Pulse cyclophosphamide therapy and clinical remission in atypical hemolytic uremic syndrome with anti-complement factor H autoantibodies

Am J Kidney Dis. 2010 May;55(5):923-7. doi: 10.1053/j.ajkd.2009.12.026. Epub 2010 Mar 3.


We report 3 children with atypical hemolytic uremic syndrome associated with anti-complement factor H (CFH) autoantibodies who presented with sustained remission with low antibody titers and normal kidney function after plasma exchanges (PEs) and cyclophosphamide pulses. The 3 children initially presented with acute vomiting, fatigue, gross hematuria, hypertension, hemolytic anemia, thrombocytopenia, nephrotic syndrome, and acute kidney injury. C3 levels were normal in patients 1 and 3 and low in patient 2 (0.376 mg/mL [0.376 g/L]). CFH antibody titers were increased (15,000 to > 32,000 arbitrary units [AU]). Patient 1, an 11-year-old boy, was treated with 12 PEs, leading to a decrease in CFH antibody titer (to 800 AU). A first relapse 1 month later was treated with 6 PEs and 4 rituximab infusions. A second relapse 3 months later required 5 PEs, and the patient received oral steroids (0.5 mg/d/kg body weight) and 5 cyclophosphamide pulses (1 g/1.73 m(2)), leading to sustained remission with normal kidney function (estimated glomerular filtration rate [eGFR], 120 mL/min/1.73 m(2) [2.0 mL/s/1.73 m(2)]) and a stable decrease in CFH antibody titer (to 2,000 AU) 3 years later. Patient 2, a 5-year-old boy, required dialysis therapy for 2 weeks. He received 3 plasma infusions without remission. Six PEs associated with 2 cyclophosphamide pulses (0.5 g/1.73 m(2)) and steroids (1 mg/d/kg body weight) led to rapid remission, with eGFR of 107 mL/min/1.73 m(2) [1.78 mL/s/1.73 m(2)] and a prolonged decrease in CFH antibody titer after 15 months (1,300 AU). Patient 3, a 16-month-old boy, was treated with oral steroids (1 mg/d/kg body weight), 2 PEs, and 2 cyclophosphamide pulses (0.5 g/1.73 m(2)), resulting in a stable decrease in CFH antibody titer to 276 AU. Kidney function quickly normalized (eGFR, 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]) and has remained normal after 14 months. All 3 patients show a homozygous deletion mutation of the CFHR1 and CFHR3 genes. Cyclophosphamide pulses with PE may lead to a prolonged decrease in CFH antibody titers and a favorable outcome of atypical hemolytic uremic syndrome and kidney function.

Publication types

  • Case Reports

MeSH terms

  • Autoantibodies / blood
  • Blood Proteins / genetics
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Complement C3b Inactivator Proteins / genetics
  • Complement Factor H / immunology
  • Cyclophosphamide / administration & dosage*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Predisposition to Disease
  • Hemolytic-Uremic Syndrome / drug therapy*
  • Hemolytic-Uremic Syndrome / genetics
  • Hemolytic-Uremic Syndrome / immunology*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Infant
  • Male
  • Pulse Therapy, Drug


  • Autoantibodies
  • Blood Proteins
  • CFHR1 protein, human
  • CFHR3 protein, human
  • Complement C3b Inactivator Proteins
  • Immunosuppressive Agents
  • Complement Factor H
  • Cyclophosphamide