Complement inhibitor eculizumab in atypical hemolytic uremic syndrome.
OBJECTIVE
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.


METHODS
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.
Mache
Christoph J
CJ
Department of Pediatrics, Medical University Graz, Auenbruggerplatz 30, Graz A-8036, Austria. christoph.mache@medunigraz.at
Acham-Roschitz
Birgit
B
Frémeaux-Bacchi
Veronique
V
Kirschfink
Michael
M
Zipfel
Peter F
PF
Roedl
Siegfried
S
Vester
Udo
U
Ring
Ekkehard
E
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D003167:Complement Activation / Q000187:drug effects*; D006463:Hemolytic-Uremic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008297:Male; D010951:Plasma Exchange; D012008:Recurrence; D006435:Renal Dialysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C481642:eculizumab