ABSTRACT
Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic
anemia, consumptive thrombocytopenia, and renal impairment. Often HUS is triggered
by Shiga-like toxin- producing Escherichia coli. Less common is atypical HUS (aHUS), which is caused by defective complement control.
aHUS is associated with mutations in genes encoding complement regulatory proteins
in ~50% of patients with this syndrome. Furthermore, autoantibodies that inactivate
to factor H have also been linked to the disease. Initial triggers include infections,
use of endothelial-affecting drugs, malignancies, transplantation, and pregnancy.
Advances in our understanding of the pathogenesis of atypical HUS suggest that complement
inhibition may be used as treatment for the disease. We discuss the potential benefit
of the complement inhibitor eculizumab for the treatment of aHUS.
KEYWORDS
Atypical hemolytic uremic syndrome - complement activation - complement inhibitor
- eculizumab
REFERENCES
- 1
Noris M, Remuzzi G.
Atypical hemolytic-uremic syndrome.
N Engl J Med.
2009;
361(17)
1676-1687
- 2
Noris M, Remuzzi G.
Hemolytic uremic syndrome.
J Am Soc Nephrol.
2005;
16(4)
1035-1050
- 3
Jokiranta T S, Zipfel P F, Frémeaux-Bacchi V, Taylor C M, Goodship T J, Noris M.
Where next with atypical hemolytic uremic syndrome?.
Mol Immunol.
2007;
44(16)
3889-3900
- 4
Atkinson J P, Goodship T H.
Complement factor H and the hemolytic uremic syndrome.
J Exp Med.
2007;
204(6)
1245-1248
- 5
Loirat C, Noris M, Frémeaux-Bacchi V.
Complement and the atypical hemolytic uremic syndrome in children.
Pediatr Nephrol.
2008;
23(11)
1957-1972
- 6
Thomas T C, Rollins S A, Rother R P et al.
Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv.
Mol Immunol.
1996;
33(17-18)
1389-1401
- 7
Hillmen P, Hall C, Marsh J C et al.
Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal
nocturnal hemoglobinuria.
N Engl J Med.
2004;
350(6)
552-559
- 8
Hillmen P, Young N S, Schubert J et al.
The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.
N Engl J Med.
2006;
355(12)
1233-1243
- 9
Shin J I, Lee J S.
More on eculizumab for congenital atypical hemolytic-uremic syndrome.
N Engl J Med.
2009;
360(20)
2142-2143; author reply 2143
- 10
Nürnberger J, Philipp T, Witzke O et al.
Eculizumab for atypical hemolytic-uremic syndrome.
N Engl J Med.
2009;
360(5)
542-544
- 11
Gruppo R A, Rother R P.
Eculizumab for congenital atypical hemolytic-uremic syndrome.
N Engl J Med.
2009;
360(5)
544-546
- 12
Mache C J, Acham-Roschitz B, Frémeaux-Bacchi V et al.
Complement inhibitor eculizumab in atypical hemolytic uremic syndrome.
Clin J Am Soc Nephrol.
2009;
4(8)
1312-1316
- 13
Chatelet V, Frémeaux-Bacchi V, Lobbedez T, Ficheux M, Hurault de Ligny B.
Safety and long-term efficacy of eculizumab in a renal transplant patient with recurrent
atypical hemolytic-uremic syndrome.
Am J Transplant.
2009;
9(11)
2644-2645
- 14
Davin J C, Gracchi V, Bouts A, Groothoff J, Strain L, Goodship T.
Maintenance of kidney function following treatment with eculizumab and discontinuation
of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome
associated with a CFH mutation.
Am J Kidney Dis.
2010;
55(4)
708-711
PD Dr. med. J. Nürnberger
Department of Nephrology, University Hospital of Essen
University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany
Email: jens.nuernberger@uni-due.de
