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

Global aHUS Registry

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)408-418
JournalKidney International
Volume94
Issue number2
DOIs
Publication statusPublished - 2018

Fingerprint

Chronic Kidney Failure
CD46 Antigens
Disease-Free Survival
Phenotype
Mutation
Registries
Complement Factor I
Thrombotic Microangiopathies
Complement Factor H
Sex Characteristics
Survival Rate
Genotype
Confidence Intervals
Atypical Hemolytic Uremic Syndrome
Therapeutics

Keywords

  • complement
  • hemolytic uremic syndrome
  • thrombotic microangiopathy

ASJC Scopus subject areas

  • Nephrology

Cite this

Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. / Global aHUS Registry.

In: Kidney International, Vol. 94, No. 2, 2018, p. 408-418.

Research output: Contribution to journalArticle

@article{019c02cdadfd4935a7964243cb860c31,
title = "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.",
keywords = "complement, hemolytic uremic syndrome, thrombotic microangiopathy",
author = "{Global aHUS Registry} and Franz Schaefer and Gianluigi Ardissino and Gema Ariceta and Fadi Fakhouri and Marie Scully and Nicole Isbel and {\AA}sa Lommel{\'e} and Varant Kupelian and Christoph Gasteyger and Greenbaum, {Larry A.} and Sally Johnson and Masayo Ogawa and Christoph Licht and {Vande Walle}, Johan and V{\'e}ronique Fr{\'e}meaux-Bacchi and Miquel Blasco and Donata Cresseri and Galina Generolova and Nicholas Webb and Patricia Hirt-Minkowski and {Lvovna Kozlovskaya}, Natalya and Danny Landau and Lapeyraque, {Anne Laure} and Chantal Loirat and Christoph Mache and Michal Malina and Leena Martola and Annick Massart and Eric Rondeau and Andrew Siedlecki and Lisa Sartz",
year = "2018",
doi = "10.1016/j.kint.2018.02.029",
language = "English",
volume = "94",
pages = "408--418",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome

AU - Global aHUS Registry

AU - Schaefer, Franz

AU - Ardissino, Gianluigi

AU - Ariceta, Gema

AU - Fakhouri, Fadi

AU - Scully, Marie

AU - Isbel, Nicole

AU - Lommelé, Åsa

AU - Kupelian, Varant

AU - Gasteyger, Christoph

AU - Greenbaum, Larry A.

AU - Johnson, Sally

AU - Ogawa, Masayo

AU - Licht, Christoph

AU - Vande Walle, Johan

AU - Frémeaux-Bacchi, Véronique

AU - Blasco, Miquel

AU - Cresseri, Donata

AU - Generolova, Galina

AU - Webb, Nicholas

AU - Hirt-Minkowski, Patricia

AU - Lvovna Kozlovskaya, Natalya

AU - Landau, Danny

AU - Lapeyraque, Anne Laure

AU - Loirat, Chantal

AU - Mache, Christoph

AU - Malina, Michal

AU - Martola, Leena

AU - Massart, Annick

AU - Rondeau, Eric

AU - Siedlecki, Andrew

AU - Sartz, Lisa

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - complement

KW - hemolytic uremic syndrome

KW - thrombotic microangiopathy

UR - http://www.scopus.com/inward/record.url?scp=85048310826&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048310826&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2018.02.029

DO - 10.1016/j.kint.2018.02.029

M3 - Article

AN - SCOPUS:85048310826

VL - 94

SP - 408

EP - 418

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 2

ER -