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1 List of authors and affiliations : Fadi Fakhouri 1, Marc Fila 2, François Provot 3, Yahsou Delmas 2, Christelle Barbet 5, Valérie Châtelet 6, Cédric afat 7, Mathilde Cailliez 8, Julien Hogan 9, Aude Servais 10, Alexandre Karras 11, aifah Makdassi 12, Feriell Louillet 13, Jean-Philippe Coindre 14, Eric ondeau 7, Chantal Loirat 9 and Véronique Frémeaux-Bacchi Department of nephrology and immunology, Institut de Transplantation, d Urologie et de Néphrologie ( ITUN) and Institut National de la Santé et de la echerche Médicale (INSEM), Unité Mixte de echerche (UM) S-1064, centre hospitalier universitaire de Nantes. 2 Department of pediatric nephrology, centre hospitalier universitaire de Montpellier. 3 Department of nephrology, centre hospitalier universitaire de Lille. 4 Department of nephrology, centre hospitalier universitaire de Bordeaux. 5 Department of nephrology, centre hospitalier universitaire de Tours. 6 Department of nephrology, centre hospitalier universitaire de Caen. 7 Department of nephrology, centre hospitalier universitaire de Tenon, Paris. 8 Department of pediatric nephrology, centre hospitalier universitaire de Marseille. 9 Department of pediatric nephrology, centre hospitalier universitaire obert Debré, Paris. 10 Department of nephrology, centre hospitalier universitaire, Hôpital Necker-Enfants Malades, Paris. 11 Department of nephrology, centre hospitalier universitaire, Hôpital Européen Georges Pompidou, Paris. 12 Department of nephrology, centre hospitalier universitaire d Amiens, Amiens. 13 Department of pediatric nephrology, centre hospitalier universitaire de ouen. 14 Department of nephrology, centre hospitalier du Mans. 15 Department of immunology, centre hospitalier universitaire, Hôpital Européen Georges Pompidou, Paris. All in France.
2 Pt SCr at relapse ( mol/l) Diagnostic criteria of relapse Time to SCr normalization/ return to baseline (days) Platelet count at relapse (10 3 / l) Time to platelet count normalization (days) Puria/Cruria at relapse (mg/g) Time to SCr normalization/ return to baseline (days) AKI + He + Tp g/l AKI + He + Tp AKI + He + Tp AKI + He + Tp g/l AKI + He + Tp AKI + He AKI + He + KB AKI + He +KB NA AKI + He + Tp AKI + KB AKI + He + Tp NA NA AKI + He Supplementary table S1: Characteristics of patients at the time of ahus relapse and after the restart of eculizumab. Abbreviations: SCr, serum creatinine, Puria/Cruria, proteinuria to creatininuria ratio. Abbreviations: AKI, acute kidney injury. He, hemolysis. Tp, thrombocytopenia. KB, kidney biopsy. NA, not available.
3 Supplemental figure 1 : Outcome of 108 ahus patients treated with eculizumab between 2010 and 2014.
4 1 Gender/ Age* Duration Ecu (M) F, (75) (76) CFH variant 2 F, (151) (125) 3 4 F, (77) 1.4 F, (97) (83) 0.95 (66) 5 F, (125) (118) 6 7 F, (61) 0.9 (60) M, (74) (73) F, (75) 0.8 (82) M, (110) (95) F, (91) 0.75 (92) M, (87) (81) Time (months)
5 Gender/ Age Duration Ecu (M) MCP variant 12 M, (90) (89) 13 M, (142) 0.45 (132) 14 M, (100) (108) 15 F, (133) (144) 16 F, (68) 1.1 (60) 17 M, (123) 0.7 (135) M, (120) 0.6 (94) F, (66) (64) 20 M, (118) 0.85 (94) C3 21 F, (37) 1.34 (42) CFI 22 F, (56) 1.3 (55) AntiFH Ab Time (months)
6 Gender/ Age Duration Ecu (M) No variant M, (26) 2.9 (25) M, (87) 1 (89) F, (111) 0.7 (99) F, (80) 0.9 (71) F, (100) 0.5 (106) M, (126) 0.6 (114) F, (67) 0.9 (64) F, (67) 1 (60) F, (65) 0.85 (84) M, (129) 0.4 (123) 33 F, (61) 0.9 (67) F, (71) 0.9 (66) F, (54) 1 (52) 36 F, (49) 1.35 (46) 37 M, (72) 1.15 (65) 38 F, (98) 0.8 (88) Time (months)
7 Supplemental figure 2: Outcome of 38 patients with atypical hemolytic uremic syndrome (ahus) who discontinued eculizumab. Patients are classified based on the presence or absence of complement genes mutations. Serum creatinine values (mg/dl) are shown for each patient above the lines (estimated GF according to the MDD or Schwartz formula in brackets). Dotted lines correspond to the period of follow-up after ahus relapse and eculizumab reintiation. Abbreviations: F/M, female/male. Ecu, eculizumab. M, months., relapse. Anti-FH Ab, anti-factor H antibodies. * age at eculizumab discontinuation.
8 Supplemental figure 3: Evolution of serum creatinine (SCr) after eculizumab intiation in 28 adults* (upper panel) and 9 children (lower panel) with ahus and with or without documented complement genes variants. There was no difference in SCr at all time-points in adults and children. * Patient 21 with anti-cfh antibody who received an immunosuppressive treatment combined to eculizumab was excluded from the analysis.
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