Complement and the atypical hemolytic uremic syndrome

Hôpitaux de Paris, Université Paris 7, Hôpital Robert Debré, Pediatric Nephrology, Paris, France.
Pediatric Nephrology (Impact Factor: 2.88). 08/2008; 23(11):1957-72. DOI: 10.1007/s00467-008-0872-4
Source: PubMed

ABSTRACT Over the past decade, atypical hemolytic uremic syndrome (aHUS) has been demonstrated to be a disorder of the regulation of the complement alternative pathway. Among approximately 200 children with the disease, reported in the literature, 50% had mutations of the complement regulatory proteins factor H, membrane cofactor protein (MCP) or factor I. Mutations in factor B and C3 have also been reported recently. In addition, 10% of children have factor H dysfunction due to anti-factor H antibodies. Early age at onset appears as characteristic of factor H and factor I mutated patients, while MCP-associated HUS is not observed before age 1 year. Low C3 level may occur in patients with factor H and factor I mutation, while C3 level is generally normal in MCP-mutated patients. Normal plasma factor H and factor I levels do not preclude the presence of a mutation in these genes. The worst prognosis is for factor H-mutated patients, as 60% die or reach end-stage renal disease (ESRD) within the first year after onset of the disease. Patients with mutations in MCP have a relapsing course, but no patient has ever reached ESRD in the first year of the disease. Half of the patients with factor I mutations have a rapid evolution to ESRD, but half recover. Early intensive plasmatherapy appears to have a beneficial effect, except in MCP-mutated patients. There is a high risk of graft loss for HUS recurrence or thrombosis in all groups except the MCP-mutated group. Recent success of liver-kidney transplantation combined with plasmatherapy opens this option for patients with mutations of factors synthesized in the liver. New therapies such as factor H concentrate or complement inhibitors offer hope for the future.

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    • "Characterized by acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia, the descriptor 'atypical' is used to differentiate this form of HUS from its 'typical' counterpart, which is caused by infection with enterohemorrhagic Escherichia E1446 Maga et al. coli (EHEC) that leads to a diarrheal illness (D+). Typical HUS generally resolves without sequelae; aHUS (usually D-), in contrast, progresses to end-stage renal failure (ESRF) in 30% to 60% of affected persons, depending on which gene is mutated (Loirat, et al., 2008). "
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