title: Pulse cyclophosphamide therapy and clinical remission in atypical hemolytic uremic syndrome with anti-complement factor H autoantibodies.
abstract: 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.
authors.affiliation: Néphrologie Pédiatrique et centre de référence MARHEA, Hôpital Necker-Enfants Malades, APHP, Université Paris Descartes, Paris, France. olivia.boyer@nck.aphp.fr
authors.forename: Olivia
authors.initials: O
authors.lastname: Boyer
authors.forename: Eve
authors.initials: E
authors.lastname: Balzamo
authors.forename: Marina
authors.initials: M
authors.lastname: Charbit
authors.forename: Nathalie
authors.initials: N
authors.lastname: Biebuyck-Gougé
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001798:Blood Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D017242:Complement Factor H / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D020551:Pulse Therapy, Drug
chemical_list: D001323:Autoantibodies; D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D007166:Immunosuppressive Agents; D017242:Complement Factor H; D003520:Cyclophosphamide