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A time for reappraisal of “atypical” hemolytic uremic syndrome: should all patients be treated the same?

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Abstract

Atypical hemolytic uremic syndrome (HUS) refers to the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury in the absence of Shiga toxin-producing Escherichia coli exposure or Streptococcus pneumoniae infection. Currently, approximately 50 % of the atypical cases have demonstrable mutations in complement regulatory proteins. Historically, the diagnosis of atypical HUS portends a poor prognosis with a high rate of disease recurrence, progression to end-stage renal disease, and death. However, it is now evident that atypical HUS actually encompasses a heterogeneous group of disorders, and there are reports suggesting that some cases of atypical HUS have a favorable prognosis, similar to that of diarrhea-associated disease. We present three patients with the atypical HUS phenotype who had complete renal recovery and no disease recurrence. We believe it is important to distinguish those cases of atypical HUS associated with disorders of complement regulatory proteins from other idiopathic causes of nondiarrheal HUS given the implications for prognosis and treatment. Conclusion: Given the heterogeneous nature and variable prognosis of atypical HUS, treatment should be carefully considered prior to the use of long-term plasma therapy and/or eculizumab.

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References

  1. 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 24:687–696

    Article  PubMed  Google Scholar 

  2. Barnard PJ, Kibel M (1965) The haemolytic–uraemic syndrome of infancy and childhood. A report of eleven cases. Cent Afr J Med 11:4–11

    PubMed  CAS  Google Scholar 

  3. 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 70:423–431

    PubMed  CAS  Google Scholar 

  4. Bhimma R, Rollins NC, Coovadia HM, Adhikari M (1997) Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal. Pediatr Nephrol 11:560–564

    Article  PubMed  CAS  Google Scholar 

  5. 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 110:371–376

    Article  PubMed  Google Scholar 

  6. 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 108:1267–1279

    Article  PubMed  CAS  Google Scholar 

  7. Copelovitch L, Kaplan BS (2010) Streptococcus pneumoniae-associated hemolytic uremic syndrome: classification and the emergence of serotype 19A. Pediatrics 125:e174–182

    Article  PubMed  Google Scholar 

  8. 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 55:708–711

    Article  PubMed  Google Scholar 

  9. 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 16:555–563

    Article  PubMed  CAS  Google Scholar 

  10. Fitzpatrick MM, Walters MD, Trompeter RS, Dillon MJ, Barratt TM (1993) Atypical (non-diarrhea-associated) hemolytic–uremic syndrome in childhood. J Pediatr 122:532–537

    Article  PubMed  CAS  Google Scholar 

  11. 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 290:1360–1370

    Article  PubMed  CAS  Google Scholar 

  12. Gruppo RA, Rother RP (2009) Eculizumab for congenital atypical hemolytic–uremic syndrome. N Engl J Med 360:544–546

    Article  PubMed  CAS  Google Scholar 

  13. Kaplan BS (1977) Hemolytic uremic syndrome with recurrent episodes: an important subset. Clin Nephrol 8:495–498

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H (1985) The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis 151:775–782

    Article  PubMed  CAS  Google Scholar 

  17. Kelles A, Van Dyck M, Proesmans W (1994) Childhood haemolytic uraemic syndrome: long-term outcome and prognostic features. Eur J Pediatr 153:38–42

    Article  PubMed  CAS  Google Scholar 

  18. Loirat C, Baudouin V, Sonsino E, Mariani-Kurdjian P, Elion J (1993) Hemolytic–uremic syndrome in the child. Adv Nephrol Necker Hosp 22:141–168

    PubMed  CAS  Google Scholar 

  19. Loirat C, Sonsino E, Hinglais N, Jais JP, Landais P, Fermanian J (1988) Treatment of the childhood haemolytic uraemic syndrome with plasma. A multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatr Nephrol 2:279–285

    Article  PubMed  CAS  Google Scholar 

  20. Matsukuma E, Gotoh Y, Kuroyanagi Y, Yamada T, Iwasa M, Yamakawa S, Nagai T, Takagi N, Mae H, Iijima K, Bresin E (2011) A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations. Clin Exp Nephrol 15:269–274

    Article  PubMed  Google Scholar 

  21. Neuhaus TJ, Calonder S, Leumann EP (1997) Heterogeneity of atypical haemolytic uraemic syndromes. Arch Dis Child 76:518–521

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. 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 360:542–544

    Article  PubMed  Google Scholar 

  24. Proesmans W (1996) Typical and atypical hemolytic uremic syndrome. Kidney Blood Press Res 19:205–208

    Article  PubMed  CAS  Google Scholar 

  25. Remuzzi G, Misiani R, Marchesi D, Livio M, Mecca G, de Gaetano G, Donati MD (1979) Treatment of the hemolytic uremic syndrome with plasma. Clin Nephrol 12:279–284

    PubMed  CAS  Google Scholar 

  26. Rizzoni G, Claris-Appiani A, Edefonti A, Facchin P, Franchini F, Gusmano R, Imbasciati E, Pavanello L, Perfumo F, Remuzzi G (1988) Plasma infusion for hemolytic–uremic syndrome in children: results of a multicenter controlled trial. J Pediatr 112:284–290

    Article  PubMed  CAS  Google Scholar 

  27. 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 18:2392–2400

    Article  PubMed  CAS  Google Scholar 

  28. Siegler RL, Pavia AT, Hansen FL, Christofferson RD, Cook JB (1996) Atypical hemolytic–uremic syndrome: a comparison with postdiarrheal disease. J Pediatr 128:505–511

    Article  PubMed  CAS  Google Scholar 

  29. Stahl AL, Kristoffersson A, Olin AI, Olsson ML, Roodhooft AM, Proesmans W, Karpman D (2009) A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome. Mol Immunol 46:2236–2243

    Article  PubMed  CAS  Google Scholar 

  30. Tonshoff B, Sammet A, Sanden I, Mehls O, Waldherr R, Scharer K (1994) Outcome and prognostic determinants in the hemolytic uremic syndrome of children. Nephron 68:63–70

    Article  PubMed  CAS  Google Scholar 

  31. Weitz M, Amon O, Bassler D, Koenigsrainer A, Nadalin S (2011) Prophylactic eculizumab prior to kidney transplantation for atypical hemolytic uremic syndrome. Pediatr Nephrol 26:1325–1329

    Article  PubMed  Google Scholar 

  32. 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 362:1746–1748

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors have no financial conflicts of interest to disclose as defined by the European Journal of Pediatrics.

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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, 1 Main, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Rebecca L. Ruebner, Bernard S. Kaplan & Lawrence Copelovitch

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  1. Rebecca L. Ruebner
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  2. Bernard S. Kaplan
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  3. Lawrence Copelovitch
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Correspondence to Lawrence Copelovitch.

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Ruebner, R.L., Kaplan, B.S. & Copelovitch, L. A time for reappraisal of “atypical” hemolytic uremic syndrome: should all patients be treated the same?. Eur J Pediatr 171, 1519–1525 (2012). https://doi.org/10.1007/s00431-012-1763-z

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  • DOI: https://doi.org/10.1007/s00431-012-1763-z

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