Jean-Michel Halimi1,2, Imad Al-Dakkak3, Katerina Anokhina3, Gianluigi Ardissino4, Christoph Licht5, Wai H Lim6,7, Annick Massart8, Franz Schaefer9, Johan Vande Walle10, Eric Rondeau11. 1. Service de Néphrologie-Hypertension Artérielle, Dialyses, Transplantation Rénale, CHRU Tours, Tours, France. jean-michel.halimi@univ-tours.fr. 2. University of Tours, Equipe d'Accueil 4245 (EA4245), Tours, France. jean-michel.halimi@univ-tours.fr. 3. Alexion, AstraZeneca Rare Disease, Boston, MA, USA. 4. Center for HUS Control, Prevention and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 5. Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada. 6. Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia. 7. Medical School, University of Western Australia, Perth, Australia. 8. Department of Nephrology and Hypertension, Antwerp University Hospital, Edegem, Belgium. 9. Division of Pediatric Nephrology, Heidelberg University Hospital, Heidelberg, Germany. 10. Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium. 11. Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, Paris, France.
Abstract
INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA. METHODS: This analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with (n = 71) and without (n = 1026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension. RESULTS: While demographics were similar, patients with aHUS + malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS + malignant hypertension (adjusted HR (95% CI), 0.11 [0.01-0.87], P = 0.036). CONCLUSIONS: These results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS ± malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA. TRIAL REGISTRATION DETAILS: Atypical Hemolytic-Uremic Syndrome (aHUS) Registry. Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012).
INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA. METHODS: This analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with (n = 71) and without (n = 1026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension. RESULTS: While demographics were similar, patients with aHUS + malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS + malignant hypertension (adjusted HR (95% CI), 0.11 [0.01-0.87], P = 0.036). CONCLUSIONS: These results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS ± malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA. TRIAL REGISTRATION DETAILS: Atypical Hemolytic-Uremic Syndrome (aHUS) Registry. Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012).
Authors: Sjoerd A M E G Timmermans; Myrurgia A Abdul-Hamid; Joris Vanderlocht; Jan G M C Damoiseaux; Chris P Reutelingsperger; Pieter van Paassen Journal: Kidney Int Date: 2017-02-07 Impact factor: 10.612
Authors: Carla Nester; Zoe Stewart; David Myers; Jennifer Jetton; Ramesh Nair; Alan Reed; Christie Thomas; Richard Smith; Patrick Brophy Journal: Clin J Am Soc Nephrol Date: 2011-05-26 Impact factor: 8.237
Authors: Andrzej Januszewicz; Tomasz Guzik; Aleksander Prejbisz; Tomasz Mikołajczyk; Grzegorz Osmenda; Włodzimierz Januszewicz Journal: Pol Arch Med Wewn Date: 2016