Abstract
Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma—citrated plasma mixed with a control sera pool (1:1)—to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome–activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6–9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.
Funder
Spanish Kidney Research Network
Instituto de Salud Carlos III
[ISCIII]-RETIC
Red de Investigación Renal [REDinREN]
Fundació Miarnau
Jazz Pharmaceuticals
German Jose Carreras Leukaemia Foundation
ISCIII
Fondo de Investigación en Salud
Integrated Project in Health Institutes
Technology Development Projects in Health 2016
Centres de Recerca de Catalunya Programme of the Generalitat de Catalunya
Generalitat de Catalunya
Fondo Europeo de Desarrollo Regional [FEDER]
FEDER
Autonomous Region of Madrid
RedInRen
“La Caixa” Foundation
Cerebra Foundation for the Brain Injured Child
L’Agència de Gestió d’Ajuts Universitaris i de Recerca
Fundació Dexeus Mujer
Publisher
American Society of Nephrology (ASN)
Subject
Transplantation,Nephrology,Critical Care and Intensive Care Medicine,Epidemiology
Cited by
64 articles.
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