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Complement Inhibitor Eculizumab in Atypical Hemolytic Uremic Syndrome

Christoph J. Mache^*, Birgit Acham-Roschitz^*, Veronique Frémeaux-Bacchi, Michael Kirschfink, Peter F. Zipfel, Siegfried Roedl^*, Udo Vester^||, and Ekkehard Ring^*

^* Department of Pediatrics, Medical University Graz, Graz, Austria; Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, and Cordeliers Research Center, INSERM UMRS 872, Paris, France; and Institute of Immunology, University of Heidelberg, Heidelberg, Department of Infection, Hans Knoell Institute for Natural Products Research and Friedrich Schiller University of Jena, Jena, and ^|| Clinic of Pediatric Nephrology, University of Duisburg-Essen, Essen, Germany

Correspondence: Dr. Christoph J. Mache, Department of Pediatrics, Medical University Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. Phone: 0043-316-385-84502; Fax: 0043-316-385-2619; E-mail: christoph.mache{at}medunigraz.at

Background and objectives: Atypical hemolytic uremic syndrome (aHUS) is associated with a congenital or acquired dysregulation of the complement alternative pathway that leads to continuous complement activation on host cells causing inflammation and damage. Eculizumab, a humanized mAb against complement protein C5, inhibits activation of the terminal complement pathway.

Design, setting, participants, & measurements: We report an adolescent with relapsing unclassified aHUS. On admission, a high plasma creatinine level indicated a poor prognosis, and hemodialysis had to be started. Plasma exchanges were initially effective against the microangiopathic hemolytic activity and allowed a temporary improvement of renal function with termination of hemodialysis after 7 wk. Subsequently, plasma exchanges (three times per week) failed to prevent ongoing aHUS activity and progressive renal failure. After 12 wk, aHUS treatment was switched to eculizumab.

Results: Eculizumab was effective in terminating the microangiopathic hemolytic process in two aHUS relapses; however, after normalization of complement activity, aHUS recurred and ultimately led to anuric end-stage renal failure.

Conclusions: In this patient, complement inhibition by eculizumab temporarily terminated the microangiopathic hemolytic activity. Nevertheless, renal damage as a result of preceding and subsequent aHUS activity resulted in end-stage renal failure; therefore, therapeutic success may depend on early administration of eculizumab. The optimal duration of treatment may be variable and remains to be determined.