title: Tailored eculizumab therapy in the management of complement factor H-mediated atypical hemolytic uremic syndrome in an adult kidney transplant recipient: a case report.
abstract: Atypical hemolytic uremic syndrome (aHUS) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury (AKI) which frequently progresses to end-stage renal disease (ESRD). In 50% of affected patients, mutations in complement regulatory proteins cause inappropriate complement activation with endothelial injury. Complement factor H (CFH) mutations cause 25% of aHUS cases; these patients have an 80% recurrence risk after kidney transplantation. Eculizumab, an anti-C5 antibody, is effective in limiting hemolysis episodes in patients with aHUS, but less is known about preventing recurrence after kidney transplantation. Herein we report the use of prophylactic eculizumab in an adult with aHUS who underwent kidney transplantation. A 31-year-old female presented with aHUS and progressive AKI associated with low complement 3 level leading to ESRD despite plasmapheresis and corticosteroids. She had a heterozygous nonsense mutation in CFH and reduced plasma CFH levels. She was given preoperative plasmapheresis and eculizumab and underwent living unrelated renal transplantation. Postoperatively, eculizumab was dosed to achieve low functional complement 5 levels and low soluble membrane attack complex levels and she has maintained excellent graft function without aHUS recurrence. We propose that eculizumab with titrated dosing should be used in CFH-mediated aHUS patients who are at a high risk of recurrence.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xie
authors.forename: C M
authors.initials: CM
authors.lastname: Nester
authors.forename: A I
authors.initials: AI
authors.lastname: Reed
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: C P
authors.initials: CP
authors.lastname: Thomas
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000601:surgery*; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D065766:Atypical Hemolytic Uremic Syndrome; D017242:Complement Factor H / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D009154:Mutation; D010956:Plasmapheresis; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D007166:Immunosuppressive Agents; D017242:Complement Factor H; C481642:eculizumab