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Review
. 2019 Feb 1;26(2):99-110.
doi: 10.5551/jat.RV17026. Epub 2018 Nov 2.

Pathogenesis of Atypical Hemolytic Uremic Syndrome

Yoko Yoshida  1 , Hideki Kato  2 , Yoichiro Ikeda  1 , Masaomi Nangaku  1
Affiliations
Review

Pathogenesis of Atypical Hemolytic Uremic Syndrome

Yoko Yoshida et al. J Atheroscler Thromb. .

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy (TMA) defined by thrombocytopenia, microangiopathic hemolytic anemia, and renal failure. aHUS is caused by uncontrolled complement activation in the alternative pathway (AP). A variety of genetic defects in complement-related factors or acquired autoantibodies to the complement regulators have been found in 50 to 60% of all cases. Recently, however, the classification and diagnosis of aHUS are becoming more complicated. One reason for this is that some factors, which have not been regarded as complement-related factors, have been reported as predisposing factors for phenotypic aHUS. Given that genotype is highly correlated with the phenotype of aHUS, careful analysis of underlying genetic abnormalities or acquired factors is needed to predict the prognosis or to decide an optimal treatment for the disease. Another reason is that complement dysregulation in the AP have also been found in a part of other types of TMA such as transplantation-related TMA and pregnancy-related complication. Based on these findings, it is now time to redefine aHUS according to the genetic or acquired background of abnormalities.Here, we review the pathogeneses and the corresponding phenotypes of aHUS and complement-related TMAs.

Keywords: Alternative pathway; Atypical hemolytic uremic syndrome; Complement.

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Conflict of interest statement

Honoraria: Hideki Kato and Masaomi Nangaku from Alexion Pharmaceuticals, Inc. Clinical research funding: Masaomi Nangaku from Alexion Pharmaceuticals, Inc.

Figures

Fig. 1.
Fig. 1.
Alternative pathway of complement CFB: complement factor B, CFD: complement factor D, CFI: complement factor I, CFH: complement factor H, MCP: membrane cofactor protein, MAC: membrane attack complex
See this image and copyright information in PMC

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