Renal Involvement in Children with HUS

Living reference work entry

Abstract

The thrombotic microangiopathies consist of a heterogeneous group of diseases which have common clinical manifestations including nonimmune hemolytic anemia, thrombocytopenia, and acute kidney injury. They also share in common endothelial cell injury and microthrombus formation as the central pathologic features (Fig. 1). While they share common clinical and pathologic manifestations, they have quite different and unique etiologies, presentations, pathogenesis, and therapies [1–6]. The most common cause of hemolytic uremic syndrome (HUS) is infectious agents with Shiga toxin-producing Escherichia coli (STEC) being the predominant cause of infectious HUS (Fig. 2). Atypical HUS (aHUS) can result from genetic mutations in complement regulatory proteins including complement factors H (FH), I (FI), and B (FB), as well as other factors. Thrombotic thrombocytopenia purpura (TTP) is caused by an inherited genetic mutation or an acquired immune deficiency in a disintegrin and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13). ADAMTS13 cleaves von Willebrand factor (VWF) facilitating its release from endothelial cells, thereby preventing the accumulation of prothrombotic ultra-large VWF oligomers. Other less common causes of HUS include drug-induced HUS, cobalamin deficiency HUS, transplant-associated HUS, and other secondary causes of HUS such as systemic lupus erythematosus and malignant hypertension.

Keywords

Acute Kidney Injury Hemolytic Uremic Syndrome Multiplex Ligation Dependent Probe Amplification Shiga Toxin Atypical Hemolytic Uremic Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Tarr PI, Gordon CA, Chandler WL. Shiga-toxin producing Escherichia coli and hemolytic uremic syndrome. Lancet. 2005;365:1073–86.PubMedGoogle Scholar
  2. 2.
    Andreoli SP, Zimmerhackl LB. Hemolytic uremic syndrome. In: Geary D, Schaefer F, editors. Comprehensive pediatric nephrology. Philadelphia: Elsevier, Inc; Chapter 25, 2008. 359–84; Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676–87.Google Scholar
  3. 3.
    George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371:654–66.PubMedGoogle Scholar
  4. 4.
    Zoja C, Buelli S, Morigi M. Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction. Pediatr Nephrol. 2010;25:2312–40.Google Scholar
  5. 5.
    Scheiring J, Andreoli SP, Zimmerhackl LB. Treatment and outcome of Shiga toxin associated hemolytic uremic syndrome (HUS). Pediatr Nephrol. 2008;23:1749–60.PubMedGoogle Scholar
  6. 6.
    Petruzziello-Pellegrini TN, Moslemi-Naeini M, Marsden EA. New insights into Shiga toxin medicated endothelial dysfunction in hemolytic uremic syndrome. Virulence. 2013;4:556–63.PubMedGoogle Scholar
  7. 7.
    Gerber A, Karch H, Allerberger F, et al. Clinical course and the role of Shiga toxin producing Escherichia coli infection in the hemolytic uremic syndrome in pediatric patients, 1997–2000 in Germany and Austria: a prospective study. J Inf Dis. 2002;186:493–500.Google Scholar
  8. 8.
    Paton JC, Paton AW. Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin Microbiol Rev. 1998;11:450–79.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Hashimoto H, Mizukoshi K, Nishi M, Kawakita T, Hasui S, Kato Y, et al. Epidemic of gastrointestinal tract infection including hemorrhagic colitis attributing to Shiga toxin 1-producing Escherichia coli 0118:H2 at a junior high school in Japan. Pediatr. 1999;103:e2.Google Scholar
  10. 10.
    Acheson DWK, Moore R, DeBreuler S. Translocation of Shiga-like toxins across polarized intestinal cells in tissue culture. Infect Immun. 1996;64:3294–300.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Uchida H, Kiyokawa N, Horie H, Fujimoto J, Takeda T. The detection of Shiga toxins in the kidney of a patient with hemolytic uremic syndrome. Pediatr Res. 1999;45:133–7.PubMedGoogle Scholar
  12. 12.
    Seigler RL, Physher TJ, Tesh VL, Taylor FB. Response to single and divided doses of Shiga toxin-1 in a primate model of hemolytic uremic syndrome. J Am Soc Nephrol. 2001;12:1458–67.Google Scholar
  13. 13.
    Repetto HA. Epidemic hemolytic uremic syndrome in children. Kidney Int. 1997;52:1708–19.PubMedGoogle Scholar
  14. 14.
    Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli 0157:H7 and the hemolytic-uremic syndrome. N Engl J Med. 1995;33:364–8.Google Scholar
  15. 15.
    Rowe PC, Orrbine E, Wells GA, Yetisir E, Clulow M, McLaine PN. Risk of hemolytic uremic syndrome after sporadic Escherichia coli 0157:H7 infection: results of a Canadian collaborative study. J Pediatr. 1998;132:777–82.PubMedGoogle Scholar
  16. 16.
    Proulz F, Sockett P. Prospective surveillance of Canadian children with the hemolytic uremic syndrome. Pediatr Nephrol. 2005;20:786–90.Google Scholar
  17. 17.
    Warwicker P, Goodship TJH, Donne RL, Pirson Y, Nicholls A, Ward RM, Turnpenny, Goodship JA. Genetic studies into inherited and sporadic hemolytic syndrome. Kidney Int. 1998;53:836–44.PubMedGoogle Scholar
  18. 18.
    Ulinski T, Lervat C, Ranchin B, et al. Neonatal hemolytic uremic syndrome after mother to child transmission of Escherichia coli O157. Pediatr Nephrol. 2005;20:1334–5.PubMedGoogle Scholar
  19. 19.
    Voss E, Paton AW, Manning PA, Paton JC. Molecular analysis of Shiga toxigenic Escherichia coli 0111:H proteins which react with sera from patients with hemolytic uremic syndrome. Infect Immun. 1998;66:1467–72.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Frank C, Werber D, Cramer JP, Askar M, Faber M, Heiden M, et al. Epidemic profile of Shiga toxin producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011;365:1771–80.PubMedGoogle Scholar
  21. 21.
    Kundzendorf U, Karch H, Werber D, Haller H. Recent outbreak of hemolytic uremic syndrome in Germany. Kidney Int. 2011;80:900–2.Google Scholar
  22. 22.
    Karmali MA. Host and pathogen determinates of verotoxin-producing Escherichia coli-associated hemolytic uremic syndrome. Kid Int. 2009;75:54–7.Google Scholar
  23. 23.
    Bell BP, Griffin PM, Lozano P, Christie DL, Kobayashi JM, Tarr PI. Predictors of hemolytic uremic syndrome in children during a larger outbreak of Escherichia coli O157:H7 infections. Pediatrics. 1997;100:e12.PubMedGoogle Scholar
  24. 24.
    Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000;342:1930–6.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Safdar N, Said A, Gangnon RE, Maki GD. Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli 0157:H7 enteritis: a metal analysis. JAMA. 2002;288:996–1001.PubMedGoogle Scholar
  26. 26.
    Zoufaly A, Cramer JP, Vettorazzi E, Sayk F, Bremer JP, Koop I, et al. Risk factors for development of hemolytic uremic syndrome in a cohort of adult patients with STEC O104:H4 Infection. PloS ONE. 2013;8:e59209.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Ake JA, Jelacic S, Ciol MA, et al. Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion. Pediatrics. 2005;115:673–80.Google Scholar
  28. 28.
    Hickey CA, Beattie J, Cowieson J, Miyashita Y, Strife CF, Frem JC, et al. Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome. Arch Pediatr Adolesc Med. 2011;165:884–9.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Brandt JR, Fouser LS, Watkins SL, Zelikovic I, Tarr PI, Nazar-Stewart V, Avner ED. Escherichia coli 0157:H7-associated hemolytic-uremic syndrome after ingestion of contaminated hamburgers. J Pediatr. 1994;125:519–26.PubMedGoogle Scholar
  30. 30.
    Buchholz U, Bernard H, Weber D, Bohmer MM, Remschmidt C, Wilking H, et al. German outbreak of Escherichia coli O104:H4 associate with sprouts. N Engl J Med. 2011;365:1763–70.PubMedGoogle Scholar
  31. 31.
    Kemper MJ. Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a pediatric perspective. Pediatr Nephrol. 2012;27:161–4.PubMedGoogle Scholar
  32. 32.
    Laider MR, Tourdjman M, Buser GL, Hostetler T, Repp KK, Leman R, et al. Escherichia coli O157:H7 infections associated with consumption of locally grown strawberries contaminated by deer. Clin Inf Dis. 2013;57:1129–34.Google Scholar
  33. 33.
    Andreoli SP, Bergstein JM. Development of insulin dependent diabetes mellitus during the hemolytic uremic syndrome. J Pediatr. 1982;100:541–5.PubMedGoogle Scholar
  34. 34.
    Masumoto K, Nishimoto Y, Taguchi T. Colonic stricture secondary to hemolytic uremic syndrome caused by Escherichia coli O-157. Pediatr Nephrol. 2005;20:1496–9.PubMedGoogle Scholar
  35. 35.
    Rahman RC, Cobenas CJ, Drut R, Amoreo OR, Ruscaso JD, Spizzirri AP, et al. Hemorrhagic colitis in postdiarrheal hemolytic uremic syndrome; retrospective analysis of 54 children. Pediatr Nephrol. 2012;27:229–33.PubMedGoogle Scholar
  36. 36.
    Bekassy ZD, Toledo CC, Leoj G, Kristoffersson AC, Leopold SR, Perez MT. Intestinal damage in enterohemorrhagic E. coli infection. Pediatr Nephrol. 2011;26:2059–71.PubMedGoogle Scholar
  37. 37.
    Brandt JR, Joseph MW, Fouser LS, et al. Cholelithiasis following Escherichia coli O157:H7 associated hemolytic uremic syndrome. Pediatr Nephrol. 1998;12:222–5.PubMedGoogle Scholar
  38. 38.
    Andreoli SP, Bergstein JM. Exocrine and endocrine pancreatic insufficiency and calcinosis following the hemolytic uremic syndrome. J Pediatr. 1987;110:816–7.PubMedGoogle Scholar
  39. 39.
    Nesmith JD, Ellis E. Childhood hemolytic uremic syndrome is associated with adolescent-onset diabetes mellitus. Pediatr Nephrol. 2007;22:294–7.PubMedGoogle Scholar
  40. 40.
    Nathanson S, Kwon T, Elmaleh M, Charbit M, Launay EA, Harambat, et al. Acute neurologic involvement in diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2010;5:1218-8.Google Scholar
  41. 41.
    Bauer A, Loos S, Wehrmann C, Horstman D, Donnerstag F, Lemke J, et al. Neurological involvement in children with E. coli O104:H4- induced hemolytic uremic syndrome. Pediatr Nephrol. 2014;29:1607–15.PubMedGoogle Scholar
  42. 42.
    Signorini E, Mastrangelo M, Rapuzzi S, Edefonti A, Fossali E. Central nervous system involvement in hemolytic uremic syndrome. Pediatr Nephrol. 2000;14:990.PubMedGoogle Scholar
  43. 43.
    Amran MY, Fujii J, Suzuki SO, Kolling GL, Villanueva SYAM, Kainuma M, et al. Investigation of encephalopathy caused by Shiga toxin 2c producing Escherichia coli infection in mice. PLoS One. 2013;8:e58959.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Loudon SE, Dorrestijn EM, Catsman-Berrevoets CE, Verdijk RM, Somonsz HJ, Jansen AJG. Blinded by Shiga toxin-producing O104 Escherichia coli and haemolytic uremic syndrome. J Pediatr. 2014;165:410.PubMedGoogle Scholar
  45. 45.
    Askitia V, Hendrickson K, Fish AJ, Braunlin E, Sinaiko AR. Troponin I levels in a hemolytic uremic syndrome patient with severe cardiac failure. Pediatr Nephrol. 2004;19:345–8.Google Scholar
  46. 46.
    Thayu M, Chandler WL, Jelacic S, Gordon CA, Rosenthal GL, Tarr PI. Cardiac ischemia during hemolytic uremic syndrome. Pediatr Nephrol. 2003;18:286–9.PubMedGoogle Scholar
  47. 47.
    Inward CD, Howie AJ, Fitzpatrick MM, Rafaat F, Milford DV, Taylor CM. Renal histopathology in fatal cases of diarrhea associated hemolytic uremic syndrome. Pediatr Nephrol. 1997;11:556–9.PubMedGoogle Scholar
  48. 48.
    Burns JC, Berman ER, Fagre J, et al. Pancreatic islet cell necrosis: association with hemolytic uremic syndrome. J Pediatr. 1982;100:582–4.PubMedGoogle Scholar
  49. 49.
    Spizzirri FD, et al. Childhood hemolytic uremic syndrome in Argentina: long-term follow up and prognostic features. Pediatr Nephrol. 1997;11:156–60.PubMedGoogle Scholar
  50. 50.
    Garg AX, Suri RS, Barrowman, et al. Long term renal prognosis of diarrhea associated hemolytic uremic syndrome. JAMA. 2003;290:1360–70.PubMedGoogle Scholar
  51. 51.
    Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS. Long-term outcomes of shiga toxin hemolytic uremic syndrome. Pediatr Nephrol. 2013;28(11):2097–105.PubMedGoogle Scholar
  52. 52.
    Oakes RS, Kirkhamm JK, Nelson RD, Siegler RL. Duration of oliguria and anuria as predictors of chronic renal-related sequelae in post-diarrheal hemolytic uremic syndrome. Pediatr Nephrol. 2008;23:1303–8.PubMedGoogle Scholar
  53. 53.
    Lou-Meda R, Oakes RS, Gilstrap JN, Williams CG, Siegler RL. Prognostic significance of microalbuminuria in post diarrheal hemolytic uremic syndrome. Pediatr Nephrol. 2007;222:117–20.Google Scholar
  54. 54.
    Caletti MG, Balestracci A, Roy AH. Levels of urinary transforming growth factor b-1 in children with D+ hemolytic uremic syndrome. Pediatr Nephrol. 2010;25:1177–80.PubMedGoogle Scholar
  55. 55.
    Moghal NE, Ferreira MAS, Howie AJ, Milford DV, Raafat F, Taylor CM. The late histologic finding in diarrhea associated hemolytic uremic syndrome. J Pediatr. 1998;133:220–3.PubMedGoogle Scholar
  56. 56.
    De Petris L, Gianviti A, Giordano U, et al. Blood pressure in the long term follow up of children with hemolytic uremic syndrome. Pediatr Nephrol. 2004;19:1244.Google Scholar
  57. 57.
    Schlieiper A, Orrbine E, Wells GA, et al. Neurological sequelae of hemolytic uremic syndrome. Arch Dis Child. 1999;80:214–20.Google Scholar
  58. 58.
    Qamar IU, Ohali M, MacGregor DL, et al. Long-term neurological sequelae of hemolytic uremic syndrome: a preliminary report. Pediatr Nephrol. 1996;10:504–6.PubMedGoogle Scholar
  59. 59.
    Karmali MA, Petric M, Lim C, et al. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing E. coli. J Infect Dis. 1985;151:775–82.PubMedGoogle Scholar
  60. 60.
    van Setten PA, van Hinsbergh VWM, van der Velden TJAN, van de Kar NCAJ, Vermeer M, Mahan JD, Assmann KJM, van den Heuvel LPWJ, Monnens LAH. Effects of TNFa on verocytotoxin cytotoxicity in purified human glomerular microvascular endothelial cells. Kidney Int. 1997;51:1245–56.PubMedGoogle Scholar
  61. 61.
    Louise CB, Obrig TG. Specific interactions of Escherichia coli O157:H7 derived Shiga-like toxin II with human endothelial cells. J Infect Dis. 1995;172:1397–401.PubMedGoogle Scholar
  62. 62.
    Pijpers AHJM, Van Satten PA, Vande Heuvel LPWJ, et al. Verocytotoxin induced apoptosis of human microvascular endothelial cells. J Am Soc Nephrol. 2001;12:767–78.PubMedGoogle Scholar
  63. 63.
    Kiarash A, Boyd B, Lingwood CA. Glycosphingolipid receptor function is modified by fatty acid content. J Biol Chem. 1994;269:1138–46.Google Scholar
  64. 64.
    Sandvig K, Garred O, van Helvoort A, van Meer G, van Deurs B. Important of glycolipid synthesis for butyric acid induced sensitization to Shiga toxin and intracellular sorting of toxin in A431 cells. Mol Biol Cell. 1996;7:1391–404.PubMedCentralPubMedGoogle Scholar
  65. 65.
    Arab S, Lingwood CA. Intracellular targeting of the endoplasmic reticulum/nuclear envelope by retrograde transport may determine cell hypersensitivity to verotoxin via globotriosyl ceramide fatty acid isoform traffic. J Cell Physiol. 1998;117:646–60.Google Scholar
  66. 66.
    Bitzan MM, Wang Y, Lin J, Marsden PA. Verotoxin and ricin have novel effects on preproendothelin-1 expression but fail to modify nitric oxide synthase (ecNOS) expression and NO production in vascular endothelium. J Clin Invest. 1998;101:372–82.PubMedCentralPubMedGoogle Scholar
  67. 67.
    Grabowski EF, Kushak RI, Liu B, Ingelfinger JR. Shiga toxin downregulates tissues factor pathway inhibitor, modulating and increased expression of functional tissue factor on endothelium. Thromb Res. 2013;131:521–8.PubMedGoogle Scholar
  68. 68.
    Nestrodidi E, Kushak RI, Tsukoruw O, Grabowski EF, Ingelfinger JR. Role of the renin angiotensin system in TNF-a and Shiga-toxin-induced tissue factor expression. Pediatr Nephrol. 2008;23:221–31.Google Scholar
  69. 69.
    Petruzziello TN, Yuen DA, Page AV, Patel S, Soltyk AM, Matouk CC, et al. The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin associated hemolytic uremic syndrome in humans and mice. J Clin Invest. 2012;122:759–76.Google Scholar
  70. 70.
    Penicot-Dubois I, Thomas GM, Furie BC, Lombardo D, Dubois C. Bile salt dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans. J Clin Invest. 2007;117:3708–19.Google Scholar
  71. 71.
    Gear AR, Suttiitanamongkol S, Viisoreanu D, Polanowska-Grabowske RK, Raha S, Camerini D. Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDR-1 to stimulate platelet function. Cell. 2006;124:18–21.Google Scholar
  72. 72.
    Simon M, Learly TG, Hernandez JD, Abboud HA. Shiga toxin 1 elicits diverse biological response in mesangial cells. Kidney Int. 1998;54:1117–27.PubMedGoogle Scholar
  73. 73.
    Van Setten PA, Van Hinsbergh VWM, Van den Heuvel LPWJ, Van der Velden TJAN, Van de Kar NCAJ, Krebbbers RJM, Karmali MA, Monnen LAH. Verocytotoxin inhibits mitogenesis and protein synthesis in purified human glomerular mesangial cells without affecting cell viability: evidence for two distinct mechanisms. J Am Soc Nephrol. 1997;8:1877–88.PubMedGoogle Scholar
  74. 74.
    Sterns-Kurosawa DJ, Oh SY, Cherla RP, Lee MS, Tesh VL, Papin J, et al. Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic Escherichia coli Shiga toxins in non-human primate models of hemolytic uremic syndrome. Am J Pathol. 2013;182:1227–38.Google Scholar
  75. 75.
    Hughes AK, Sticklett PK, Kohan DE. Cytotoxic effect of Shiga toxin-1 on human proximal tubular epithelial cells. Kidney Int. 1998;54:426–37.PubMedGoogle Scholar
  76. 76.
    Hughes AK, Stricklett PK, Kohan DE. Shiga toxin-1 regulation of cytokine production by human proximal tubule cells. Kidney Int. 1998;54:1093–106.PubMedGoogle Scholar
  77. 77.
    Silberstein C, Crydt VP, Gerhardt E, Nunez P, Ibara C. Inhibition of water reabsorption in human proximal tubular epithelial cells in response to Shiga tozin-2. Pediatr Nephrol. 2008;23:1981–90.PubMedGoogle Scholar
  78. 78.
    Taghchi T, Uchida H, Kiyokawa N, Mori T, Sato N, Horie H, Takeda T, Fujimoto J. Verotoxins induce apoptosis in human renal tubular epithelium derived cells. Kidney Int. 1998;53:1681–8.Google Scholar
  79. 79.
    Hughes AK, Stricklett PK, Schmid D, Kohan DE. Cytotoxic effect of Shiga-toxin on human glomerular epithelial cells. Kid Int. 2000;57:235–9.Google Scholar
  80. 80.
    Karpman D, Hakansson A, Perez MT, Isaksson C, Carlemalm E, Caprioli A, Svanborg C. Apoptosis of renal cortical cells in the hemolytic uremic syndrome: in vivo and in vitro studies. Infect Immun. 1998;66:636–44.PubMedCentralPubMedGoogle Scholar
  81. 81.
    Van Setten PA, van Hinsbergh VWM, van den Heuvel LPWJ, Preyers F, Dijkman HBPM, Assmann KJM, van der Velden TJAM, Monnens LAH. Monocytes chemoattractant protein-1 and interleukin-8 levels in urine and serum of patients with hemolytic uremic syndrome. Pediatr Res. 1998;43:759–67.PubMedGoogle Scholar
  82. 82.
    Fitzpatrick MM, Shah V, Trompeter RS, Dillon MJ, Barratt TM. Interleukin-8 and polymorphonuclear leukocyte activation in hemolytic uremic syndrome of childhood. Kidney Int. 1992;42:951–6.PubMedGoogle Scholar
  83. 83.
    Walters MDS, Matthei IU, Kay R, Dillon MJ, Barratt TM. The polymorphonuclear leukocyte count in childhood hemolytic uremic syndrome. Pediatr Nephrol. 1989;3:130–4.PubMedGoogle Scholar
  84. 84.
    Andreoli SP. The pathophysiology of the hemolytic uremic syndrome. Curr Opin Nephrol Hypertens. 1999;8:459–64.PubMedGoogle Scholar
  85. 85.
    Fernandez GC, Gomez SA, Rubel CJ, et al. Impaired neutrophils in children with the typical form of hemolytic uremic syndrome. Pediatr Nephrol. 2005;20:1306–14.PubMedGoogle Scholar
  86. 86.
    Trachtman H, Christen E, Cnaan A, et al. Urinary neutrophil gelatinase-associated lipocalin in D+ HUS: a novel marker of renal injury. Pediatr Nephrol. 2006;21:989–94.PubMedGoogle Scholar
  87. 87.
    Lukasz A, Beneke J, Menne J, Vetter F, Schmidt BMW, Schiffer M, et al. Serum neutrophil gelatinase-associated lipocalin (NGAL) in patients with Shiga toxin medicated haemolytic uremic syndrome (STEC-HUS). Thromb Hemost. 2014;111:365–72.Google Scholar
  88. 88.
    Maroeska D, Loo WM, Monnens LAH, et al. Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome. Blood. 2000;95:3396–402.Google Scholar
  89. 89.
    Brigotti M, Carnicelli D, Affilli V, Tamassia N, Borsetti F, Fabbri E, et al. Identification of TRL4 as the receptor that recognizes Shiga toxin in human neutrophils. J Immunol. 2013;191:4748–58.PubMedGoogle Scholar
  90. 90.
    Morigi M, Micheletti G, Figliuzzi M, Imberti B, Karmali MA, Remuzzi A, Remuzzi G, Zoja C. Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood. 1995;86:4553–8.PubMedGoogle Scholar
  91. 91.
    Kamitsuji H, Nonaami K, Ishikawa N, et al. Elevated tissue factor circulating levels in children with hemolytic uremic syndrome caused by verotoxin producing E. coli. Clin Nephrol. 2000;53:319–24.PubMedGoogle Scholar
  92. 92.
    Fernandez GC, Te Loo MW, van der Velden TJA, et al. Decrease of thrombomodulin contributes to the procoagulant state of the endothelium in hemolytic uremic syndrome. Pediatr Nephrol. 2003;18:1066–8.PubMedGoogle Scholar
  93. 93.
    Keir LS, Saleem MA. Current evidence for the role of complement in the pathogenesis of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol. 2014;29:1895–902.PubMedGoogle Scholar
  94. 94.
    Monnens L, Molenaar J, Lambert PH, Proesmans W, van Munster P. The complement system in hemolytic uremic syndrome. Clin Nephrol. 1980;13:168–71.PubMedGoogle Scholar
  95. 95.
    Thurman JM, Marians R, Emlen W, Wood S, Smith C, Akana H, et al. Alternative pathway of complement in children with diarrhea associated hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2009;4:1920–4.PubMedCentralPubMedGoogle Scholar
  96. 96.
    Dammermann W, Schipper P, Ullrich S, Fraedrich K, Weisch JS, Frundt T. Increased expression of complement regulators CD55 and CD59 on peripheral smear in patients with EAHEC O104:H4 Infection. PloS ONE. 2013;8:e74880.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Ehrlenbach S, Rosales A, Posch W, Wilflingseder D, Hermann M, Brockmeyer J, et al. Shiga toxin 2 reduces complement inhibitor protein CD59 expression on human renal tubular epithelial and glomerular endothelial cells. Infect Immun. 2013;81:2678–85.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Michael M, Elliott EJ, Craig JC, Ridley G, Hodson EM. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials. Am J Kid Dis. 2009;53:259–72.PubMedGoogle Scholar
  99. 99.
    Pape L, Ahlensteil T, Kreuzer M, Drube J, Froede K, Franke D, et al. Early erythropoietin therapy reduced the need for red blood cell transfusion in childhood hemolytic uremic syndrome – a randomized prospective pilot trials. Pediatr Nephrol. 2009;24:1061–4.PubMedGoogle Scholar
  100. 100.
    Weil B, Andreoli SP, Billmire D. Bleeding risk for surgical dialysis procedures in children with hemolytic uremic syndrome. Pediatr Nephrol. 2010;25:1693–8.PubMedGoogle Scholar
  101. 101.
    Molbak K, Mead PS, Griffin PM. Antimicrobial therapy in patients with Escherichia coli 0157:H7 infection. JAMA. 2002;288:1014–6.PubMedGoogle Scholar
  102. 102.
    Grif K, Kierich MP, Karch H, Allerberger F. Strain-specific differences in the amount of shiga toxin released from enterohemorrhagic Escherichia coli 0157 following exposure to subinhibitory concentrations of antimicrobial agents. Eur J Clin Microbiol Infect Dis. 1998;17:761–6.PubMedGoogle Scholar
  103. 103.
    Rizzoni G, Claris-Appaini A, Edefonti A, et al. Plasma infusion for hemolytic uremic syndrome in children: results of a multicenter controlled trial. J Pediatr. 1988;112:284–90.PubMedGoogle Scholar
  104. 104.
    Trachtman H, Cnaan A, Christen E, Gibbs K, Christen E, Acheson D, et al. Effect of an oral Shiga toxin binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized control trial. JAMA. 2003;290:1337–44.PubMedGoogle Scholar
  105. 105.
    Sielger RL, Pysher TJ, Tesh VL, Denkers ND, Taylor FB. Prophylactic heparinization is ineffective in a primate model of hemolytic uremic syndrome. Pediatr Nephrol. 2002;17:1053–8.Google Scholar
  106. 106.
    Luth S, Frundt TW, Rosch T, Schlee C, Lohse AW. Prevention of hemolytic uremic syndrome with daily bowel lavage in patients with Shiga-toxin producing enterohemorrhagic Escherichia coli 0104:H4 infection. JAMA Int Med. 2014;174:1003–5.Google Scholar
  107. 107.
    Kawasaki Y, Suyama S, Ono A, Oikawa T, Ohara S, et al. Efficacy of recombinant human soluble thrombomodulin for childhood hemolytic uremic syndrome. Pediatr Int. 2013;55:e139–42.PubMedGoogle Scholar
  108. 108.
    Lapeyraque AL, Malina M, Fremeaux-Bacchi V, Boppel T, Kirschfink M, Oualha M, et al. Eculizamab in severe Shiga-toxin associated HUS. N Engl J Med. 2011;364:2561–3.PubMedGoogle Scholar
  109. 109.
    Menne J, Nitschke M, Stingele R, Abu-Tair M, Beneke J, Bramsstedt J, et al. Validation of treatment strategies for enterohemorrhagic Escherichia coli O104:H4 induced hemolytic uremic syndrome. BMJ. 2012;345:e4565.PubMedCentralPubMedGoogle Scholar
  110. 110.
    Kielstein JT, Beutel G, Fleig S, Steinhoff J, Meyer TN, Hafer C, et al. Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin producing E. coli O104:H4 induced hemolytic uremic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant. 2012;27:3807–15.PubMedGoogle Scholar
  111. 111.
    Sheoran AS, Chapman-Bonofiglio S, Harvey BR, et al. Human antibody against shiga toxin 2 administered to piglets after the onset of diarrhea due to Escherichia coli O157:H7 prevents fatal systemic complications. Infect Immun. 2005;73:4607–13.PubMedCentralPubMedGoogle Scholar
  112. 112.
    Tremblay JM, Mukherjee J, Leysath CE, Debatis M, Ofori K, Baldwin K. A single VHH-based toxin neutralizing agent and an effector antibody protect mice against challenge with Shiga toxin 1 and 2. Infect Immun. 2013;81:4592–603.PubMedCentralPubMedGoogle Scholar
  113. 113.
    Russo LM, Melton-Celsa AR, Smith MA, Smith MJ, O’Brian AD. Oral intoxication of mice with Shiga toxin type 2a (STX2a) and protection by anti-STX2a monoclonal antibody 11E10. Infect Immun. 2014;82:1213–21.PubMedCentralPubMedGoogle Scholar
  114. 114.
    Silverstein C, Lucero MS, Zotta E, Copeland DP, Lingyun L, Repetto HA, et al. A glucosylceramide synthase inhibitors protects rats against the cytotoxic effects of Shiga toxin 2. Pediatr Res. 2011;69:390–5.Google Scholar
  115. 115.
    Stearns-Kurosawa DJ, Collins V, Freeman S, Debord D, Nishikawa K, Oh SY, et al. Rescue from lethal Shiga toxin 2-induced renal failure with a cell-permeable peptide. Pediatr Nephrol. 2011;26:2031–9.PubMedCentralPubMedGoogle Scholar
  116. 116.
    Garcia-Angulo VA, Kalita A, Torres AG. Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection. Vaccine. 2013;31:3229–35.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Mejias MP, Ghersi G, Craig PO, Panek CA, Bentancor LV, Baschikier A, et al. Immunization with a chimera consisting of the B subunit of shiga toxin type 2 and brucella lumazine synthase confers total protection against Shiga toxins in mice. J Immun. 2013;191:2403–11.PubMedGoogle Scholar
  118. 118.
    Van Dyck R, Proesmans W. Renoprotection by ACE inhibitors after sever haemolytic uremic syndrome. Pediatr Nephrol. 2004;19:688–90.PubMedGoogle Scholar
  119. 119.
    Caletti MG, Missoni M, Vezzani C, Grignoli M, Pintania JJ, Repetto R, et al. Effect of diet, enalapril, or losartan in post-diarrheal hemolytic uremic syndrome nephropathy. Pediatr Nephrol. 2011;26:1247–54.PubMedGoogle Scholar
  120. 120.
    Butler T, Islam MR, Azad MAK, Jones PK. Risk factors for development of hemolytic uremic syndrome during shigellosis. J Pediatr. 1987;110:894–7.PubMedGoogle Scholar
  121. 121.
    Bhimma R, Rollins NC, Coovadia HM, Adhikari M. Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal. Pediatr Nephrol. 1997;11:560–4.PubMedGoogle Scholar
  122. 122.
    Houdouin V, Doit C, Mariana P, et al. A pediatric cluster of Shigella dysenteriae serotype 1 diarrhea with hemolytic uremic syndrome in 2 families from France. Clin Infect Dis. 2004;38:96–9.Google Scholar
  123. 123.
    Taylor CM. Enterohemorrhagic Escherichia coli and Shigella dysenteriae type 1 induced hemolytic uremic syndrome. Pediatr Nephrol. 2008;23:1425–31.Google Scholar
  124. 124.
    Cabagnaro F, Guzman C, Harris P. Hemolytic uremic syndrome associated with Entamoeba histolytica intestinal infection. Pediatr Nephrol. 2006;21:126–8.Google Scholar
  125. 125.
    Turner ME, Kher K, Rakusan T, et al. Atypical HUS in human immunodeficiency virus 1 infected children. Pediatr Nephrol. 1997;11:161–3.PubMedGoogle Scholar
  126. 126.
    Ucar A, Fernandez HF, Byrnes JJ, et al. Thrombotic microangiopathy and retroviral infections: a 13 year experience. Am J Hematol. 1994;45:304–9.PubMedGoogle Scholar
  127. 127.
    Gordon A, Pereyre S, Monet C, Llanas B, Harambat J. Hemolytic uremic syndrome complicating mycoplasma pneumoniae infections. Pediatr Nephrol. 2013;28:2057–60.Google Scholar
  128. 128.
    Copelovitch L, Kaplan BS. Streptococcus pneumoniae-associated haemolytic uremic syndrome. Pediatr Nephrol. 2008;23:1951–6.PubMedGoogle Scholar
  129. 129.
    Nathanson S, Deschenes G. Prognosis of Streptococcus pneumoniae induced hemolytic uremic syndrome. Pediatr Nephrol. 2001;16:362–5.PubMedGoogle Scholar
  130. 130.
    Proulz F, Liet JM, Michele D, et al. Hemolytic uremic syndrome associated with invasive streptococcus infection. Pediatrics. 2000;105:462–3.Google Scholar
  131. 131.
    Brandt J, Wong C, Mihm S, et al. Invasive pneumococcal disease and hemolytic uremic syndrome. Pediatrics. 2002;110:371–5.PubMedGoogle Scholar
  132. 132.
    Cochran JB, Panzarino VM, Maes LY, Tecklenburg FW. Pneumococcus-induced T-antigen activation in hemolytic uremic syndrome. Pediatr Nephrol. 2004;19:317–21.PubMedGoogle Scholar
  133. 133.
    Loirat C, Girma JP, Desconclois C, Coppo P, Veyradier A. Thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. Pediatr Nephrol. 2009;24:19–29.PubMedGoogle Scholar
  134. 134.
    Osborn JD, Rodgers GM. Update on thrombotic thrombocytopenic purpura. Clin Adv Hematol Oncol. 2011;9:531–6.PubMedGoogle Scholar
  135. 135.
    Moake JL, Byrnes JJ, Troll JH, Weinstein MJ, Colannini MN, Azocar J, et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenia purpura. N Engl J Med. 1982;307:1432–5.PubMedGoogle Scholar
  136. 136.
    Furan MF, Robles R, Galbuserea M, Remuzzi, et al. Von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenia purpura. N Engl J Med. 1997;339:1578–84.Google Scholar
  137. 137.
    Tsai HM, Chun-Yet LE. Autoantibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenia purpura. N Engl J Med. 1998;338:1585–94.Google Scholar
  138. 138.
    Levy GC, Nichols WC, Lian EC, Foroud T, et al. Mutations in a member of the ADAMTS13 gene family cause thrombotic thrombocytopenia purpura. Nature. 2001;413:488–94.PubMedGoogle Scholar
  139. 139.
    Chapman K, Yeun S. Therapy for thrombotic thrombocytopenia purpura: past. Present, future. Semin Thromb Hemost. 2014;40:34–40.PubMedGoogle Scholar
  140. 140.
    Noris M, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5(10):1844–59.PubMedCentralPubMedGoogle Scholar
  141. 141.
    Fremeaux-Bacchi V, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Sellier-Leclerc AL, et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2007;18(8):2392–400.PubMedGoogle Scholar
  143. 143.
    Edey MM, et al. Association of a factor H mutation with hemolytic uremic syndrome following a diarrheal illness. Am J Kidney Dis. 2008;51(3):487–90.PubMedGoogle Scholar
  144. 144.
    Sule SD, et al. Reduced albumin levels and utilization of arteriovenous access in pediatric patients with systemic lupus erythematosus (SLE). Pediatr Nephrol. 2007;22(12):2041–6.PubMedGoogle Scholar
  145. 145.
    Lee BH, et al. Atypical hemolytic uremic syndrome associated with complement factor H autoantibodies and CFHR1/CFHR3 deficiency. Pediatr Res. 2009;66(3):336–40.PubMedGoogle Scholar
  146. 146.
    Carter JE, Cimolai N. Hemolytic-uremic syndrome associated with acute Campylobacter upsaliensis gastroenteritis. Nephron. 1996;74(2):489.PubMedGoogle Scholar
  147. 147.
    Alvarado AS, et al. Hemolytic uremic syndrome associated with Clostridium difficile infection. Clin Nephrol. 2014;81(4):302–6.PubMedGoogle Scholar
  148. 148.
    Berner R, et al. Hemolytic uremic syndrome due to an altered factor H triggered by neonatal pertussis. Pediatr Nephrol. 2002;17(3):190–2.PubMedGoogle Scholar
  149. 149.
    Waters AM, et al. Hemolytic uremic syndrome associated with invasive pneumococcal disease: the United kingdom experience. J Pediatr. 2007;151(2):140–4.PubMedGoogle Scholar
  150. 150.
    Geerdink LM, et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol. 2012;27(8):1283–91.PubMedCentralPubMedGoogle Scholar
  151. 151.
    Fakhouri F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010;21(5):859–67.PubMedCentralPubMedGoogle Scholar
  152. 152.
    Chand DH, Brady RC, Bissler JJ. Hemolytic uremic syndrome in an adolescent with Fusobacterium necrophorum bacteremia. Am J Kidney Dis. 2001;37(3):E22.PubMedGoogle Scholar
  153. 153.
    Kwon T, et al. Varicella as a trigger of atypical haemolytic uraemic syndrome associated with complement dysfunction: two cases. Nephrol Dial Transplant. 2009;24(9):2752–4.PubMedGoogle Scholar
  154. 154.
    Waiser J, et al. De novo hemolytic uremic syndrome postrenal transplant after cytomegalovirus infection. Am J Kidney Dis. 1999;34(3):556–9.PubMedGoogle Scholar
  155. 155.
    Bento D, et al. Triggering of atypical hemolytic uremic syndrome by influenza A (H1N1). Ren Fail. 2010;32(6):753–6.PubMedGoogle Scholar
  156. 156.
    Tagle M, et al. Relapsing viral hepatitis type A complicated with renal failure. Rev Gastroenterol Peru. 2004;24(1):92–6.PubMedGoogle Scholar
  157. 157.
    Baid S, et al. Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients. J Am Soc Nephrol. 1999;10(1):146–53.PubMedGoogle Scholar
  158. 158.
    Benitez M, et al. Haemolytic-uraemic syndrome in a patient infected by HIV. Nephrol Dial Transplant. 1997;12(2):362–3.PubMedGoogle Scholar
  159. 159.
    Austin TW, Ray CG. Coxsackie virus group B infections and the hemolytic-uremic syndrome. J Infect Dis. 1973;127(6):698–701.PubMedGoogle Scholar
  160. 160.
    Watanabe T. Hemolytic uremic syndrome associated with Epstein-Barr virus infection. Pediatr Nephrol. 2004;19(5):569.PubMedGoogle Scholar
  161. 161.
    Wiersinga WJ, et al. Dengue fever-induced hemolytic uremic syndrome. Clin Infect Dis. 2006;43(6):800–1.PubMedGoogle Scholar
  162. 162.
    Matsuda Y, et al. Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children. Bone Marrow Transplant. 1999;24(8):919–23.PubMedGoogle Scholar
  163. 163.
    Hartel C, et al. Renal complications associated with human parvovirus B19 infection in early childhood. Klin Padiatr. 2007;219(2):74–5.PubMedGoogle Scholar
  164. 164.
    Adonis-koffy L. May Plasmodium falciparum induce a hemolytic uremic syndrome? Arch Pediatr. 2004;11(1):55–6.PubMedGoogle Scholar
  165. 165.
    Canpolat C, Pearson P, Jaffe N. Cisplatin-associated hemolytic uremic syndrome. Cancer. 1994;74(11):3059–62.PubMedGoogle Scholar
  166. 166.
    Boeck S, et al. Hemolytic-uremic syndrome associated with gemcitabine treatment for metastatic pancreatic cancer. J Clin Gastroenterol. 2008;42(5):551–2.PubMedGoogle Scholar
  167. 167.
    Ariyoshi K, Shinohara K, Ruirong X. Thrombotic thrombocytopenic purpura caused by ticlopidine, successfully treated by plasmapheresis. Am J Hematol. 1997;54(2):175–6.PubMedGoogle Scholar
  168. 168.
    Andersohn F, Hagmann FG, Garbe E. Thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome associated with clopidogrel: report of two new cases. Heart. 2004;90(9):e57.PubMedCentralPubMedGoogle Scholar
  169. 169.
    Aster RH. Quinine sensitivity: a new cause of the hemolytic uremic syndrome. Ann Intern Med. 1993;119(3):243–4.PubMedGoogle Scholar
  170. 170.
    Gottschall JL, et al. Quinine-induced immune thrombocytopenia with hemolytic uremic syndrome: clinical and serological findings in nine patients and review of literature. Am J Hematol. 1994;47(4):283–9.PubMedGoogle Scholar
  171. 171.
    Ubara Y, et al. Hemolytic uremic syndrome associated with beta-interferon therapy for chronic hepatitis C. Nephron. 1998;80(1):107–8.PubMedGoogle Scholar
  172. 172.
    Badid C, et al. Renal thrombotic microangiopathy induced by interferon-alpha. Nephrol Dial Transplant. 2001;16(4):846–8.PubMedGoogle Scholar
  173. 173.
    Keir L, et al. Beware renal adverse effects of anti-vascular endothelial growth factor treatment. BMJ. 2012;344:e3838.PubMedGoogle Scholar
  174. 174.
    Bonatti H, et al. Hemolytic uremic syndrome following Campath-1H induction. Transpl Int. 2007;20(4):386–9.PubMedGoogle Scholar
  175. 175.
    Abraham KA, et al. Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus. Transpl Int. 2000;13(6):443–7.PubMedGoogle Scholar
  176. 176.
    Allan DS, et al. Ciprofloxacin-associated hemolytic-uremic syndrome. Ann Pharmacother. 2002;36(6):1000–2.PubMedGoogle Scholar
  177. 177.
    Blumberg A, Studer U, Briner J. Hemolytic-uremic syndrome in a young woman following the use of ovulation inhibitors. Schweiz Med Wochenschr. 1975;105(41):1324–7.PubMedGoogle Scholar
  178. 178.
    Ashouri OS, et al. Hemolytic uremic syndrome in two postmenopausal women taking a conjugated estrogen preparation. Clin Nephrol. 1982;17(4):212–5.PubMedGoogle Scholar
  179. 179.
    Au WY, et al. A post-menopausal woman with anuria and uterus bulk: the spectrum of estrogen-induced TTP/HUS. Am J Hematol. 2002;71(1):59–60.PubMedGoogle Scholar
  180. 180.
    Tumlin JA, Sands JM, Someren A. Hemolytic-uremic syndrome following “crack” cocaine inhalation. Am J Med Sci. 1990;299(6):366–71.PubMedGoogle Scholar
  181. 181.
    Ardiles LG, et al. Anticardiolipin antibodies in classic pediatric hemolytic-uremic syndrome: a possible pathogenic role. Nephron. 1998;78(3):278–83.PubMedGoogle Scholar
  182. 182.
    Barre P, et al. Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3. Arch Pathol Lab Med. 1977;101(7):357–61.PubMedGoogle Scholar
  183. 183.
    Nesher G, et al. Thrombotic microangiographic hemolytic anemia in systemic lupus erythematosus. Semin Arthritis Rheum. 1994;24(3):165–72.PubMedGoogle Scholar
  184. 184.
    Hale GA, et al. Hemolytic uremic syndrome after bone marrow transplantation: clinical characteristics and outcome in children. Biol Blood Marrow Transplant. 2005;11(11):912–20.PubMedGoogle Scholar
  185. 185.
    Lechner K, Obermeier HL. Cancer-related microangiopathic hemolytic anemia: clinical and laboratory features in 168 reported cases. Medicine (Baltimore). 2012;91(4):195–205.Google Scholar
  186. 186.
    Kind T, et al. Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period. J Pediatr Hematol Oncol. 2002;24(4):327–9.PubMedGoogle Scholar
  187. 187.
    Constantinescu AR, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis. 2004;43(6):976–82.PubMedGoogle Scholar
  188. 188.
    Taylor CM, et al. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010;148(1):37–47.PubMedGoogle Scholar
  189. 189.
    Caprioli J, et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108(4):1267–79.PubMedCentralPubMedGoogle Scholar
  190. 190.
    Espie E, et al. Surveillance of hemolytic uremic syndrome in children less than 15 years of age, a system to monitor O157 and non-O157 Shiga toxin-producing Escherichia coli infections in France, 1996-2006. Pediatr Infect Dis J. 2008;27(7):595–601.PubMedGoogle Scholar
  191. 191.
    Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16(4):1035–50.PubMedGoogle Scholar
  192. 192.
    Allen U, Licht C. Pandemic H1N1 influenza A infection and (atypical) HUS–more than just another trigger? Pediatr Nephrol. 2011;26(1):3–5.PubMedGoogle Scholar
  193. 193.
    Fang CJ, et al. Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood. 2008;111(2):624–32.PubMedCentralPubMedGoogle Scholar
  194. 194.
    Dragon-Durey MA, et al. Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol. 2010;21(12):2180–7.PubMedCentralPubMedGoogle Scholar
  195. 195.
    Sallee M, et al. Myocardial infarction is a complication of factor H-associated atypical HUS. Nephrol Dial Transplant. 2010;25(6):2028–32.PubMedGoogle Scholar
  196. 196.
    Maga TK, et al. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat. 2010;31(6):E1445–60.PubMedGoogle Scholar
  197. 197.
    Kavanagh D, Goodship TH, Richards A. Atypical hemolytic uremic syndrome. Semin Nephrol. 2013;33(6):508–30.PubMedCentralPubMedGoogle Scholar
  198. 198.
    Moore I, et al. 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. 2010;115(2):379–87.PubMedCentralPubMedGoogle Scholar
  199. 199.
    Delvaeye M, et al. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361(4):345–57.PubMedCentralPubMedGoogle Scholar
  200. 200.
    Lee JW. Early infantile onset of atypical hemolytic-uremic syndrome is caused by recessive mutations in DGKE. Clin Genet. 2013;84(4):342–3.PubMedGoogle Scholar
  201. 201.
    Lemaire M, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet. 2013;45(5):531–6.PubMedCentralPubMedGoogle Scholar
  202. 202.
    Heurich M, et al. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc Natl Acad Sci U S A. 2011;108(21):8761–6.PubMedCentralPubMedGoogle Scholar
  203. 203.
    Ermini L, et al. Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS. Mol Immunol. 2012;49(4):640–8.PubMedCentralPubMedGoogle Scholar
  204. 204.
    Campistol JM, et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2013;33(1):27–45.PubMedGoogle Scholar
  205. 205.
    Richards A, Kavanagh D, Atkinson JP. Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory states the examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration. Adv Immunol. 2007;96:141–77.PubMedGoogle Scholar
  206. 206.
    Ferreira VP, Pangburn MK, Cortes C. Complement control protein factor H: the good, the bad, and the inadequate. Mol Immunol. 2010;47(13):2187–97.PubMedCentralPubMedGoogle Scholar
  207. 207.
    Dragon-Durey MA, et al. The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome. J Med Genet. 2009;46(7):447–50.PubMedGoogle Scholar
  208. 208.
    Jozsi M, et al. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008;111(3):1512–4.PubMedGoogle Scholar
  209. 209.
    Goicoechea de Jorge E, et al. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proc Natl Acad Sci U S A. 2013;110(12):4685–90.PubMedCentralPubMedGoogle Scholar
  210. 210.
    Fremeaux-Bacchi V, et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood. 2008;112(13):4948–52.PubMedCentralPubMedGoogle Scholar
  211. 211.
    Goicoechea de Jorge E, et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2007;104(1):240–5.PubMedGoogle Scholar
  212. 212.
    Bresin E, et al. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol. 2013;24(3):475–86.PubMedCentralPubMedGoogle Scholar
  213. 213.
    Bu F, et al. Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2014;25(1):55–64.PubMedCentralPubMedGoogle Scholar
  214. 214.
    Ariceta G, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009;24(4):687–96.PubMedGoogle Scholar
  215. 215.
    Legendre CM, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368(23):2169–81.PubMedGoogle Scholar
  216. 216.
    Le Quintrec M, et al. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant. 2013;13(3):663–75.PubMedGoogle Scholar
  217. 217.
    Guigonis V, et al. Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation. Am J Kidney Dis. 2005;45(3):588–95.PubMedGoogle Scholar
  218. 218.
    Geraghty MT, et al. Cobalamin C defect associated with hemolytic-uremic syndrome. J Pediatr. 1992;120(6):934–7.PubMedGoogle Scholar
  219. 219.
    Chenel C, et al. Neonatal hemolytic-uremic syndrome, methylmalonic aciduria and homocystinuria caused by intracellular vitamin B 12 deficiency. Value of etiological diagnosis. Arch Fr Pediatr. 1993;50(9):749–54.PubMedGoogle Scholar
  220. 220.
    Rosenblatt DS, et al. Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC). J Inherit Metab Dis. 1997;20(4):528–38.PubMedGoogle Scholar
  221. 221.
    Lerner-Ellis JP, et al. Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. Hum Mutat. 2009;30(7):1072–81.PubMedGoogle Scholar
  222. 222.
    Cornec-Le Gall E, et al. Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency. Am J Kidney Dis. 2014;63(1):119–23.PubMedGoogle Scholar
  223. 223.
    Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585–94.PubMedCentralPubMedGoogle Scholar
  224. 224.
    Thauvin-Robinet C, et al. The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum. J Neurol Neurosurg Psychiatry. 2008;79(6):725–8.PubMedGoogle Scholar
  225. 225.
    Rock GA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991;325(6):393–7.PubMedGoogle Scholar
  226. 226.
    Carrillo-Carrasco N, Chandler RJ, Venditti CP. Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management. J Inherit Metab Dis. 2012;35(1):91–102.PubMedCentralPubMedGoogle Scholar
  227. 227.
    Menni F, et al. Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria. Pediatr Nephrol. 2012;27(8):1401–5.PubMedGoogle Scholar
  228. 228.
    Huemer M, et al. Prenatal and postnatal treatment in cobalamin C defect. J Pediatr. 2005;147(4):469–72.PubMedGoogle Scholar
  229. 229.
    Russo P, et al. A congenital anomaly of vitamin B12 metabolism: a study of three cases. Hum Pathol. 1992;23(5):504–12.PubMedGoogle Scholar
  230. 230.
    Zakarija A, et al. Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008). Kidney Int Suppl. 2009;75(112):S20–4.Google Scholar
  231. 231.
    Steinhubl SR, et al. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT investigators. Evaluation of platelet IIb/IIIa inhibitor for stenting. JAMA. 1999;281(9):806–10.PubMedGoogle Scholar
  232. 232.
    Webb RF, et al. Acute intravascular haemolysis due to quinine. N Z Med J. 1980;91(651):14–6.PubMedGoogle Scholar
  233. 233.
    Kojouri K, Vesely SK, George JN. Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes. Ann Intern Med. 2001;135(12):1047–51.PubMedGoogle Scholar
  234. 234.
    Trimarchi HM, et al. FK506-associated thrombotic microangiopathy: report of two cases and review of the literature. Transplantation. 1999;67(4):539–44.PubMedGoogle Scholar
  235. 235.
    Bennett CL, et al. Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention. Arch Intern Med. 1999;159(21):2524–8.PubMedGoogle Scholar
  236. 236.
    Neild GH, et al. Effect of cyclosporin A on prostacyclin synthesis by vascular tissue. Thromb Res. 1983;32(4):373–9.PubMedGoogle Scholar
  237. 237.
    Lyman NW, et al. Mitomycin-induced hemolytic-uremic syndrome. Successful treatment with corticosteroids and intense plasma exchange. Arch Intern Med. 1983;143(8):1617–8.PubMedGoogle Scholar
  238. 238.
    Teixeira L, et al. Gemcitabine-induced thrombotic microangiopathy. Presse Med. 2002;31(16):740–2.PubMedGoogle Scholar
  239. 239.
    Izzedine H, et al. Gemcitabine-induced thrombotic microangiopathy: a systematic review. Nephrol Dial Transplant. 2006;21(11):3038–45.PubMedGoogle Scholar
  240. 240.
    Gilbert RD, et al. Cisplatin-induced haemolytic uraemic syndrome associated with a novel intronic mutation of treated with eculizumab. Clin Kidney J. 2013;6(4):421–5.PubMedCentralPubMedGoogle Scholar
  241. 241.
    Kohn S, et al. Hepatotoxicity of combined treatment with cisplatin and gentamicin in the guinea pig. Ultrastruct Pathol. 2005;29(2):129–37.PubMedGoogle Scholar
  242. 242.
    Dieckmann KP, Struss WJ, Budde U. Evidence for acute vascular toxicity of cisplatin-based chemotherapy in patients with germ cell tumour. Anticancer Res. 2011;31(12):4501–5.PubMedGoogle Scholar
  243. 243.
    Choi MK, et al. TTP-HUS associated with sunitinib. Cancer Res Treat. 2008;40(4):211–3.PubMedCentralPubMedGoogle Scholar
  244. 244.
    Eremina V, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358(11):1129–36.PubMedCentralPubMedGoogle Scholar
  245. 245.
    Sartelet H, et al. Sirolimus-induced thrombotic microangiopathy is associated with decreased expression of vascular endothelial growth factor in kidneys. Am J Transplant. 2005;5(10):2441–7.PubMedGoogle Scholar
  246. 246.
    Zupancic M, Shah PC, Shah-Khan F. Gemcitabine-associated thrombotic thrombocytopenic purpura. Lancet Oncol. 2007;8(7):634–41.PubMedGoogle Scholar
  247. 247.
    Ho VT, et al. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11(8):571–5.PubMedGoogle Scholar
  248. 248.
    Jodele S, et al. A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2014 (in press).Google Scholar
  249. 249.
    Veyradier A, et al. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood. 2001;98(6):1765–72.PubMedGoogle Scholar
  250. 250.
    Qu L, Kiss JE. Thrombotic microangiopathy in transplantation and malignancy. Semin Thromb Hemost. 2005;31(6):691–9.PubMedGoogle Scholar
  251. 251.
    Zarifian A, et al. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int. 1999;55(6):2457–66.PubMedGoogle Scholar
  252. 252.
    Jackson AM, et al. Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Ann Intern Med. 1984;101(1):41–4.PubMedGoogle Scholar
  253. 253.
    Crocker J, Jones EL. Haemolytic-uraemic syndrome complicating long-term mitomycin C and 5-fluorouracil therapy for gastric carcinoma. J Clin Pathol. 1983;36(1):24–9.PubMedCentralPubMedGoogle Scholar
  254. 254.
    George JN, et al. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion. 2004;44(2):294–304.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Stead Family Department of Pediatrics, Department of Internal Medicine, Divisions of NephrologyUniversity of Iowa Children’s Hospital, Carver College of MedicineIowa CityUSA
  2. 2.Division of NephrologyIndianapolisUSA

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