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Kidney Int. 2018 Aug;94(2):408-418. doi: 10.1016/j.kint.2018.02.029. Epub 2018 Jun 19.

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

Author information

1
Division of Pediatric Nephrology, Heidelberg University Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany. Electronic address: Franz.Schaefer@med.uni-heidelberg.de.
2
Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
3
Pediatric Nephrology, University Hospital Vall d'Hebron, Barcelona, Spain.
4
Department of Nephrology and Immunology, Centre Hospitalier Universitaire de Nantes, Nantes, France.
5
Department of Haematology, University College London Hospital and Cardiometabolic Programme-National Institute for Health Research University College London Hospitals National Health Service Foundation Trust/University College London Biomedical Research Center, London, UK.
6
Department of Nephrology, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia.
7
Alexion Pharma GmbH, Zurich, Switzerland.
8
Alexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
9
Division of Pediatric Nephrology, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
10
Paediatric Nephrology, Great North Children's Hospital, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle, UK.
11
Division of Nephrology and Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
12
Pediatric Nephrology, Safepedrug Consortium, Ghent University Hospital, Ghent, Belgium.
13
Department of Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.

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

PMID:
29907460
DOI:
10.1016/j.kint.2018.02.029

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