Genetics and Outcome of Atypical Hemolytic Uremic Syndrome: A Nationwide French Series Comparing Children and Adults

• Published in: Clinical journal of the American Society of Nephrology Vol. 8; no. 4; pp. 554 - 562
• Main Authors: Fremeaux-Bacchi, Véronique, Fakhouri, Fadi, Garnier, Arnaud, Bienaimé, Frank, Dragon-Durey, Marie-Agnès, Ngo, Stéphanie, Moulin, Bruno, Servais, Aude, Provot, François, Rostaing, Lionel, Burtey, Stéphane, Niaudet, Patrick, Deschênes, Georges, Lebranchu, Yvon, Zuber, Julien, Loirat, Chantal
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.04.2013
• Subjects: Adolescent; Adult; Age of Onset; Aged; Aged, 80 and over; Atypical Hemolytic Uremic Syndrome; Child; Child, Preschool; Complement System Proteins - genetics; Female; France - epidemiology; Genetic Association Studies; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Testing - statistics & numerical data; Hemolytic-Uremic Syndrome - genetics; Hemolytic-Uremic Syndrome - mortality; Hemolytic-Uremic Syndrome - therapy; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Male; Middle Aged; Original; Outcome Assessment (Health Care); Prognosis; Young Adult; France
• ISSN: 1555-9041; 1555-905X; 1555-905X
• DOI: 10.2215/CJN.04760512

Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease that was first recognized in children but also affects adults. This study assessed the disease presentation and outcome in a nationwide cohort of patients with aHUS according to the age at onset and the underlying complement abnormalities. A total of 214 patients with aHUS were enrolled between 2000 and 2008 and screened for mutations in the six susceptibility factors for aHUS and for anti-factor H antibodies. Onset of aHUS occurred as frequently during adulthood (58.4%) as during childhood (41.6%). The percentages of patients who developed the disease were 23%, 40%, 70%, and 98% by age 2, 18, 40, and 60 years, respectively. Mortality was higher in children than in adults (6.7% versus 0.8% at 1 year) (P=0.02), but progression to ESRD after the first aHUS episode was more frequent in adults (46% versus 16%; P<0.001). Sixty-one percent of patients had mutations in their complement genes. The renal outcome was not significantly different in adults regardless of genetic background. Only membrane cofactor protein (MCP) and undetermined aHUS were less severe in children than adults. The frequency of relapse after 1 year was 92% in children with MCP-associated HUS and approximately 30% in all other subgroups. Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background.