Fadi Fakhouri1, Yahsou Delmas2, François Provot3, Christelle Barbet4, Alexandre Karras5, Raifah Makdassi6, Cécile Courivaud7, Khair Rifard8, Aude Servais9, Catherine Allard10, Virginie Besson11, Maud Cousin11, Valérie Châtelet12, Jean-Michel Goujon13, Jean-Philippe Coindre14, Guillaume Laurent15, Chantal Loirat16, Véronique Frémeaux-Bacchi17. 1. Department of Nephrology and Immunology, ITUN and INSERM UMR S-1064, CHU de Nantes, Nantes, France. Electronic address: fadi.fakhouri@univ-nantes.fr. 2. Department of Nephrology, CHU de Bordeaux, Bordeaux, France. 3. Department of Nephrology, CHU de Lille, Lille, France. 4. Department of Nephrology, CHU de Tours, Tours, France. 5. Department of Nephrology, Hôpital Européen Georges Pompidou, Paris, France. 6. Department of Nephrology, CHU d'Amiens, Amiens, France. 7. Department of Nephrology, CHU de Besançon, Besançon, France. 8. Department of Nephrology, CH de Bourges, Bourges, France. 9. Department of Nephrology, Hôpital Necker-Enfants Malades, Paris, France. 10. Department of Nephrology, CHR de Metz-Thionville, Metz, France. 11. Department of Nephrology, CHU d'Angers, Angers, France. 12. Department of Nephrology, CHU de Caen, Caen, France. 13. Department of Pathology, CHU de Poitiers, Poitiers, France. 14. Department of Nephrology, CH du Mans, Le Mans, France. 15. Department of Nephrology, CH de Perpignan, Perpignan, France. 16. Department of Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Université Paris 7, Paris, France. 17. Department of Immunology, Assistance Publique-Hôpitaux de Paris Hôpital Européen Georges Pompidou, Paris, France.
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. STUDY DESIGN: 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. SETTING & PARTICIPANTS: 19 patients were identified through a query sent to all French nephrology centers. OUTCOMES & MEASUREMENTS: 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. LIMITATIONS: Retrospective study and use of historical controls. CONCLUSIONS: Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.
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. STUDY DESIGN: 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. SETTING & PARTICIPANTS: 19 patients were identified through a query sent to all French nephrology centers. OUTCOMES & MEASUREMENTS: 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. LIMITATIONS: Retrospective study and use of historical controls. CONCLUSIONS: Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.
Authors: Donal J Sexton; Scott Reule; Craig A Solid; Shu-Cheng Chen; Allan J Collins; Robert N Foley Journal: Hemodial Int Date: 2015-02-17 Impact factor: 1.812
Authors: Chantal Loirat; Fadi Fakhouri; Gema Ariceta; Nesrin Besbas; Martin Bitzan; Anna Bjerre; Rosanna Coppo; Francesco Emma; Sally Johnson; Diana Karpman; Daniel Landau; Craig B Langman; Anne-Laure Lapeyraque; Christoph Licht; Carla Nester; Carmine Pecoraro; Magdalena Riedl; Nicole C A J van de Kar; Johan Van de Walle; Marina Vivarelli; Véronique Frémeaux-Bacchi Journal: Pediatr Nephrol Date: 2015-04-11 Impact factor: 3.714