentioning

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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Section: Atypical Haemolytic Uraemic Syndromementioning

confidence: 99%

Section: Atypical Haemolytic Uraemic Syndromementioning

confidence: 99%

Section: Hus: Stec-hus and Ahusmentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

Section: Diagnosismentioning

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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Dengue virus and the complement alternative pathway

et al. 2020

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Dengue disease is an inflammatory-driven pathology, and complement overactivation is linked to disease severity and vascular leakage. Additionally, dysregulation of complement alternative pathway (AP) components has been described, such as upregulation of complement factor D and downregulation of complement factor H (FH), which activate and inhibit the AP, respectively. Thus, the pathology of severe dengue could in part result from AP dysfunction, even though complement and AP activation usually provide protection against viral infections. In dengue virus-infected macrophages and endothelial cells (ECs), the site of replication and target for vascular pathology, respectively, the AP is activated. The AP activation, reduced FH and vascular leakage seen in dengue disease in part parallels other complement AP pathologies associated with FH deficiency, such as atypical haemolytic uraemic syndrome (aHUS). aHUS can be therapeutically targeted with inhibitors of complement terminal activity, raising the idea that strategies such as inhibition of complement or delivery of FH or other complement regulatory components to EC may be beneficial to combat the vascular leakage seen in severe dengue.

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