Complement inhibitor eculizumab in atypical hemolytic uremic syndrome.

Abstract

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.

• Authors: Christoph J Mache, Birgit Acham-Roschitz, Veronique Frémeaux-Bacchi, Michael Kirschfink, Peter F Zipfel, Siegfried Roedl, Udo Vester, Ekkehard Ring
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 4 Issue 8 Pg. 1312-6 (Aug 2009) ISSN: 1555-905X [Electronic] United States
• PMID: 19556379 (Publication Type: Case Reports, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunologic Factors
• eculizumab

Topics

• Adolescent
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Complement Activation (drug effects)
• Hemolytic-Uremic Syndrome (complications, drug therapy, immunology)
• Humans
• Immunologic Factors (administration & dosage)
• Kidney Failure, Chronic (immunology, therapy)
• Male
• Plasma Exchange
• Recurrence
• Renal Dialysis
• Treatment Outcome