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Seminars in Immunopathology

Erschienen in:

01.07.2014 | Review

Hemolytic uremic syndrome

verfasst von: Caterina Mele, Giuseppe Remuzzi, Marina Noris

Erschienen in: Seminars in Immunopathology | Ausgabe 4/2014

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Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute renal failure. The most frequent form is associated with infections by Shiga-like toxin-producing bacteria (STEC-HUS). Rarer cases are triggered by neuraminidase-producing Streptococcus pneumoniae (pneumococcal-HUS). The designation of aHUS is used to refer to those cases in which an infection by Shiga-like toxin-producing bacteria or S. pneumoniae can be excluded. Studies performed in the last two decades have documented that hyperactivation of the complement system is the pathogenetic effector mechanism leading to the endothelial damage and the microvascular thrombosis in aHUS. Recent data suggested the involvement of the complement system in the pathogenesis of STEC-HUS and pneumococcal-HUS as well. Clinical signs and symptoms may overlap among the different forms of HUS; however, pneumococcal-HUS and aHUS have a worse prognosis compared with STEC-HUS. Early diagnosis and identification of underlying pathogenetic mechanism allows instating specific support measures and therapies. In clinical trials in patients with aHUS, complement inhibition by eculizumab administration leads to a rapid and sustained normalization of hematological parameters with improvement in long-term renal function. This review summarizes current concepts about the epidemiological findings, the pathological and clinical aspects of STEC-HUS, pneumococcal-HUS, and aHUS, and their diagnosis and management.

Gianantonio CA, Vitacco M, Mendilaharzu F, Gallo GE, Sojo ET (1973) The hemolytic-uremic syndrome. Nephron 11:174–192PubMed

Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R (1955) Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia. Schweiz Med Wochenschr 85:905–909PubMed

Noris M, Remuzzi G (2009) Atypical hemolytic-uremic syndrome. N Engl J Med 361:1676–1687PubMed

Ruggenenti P, Noris M, Remuzzi G (2001) Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 60:831–846PubMed

Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB (2006) A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int 70:423–431PubMed

Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, Bernard H, Fruth A, Prager R, Spode A, Wadl M, Zoufaly A, Jordan S, Kemper MJ, Follin P, Muller L, King LA, Rosner B, Buchholz U, Stark K, Krause G (2011) Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 365:1771–1780PubMed

Tarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365:1073–1086PubMed

Copelovitch L, Kaplan BS (2010) Streptococcus pneumoniae-associated hemolytic uremic syndrome: classification and the emergence of serotype 19A. Pediatrics 125:e174–e182PubMed

Shimizu M, Yokoyama T, Sakashita N, Sato A, Ueno K, Akita C, Ohta K, Kitano E, Hatanaka M, Kitamura H, Saikawa Y, Yachie A (2012) Thomsen-Friedenreich antigen exposure as a cause of Streptococcus pyogenes-associated hemolytic-uremic syndrome. Clin Nephrol 78:328–331PubMed

10.

Kaplan BS, Chesney RW, Drummond KN (1975) Hemolytic uremic syndrome in families. N Engl J Med 292:1090–1093PubMed

11.

Sharma AP, Greenberg CR, Prasad AN, Prasad C (2007) Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder. Pediatr Nephrol 22:2097–2103PubMed

12.

Fakhouri F, Roumenina L, Provot F, Sallee M, Caillard S, Couzi L, Essig M, Ribes D, Dragon-Durey MA, Bridoux F, Rondeau E, Fremeaux-Bacchi V (2010) Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 21:859–867PubMedCentralPubMed

13.

Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859PubMedCentralPubMed

14.

Noris M, Mescia F, Remuzzi G (2012) STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 8:622–633PubMed

15.

Crump JA, Sulka AC, Langer AJ, Schaben C, Crielly AS, Gage R, Baysinger M, Moll M, Withers G, Toney DM, Hunter SB, Hoekstra RM, Wong SK, Griffin PM, Van Gilder TJ (2002) An outbreak of Escherichia coli O157:H7 infections among visitors to a dairy farm. N Engl J Med 347:555–560PubMed

16.

Haack JP, Jelacic S, Besser TE, Weinberger E, Kirk DJ, McKee GL, Harrison SM, Musgrave KJ, Miller G, Price TH, Tarr PI (2003) Escherichia coli O157 exposure in Wyoming and Seattle: serologic evidence of rural risk. Emerg Infect Dis 9:1226–1231PubMed

17.

Boyce TG, Swerdlow DL, Griffin PM (1995) Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N Engl J Med 333:364–368PubMed

18.

Palermo MS, Exeni RA, Fernandez GC (2009) Hemolytic uremic syndrome: pathogenesis and update of interventions. Expert Rev Anti Infect Ther 7:697–707PubMed

19.

Navarro A, Eslava C, Hernandez U, Navarro-Henze JL, Aviles M, Garcia-de la Torre G, Cravioto A (2003) Antibody responses to Escherichia coli O157 and other lipopolysaccharides in healthy children and adults. Clin Diagn Lab Immunol 10:797–801PubMedCentralPubMed

20.

Mead PS, Griffin PM (1998) Escherichia coli O157:H7. Lancet 352:1207–1212PubMed

21.

Rivas M, Miliwebsky E, Chinen I, Roldan CD, Balbi L, Garcia B, Fiorilli G, Sosa-Estani S, Kincaid J, Rangel J, Griffin PM (2006) Characterization and epidemiologic subtyping of Shiga toxin-producing Escherichia coli strains isolated from hemolytic uremic syndrome and diarrhea cases in Argentina. Foodborne Pathog Dis 3:88–96PubMed

22.

Manning SD, Motiwala AS, Springman AC, Qi W, Lacher DW, Ouellette LM, Mladonicky JM, Somsel P, Rudrik JT, Dietrich SE, Zhang W, Swaminathan B, Alland D, Whittam TS (2008) Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks. Proc Natl Acad Sci U S A 105:4868–4873PubMedCentralPubMed

23.

Isaacson M, Canter PH, Effler P, Arntzen L, Bomans P, Heenan R (1993) Haemorrhagic colitis epidemic in Africa. Lancet 341:961PubMed

24.

Buchholz U, Bernard H, Werber D, Bohmer MM, Remschmidt C, Wilking H, Delere Y, an der Heiden M, Adlhoch C, Dreesman J, Ehlers J, Ethelberg S, Faber M, Frank C, Fricke G, Greiner M, Hohle M, Ivarsson S, Jark U, Kirchner M, Koch J, Krause G, Luber P, Rosner B, Stark K, Kuhne M (2011) German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 365:1763–1770PubMed

25.

Keene WE, McAnulty JM, Hoesly FC, Williams LP Jr, Hedberg K, Oxman GL, Barrett TJ, Pfaller MA, Fleming DW (1994) A swimming-associated outbreak of hemorrhagic colitis caused by Escherichia coli O157:H7 and Shigella sonnei. N Engl J Med 331:579–584PubMed

26.

Brandt J, Wong C, Mihm S, Roberts J, Smith J, Brewer E, Thiagarajan R, Warady B (2002) Invasive pneumococcal disease and hemolytic uremic syndrome. Pediatrics 110:371–376PubMed

27.

Szilagyi A, Kiss N, Bereczki C, Talosi G, Racz K, Turi S, Gyorke Z, Simon E, Horvath E, Kelen K, Reusz GS, Szabo AJ, Tulassay T, Prohaszka Z (2013) The role of complement in Streptococcus pneumoniae-associated haemolytic uraemic syndrome. Nephrol Dial Transplant 28:2237–2245PubMed

28.

Mizusawa Y, Pitcher LA, Burke JR, Falk MC, Mizushima W (1996) Survey of haemolytic-uraemic syndrome in Queensland 1979–1995. Med J Aust 165:188–191PubMed

29.

Constantinescu AR, Bitzan M, Weiss LS, Christen E, Kaplan BS, Cnaan A, Trachtman H (2004) Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis 43:976–982PubMed

30.

Ohanian M, Cable C, Halka K (2011) Eculizumab safely reverses neurologic impairment and eliminates need for dialysis in severe atypical hemolytic uremic syndrome. Clin Pharmacol 3:5–12PubMedCentralPubMed

31.

Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, Boudailliez B, Bouissou F, Deschenes G, Gie S, Tsimaratos M, Fischbach M, Morin D, Nivet H, Alberti C, Loirat C (2007) Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 18:2392–2400PubMed

32.

Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F, Bettinaglio P, Mele C, Bresin E, Cassis L, Gamba S, Porrati F, Bucchioni S, Monteferrante G, Fang CJ, Liszewski MK, Kavanagh D, Atkinson JP, Remuzzi G (2006) Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 108:1267–1279PubMedCentralPubMed

33.

Milford DV, Taylor CM, Guttridge B, Hall SM, Rowe B, Kleanthous H (1990) Haemolytic uraemic syndromes in the British Isles 1985–8: association with verocytotoxin producing Escherichia coli. Part 1: Clinical and epidemiological aspects. Arch Dis Child 65:716–721PubMedCentralPubMed

34.

Sullivan M, Erlic Z, Hoffmann MM, Arbeiter K, Patzer L, Budde K, Hoppe B, Zeier M, Lhotta K, Rybicki LA, Bock A, Berisha G, Neumann HP (2010) Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome. Ann Hum Genet 74:17–26PubMed

35.

Loirat C, Fremeaux-Bacchi V (2011) Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 6:60PubMedCentralPubMed

36.

Gilbert RD, Fowler DJ, Angus E, Hardy SA, Stanley L, Goodship TH (2013) Eculizumab therapy for atypical haemolytic uraemic syndrome due to a gain-of-function mutation of complement factor B. Pediatr Nephrol 28:1315–1318PubMed

37.

Kaplan BS, Proesmans W (1987) The hemolytic uremic syndrome of childhood and its variants. Semin Hematol 24:148–160PubMed

38.

Habib R (1992) Pathology of the hemolytic uremic syndrome. In: TR Kaplan B, Moake J (eds) Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Marcel Dekker, New York, p 315

39.

Inward CD, Howie AJ, Fitzpatrick MM, Rafaat F, Milford DV, Taylor CM (1997) Renal histopathology in fatal cases of diarrhoea-associated haemolytic uraemic syndrome. British Association for Paediatric Nephrology. Pediatr Nephrol 11:556–559PubMed

40.

Alberti M, Valoti E, Piras R, Bresin E, Galbusera M, Tripodo C, Thaiss F, Remuzzi G, Noris M (2013) Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations. Am J Transplant 13:2201–2206PubMed

41.

Landau D, Shalev H, Levy-Finer G, Polonsky A, Segev Y, Katchko L (2001) Familial hemolytic uremic syndrome associated with complement factor H deficiency. J Pediatr 138:412–417PubMed

42.

Moghal NE, Ferreira MA, Howie AJ, Milford DV, Raafat E, Taylor CM (1998) The late histologic findings in diarrhea-associated hemolytic uremic syndrome. J Pediatr 133:220–223PubMed

43.

Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, Clark WF (2003) Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA 290:1360–1370PubMed

44.

Grodinsky S, Telmesani A, Robson WL, Fick G, Scott RB (1990) Gastrointestinal manifestations of hemolytic uremic syndrome: recognition of pancreatitis. J Pediatr Gastroenterol Nutr 11:518–524PubMed

45.

Abu-Arafeh I, Gray E, Youngson G, Auchterlonie I, Russell G (1995) Myocarditis and haemolytic uraemic syndrome. Arch Dis Child 72:46–47PubMedCentralPubMed

46.

Ruggenenti P, Remuzzi G (2011) A German outbreak of haemolytic uraemic syndrome. Lancet 378:1057–1058PubMed

47.

Blaser MJ (2011) Deconstructing a lethal foodborne epidemic. N Engl J Med 365:1835–1836PubMed

48.

Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A, Prior K, Szczepanowski R, Ji Y, Zhang W, McLaughlin SF, Henkhaus JK, Leopold B, Bielaszewska M, Prager R, Brzoska PM, Moore RL, Guenther S, Rothberg JM, Karch H (2011) Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One 6:e22751PubMedCentralPubMed

49.

Qin J, Cui Y, Zhao X, Rohde H, Liang T, Wolters M, Li D, Belmar Campos C, Christner M, Song Y, Yang R (2011) Identification of the Shiga toxin-producing Escherichia coli O104:H4 strain responsible for a food poisoning outbreak in Germany by PCR. J Clin Microbiol 49:3439–3440PubMedCentralPubMed

50.

Tarr PI, Neill MA, Clausen CR, Watkins SL, Christie DL, Hickman RO (1990) Escherichia coli O157:H7 and the hemolytic uremic syndrome: importance of early cultures in establishing the etiology. J Infect Dis 162:553–556PubMed

51.

Gerritzen A, Wittke JW, von Ahsen N, Wolff D (2012) Direct faecal PCR for diagnosis of Shiga-toxin-producing Escherichia coli. Lancet Infect Dis 12:102PubMed

52.

Donnenberg MS, Tacket CO, James SP, Losonsky G, Nataro JP, Wasserman SS, Kaper JB, Levine MM (1993) Role of the eaeA gene in experimental enteropathogenic Escherichia coli infection. J Clin Invest 92:1412–1417PubMedCentralPubMed

53.

Brigotti M, Carnicelli D, Arfilli V, Tamassia N, Borsetti F, Fabbri E, Tazzari PL, Ricci F, Pagliaro P, Spisni E, Cassatella MA (2013) Identification of TLR4 as the receptor that recognizes Shiga toxins in human neutrophils. J Immunol 191:4748–4758PubMed

54.

Cooling LL, Walker KE, Gille T, Koerner TA (1998) Shiga toxin binds human platelets via globotriaosylceramide (Pk antigen) and a novel platelet glycosphingolipid. Infect Immun 66:4355–4366PubMedCentralPubMed

55.

van Setten PA, Monnens LA, Verstraten RG, van den Heuvel LP, van Hinsbergh VW (1996) Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood 88:174–183PubMed

56.

Hurley BP, Thorpe CM, Acheson DW (2001) Shiga toxin translocation across intestinal epithelial cells is enhanced by neutrophil transmigration. Infect Immun 69:6148–6155PubMedCentralPubMed

57.

O'Brien AD, Lively TA, Chang TW, Gorbach SL (1983) Purification of Shigella dysenteriae 1 (Shiga)-like toxin from Escherichia coli O157:H7 strain associated with haemorrhagic colitis. Lancet 2:573PubMed

58.

Cimolai N, Carter JE, Morrison BJ, Anderson JD (1990) Risk factors for the progression of Escherichia coli O157:H7 enteritis to hemolytic-uremic syndrome. J Pediatr 116:589–592PubMed

59.

Scotland SM, Willshaw GA, Smith HR, Rowe B (1987) Properties of strains of Escherichia coli belonging to serogroup O157 with special reference to production of Vero cytotoxins VT1 and VT2. Epidemiol Infect 99:613–624PubMedCentralPubMed

60.

Jenkins C, Willshaw GA, Evans J, Cheasty T, Chart H, Shaw DJ, Dougan G, Frankel G, Smith HR (2003) Subtyping of virulence genes in verocytotoxin-producing Escherichia coli (VTEC) other than serogroup O157 associated with disease in the United Kingdom. J Med Microbiol 52:941–947PubMed

61.

O'Loughlin EV, Robins-Browne RM (2001) Effect of Shiga toxin and Shiga-like toxins on eukaryotic cells. Microbes Infect 3:493–507PubMed

62.

Chaisri U, Nagata M, Kurazono H, Horie H, Tongtawe P, Hayashi H, Watanabe T, Tapchaisri P, Chongsa-nguan M, Chaicumpa W (2001) Localization of Shiga toxins of enterohaemorrhagic Escherichia coli in kidneys of paediatric and geriatric patients with fatal haemolytic uraemic syndrome. Microb Pathog 31:59–67PubMed

63.

Auray-Blais C, Cyr D, Ntwari A, West ML, Cox-Brinkman J, Bichet DG, Germain DP, Laframboise R, Melancon SB, Stockley T, Clarke JT, Drouin R (2008) Urinary globotriaosylceramide excretion correlates with the genotype in children and adults with Fabry disease. Mol Genet Metab 93:331–340PubMed

64.

Zoja C, Angioletti S, Donadelli R, Zanchi C, Tomasoni S, Binda E, Imberti B, te Loo M, Monnens L, Remuzzi G, Morigi M (2002) Shiga toxin-2 triggers endothelial leukocyte adhesion and transmigration via NF-kappaB dependent up-regulation of IL-8 and MCP-1. Kidney Int 62:846–856PubMed

65.

Petruzziello-Pellegrini TN, Yuen DA, Page AV, Patel S, Soltyk AM, Matouk CC, Wong DK, Turgeon PJ, Fish JE, Ho JJ, Steer BM, Khajoee V, Tigdi J, Lee WL, Motto DG, Advani A, Gilbert RE, Karumanchi SA, Robinson LA, Tarr PI, Liles WC, Brunton JL, Marsden PA (2012) The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice. J Clin Invest 122:759–776PubMedCentralPubMed

66.

Morigi M, Micheletti G, Figliuzzi M, Imberti B, Karmali MA, Remuzzi A, Remuzzi G, Zoja C (1995) Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood 86:4553–4558PubMed

67.

Morigi M, Galbusera M, Binda E, Imberti B, Gastoldi S, Remuzzi A, Zoja C, Remuzzi G (2001) Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 98:1828–1835PubMed

68.

Karpman D, Papadopoulou D, Nilsson K, Sjogren AC, Mikaelsson C, Lethagen S (2001) Platelet activation by Shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome. Blood 97:3100–3108PubMed

69.

Morigi M, Galbusera M, Gastoldi S, Locatelli M, Buelli S, Pezzotta A, Pagani C, Noris M, Gobbi M, Stravalaci M, Rottoli D, Tedesco F, Remuzzi G, Zoja C (2011) Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol 187:172–180PubMed

70.

Lo NC, Turner NA, Cruz MA, Moake J (2013) Interaction of Shiga toxin with the A-domains and multimers of von Willebrand factor. J Biol Chem 288:33118–33123PubMedCentralPubMed

71.

Hughes AK, Stricklett PK, Kohan DE (1998) Cytotoxic effect of Shiga toxin-1 on human proximal tubule cells. Kidney Int 54:426–437PubMed

72.

Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11:785–797PubMedCentralPubMed

73.

Cameron JS, Vick R (1973) Letter: Plasma-C3 in haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura. Lancet 2:975PubMed

74.

Robson WL, Leung AK, Fick GH, McKenna AI (1992) Hypocomplementemia and leukocytosis in diarrhea-associated hemolytic uremic syndrome. Nephron 62:296–299PubMed

75.

Lapeyraque AL, Malina M, Fremeaux-Bacchi V, Boppel T, Kirschfink M, Oualha M, Proulx F, Clermont MJ, Le Deist F, Niaudet P, Schaefer F (2011) Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 364:2561–2563PubMed

76.

Monnens L, Molenaar J, Lambert PH, Proesmans W, van Munster P (1980) The complement system in hemolytic-uremic syndrome in childhood. Clin Nephrol 13:168–171PubMed

77.

Thurman JM, Marians R, Emlen W, Wood S, Smith C, Akana H, Holers VM, Lesser M, Kline M, Hoffman C, Christen E, Trachtman H (2009) Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 4:1920–1924PubMedCentralPubMed

78.

Stahl AL, Sartz L, Karpman D (2011) Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood 117:5503–5513PubMed

79.

Del Conde I, Cruz MA, Zhang H, Lopez JA, Afshar-Kharghan V (2005) Platelet activation leads to activation and propagation of the complement system. J Exp Med 201:871–879PubMedCentralPubMed

80.

Orth D, Khan AB, Naim A, Grif K, Brockmeyer J, Karch H, Joannidis M, Clark SJ, Day AJ, Fidanzi S, Stoiber H, Dierich MP, Zimmerhackl LB, Wurzner R (2009) Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome. J Immunol 182:6394–6400PubMed

81.

Fischer K, Poschmann A, Oster H (1971) Severe pneumonia with hemolysis caused by neuraminidase. Detection of cryptantigens by indirect immunofluorescent technic. Monatsschr Kinderheilkd 119:2–8PubMed

82.

Cochran JB, Panzarino VM, Maes LY, Tecklenburg FW (2004) Pneumococcus-induced T-antigen activation in hemolytic uremic syndrome and anemia. Pediatr Nephrol 19:317–321PubMed

83.

McGraw ME, Lendon M, Stevens RF, Postlethwaite RJ, Taylor CM (1989) Haemolytic uraemic syndrome and the Thomsen Friedenreich antigen. Pediatr Nephrol 3:135–139PubMed

84.

Eder AF, Manno CS (2001) Does red-cell T activation matter? Br J Haematol 114:25–30PubMed

85.

Sallee M, Daniel L, Piercecchi MD, Jaubert D, Fremeaux-Bacchi V, Berland Y, Burtey S (2010) Myocardial infarction is a complication of factor H-associated atypical HUS. Nephrol Dial Transplant 25:2028–2032PubMed

86.

Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B, Andre JL, Takagi N, Cheong HI, Hari P, Le Quintrec M, Niaudet P, Loirat C, Fridman WH, Fremeaux-Bacchi V (2010) Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol 21:2180–2187PubMedCentralPubMed

87.

Loirat C, Noris M, Fremeaux-Bacchi V (2008) Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 23:1957–1972PubMed

88.

Loirat C, Macher MA, Elmaleh-Berges M, Kwon T, Deschenes G, Goodship TH, Majoie C, Davin JC, Blanc R, Savatovsky J, Moret J, Fremeaux-Bacchi V (2010) Non-atheromatous arterial stenoses in atypical haemolytic uraemic syndrome associated with complement dysregulation. Nephrol Dial Transplant 25:3421–3425PubMed

89.

Bekassy ZD, Kristoffersson AC, Cronqvist M, Roumenina LT, Rybkine T, Vergoz L, Hue C, Fremeaux-Bacchi V, Karpman D (2013) Eculizumab in an anephric patient with atypical haemolytic uraemic syndrome and advanced vascular lesions. Nephrol Dial Transplant 28:2899–2907PubMed

90.

Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181PubMed

91.

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:e003573PubMedCentralPubMed

92.

Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschenes G, Lebranchu Y, Zuber J, Loirat C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562PubMedCentralPubMed

93.

Schmidt CQ, Herbert AP, Kavanagh D, Gandy C, Fenton CJ, Blaum BS, Lyon M, Uhrin D, Barlow PN (2008) A new map of glycosaminoglycan and C3b binding sites on factor H. J Immunol 181:2610–2619PubMed

94.

Ferreira VP, Pangburn MK, Cortes C (2010) Complement control protein factor H: the good, the bad, and the inadequate. Mol Immunol 47:2187–2197PubMedCentralPubMed

95.

Clark SJ, Ridge LA, Herbert AP, Hakobyan S, Mulloy B, Lennon R, Wurzner R, Morgan BP, Uhrin D, Bishop PN, Day AJ (2013) Tissue-specific host recognition by complement factor H is mediated by differential activities of its glycosaminoglycan-binding regions. J Immunol 190:2049–2057PubMedCentralPubMed

96.

Thompson RA, Winterborn MH (1981) Hypocomplementaemia due to a genetic deficiency of beta 1H globulin. Clin Exp Immunol 46:110–119PubMedCentralPubMed

97.

Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM, Turnpenny P, Goodship JA (1998) Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int 53:836–844PubMed

98.

Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ (2010) Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat 31:E1445–E1460PubMed

99.

Venables JP, Strain L, Routledge D, Bourn D, Powell HM, Warwicker P, Diaz-Torres ML, Sampson A, Mead P, Webb M, Pirson Y, Jackson MS, Hughes A, Wood KM, Goodship JA, Goodship TH (2006) Atypical haemolytic uraemic syndrome associated with a hybrid complement gene. PLoS Med 3:e431PubMedCentralPubMed

100.

Francis NJ, McNicholas B, Awan A, Waldron M, Reddan D, Sadlier D, Kavanagh D, Strain L, Marchbank KJ, Harris CL, Goodship TH (2012) A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome. Blood 119:591–601PubMed

101.

Eyler SJ, Meyer NC, Zhang Y, Xiao X, Nester CM, Smith RJ (2013) A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome. Pediatr Nephrol 28:2221–2225PubMed

102.

Dragon-Durey MA, Loirat C, Cloarec S, Macher MA, Blouin J, Nivet H, Weiss L, Fridman WH, Fremeaux-Bacchi V (2005) Anti-factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol 16:555–563PubMed

103.

Moore I, Strain L, Pappworth I, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Staniforth SJ, Holmes LV, Ward R, Morgan L, Goodship TH, Marchbank KJ (2010) Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood 115:379–387PubMedCentralPubMed

104.

Hofer J, Janecke AR, Zimmerhackl LB, Riedl M, Rosales A, Giner T, Cortina G, Haindl CJ, Petzelberger B, Pawlik M, Jeller V, Vester U, Gadner B, van Husen M, Moritz ML, Wurzner R, Jungraithmayr T (2013) Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 8:407–415PubMedCentralPubMed

105.

Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, Saini H, Kotresh ST, Ali U, Bhatia D, Ohri A, Kumar M, Agarwal I, Gulati S, Anand K, Vijayakumar M, Sinha R, Sethi S, Salmona M, George A, Bal V, Singh G, Dinda AK, Hari P, Rath S, Dragon-Durey MA, Bagga A (2013) Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int. doi:10.1038/ki.2013.373 PubMed

106.

Jozsi M, Licht C, Strobel S, Zipfel SL, Richter H, Heinen S, Zipfel PF, Skerka C (2008) Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood 111:1512–1514PubMed

107.

Zipfel PF, Edey M, Heinen S, Jozsi M, Richter H, Misselwitz J, Hoppe B, Routledge D, Strain L, Hughes AE, Goodship JA, Licht C, Goodship TH, Skerka C (2007) Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS Genet 3:e41PubMedCentralPubMed

108.

Abarrategui-Garrido C, Martinez-Barricarte R, Lopez-Trascasa M, de Cordoba SR, Sanchez-Corral P (2009) Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome. Blood 114:4261–4271PubMed

109.

Jozsi M, Strobel S, Dahse HM, Liu WS, Hoyer PF, Oppermann M, Skerka C, Zipfel PF (2007) Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome. Blood 110:1516–1518PubMed

110.

Blanc C, Roumenina LT, Ashraf Y, Hyvarinen S, Sethi SK, Ranchin B, Niaudet P, Loirat C, Gulati A, Bagga A, Fridman WH, Sautes-Fridman C, Jokiranta TS, Fremeaux-Bacchi V, Dragon-Durey MA (2012) Overall neutralization of complement factor H by autoantibodies in the acute phase of the autoimmune form of atypical hemolytic uremic syndrome. J Immunol 189:3528–3537PubMed

111.

Richards A, Kathryn Liszewski M, Kavanagh D, Fang CJ, Moulton E, Fremeaux-Bacchi V, Remuzzi G, Noris M, Goodship TH, Atkinson JP (2007) Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome. Mol Immunol 44:111–122PubMed

112.

Noris M, Brioschi S, Caprioli J, Todeschini M, Bresin E, Porrati F, Gamba S, Remuzzi G (2003) Familial haemolytic uraemic syndrome and an MCP mutation. Lancet 362:1542–1547PubMed

113.

Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Muslumanoglu MH, Kavukcu S, Filler G, Pirson Y, Wen LS, Atkinson JP, Goodship TH (2003) Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci U S A 100:12966–12971PubMedCentralPubMed

114.

Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, Vigneau C, Kuypers D, Boudailliez B, Loirat C, Rondeau E, Fridman WH (2004) Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet 41:e84PubMedCentralPubMed

115.

Bienaime F, Dragon-Durey MA, Regnier CH, Nilsson SC, Kwan WH, Blouin J, Jablonski M, Renault N, Rameix-Welti MA, Loirat C, Sautes-Fridman C, Villoutreix BO, Blom AM, Fremeaux-Bacchi V (2010) Mutations in components of complement influence the outcome of factor I-associated atypical hemolytic uremic syndrome. Kidney Int 77:339–349PubMed

116.

Kavanagh D, Richards A, Noris M, Hauhart R, Liszewski MK, Karpman D, Goodship JA, Fremeaux-Bacchi V, Remuzzi G, Goodship TH, Atkinson JP (2008) Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. Mol Immunol 45:95–105PubMed

117.

Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, Garrido CA, Lopez-Trascasa M, Sanchez-Corral P, Morgan BP, Rodriguez de Cordoba S (2007) Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A 104:240–245PubMed

118.

Fremeaux-Bacchi V, Miller EC, Liszewski MK, Strain L, Blouin J, Brown AL, Moghal N, Kaplan BS, Weiss RA, Lhotta K, Kapur G, Mattoo T, Nivet H, Wong W, Gie S, Hurault de Ligny B, Fischbach M, Gupta R, Hauhart R, Meunier V, Loirat C, Dragon-Durey MA, Fridman WH, Janssen BJ, Goodship TH, Atkinson JP (2008) Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 112:4948–4952PubMedCentralPubMed

119.

Lhotta K, Janecke AR, Scheiring J, Petzlberger B, Giner T, Fally V, Wurzner R, Zimmerhackl LB, Mayer G, Fremeaux-Bacchi V (2009) A large family with a gain-of-function mutation of complement C3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure. Clin J Am Soc Nephrol 4:1356–1362PubMedCentralPubMed

120.

Roumenina LT, Jablonski M, Hue C, Blouin J, Dimitrov JD, Dragon-Durey MA, Cayla M, Fridman WH, Macher MA, Ribes D, Moulonguet L, Rostaing L, Satchell SC, Mathieson PW, Sautes-Fridman C, Loirat C, Regnier CH, Halbwachs-Mecarelli L, Fremeaux-Bacchi V (2009) Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome. Blood 114:2837–2845PubMed

121.

Roumenina LT, Frimat M, Miller EC, Provot F, Dragon-Durey MA, Bordereau P, Bigot S, Hue C, Satchell SC, Mathieson PW, Mousson C, Noel C, Sautes-Fridman C, Halbwachs-Mecarelli L, Atkinson JP, Lionet A, Fremeaux-Bacchi V (2012) A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function. Blood 119:4182–4191PubMedCentralPubMed

122.

Tawadrous H, Maga T, Sharma J, Kupferman J, Smith RJ, Schoeneman M (2010) A novel mutation in the complement factor B gene (CFB) and atypical hemolytic uremic syndrome. Pediatr Nephrol 25:947–951PubMed

123.

Weiler H, Isermann BH (2003) Thrombomodulin. J Thromb Haemost 1:1515–1524PubMed

124.

Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, Del-Favero J, Plaisance S, Claes B, Lambrechts D, Zoja C, Remuzzi G, Conway EM (2009) Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 361:345–357PubMedCentralPubMed

125.

Fan X, Yoshida Y, Honda S, Matsumoto M, Sawada Y, Hattori M, Hisanaga S, Hiwa R, Nakamura F, Tomomori M, Miyagawa S, Fujimaru R, Yamada H, Sawai T, Ikeda Y, Iwata N, Uemura O, Matsukuma E, Aizawa Y, Harada H, Wada H, Ishikawa E, Ashida A, Nangaku M, Miyata T, Fujimura Y (2013) Analysis of genetic and predisposing factors in Japanese patients with atypical hemolytic uremic syndrome. Mol Immunol 54:238–246PubMed

126.

Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, Pinto S, Goodship TH, Alberti M, Ribes D, Valoti E, Remuzzi G, Noris M (2013) Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol 24:475–486PubMedCentralPubMed

127.

Lemaire M, Fremeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji W, Overton JD, Mane SM, Nurnberg G, Altmuller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, Simkova E, Nurnberg P, Rioux-Leclerc N, Moeckel GW, Gubler MC, Hwa J, Loirat C, Lifton RP (2013) Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 45:531–536PubMedCentralPubMed

128.

Esparza-Gordillo J, Goicoechea de Jorge E, Buil A, Carreras Berges L, Lopez-Trascasa M, Sanchez-Corral P, Rodriguez de Cordoba S (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 14:703–712PubMed

129.

Esparza-Gordillo J, Jorge EG, Garrido CA, Carreras L, Lopez-Trascasa M, Sanchez-Corral P, de Cordoba SR (2006) Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree. Mol Immunol 43:1769–1775PubMed

130.

Fremeaux-Bacchi V, Kemp EJ, Goodship JA, Dragon-Durey MA, Strain L, Loirat C, Deng HW, Goodship TH (2005) The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts. J Med Genet 42:852–856PubMedCentralPubMed

131.

Caprioli J, Castelletti F, Bucchioni S, Bettinaglio P, Bresin E, Pianetti G, Gamba S, Brioschi S, Daina E, Remuzzi G, Noris M (2003) Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet 12:3385–3395PubMed

132.

Kwon T, Belot A, Ranchin B, Baudouin V, Fremeaux-Bacchi V, Dragon-Durey MA, Cochat P, Loirat C (2009) Varicella as a trigger of atypical haemolytic uraemic syndrome associated with complement dysfunction: two cases. Nephrol Dial Transplant 24:2752–2754PubMed

133.

Allen U, Licht C (2011) Pandemic H1N1 influenza A infection and (atypical) HUS—more than just another trigger? Pediatr Nephrol 26:3–5PubMed

134.

Fang CJ, Fremeaux-Bacchi V, Liszewski MK, Pianetti G, Noris M, Goodship TH, Atkinson JP (2008) Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood 111:624–632PubMedCentralPubMed

135.

Bitzan M, Schaefer F, Reymond D (2010) Treatment of typical (enteropathic) hemolytic uremic syndrome. Semin Thromb Hemost 36:594–610PubMed

136.

Copelovitch L, Kaplan BS (2008) Streptococcus pneumoniae-associated hemolytic uremic syndrome. Pediatr Nephrol 23:1951–1956PubMed

137.

Remuzzi G (1987) HUS and TTP: variable expression of a single entity. Kidney Int 32:292–308PubMed

138.

Sadler JE (2008) Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 112:11–18PubMedCentralPubMed

139.

Kavanagh D, Richards A, Fremeaux-Bacchi V, Noris M, Goodship T, Remuzzi G, Atkinson JP (2007) Screening for complement system abnormalities in patients with atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 2:591–596PubMed

140.

Ake JA, Jelacic S, Ciol MA, Watkins SL, Murray KF, Christie DL, Klein EJ, Tarr PI (2005) Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion. Pediatrics 115:e673–e680PubMed

141.

Hickey CA, Beattie TJ, Cowieson J, Miyashita Y, Strife CF, Frem JC, Peterson JM, Butani L, Jones DP, Havens PL, Patel HP, Wong CS, Andreoli SP, Rothbaum RJ, Beck AM, Tarr PI (2011) Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome. Arch Pediatr Adolesc Med 165:884–889PubMedCentralPubMed

142.

Tarr PI, Neill MA (2001) Escherichia coli O157:H7. Gastroenterol Clin North Am 30:735–751PubMed

143.

Cavari Y, Pitfield AF, Kissoon N (2013) Intravenous maintenance fluids revisited. Pediatr Emerg Care 29:1225–1228PubMed

144.

Chowdhury AH, Cox EF, Francis ST, Lobo DN (2012) A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 256:18–24PubMed

145.

Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M (2012) Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 308:1566–1572PubMed

146.

Bitzan M (2009) Treatment options for HUS secondary to Escherichia coli O157:H7. Kidney Int Suppl: S62-6

147.

Van Dyck M, Proesmans W (2004) Renoprotection by ACE inhibitors after severe hemolytic uremic syndrome. Pediatr Nephrol 19:688–690PubMed

148.

Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI (2000) The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342:1930–1936PubMedCentralPubMed

149.

Safdar N, Said A, Gangnon RE, Maki DG (2002) Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA 288:996–1001PubMed

150.

Nitschke M, Sayk F, Hartel C, Roseland RT, Hauswaldt S, Steinhoff J, Fellermann K, Derad I, Wellhoner P, Buning J, Tiemer B, Katalinic A, Rupp J, Lehnert H, Solbach W, Knobloch JK (2012) Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4. JAMA 307:1046–1052PubMed

151.

Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WT (1999) Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 354:1327–1330PubMed

152.

Carter AO, Borczyk AA, Carlson JA, Harvey B, Hockin JC, Karmali MA, Krishnan C, Korn DA, Lior H (1987) A severe outbreak of Escherichia coli O157:H7–associated hemorrhagic colitis in a nursing home. N Engl J Med 317:1496–1500PubMed

153.

Kielstein JT, Beutel G, Fleig S, Steinhoff J, Meyer TN, Hafer C, Kuhlmann U, Bramstedt J, Panzer U, Vischedyk M, Busch V, Ries W, Mitzner S, Mees S, Stracke S, Nurnberger J, Gerke P, Wiesner M, Sucke B, Abu-Tair M, Kribben A, Klause N, Schindler R, Merkel F, Schnatter S, Dorresteijn EM, Samuelsson O, Brunkhorst R (2012) Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant 27:3807–3815PubMed

154.

Ruggenenti P, Remuzzi G (2012) Thrombotic microangiopathy: E. coli O104:H4 German outbreak: a missed opportunity. Nat Rev Nephrol 8:558–560PubMed

155.

Delmas Y, Vendrely B, Clouzeau B, Bachir H, Bui HN, Lacraz A, Helou S, Bordes C, Reffet A, Llanas B, Skopinski S, Rolland P, Gruson D, Combe C. 2013. Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab. Nephrol Dial Transplant 0: 1–9 doi: 10.1093/ndt/gft470

156.

Ferraris JR, Ramirez JA, Ruiz S, Caletti MG, Vallejo G, Piantanida JJ, Araujo JL, Sojo ET (2002) Shiga toxin-associated hemolytic uremic syndrome: absence of recurrence after renal transplantation. Pediatr Nephrol 17:809–814PubMed

157.

Artz MA, Steenbergen EJ, Hoitsma AJ, Monnens LA, Wetzels JF (2003) Renal transplantation in patients with hemolytic uremic syndrome: high rate of recurrence and increased incidence of acute rejections. Transplantation 76:821–826PubMed

158.

Loirat C, Niaudet P (2003) The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children. Pediatr Nephrol 18:1095–1101PubMed

159.

Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB (2009) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24:687–696PubMed

160.

Taylor CM, Machin S, Wigmore SJ, Goodship TH (2010) Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol 148:37–47PubMed

161.

Nathanson S, Fremeaux-Bacchi V, Deschenes G (2001) Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency. Pediatr Nephrol 16:554–556PubMed

162.

de Jorge EG, Macor P, Paixao-Cavalcante D, Rose KL, Tedesco F, Cook HT, Botto M, Pickering MC (2011) The development of atypical hemolytic uremic syndrome depends on complement C5. J Am Soc Nephrol 22:137–145PubMedCentralPubMed

163.

Salant DJ (2011) Targeting complement C5 in atypical hemolytic uremic syndrome. J Am Soc Nephrol 22:7–9PubMed

164.

Wong EK, Goodship TH, Kavanagh D (2013) Complement therapy in atypical haemolytic uraemic syndrome (aHUS). Mol Immunol 56:199–212PubMedCentralPubMed

165.

Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyo JM, Praga M, Torra R, Vilalta R, Rodriguez de Cordoba S (2013) An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 33:27–45PubMed

166.

Noris M, Remuzzi G (2013) Managing and preventing atypical hemolytic uremic syndrome recurrence after kidney transplantation. Curr Opin Nephrol Hypertens 22:704–712PubMed

167.

Hirt-Minkowski P, Schaub S, Mayr M, Schifferli JA, Dickenmann M, Fremeaux-Bacchi V, Steiger J (2009) Haemolytic uraemic syndrome caused by factor H mutation: is single kidney transplantation under intensive plasmatherapy an option? Nephrol Dial Transplant 24:3548–3551PubMed

168.

Remuzzi G, Ruggenenti P, Codazzi D, Noris M, Caprioli J, Locatelli G, Gridelli B (2002) Combined kidney and liver transplantation for familial haemolytic uraemic syndrome. Lancet 359:1671–1672PubMed

169.

Remuzzi G, Ruggenenti P, Colledan M, Gridelli B, Bertani A, Bettinaglio P, Bucchioni S, Sonzogni A, Bonanomi E, Sonzogni V, Platt JL, Perico N, Noris M (2005) Hemolytic uremic syndrome: a fatal outcome after kidney and liver transplantation performed to correct factor h gene mutation. Am J Transplant 5:1146–1150PubMed

170.

Koskinen AR, Tukiainen E, Arola J, Nordin A, Hockerstedt HK, Nilsson B, Isoniemi H, Jokiranta TS (2011) Complement activation during liver transplantation—special emphasis on patients with atypical hemolytic uremic syndrome. Am J Transplant 11:1885–1895PubMed

171.

Saland JM, Ruggenenti P, Remuzzi G (2009) Liver-kidney transplantation to cure atypical hemolytic uremic syndrome. J Am Soc Nephrol 20:940–949PubMed

172.

Haller W, Milford DV, Goodship TH, Sharif K, Mirza DF, McKiernan PJ (2010) Successful isolated liver transplantation in a child with atypical hemolytic uremic syndrome and a mutation in complement factor H. Am J Transplant 10:2142–2147PubMed

173.

Jalanko H, Peltonen S, Koskinen A, Puntila J, Isoniemi H, Holmberg C, Pinomaki A, Armstrong E, Koivusalo A, Tukiainen E, Makisalo H, Saland J, Remuzzi G, de Cordoba S, Lassila R, Meri S, Jokiranta TS (2008) Successful liver-kidney transplantation in two children with aHUS caused by a mutation in complement factor H. Am J Transplant 8:216–221PubMed

174.

Forbes TA, Bradbury MG, Goodship TH, McKiernan PJ, Milford DV (2013) Changing strategies for organ transplantation in atypical haemolytic uraemic syndrome: a tertiary case series. Pediatr Transplant 17:E93–E99PubMed

175.

Saland JM, Shneider BL, Bromberg JS, Shi PA, Ward SC, Magid MS, Benchimol C, Seikaly MG, Emre SH, Bresin E, Remuzzi G (2009) Successful split liver-kidney transplant for factor H associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 4:201–206PubMedCentralPubMed

176.

Tran H, Chaudhuri A, Concepcion W, Grimm PC (2013) 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. doi:10.1007/s00467-013-2630-5

177.

Zimmerhackl LB, Hofer J, Cortina G, Mark W, Wurzner R, Jungraithmayr TC, Khursigara G, Kliche KO, Radauer W (2010) Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome. N Engl J Med 362:1746–1748PubMed

178.

Zuber J, Le Quintrec M, Krid S, Bertoye C, Gueutin V, Lahoche A, Heyne N, Ardissino G, Chatelet V, Noel LH, Hourmant M, Niaudet P, Fremeaux-Bacchi V, Rondeau E, Legendre C, Loirat C (2012) Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant 12:3337–3354PubMed

179.

Nester C, Stewart Z, Myers D, Jetton J, Nair R, Reed A, Thomas C, Smith R, Brophy P (2011) Pre-emptive eculizumab and plasmapheresis for renal transplant in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 6:1488–1494PubMedCentralPubMed

180.

Krid S, Roumenina LT, Beury D, Charbit M, Boyer O, Fremeaux-Bacchi V, Niaudet P (2012) Renal transplantation under prophylactic eculizumab in atypical hemolytic uremic syndrome with CFH/CFHR1 hybrid protein. Am J Transplant 12:1938–1944PubMed

181.

Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Fremeaux-Bacchi V (2013) Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant 13:663–675PubMed

182.

Davin JC, 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 55:708–711PubMed

183.

Nurnberger J, Philipp T, Witzke O, Opazo Saez A, Vester U, Baba HA, Kribben A, Zimmerhackl LB, Janecke AR, Nagel M, Kirschfink M (2009) Eculizumab for atypical hemolytic-uremic syndrome. N Engl J Med 360:542–544PubMed

184.

Al-Akash SI, Almond PS, Savell VH Jr, Gharaybeh SI, Hogue C (2011) Eculizumab induces long-term remission in recurrent post-transplant HUS associated with C3 gene mutation. Pediatr Nephrol 26:613–619PubMed

185.

Alachkar N, Bagnasco SM, Montgomery RA (2012) Eculizumab for the treatment of two recurrences of atypical hemolytic uremic syndrome in a kidney allograft. Transpl Int 25:e93–e95PubMed

186.

Barrow M (2013) Health chiefs refuse to pay for lifesaving kidney treatment. In The Times 16 January

187.

Laurance J (2013) At what cost? Live saving drug withheld. In The Independent 26 May 2013

Titel: Hemolytic uremic syndrome
verfasst von: Caterina Mele
Giuseppe Remuzzi
Marina Noris
Publikationsdatum: 01.07.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Seminars in Immunopathology / Ausgabe 4/2014
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-014-0416-x

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