Hemolytic Uremic Syndrome

Noris, Marina; Remuzzi, Giuseppe

doi:10.1681/asn.2004100861

Cited by 502 publications

(477 citation statements)

References 165 publications

(150 reference statements)

Supporting

Mentioning

436

Contrasting

Unclassified

Order By: Relevance

“…Deficiency of complement regulators is a major risk factor for development of aHUS (DragonDurey and Fremeaux-Bacchi, 2005;Esparza-Gordillo et al, 2005;Goodship et al, 2004;Noris and Remuzzi, 2005;Zipfel et al, 2006). More than 50% of patients with aHUS have mutations in one of three complement control proteins: factor H (fH), membrane cofactor protein (MCP; CD46) or factor I (fI) Esparza-Gordillo et al, 2005;Goodship et al, 2004 ;Zipfel et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome

Liszewski

Leung

Schraml

et al. 2007

Molecular Immunology

View full text Add to dashboard Cite

Mutations in complement regulatory proteins predispose to the development of aHUS. Approximately 50% of patients bear a mutation in one of three complement control proteins, factor H, factor I, or membrane cofactor protein (MCP; CD46). Another membrane regulator that is closely related to MCP, decay accelerating factor (DAF; CD55) thus far has shown no association with aHUS and continues to be investigated. The goal of this study was to compare the regulatory profile of MCP and DAF and to assess how alterations in MCP predispose to complement dysregulation. We employed a model system of complement activation on Chinese hamster ovary (CHO) cell transfectants. The four regularly expressed isoforms of MCP and DAF inhibited C3b deposition by the alternative pathway. DAF, but not MCP, inhibited the classical pathway. Most patients with MCPaHUS are heterozygous and express only 25-50 % of the wild-type protein. We, therefore, analyzed the effect of reduced levels of wild-type MCP and found that cells with lowered expression levels were less efficient in inhibiting alternative pathway activation. Further, a dysfunctional MCP mutant, expressed at normal levels and identified in five patients with aHUS (S206P), failed to protect against C3b amplification on CHO cells, even if expression levels were increased 10-fold. Our results add new information relative to the necessity for appropriate expression levels of MCP and further implicate the alternative pathway in disease processes such as aHUS.

show abstract

Section: Introductionmentioning

confidence: 99%

Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome

Liszewski

Leung

Schraml

et al. 2007

Molecular Immunology

View full text Add to dashboard Cite

show abstract

“…2 . It typically affects children, with 90 % of cases following gastroenteritis secondary to Shiga toxin (Stx)-producing Escherichia coli 3 .…”

Section: Discussionmentioning

confidence: 99%

“…Stx-producing Shigella dysenteriae and Campylobacter jejuni have also been linked to diarrhea-associated HUS (D+HUS). 2,4 D+HUS is much more common in children than adults, due to high expression of Stx receptors in their renal glomeruli. 5 Therefore, adult cases tend to be sporadic or in association with outbreaks of E.coli infection, such as that reported in Germany in 2011.…”

Section: Discussionmentioning

confidence: 99%

Campylobacter-Associated Hemolytic Uremic Syndrome Associated with Pulmonary-Renal Syndrome

2015

View full text Add to dashboard Cite

“…Damage of endothelial cells would in itself activate complement [10]. Together the platelet and complement activation and endothelial damage leads to platelet aggregation, small vessel obstruction, mechanical haemolysis and TMA, mainly in the kidney but also in other organs, notably the central nervous system (CNS) and gastrointestinal tract [9,11,12]. The alternative pathway involves the constitutive low level activation of C3 and the subsequent deposit of C3b on cell membranes, ultimately leading to the generation of the membrane attack complex, (MAC), C5b-9.…”

Section: Haemolytic Uraemic Syndromementioning

confidence: 99%

Atypical hemolytic uremic syndrome: from diagnosis to treatment

Franchini¹

2015

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

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.

show abstract

Hemolytic Uremic Syndrome

Cited by 502 publications

References 165 publications

Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome

Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome

Campylobacter-Associated Hemolytic Uremic Syndrome Associated with Pulmonary-Renal Syndrome

Atypical hemolytic uremic syndrome: from diagnosis to treatment

Contact Info

Product

Resources

About