Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

TLDR

Atypical hemolytic uremic syndrome is a rare complement‑mediated kidney disease that affects both children and adults. The study aimed to evaluate disease presentation and outcomes in a nationwide cohort of aHUS patients by age of onset and underlying complement abnormalities. 214 patients were enrolled from 2000 to 2008 and screened for mutations in six complement susceptibility genes and for anti‑factor H antibodies. Incidence rose with age (23% at 2 y to 98% at 60 y); children had higher 1‑year mortality (6.7% vs 0.8%) but adults progressed to ESRD more often (46% vs 16%); 61% carried complement mutations; renal outcomes were similar in adults regardless of genetics, while MCP‑associated disease was milder in children; relapse after one year was 92% in children with MCP‑HUS versus ~30% in other groups, highlighting that children face higher mortality but adults have worse renal prognosis.

Abstract

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.