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Hemostasis
Impact of hypertensive emergency and rare complement variants on the presentation and outcome of atypical hemolytic uremic syndrome
Ferrata Storti Foundation
Haematologica 2019 Volume 104(12):2501-2511
Khalil El Karoui,1 Idris Boudhabhay,1 Florent Petitprez,2 Paula Vieira-Martins,3 Fadi Fakhouri,4 Julien Zuber,5 Florence Aulagnon,5 Marie Matignon,1
Eric Rondeau,6 Laurent Mesnard,6 Jean-Michel Halimi7 and
Véronique Frémeaux-Bacchi3,8
1Service de Néphrologie et Transplantation Rénale, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, INSERM U955, Créteil; 2INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris; 3Assistance Publique-Hôpitaux de Paris, Laboratoire d’Immunologie, Hôpital Européen Georges Pompidou, Paris; 4Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes and Department of Nephrology and immunology, Centre Hospitalier Universitaire de Nantes, Nantes; 5Service de Néphrologie et Transplantation Rénale, Hôpital Necker Enfant malades, Assistance Publique-Hôpitaux de Paris, Paris; 6Intensive Care and Renal Transplant Unit, Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire de Tenon and Inserm UMR S 1155, Sorbonne University, Paris; 7Department of Nephrology and Clinical immunology, Centre Hospitalier Universitaire de Tours and EA4245, François Rabelais University, Tours and 8INSERM UMR_S 1138, Complément et Maladies, Centre de Recherche des Cordeliers, Paris, France
ABSTRACT
Atypical hemolytic uremic syndrome (aHUS) is a prototypic throm- botic microangiopathy attributable to complement dysregulation. Hypertensive emergency, characterized by elevation of systolic (>180 mmHg) or diastolic (>120 mmHg) blood pressure together with end- organ damage, can cause thrombotic microangiopathy which may mimic aHUS. We retrospectively evaluated the clinical, biological and complement genetic characteristics of 76 and 61 aHUS patients with and without hyper- tensive emergency, respectively. Patients with hypertensive emergency- aHUS were more frequently males, with neurological involvement, and a slightly higher hemoglobin level. At least one rare complement variant was identified in 51.3% (39/76) and 67% (41/61) patients with or without hypertensive emergency, respectively (P=0.06). In both groups, renal prog- nosis was severe with 23% and 40% of patients reaching end-stage renal disease after a 5-year follow-up (P=0.1). The 5-year renal survival was 77% in patients without hypertensive emergency or a complement variant, and below 25% in the three groups of patients with hypertensive emergency and/or a complement variant (P=0.02). Among patients without hyperten- sive emergency, the 5-year renal survival was 100% vs. 40% in those treat- ed or not with eculizumab, respectively (P<0.001). Conversely, the 5-year renal survival of patients with hypertensive emergency was 46% vs. 23% in those treated or not with eculizumab, respectively (P=0.18). In conclu- sion, information on the presence or absence of hypertensive emergency and rare complement variants is essential to stratify the long-term renal prognosis of patients with aHUS.
Introduction
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy affecting predominantly the kidney and encompasses a heterogeneous group of disorders, including Shiga toxin producing E. coli-associated HUS (typical HUS), secondary HUS (related to co-existing condition such as malignancy, drugs or autoimmune diseases), and atypical HUS (aHUS).1–3 The classification of HUS has evolved with the identification of the mechanisms of endothelial injury. Among patients pre-
Correspondence:
KHALIL EL KAROUI
khalil.el-karoui@aphp.fr
VÉRONIQUE FRÉMEAUX-BACCHI
veronique.fremeaux-bacchi@aphp.fr
Received: January 21, 2019. Accepted: March 18, 2019. Pre-published: March 19, 2019.
doi:10.3324/haematol.2019.216903
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