Hemolytic Uremic Syndrome

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Key points

  • Shiga toxin–associated hemolytic uremic syndrome (HUS) is responsible for approximately 90% of cases of HUS in children, and supportive care remains the backbone of therapy.

  • With early fluid resuscitation in the enteritis phase, outcomes for Shiga toxin–associated HUS have improved; however, up to 25% of patients develop chronic kidney disease, hypertension, or proteinuria.

  • Streptococcus pneumoniae is likely an underrepresented cause of HUS, responsible for about 5% of cases in children, most

Epidemiology and Pathomechanism

HUS associated with STEC (STEC-HUS) is classically a disease of children, with a peak incidence from 3 to 5 years of age. In the United States and Europe, the predominant pathogen is E coli O157:H7, whereas Shigella dysenteriae type 1 remains a predominant cause of disease in other countries.5 The overall incidence of HUS is 1 to 2 cases per 100,000 per year, with most cases attributed to STEC-HUS.3 In children presenting with E coli enterocolitis, approximately 15% will progress to the

Epidemiology and Pathomechanism

Estimated to account for approximately 5% of all cases of HUS in children, and 38% to 43% of HUS not caused by Shiga toxin,36 pneumococcal HUS or S pneumoniae-associated HUS (SP-HUS) has an annual incidence of approximately 0.06 per 100,000 children less than 18 years of age.3 The incidence of HUS following invasive pneumococcal infections is estimated to be about 0.4% to 0.6%, most commonly occurring after pneumonia, particularly complicated by empyema, or meningitis.37 With the introduction

Epidemiology and Pathomechanism

aHUS, also termed complement-mediated TMA,4 is responsible for approximately 5% to 10% of HUS seen in children. Overall incidence is estimated at 2 per 1,000,000 individuals in the United States, with 70% of children having their first episode before 2 years of age, and with equal frequency in boys and girls when onset is in childhood.2, 43 The disease is frequently sporadic despite heterozygous pathogenic variants in complement genes often identified in the patient and one of their healthy

Epidemiology and Pathomechanism

Cobalamin C hemolytic uremic syndrome is a form of HUS that is a rare autosomal recessive disorder of cobalamin (vitamin B12) metabolism that causes TMA and multiorgan dysfunction in infants, although there is 1 reported case with presentation in adulthood.2, 4 Its incidence is estimated at 1 in 100,000 live births66 with more than 300 cases described.67 The mutations are on the MMACHC gene encoding the methylmalonic aciduria and homocystinuria type C protein, leading to hyperhomocysteinemia,

Clinical features

The clinical presentations of cobalamin C deficiency vary considerably and are generally divided into early-onset and late-onset disease, with early-onset disease having a more severe phenotype.66 Early-onset disease usually manifests within the first year of life and has multisystem involvement, presenting with feeding difficulties, failure to thrive, somnolence/lethargy, and hypotonia.66 Patients with late-onset disease are rare and can present any time from childhood to adulthood, generally

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References (68)

  • D. Ricklin et al.

    Complement in clinical medicine: Clinical trials, case reports and therapy monitoring

    Mol Immunol

    (2017)
  • G. Ardissino et al.

    Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update

    Am J Kidney Dis

    (2015)
  • T.H. Goodship et al.

    Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) controversies conference

    Kidney Int

    (2017)
  • M. Cugno et al.

    Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome

    J Thromb Haemost

    (2014)
  • C. Gasser et al.

    Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia

    Schweiz Med Wochenschr

    (1955)
  • M. Salvadori et al.

    Update on hemolytic uremic syndrome: diagnostic and therapeutic recommendations

    World J Nephrol

    (2013)
  • J.N. George et al.

    Syndromes of thrombotic microangiopathy

    N Engl J Med

    (2014)
  • K. Kottke-Marchant

    Diagnostic approach to microangiopathic hemolytic disorders

    Int J Lab Hematol

    (2017)
  • J.C. Chan et al.

    The hemolytic-uremic syndrome in nonrelated adopted siblings

    J Pediatr

    (1969)
  • D. Orth et al.

    Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome

    J Immunol

    (2009)
  • J.M. Thurman et al.

    Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome

    Clin J Am Soc Nephrol

    (2009)
  • N. Safdar et al.

    Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis

    JAMA

    (2002)
  • S. Nathanson et al.

    Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome

    Clin J Am Soc Nephrol

    (2010)
  • S. Loos et al.

    An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children

    Clin Infect Dis

    (2012)
  • J.M. Spinale et al.

    Long-term outcomes of Shiga toxin hemolytic uremic syndrome

    Pediatr Nephrol

    (2013)
  • J.A. Ake et al.

    Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion

    Pediatrics

    (2005)
  • C.A. Hickey et al.

    Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome

    Arch Pediatr Adolesc Med

    (2011)
  • S. Grisaru et al.

    Associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga Toxin-producing Escherichia coli: a systematic review and meta-analysis

    JAMA Pediatr

    (2017)
  • G. Ardissino et al.

    Early volume expansion and outcomes of hemolytic uremic syndrome

    Pediatrics

    (2016)
  • C.S. Wong et al.

    The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections

    N Engl J Med

    (2000)
  • K.E. Smith et al.

    Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic uremic syndrome, Minnesota

    Pediatr Infect Dis J

    (2012)
  • M. Nitschke et al.

    Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4

    JAMA

    (2012)
  • J. Menne et al.

    Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study

    BMJ

    (2012)
  • B.R. Weil et al.

    Bleeding risk for surgical dialysis procedures in children with hemolytic uremic syndrome

    Pediatr Nephrol

    (2010)
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      It can be caused by infection with either STX producing Escherichia coli (STEC) serotype 0157:H7 or Shigella dysenteriae type 1.77–79 Other causes include infection with Streptococcus pneumoniae (SpHUS),80–83 influenza,84 H1N1,85,86 HIV,87 and inborn errors of metabolism including cobalamin C deficiency88,89 and diacylglycerol kinase epsilon (DGKE) deficiency.90,91 Secondary forms of HUS also occur in various disease states and conditions including bone marrow or solid organ transplant, malignancy, autoimmune disorders, malignant hypertension, and drug-associated HUS.92–96

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    Disclosure Statement: The authors have nothing to disclose.

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