Prophylactic eculizumab prior to kidney transplantation for atypical hemolytic uremic syndrome
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BRIEF REPORT
Prophylactic eculizumab prior to kidney transplantation for atypical hemolytic uremic syndrome Marcus Weitz & Oliver Amon & Dirk Bassler & Alfred Koenigsrainer & Silvio Nadalin
Received: 29 October 2010 / Revised: 21 March 2011 / Accepted: 21 March 2011 / Published online: 10 May 2011 # IPNA 2011
Abstract Atypical hemolytic uremic syndrome (aHUS) in childhood is a rare disease associated with high morbidity and mortality. Most cases progress to end-stage renal failure. In approximately 50% of affected patients, mutations in genes encoding complement proteins are causative of the impairment in the regulation of the complement alternative pathway. This leads to deficient host cell protection and inappropriate complement activation on platelets and endothelial cells, particularly in the kidneys. Complement factor H (FH) heterozygosity induces unregulated activation of the membrane attack complex (MAC) C5b-9. Present therapeutic strategies for aHUS include lifelong plasmapheresis and renal dialysis. Unfortunately, kidney transplantation is frequently an unsatisfactory intervention due to the high rate of post-transplantation HUS recurrence, particularly in patients with FH mutation. Combined liver–kidney transplantation is also associated with poor outcome, mostly as a result of premature liver failure secondary to uncontrolled complement activation. Eculizumab is a complement C5 antibody that inhibits complement factor 5a (C5a) and the formation of the MAC. Thus, this antibody may be a promising new agent for M. Weitz : O. Amon : D. Bassler University Children’s Hospital Tuebingen, Tuebingen, Germany A. Koenigsrainer : S. Nadalin Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany M. Weitz (*) Division of Paediatric Nephrology, Department of Paediatrics, Hoppe Seyler Street 1, 72076 Tuebingen, Germany e-mail: [email protected]
patients with an aHUS undergoing kidney transplantation. We present the first case of a young patient with aHUS who received eculizumab as prophylactic treatment prior to a successful kidney transplantation. Keywords Complement factor H . Complement inhibition . C5 antibody . Membrane attack complex . Disease recurrence . Renal transplantation
Introduction Atypical hemolytic uremic syndrome (aHUS) in childhood is a rare disease associated with thrombotic microangiopathy, thrombocytopenia, and acute renal failure. The mortality rate varies between 10% and approximately 25%, with 50% progressing to end-stage renal failure [1]. An innate disorder in the activation of the complement cascade is probably the origin of this disease. In approximately 50% of affected patients, mutations in genes (incomplete penetrance) encoding complement proteins are causative of the impairment in the regulation of the complement alternative pathway, leading to deficient host cell protection and inappropriate complement activation on platelets and endothelial cells, particularly in the kidneys [2]. In some cases, a complement factor H
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