Advances and challenges in the management of complement-mediated thrombotic microangiopathies

Therapeutic Advances in Hematology

Volumn 6, Issue 4, 2015, Pages 171-185

  Davin, Jean Claude ^a   Van Kar, Nicole C A J ^b  

^a EMMA CHILDREN S HOSPITAL   (Netherlands)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

atypical haemolytic uremic syndrome; combined kidney liver transplantation; complement related HUS; eculizumab; mutations; plasma exchange

Indexed keywords

EID: 84993783640     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620715577613     Document Type: Review

References (109)

1. Andrews S. Pollard A. (2014) A vaccine against serogroup B Neisseria meningitidis: dealing with uncertainty. Lancet Infect Dis 14: 426–434.
2. Ardissino G. Ossola M. Baffero G. Rigotti A. Cugno M. (2013) Eculizumab for atypical hemolytic uremic syndrome in pregnancy. Obstet Gynecol 122: 487–489.
3. Ardissino G. Testa S. Possenti I. Tel F. Paglialonga F. Salardi S. Tedeschi S. et al. (2014) Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis 64: 633–637.
4. Ariceta G. Arrizabalaga B. Aguirre M. Morteruel E. Lopez-Trascasa M. (2012) Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants. Am J Kidney Dis 59: 707–710.
5. Ariceta G. Besbas N. Johnson S. Karpman D. Landau D. Licht C. et al. (2009) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24: 687–696.
6. Belingheri M. Possenti I. Tel F. Paglialonga F. Testa S. Salardi S. et al. (2014) Cryptic activity of atypical hemolytic uremic syndrome and eculizumab treatment. Pediatrics 133: e1769–e1771.
7. Berger S. Roos A. Daha M. (2005) Complement and the kidney: what the nephrologist needs to know in 2006? Nephrol Dial Transplant 20: 2613–2619.
8. Besbas N. Karpman D. Landau D. Loirat C. Proesmans W. Remuzzi G. et al. (2006) A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int 70: 423–431.
9. Bienaimé F. Dragon-Durey M. Regnier C. Nillson S. Kwan W. Blouin J. et al. (2009) Mutations in components of complement influences the outcome of Factor I associated atypical hemolytic uremic syndrome. Kidney Int 77: 339–349.
10. Bouts A. Monnens L. Davin J. Struijk G. Spanjaard L. (2011) Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy. Pediatr Nephrol 26: 1919–1920.
11. Bouts A. Roofthooft M. Salomons G. Davin J. (2010) CD46-associated atypical haemolytic uremic syndrome with uncommon course caused by cblC deficiency. Pediatr Nephrol 25: 2547–2548.
12. Bresin E. Rurali E. Caprioli J. Sanchez-Corral P. Frémeaux-Bacchi V. Rodriguez de Cordoba S. et al. (2013) Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol 24: 475–486.
13. Cameron J. Vick R. (1973) Plasma-C3 in haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura. Lancet 2: 975.
14. Cañigral C. Moscardó F. Castro C. Pajares A. Lancharro A. Solves P. de la Rubia J. et al. (2013) Eculizumab for the treatment of pregnancy-related atypical hemolytic uremic syndrome. Ann Hematol 93: 1421–1422.
15. Caprioli J. Noris M. Brioschi S. Pianetti G. Castelleti F. Bettinaglio P. et al. (2006) Genetics of HUS: the impact of MCP, CFH and IF mutations on clinical presentation, response to treatment, and outcome. Blood 108: 1267–1279.
16. Chatelet V. Frémeaux-Bacchi V. Lobbedez T. Ficheux M. de Ligny B. (2009) Safety and long-term efficacy of eculizumab in a renal transplant patient with recurrent atypical hemolytic-uremic syndrome. Am J Transplant 9: 2644–2645.
17. Châtelet V. Lobbedez T. Frémeaux-Bacchi V. Ficheux M. Ryckelynck J. Hurault de Ligny B. (2010) Eculizumab: safety and efficacy after 17 months of treatment in a renal transplant patient with recurrent atypical hemolytic-uremic syndrome: case report. Transplant Proc 42: 4353–4355.
18. Chiodini B. Davin J. Corazza F. Khaldi K. Dahan K. Ismaili K. et al. (2014) Eculizumab in anti-factor H antibodies associated with atypical hemolytic uremic syndrome. Pediatrics 133: e1764–e1768.
19. Christmann M. Hansen M. Bergmann C. Schwabe D. Brand J. Schneider W. (2014) Eculizumab as first-line therapy for atypical hemolytic uremic syndrome. Pediatrics 133: e1759–e1763.
20. Constantinescu A. Bitzan M. Weiss L. Christen E. Kaplan B. Cnaan A. et al. (2004) Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis 43: 976–982.
21. Coppo P. Schwarzinger M. Buffet M. Wynckel A. Clabault K. Presne C. et al. (2010) Predictive features of severe acquired ADAMTS 13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PloS ONE 5: e10208.
22. Cugno M. Gualtierotti R. Possenti I. Testa S. Tel F. Griffini S. et al. (2014) Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome. J Thromb Haemost 12: 1440–1448.
23. Davin J. Gracchi V. Bouts A. Groothoff J. Strain L. Goodship T. (2010) 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 55: 708–711.
24. Davin J. Groothoff J. Gracchi V. Bouts A. (2011 a) Long-term renal function under plasma exchange in atypical hemolytic uremic syndrome. Pediatr Nephrol 26: 1915–1916.
25. Davin J. Majoie C. Groothoff J. Gracchi V. Bouts A. Goodship T. et al. (2011 b) Prevention of large-vessel stenoses in atypical hemolytic uremic syndrome associated with complement dysregulation. Pediatr Nephrol 26: 155–157.
26. Davin J. Strain L. Goodship T. (2008) Plasma therapy in atypical haemolytic uremic syndrome: lessons from a family with a factor H mutation. Pediatr Nephrol 23: 1517–1521.
27. Delvaeye M. Noris M. de Vriese A. Esmon C. Esmon N. Ferrell G. et al. (2009) Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 361: 345–357.
28. Dorresteijn E. van De Kar N. Cransberg K. (2012) Child with plasma resistant atypical HUS escaped end stage renal failure by eculizumab therapy. Ped Nephrol 27: 1193–1195.
29. Dragon-Durey M. Sethi S. Bagga A. Blanc C. Blouin J. Ranchin B. et al. (2010) Clinical features of anti-factor h autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol 21: 2180–2187.
30. Esparza-Gordillo J. Goicoechea de Jorge E. Buil A. Carreras Berges L. López-Trascasa M. Sánchez-Corral P. et al. (2005) Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32. Hum Mol Genet 14: 703–712.
31. Esparza-Gordillo J. Jorge E. Garrido C. Carreras L. López-Trascasa M. Sánchez-Corral P. et al. (2006) Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree. Mol Immunol 43: 1769–1775.
32. Espié E. Grimont F. Mariani-Kurkdjian P. Bouvet P. Haeghebaert S. Filliol I. et al. (2008) Surveillance of hemolytic uremic syndrome in children less than 15 years of age, a system to monitor O 157 and non-O157 Shiga toxin-producing Escherichia coli infections in France, 1996–2006. Pediatr Infect Dis J 27: 595–601.
33. Fakhouri F. Delmas Y. Provot F. Barbet C. Karras A. Makdassi R. et al. (2014) Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases. Am J Kidney Dis 63: 40–48.
34. Fakhouri F. Roumenina L. Provot F. Sallée M. Caillard S. Couzi L. et al. (2010) Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 21: 859–867.
35. Fang C. Frémeaux-Bacchi V. Liszewski M. Pianetti G. Noris M. Goodship T. et al. (2007) Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C 3 glomerulonephritis and the HELLP syndrome. Blood 111: 624–632.
36. Frémeaux-Bacchi V. Fakhouri F. Garnier A. Bienaimé F. Dragon-Durey M. Ngo S. et al. (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8: 554–562.
37. Frémeaux-Bacchi V. Miller E. Liszewski M. Strain L. Blouin J. Brown A. et al. (2008) Mutations in complement C 3 predispose to development of atypical hemolytic uremic syndrome. Blood 112: 4948–4952.
38. Geerdink L. Westra D. van Wijk J. Dorresteijn E. Lilien M. Davin J. et al. (2012) Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol 27: 1283–1291.
39. Gilbert R. Fowler D. Angus E. Hardy S. Stanley L. Goodship T. (2013) Eculizumab therapy for atypical haemolytic uraemic syndrome due to a gain-of-function mutation of complement factor, B. Pediatr Nephrol 28: 1315–1318.
40. Goicoechea de Jorge E. Harris C. Esparza-Gordillo J. Carreras L. Arranz E. Garrido C. et al. (2007) Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A 104: 240–245.
41. Green H. Harari E. Davidovits M. Blickstein D. Grossman A. Gafter U. et al. (2014) Atypical HUS due to factor H antibodies in an adult patient successfully treated with eculizumab. Ren Fail 36: 1119–1121.
42. Gruppo R. Rother R. (2009) Eculizumab for congenital atypical hemolyticuremic syndrome. N Engl J Med 360: 544–546.
43. Gulleroglu K. Fidan K. Hançer V. Bayrakci U. Baskin E. Soylemezoglu O. (2013) Neurologic involvement in atypical hemolytic uremic syndrome and successful treatment with eculizumab. Pediatr Nephrol 28: 827–830.
44. Heyne N. Weitz M. Guthoff M. Alscher M. Haering H. Nadalin S. (2011) Terminal complement blockade by eculizumab effectively reverses recurrent atypical hemolytic uremic syndrome after kidney transplantation. J Am Soc Nephrol 22: 952A.
45. Johnson S. Stojanovic J. Ariceta G. Bitzan M. Besbas N. Frieling M. et al. (2014) An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome. Pediatr Nephrol 29: 1967–1978.
46. Johnson S. Taylor C. (2008) What's new in haemolytic uraemic syndrome? Eur J Pediatr 167: 965–971.
47. Kavanagh D. Goodship T. (2010) Genetics and complement in atypical HUS. Pediatr Nephrol 25: 2431–2442.
48. Kavanagh D. Goodship T. Richards A. (2013) Atypical hemolytic uremic syndrome. Semin Nephrol 33: 508–530.
49. Keir L. Coward R. (2011) Advances in our understanding of the pathogenesis of glomerular thrombotic microangiopathy. Pediatr Nephrol 26: 523–533.
50. Lameire N. Bagga A. Cruz D. de Maeseneer J. Endre Z. Kellum J. et al. (2013) Acute kidney injury: an increasing global concern. Lancet 382: 170–179.
51. Lee B. Kwak S. Shin J. Lee S. Choi H. Kang H. et al. (2009) Atypical hemolytic uremic syndrome associated with complement factor H autoantibodies and CFHR1/CFHR3 deficiency. Pediatr Res 66: 336–340.
52. Legendre C. Licht C. Muus P. Greenbaum L. Babu S. Bedrosian C. et al. (2013 a) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368: 2169–2181.
53. Legendre C. Sberro-Soussan R. Zuber J. Rabant M. Loupy A. Timsit M. et al. (2013 b) Eculizumab in renal transplantation. Transplant Rev 27: 90–92.
54. Lemaire M. Frémeaux-Bacchi V. Schaefer F. Choi M. Tang W. Le Quintrec M. et al. (2013) Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 45: 531–536.
55. Lhotta K. Janecke A. Scheiring J. Petzlberger B. Giner T. Fally V. et al. (2009) A large family with a gain-of- function mutation of complement C 3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure. Clin J Am Soc Nephrol 4: 1356–1362.
56. Loirat C. (1992) Treatment of hemolytic uremic syndrome with fresh frozen plasma or with plasmapheresis. In: Ed. Kaplan B. Trompeter R. Moake J. (eds), Hemolytic Uremic Syndrome and Thrombocytopenic Purpura. New York, Hog Kong and Basel: Marcel Dekker, pp. 431–440.
57. Loirat C. Frémeaux-Bacchi V. (2008) Hemolytic uremic syndrome recurrence after renal transplantation. Pediatr Transpl 12: 619–629.
58. Loirat C. Frémeaux-Bacchi V. (2011) Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 6: 60.
59. Loirat C. Noris M. Frémeaux-Bacchi V. (2008) Complement and the atypical hemolytic uremic syndrome. Pediatr Nephrol 23: 1957–1972.
60. Loirat C. Macher M. Elmaleh-Berges M. Kwon T. Deschênes G. Goodship T. et al. (2010) Non-atheromatous arterial stenoses in atypical haemolytic uraemic syndrome associated with complement dysregulation. Nephrol Dial Transplant 25: 3421–3425.
61. Maga T. Nishimura C. Weaver A. Frees K. Smith R. (2010) Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat 31: E1445–E1460.
62. McKeage K. (2011) Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. Drugs 71: 2327–2345.
63. Monnens L. Hendrickx G. van Wieringen P. van Munster P. (1974) Letter: serum complement levels in haemolytic–uraemic syndrome. Lancet 2: 294.
64. Moore I. Strain L. Pappworth I. Kavanagh D. Barlow P. Herbert A. et al. (2010) Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR 4 and with mutations in CFH, CFI, CD46, and C 3 in patients with atypical haemolytic uraemic syndrome. Blood 115: 379–387.
65. Nester C. Stewart Z. Myers D. Jetton J. Nair R. Reed A. et al. (2011) Pre-emptive eculizumab and plasmapheresis for renal transplant in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 6: 1488–1494.
66. Neumann H. Salzmann M. Bohnert-Iwan B. Mannuelian T. Skerka C. Lenk D. et al. (2003) Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries. J Med Genet 40: 676–681.
67. Noris M. Caprioli J. Bresin E. Mossali C. Pianetti G. Gamba S. et al. (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5: 1844–1859.
68. Noris M. Remuzzi G. (2005) Hemolytic uremic syndrome. J Am Soc Nephrol 16: 1035–1050.
69. Noris M. Remuzzi G. (2009) Atypical hemolytic-uremic syndrome. N Engl J Med 361: 1676–1687.
70. Noris M. Remuzzi G. (2010) Thrombotic microangiopathy after kidney transplantation. Am J Transplant 10: 1517–1523.
71. Nürnberger J. Philipp T. Witzke O. Opazo Saez A. Vester U. Baba H. et al. (2009) Eculizumab for atypical haemolytic–uremic syndrome. N Engl J Med 360: 542–544.
72. Olie K. Florquin S. Groothoff J. Verlaak R. Strain L. Goodship T. et al. (2004) Atypical relapse of hemolytic uremic syndrome after transplantation. Pediatr Nephrol 19: 1173–1176.
73. Olie K. Goodship T. Verlaak R. Florquin S. Groothoff J. Strain L. et al. (2005) Posttransplantation cytomegalovirus-induced recurrence of atypical hemolytic uremic syndrome associated with a factor H mutation: successful treatment with intensive plasma exchanges and ganciclovir. Am J Kidney Dis 45: e12–e15.
74. Orth D. Khan A. Naim A. Grif K. Brockmeyer J. Karch H. et al. (2009) Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome. J Immunol 182: 6394–6400.
75. Parker C. (2009) Eculizumab for paroxysmal nocturnal haemoglobinuria. Lancet 373: 759–767.
76. Pelicano M. de Córdoba S. Diekmann F. Saiz M. Herrero S. Oppenheimer F. et al. (2013) Anti-C5 as prophylactic therapy in atypical hemolytic uremic syndrome in living-related kidney transplantation. Transplantation 96: e26–e29.
77. Povey H. Vundru R. Junglee N. Jibani M. (2013) Renal recovery with eculizumab in atypical hemolytic uremic syndrome following prolonged dialysis. Clin Nephrol 82: 326–331.
78. Rathbone J. Kaltenthaler E. Richards A. Tappenden P. Bessey A. Cantrell A. (2013) A systematic review of eculizumab for atypical haemolytic uraemic syndrome (aHUS). BMJ Open 3: e003573.
79. Reuter S. Heitplatz B. Pavenstädt H. Suwelack B. (2013) Successful long-term treatment of TMA with eculizumab in a transplanted patient with atypical hemolytic uremic syndrome due to MCP mutation. Transplantation 27: e74–e76.
80. Rock G. Shumak K. Buskard N. Blanchette V. Kelton J. Nair R. et al. (1991) Comparison of plasma exchange with plasma infusion in the treatment of thrombotic hrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 325: 393–397.
81. Rodrigues de Cordoba S. de Jorge E. (2008) Translational mini-review series on complement factor H: genetics and disease associations of human complement factor, H. Clin Exp Immunol 151: 1–13.
82. Román-Ortiz E. Mendizabal Oteiza S. Pinto S. López-Trascasa M. Sánchez-Corral P. Rodríguez de Cordoba S. (2014) Eculizumab long-term therapy for pediatric renal transplant in aHUS with CFH/CFHR1 hybrid gene. Pediatr Nephrol 29: 149–153.
83. Roumenina L. Jablonski M. Hue C. Blouin J. Dimitrov J. Dragon-Durey M. Cayla M. et al. (2009) Hyperfunctional C 3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome. Blood 114: 2837–2845.
84. Ruggenenti P. (2002) Post-transplant hemolytic-uremic syndrome. Kidney Int 62: 1093–1104.
85. Saland J. Ruggenenti P. Remuzzi G. and Consensus Study Group. (2009) Liver–kidney transplantation to cure atypical hemolytic uremic syndrome. J Am Soc Nephrol 20: 940–949.
86. Sana G. Dragon-Durey M. Charbit M. Bouchireb K. Rousset-Rouvière C. Bérard E. et al. (2014) Long-term remission of atypical HUS with anti-factor H antibodies after cyclophosphamide pulses. Pediatr Nephrol 29: 75–83.
87. Sánchez-Corral P. Melgosa M. (2010) Advances in understanding the aetiology of atypical Haemolytic Uraemic Syndrome. Br J Haematol 150: 529–542.
88. Scheiring J. Rosales A. Zimmerhackl L. (2010) Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Eur J Pediatr 169: 7–13.
89. Scully M. Goodship T. (2014). How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol 164: 759–766.
90. Sellier-Leclerc A. Frémeaux-Bacchi V. Macher M. Niaudet P. Guest G. Boudailliez B. et al. (2007) Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 18: 2392–2400.
91. Sinha A. Gulati A. Saini S. Blanc C. Gupta A. Gurjar B. et al. (2014) Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 85: 1151–1160.
92. Sinibaldi S. Guzzo I. Piras R. Bresin E. Emma F. Dello Strologo L. (2013) Post-transplant recurrence of atypical hemolytic uremic syndrome in a patient with thrombomodulin mutation. Pediatr Transplant 17: E177–E181.
93. Skerka C. Chen Q. Frémeaux-Bacchi V. Roumenina L. (2013) Complement factor H related proteins (CFHRs). Mol Immunol 56: 170–180.
94. Struijk G. Bouts A. Rijkers G. Kuin E. ten Berge I. Bemelman F. (2013) Meningococcal sepsis complicating eculizumab treatment despite prior vaccination. Am J Transplant 13: 819–820.
95. Sullivan M. Erlic Z. Hoffmann M. Arbeiter K. Patzer L. Budde K. et al. (2010) Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome. Ann Hum Genet 74: 17–26.
96. Tawadrous H. Maga T. Sharma J. Kupferman J. Smith R. Schoeneman M. (2010) A novel mutation in the complement factor B gene (CFB) and atypical hemolytic uremic syndrome. Pediatr Nephrol 25: 947–951.
97. Thajudeen B. Sussman A. Bracamonte E. (2013) A case of atypical hemolytic uremic syndrome successfully treated with eculizumab. Case Rep Nephrol Urol 3: 139–146.
98. Thompson R. Winterborn M. (1981) Hypocomplementaemia due to a genetic deficiency of beta 1H globulin. Clin Exp Immunol 46: 110–119.
99. Tran H. Chaudhuri A. Concepcion W. Grimm P. (2014) Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation. Pediatr Nephrol 29: 477–480.
100. Vaisbich M. Henriques Ldos S. Watanabe A. Pereira L. Metran C. Malheiros D. et al. (2013) [Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature]. J Bras Nefrol 35: 237–241.
101. Verhave J. Westra D. van Hamersvelt H. van Helden M. van de Kar N. Wetzels J. (2013) Living kidney transplantation in adult patients with atypical haemolytic uraemic syndrome. Neth J Med 71: 342–347.
102. Verhave J. Wetzels J. van de Kar N. (2014) Novel aspects of atypical haemolytic uraemic syndrome and the role of eculizumab. Nephrol Dial Transplant 29(Suppl. 4): iv131–iv141.
103. Wada H. Matsumoto T. Yamashita Y. (2014) Natural history of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Thromb Hemost 40: 866–873.
104. Warwicker P. Goodship T. Donne R. Pirson Y. Nicholls A. Ward R. et al. (1998) Genetic studies into inherited and sporadic haemolytic uremic syndrome. Kidney Int 53: 836–844.
105. Weitz M. Amon O. Bassler D. Koenigsrainer A. Nadalin S. (2011) Prophylactic eculizumab prior to kidney transplantation for atypical hemolytic uremic syndrome. Pediatr Nephrol 26: 1325–1329.
106. Westra D. Volokhina E. van der Heijden E. Vos A. Huigen M. Jansen J. et al. (2010) Genetic disorders in complement (regulating) genes in patients with atypical haemolytic uraemic syndrome (aHUS). Nephrol Dial Transplant 25: 2195–2202.
107. Wilson C. Brown A. White S. Goodship T. Sheerin N. Manas D. (2011) Successful treatment of de novo posttransplant thrombotic microangiopathy with eculizumab. Transplantation 92: e42–e43.
108. Zimmerhackl L. Hofer J. Cortina G. Mark W. Wurzner R. Jungraithmayr T. et al. (2010) Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome. N Engl J Med 362: 1746–1748.
109. Zuber J. Le Quintrec M. Sberro-Soussan R. Loirat C. Frémeaux-Bacchi V. Legendre C. (2011) New insights into postrenal transplant hemolytic uremic syndrome. Nat Rev Nephrol 7: 23–35.