Familial Hemolytic-Uremic Syndrome and Homozygous Factor H Deficiency

Pichette, Vincent; Quérin, Serge; Schürch, Walter; Brun, G; Lehner-Netsch, G; Delage, J

doi:10.1016/s0272-6386(12)81065-1

Cited by 119 publications

(74 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the percentage of complete recovery under plasmatherapy was only 5% and evolution to death or end stage renal disease 37% [18]. Twelve observations, mainly in children, show that early intensive plasmatherapy can rescue HUS and long term plasmatherapy prevent relapses and evolution to end stage renal failure (ESRF) in CFH-mutated patients [17,[103][104][105][106][107][108][109][110][111][112][113][114][115]. These patients received PE (40-60 ml/kg with FFP for restitution) or PI (10-15 ml/kg) at the acute phase, most of them daily during at least 5 days and up to 2 weeks, then tapered to long term maintenance plasmatherapy (PE or PI from weekly to every 2 to 4 weeks).…”

Section: Plasmatherapy In Patients With Cfh Mutationmentioning

confidence: 99%

Atypical Hemolytic Uremic Syndrome

Loirat¹,

Frémeaux‐Bacchi²

2016

Pediatric Kidney Disease

View full text Add to dashboard Cite

Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early.

show abstract

Section: Plasmatherapy In Patients With Cfh Mutationmentioning

confidence: 99%

Atypical Hemolytic Uremic Syndrome

Loirat¹,

Frémeaux‐Bacchi²

2016

Pediatric Kidney Disease

View full text Add to dashboard Cite

show abstract

“…The first examined candidate gene in this region was factor H (HF1), because an association between familial HUS and HF1 abnormalities had been reported previously (103,111,112). HF1 is a 150-kD multifunctional singlechain plasma glycoprotein that plays an important role in the regulation of the alternative pathway of complement (113).…”

Section: Genetic Studiesmentioning

confidence: 99%

Hemolytic Uremic Syndrome

Noris¹,

Remuzzi²

2005

Journal of the American Society of Nephrology

502

428

View full text Add to dashboard Cite

“…In addition to the previously described recombinant fragments of fH we generated new mutant proteins spanning the middle and carboxy-terminal parts of fH (constructs containing [15][16][17][18] as tools for the fH-C3b interaction studies.…”

Section: Expression Of the New Recombinant Fragments Of Fhmentioning

confidence: 99%

“…basement membranes in kidney glomeruli) (12)(13)(14). This is exemplified by rare cases of fH deficiency in human beings (15)(16)(17)(18) and pigs (19,20) that lead to complement-dependent kidney damage. The ability of AP to discriminate between activating and nonactivating structures depends on the differential binding of fH to C3b on different types of surfaces.…”

Section: Introductionmentioning

confidence: 99%