atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is a disease characterized by excessive complement activation in the microvasculature.

In both the familial and sporadic forms, inherited and acquired abnormalities affecting components of the alternative complement pathway are found in ∼ 60% of patients.

These include mutations in the genes encoding both complement regulators (factor H, factor I, membrane cofactor protein, and thrombomodulin) and activators (factors B and C3) and autoantibodies against factor H.

Multiple hits are necessary for the disease to manifest, including a trigger, mutations, and at-risk haplotypes in complement genes.

The prognosis for aHUS is poor, with most patients developing end-stage renal failure.

Renal transplantation in most patients also has a poor prognosis, with frequent loss of the allograft to recurrent disease.

However, improving results with combined liver-kidney transplantation and the advent of complement inhibitors such as eculizumab offer hope that the prognosis for aHUS will improve in future years.

Open references

 Atypical hemolytic uremic syndrome, genetic basis, and clinical manifestations. Kavanagh D, Goodship TH. Hematology Am Soc Hematol Educ Program. 2011;2011:15-20. PMID: 22160007 [Free]