Title |
Complement and the atypical hemolytic uremic syndrome in children
|
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Published in |
Pediatric Nephrology, November 2008
|
DOI | 10.1007/s00467-008-0872-4 |
Pubmed ID | |
Authors |
Chantal Loirat, Marina Noris, Véronique Fremeaux-Bacchi |
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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Geographical breakdown
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Czechia | 1 | <1% |
Tanzania, United Republic of | 1 | <1% |
Canada | 1 | <1% |
Unknown | 107 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 19 | 17% |
Other | 16 | 14% |
Researcher | 13 | 12% |
Student > Ph. D. Student | 9 | 8% |
Student > Doctoral Student | 7 | 6% |
Other | 29 | 26% |
Unknown | 18 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 63 | 57% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 7% |
Biochemistry, Genetics and Molecular Biology | 6 | 5% |
Agricultural and Biological Sciences | 6 | 5% |
Nursing and Health Professions | 2 | 2% |
Other | 9 | 8% |
Unknown | 17 | 15% |