Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome.

Abstract:

:Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic background of 851 patients in the registry, prior to eculizumab treatment. A sex-specific difference was apparent according to age at initial disease onset as the ratio of males to females was 1.3:1 for childhood presentation and 1:2 for adult presentation. Complement Factor I and Membrane Cofactor Protein mutations were more common in patients with initial presentation as adults and children, respectively. Initial presentation in childhood significantly predicted ESRD risk (adjusted hazard ratio 0.55 [95% confidence interval 0.41-0.73], whereas sex, race, family history of aHUS, and time from initial presentation to diagnosis, did not. Patients with a Complement Factor H mutation had reduced ESRD-free survival, whereas Membrane Cofactor Protein mutation was associated with longer ESRD-free survival. Additionally extrarenal organ manifestations occur in 19%-38% of patients within six months of initial disease presentation (dependent on organ). Thus, our real-world results provide novel insights regarding phenotypic variables and genotypes on the clinical manifestation and progression of aHUS.

journal_name

Kidney Int

journal_title

Kidney international

authors

Schaefer F,Ardissino G,Ariceta G,Fakhouri F,Scully M,Isbel N,Lommelé Å,Kupelian V,Gasteyger C,Greenbaum LA,Johnson S,Ogawa M,Licht C,Vande Walle J,Frémeaux-Bacchi V,Global aHUS Registry.

doi

10.1016/j.kint.2018.02.029

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

408-418

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(18)30243-6

journal_volume

94

pub_type

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