title: Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases.
abstract: BACKGROUND
  Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys.
  
  
  METHODS
  A retrospective study was conducted. aHUS was defined as the presence of 3 or more of the following: acute kidney injury (serum creatinine >1.4 mg/dL [120 μmol/L]), mechanical hemolytic anemia, thrombocytopenia, and the presence of thrombotic microangiopathy features in a kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg infusions of eculizumab were included.
  
  
  METHODS
  19 patients were identified through a query sent to all French nephrology centers.
  
  
  METHODS
  Evolution of kidney function, hemolysis, and thrombocytopenia after the initiation of eculizumab therapy.
  
  
  RESULTS
  All patients had acute kidney injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis. Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3 patients received eculizumab. Median time between aHUS onset and eculizumab therapy initiation was 6 (range, 1-60) days and median time to platelet count normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis-dependent chronic kidney disease, and 7 had normalized kidney function. At last follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate, 17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end-stage renal disease within 3 months and 1 year of aHUS onset were reduced by half in eculizumab-treated patients compared with recent historical controls.
  
  
  CONCLUSIONS
  Retrospective study and use of historical controls.
  
  
  CONCLUSIONS
  Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.
authors.affiliation: Department of Nephrology and Immunology, ITUN and INSERM UMR S-1064, CHU de Nantes, Nantes, France. Electronic address: fadi.fakhouri@univ-nantes.fr.
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.affiliation: Department of Nephrology, CHU de Bordeaux, Bordeaux, France.
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.affiliation: Department of Nephrology, CHU de Lille, Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Provot
authors.affiliation: Department of Nephrology, CHU de Tours, Tours, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Barbet
authors.affiliation: Department of Nephrology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Karras
authors.affiliation: Department of Nephrology, CHU d'Amiens, Amiens, France.
authors.forename: Raifah
authors.initials: R
authors.lastname: Makdassi
authors.affiliation: Department of Nephrology, CHU de Besançon, Besançon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Courivaud
authors.affiliation: Department of Nephrology, CH de Bourges, Bourges, France.
authors.forename: Khair
authors.initials: K
authors.lastname: Rifard
authors.affiliation: Department of Nephrology, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Servais
authors.affiliation: Department of Nephrology, CHR de Metz-Thionville, Metz, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Allard
authors.affiliation: Department of Nephrology, CHU d'Angers, Angers, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Besson
authors.affiliation: Department of Nephrology, CHU d'Angers, Angers, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Cousin
authors.affiliation: Department of Nephrology, CHU de Caen, Caen, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Châtelet
authors.affiliation: Department of Pathology, CHU de Poitiers, Poitiers, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Goujon
authors.affiliation: Department of Nephrology, CH du Mans, Le Mans, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Coindre
authors.affiliation: Department of Nephrology, CH de Perpignan, Perpignan, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Laurent
authors.affiliation: Department of Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Université Paris 7, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.affiliation: Department of Immunology, Assistance Publique-Hôpitaux de Paris Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D065766:Atypical Hemolytic Uremic Syndrome; D001706:Biopsy / Q000379:methods / Q000706:statistics & numerical data; D003404:Creatinine / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005602:France; D006463:Hemolytic-Uremic Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000209:etiology; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D010976:Platelet Count / Q000379:methods; D006435:Renal Dialysis / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C481642:eculizumab; D003404:Creatinine
keywords: Atypical hemolytic uremic syndrome; complement; eculizumab; thrombotic microangiopathy