Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening, chronic disease that can affect patients of all ages. aHUS is caused by uncontrolled complement activation due to genetic defects of complement regulation. Plasma exchange or infusion has been used to manage aHUS and may transiently maintain hematologic variables in some patients, but as the underlying complement dysregulation persists, end-stage renal disease or death occurs in 33% to 40% of patients during the first clinical manifestation. Here we present a pediatric case showing that first-line eculizumab treatment successfully blocked the progression of thrombotic microangiopathy in aHUS.

Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan

“…Our results mostly correspond with the results of previous case reports and clinical trials of eculizumab for aHUS patients [9][10][11][12][13][14][15][16].…”

“…This new drug received approval for the indication of aHUS in the United States and Europe in 2012, and in Japan in 2013. The previous case series and the results of clinical trials demonstrated that eculizumab was significantly more effective than conventional plasma therapy for aHUS patients [9][10][11][12][13][14][15][16]. Zuber et al [9] reviewed the case series of aHUS patients who were treated with eculizumab as a first-line therapy or a rescue therapy.…”

“…This drug terminates the activated complement pathway by binding C5 and inhibiting the generation of pro-inflammatory C5a and the lytic C5b-9 membrane attack complex [9]. To date, some reports have demonstrated that eculizumab is effective in pediatric aHUS patients [9,[12][13][14][15][16]. However, the efficacy and safety of eculizumab for Japanese pediatric aHUS patients remain unclear.…”

Eculizumab to Treat Antibody-Mediated Rejection in a 7-Year-Old Kidney Transplant Recipient

“…20 It should be noted that eculizumab has also been used successfully in children, including transplant recipients, to treat atypical hemolytic uremic syndrome. 21,22 In our case, complement levels of CH50, C3, C4, factor H, and factor I were normal, and no anti-factor H autoantibody was present. Genetic analysis of complement regulatory genes was also negative for mutations on complement factor H, factor I, MCP/CD46, and complement factor H-related protein 5 and for hybrid complement gene.…”

An Atypical Cause Of Atypical Hemolytic Uremic Syndrome

“…In these cases Eculizumab, a humanized monoclonal antibody to C5, is a life altering tool. 7,8 Although Plavix is known to cause TTP/HUS independent of ADAMSTS-13 levels, most cases occur within two weeks of initiation of the drug. Our patient had been on Plavix for years making Plavix induced TTP/HUS unlikely in this case.…”