title: Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment.
abstract: BACKGROUND
  Eculizumab is approved for atypical hemolytic uremic syndrome (aHUS). Guidelines discuss the importance of prompt treatment. We report a post hoc analysis investigating the effect of baseline factors, including patient characteristics and time from the latest aHUS manifestation to eculizumab initiation, on change from baseline in estimated glomerular filtration rate (eGFR) and other outcomes.
  
  
  METHODS
  Data were pooled from four phase 2, open-label, single-arm, prospective clinical studies of eculizumab for patients with aHUS. Multivariate regressions identified predictors of eGFR change from baseline. The proportion of patients achieving sustained eGFR increase (defined: ≥15 ml/min/1.73 m2for ≥28 days) and platelet count normalization were evaluated 1 year post-treatment. Baseline characteristics and eGFR outcomes were summarized by time to treatment from last aHUS manifestation [≤7 days (n = 21) versus >7 days (n = 76)].
  
  
  RESULTS
  Baseline eGFR were similar between groups. Multivariate regression analysis demonstrated time from aHUS manifestation to eculizumab treatment, age, baseline lactate dehydrogenase (LDH) and baseline hemoglobin were independently predictive of eGFR change from baseline. Mean eGFR change from baseline at 1 year was significantly higher in patients treated in ≤7 days than >7 days (57 vs. 23 ml/min/1.73 m2, p = 0.0098). After 1 year, 17/21 and 36/76 patients in the ≤7 and >7 day groups, respectively, achieved a sustained increase in eGFR. Mean time to platelet count normalization was similar between groups.
  
  
  CONCLUSIONS
  Younger age, higher baseline LDH and lower baseline hemoglobin were associated with greater eGFR improvements. Early eculizumab initiation led to improved renal recovery, demonstrating the importance of rapid diagnosis and treatment of patients with aHUS.
authors.affiliation: University Hospital Ghent, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Johan Vande
authors.initials: JV
authors.lastname: Walle
authors.affiliation: Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.affiliation: Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ardissino
authors.affiliation: Alexion Pharmaceuticals, Cheshire, CT, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Wang
authors.affiliation: Alexion Pharmaceuticals, Cheshire, CT, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Kincaid
authors.affiliation: Medical School Hannover, Hannover, Germany. Haller.Hermann@mh-hannover.de.
authors.forename: Herman
authors.initials: H
authors.lastname: Haller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; C481642:eculizumab; D007770:L-Lactate Dehydrogenase
keywords: Atypical hemolytic uremic syndrome; Chronic kidney disease; Eculizumab; Thrombocytopenia; Thrombotic microangiopathy