American Journal of Kidney Diseases

Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome in Infants

Published:December 26, 2011DOI:
      A 28-day-old male newborn weighing 3.6 kg was given a diagnosis of atypical hemolytic-uremic syndrome, new-onset thrombotic microangiopathy (TMA; hemoglobin, 7.7 g/dL; schistocytes, 9%), thrombocytopenia (platelets, 49 × 103/μL [49 × 109/L]), and acute kidney failure (serum creatinine, 1.13 mg/dL [99.8 μmol/L], corresponding to estimated glomerular filtration rate [eGFR] of 15 mL/min/1.73 m2 [0.25 mL/s/1.73 m2]). Repeated high-volume plasma infusions were ineffective. Plasma exchange was attempted, but not tolerated. The patient required mechanical ventilation and continuous renal replacement therapy. He developed multiple intestinal perforations and leg skin necrosis due to systemic TMA. A low C3 level (36 mg/dL) suggested complement activation. Eculizumab, 300 mg, was administered, and within 48 hours the patient recovered from acute kidney failure, with complete hematologic remission 2 weeks later. The infant, 14 months old at the time of writing, continues to receive eculizumab, 300 mg, every 3 weeks; he is free of disease activity and has a normal creatinine level of 0.2 mg/dL (17.68 μmol/L; corresponding to eGFR of 110 mL/min/1.73 m2 [1.83 mL/s/1.73 m2]), but mild proteinuria (urinary protein-creatine ratio, 1 mg/g). Results of additional studies, including probing for cobalamin anomalies and measuring levels of ADAMTS13, complement factor H (CFH), factor I (CFI), and membrane cofactor protein (MCP), were unremarkable. Antibodies to CFH were undetectable, and mutation testing of the genes for CFH, CFI, and MCP gave negative results. Treatment with eculizumab was life saving, and with continued treatment, the patient showed sustained freedom from clinical TMA complications.

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        • Noris M.
        • Remuzzi G.
        Atypical hemolytic–uremic syndrome.
        N Engl J Med. 2009; 361: 1676-1687
        • Noris M.
        • Caprioli J.
        • Bresin E.
        • 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: 1844-1859
        • Sellier-Leclerc A.L.
        • Fremeaux-Bacchi V.
        • Dragon-Durey M.A.
        • et al.
        • French Society of Pediatric Nephrology
        Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.
        J Am Soc Nephrol. 2007; 18: 2392-2400
        • Benz K.
        • Amann K.
        Thrombotic microangiopathy: new insights.
        Curr Opin Nephrol Hypertens. 2010; 19: 242-247
        • Ariceta G.
        • Besbas N.
        • Johnson S.
        • et al.
        • European Paediatric Study Group for HUS
        Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome.
        Pediatr Nephrol. 2009; 24: 687-696
        • Loirat C.
        • Garnier A.
        • Sellier-Leclerc L.
        • Kwon T.
        Plasmatherapy in atypical uremic syndrome.
        Semin Thromb Hemost. 2010; 36: 673-681
        • Michon B.
        • Moghrabi A.
        • Winikoff R.
        • et al.
        Complications of apheresis in children.
        Transfusion. 2007; 47: 1837-1842
        • Thomas T.C.
        • Rollins S.A.
        • Rother R.P.
        • et al.
        Inhibition of complement activity by humanized anti-C5 antibody and single chain Fv.
        Mol Immunol. 1996; 33: 1389-1401
      1. Soliris (eculizumab) package insert.
        (Accessed October 25, 2011)
        • Levy G.G.
        • Nichols W.C.
        • Lian E.C.
        • et al.
        Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura.
        Nature. 2001; 413: 488-494
        • Sharma A.P.
        • Greenberg C.R.
        • Prasad A.N.
        • Prasad C.
        Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder.
        Pediatr Nephrol. 2007; 22: 2097-2103
        • Abarrategui-Garrido C.
        • Melgosa M.
        • Peña-Carrión A.
        • et al.
        Mutations in proteins of the alternative pathway of complement and the pathogenesis of atypical hemolytic uremic syndrome.
        Am J Kidney Dis. 2008; 52: 171-180
        • Loirat C.
        • Noris M.
        • Fremeaux-Bacchi V.
        Complement and the atypical hemolytic uremic syndrome in children.
        Pediatr Nephrol. 2008; 23: 1957-1972
        • Gruppo R.A.
        • Rother R.P.
        Eculizumab for congenital atypical hemolytic-uremic syndrome.
        N Engl J Med. 2009; 360: 544-546
      2. An open-label, multi-center clinical trial of eculizumab in pediatric patients with atypical hemolytic-uremic syndrome.
        (Accessed October 25, 2011)