Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome.
OBJECTIVE
Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common cause of acute kidney injury in children. Mutations in alternative pathway (AP) complement regulatory proteins have been identified in severe cases of thrombotic microangiopathy, but the role of the AP in D+HUS has not been studied. Therefore, we determined whether plasma levels of markers of activation of the AP are increased in D+HUS and are biomarkers of the severity of renal injury that predict the need for dialysis.


METHODS
Patients were randomly selected from among participants in the HUS-SYNSORB Pk trial. Plasma samples were collected on days 1, 4, 7, and 10 after enrollment and day 28 after discharge from the hospital. Levels of two complement pathway products, Bb and SC5b-9, were determined by ELISA.


RESULTS
Seventeen children (6 boys and 11 girls; age, 5.4 +/- 3.5 yr) were studied. Eight (47%) required dialysis support, and two had serious extrarenal events. On the day of enrollment, plasma levels of Bb and SC5b-9 were significantly increased in all patients compared with healthy controls (P < 0.01). The elevated concentrations normalized by day 28 after discharge. Circulating levels of complement pathway fragments did not correlate with severity of renal injury or occurrence of complications.


CONCLUSIONS
Patients with acute-onset D+HUS manifest activation of the AP of complement that is temporally related to the onset of disease and that resolves within 1 mo. Therapies to inhibit the AP of complement may be useful in attenuating the severity of renal injury and extrarenal complications.
Thurman
Joshua M
JM
Department of Medicine, Division of Nephrology, University of Colorado, Denver School of Medicine, Aurora, CO, USA.
Marians
Russell
R
Emlen
Woodruff
W
Wood
Susan
S
Smith
Christopher
C
Akana
Hillary
H
Holers
V Michael
VM
Lesser
Martin
M
Kline
Myriam
M
Hoffman
Cathy
C
Christen
Erica
E
Trachtman
Howard
H
D058186:Acute Kidney Injury / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D011415:Complement Factor B / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003170:Complement Pathway, Alternative; D003967:Diarrhea / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007223:Infant; D008297:Male; D006435:Renal Dialysis; D012720:Severity of Illness Index; D057049:Thrombotic Microangiopathies / Q000097:blood* / Q000503:physiopathology
D015415:Biomarkers; D015938:Complement Membrane Attack Complex; C047610:SC5b-9 protein complex; D011415:Complement Factor B