Sellier-Leclerc A-L et al. (2007) Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 18: 2392–2400

Several studies have linked mutations in the genes encoding factor H (CFH), factor I (CFI), and membrane cofactor protein (MCP)—all regulators of complement activation—to atypical hemolytic uremic syndrome (HUS). Now, Sellier-Leclerc et al. report that the clinical characteristics of pediatric atypical HUS depend upon the form of complement dysregulation.

In a population of 46 children with atypical HUS, 52% had a mutation in at least one of the three complement-system genes examined. Patients harboring CFH or CFI mutations were markedly younger at disease onset (median ages 6 months and 2 months, respectively) than were patients with an MCP mutation (median age 4.5 years). Within 1 year of disease onset, 37% of the patients died or developed end-stage renal disease (ESRD). Serum creatinine level at first flare was significantly associated with outcome at 1 year.

Patients with a CFH mutation had the worst prognosis, with 40% reaching ESRD at first flare and 60% progressing to this stage within 10 years. By contrast, only about 30% of patients with either an MCP or CFI mutation had reached ESRD at 10 years' follow-up. Of the 24 kidney transplantations performed in 15 patients, only 8 were successful. Interestingly, 8 of the 16 graft failures were due to vascular thrombosis rather than recurrence of atypical HUS. Identifying the mutations that underlie atypical HUS could provide valuable prognostic information and help to guide management of individual patients.