16 results on '"Ferielle Louillet"'
Search Results
2. The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies
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Friederike Petzold, Katy Billot, Xiaoyi Chen, Charline Henry, Emilie Filhol, Yoann Martin, Marina Avramescu, Maxime Douillet, Vincent Morinière, Pauline Krug, Cécile Jeanpierre, Kalman Tory, Olivia Boyer, Anita Burgun, Aude Servais, Remi Salomon, Alexandre Benmerah, Laurence Heidet, Nicolas Garcelon, Corinne Antignac, Mohamad Zaidan, Sophie Saunier, Tania Attié-Bitach, Valerie Comier-Daire, Jean-Michel Rozet, Yaacov Frishberg, Brigitte Llanas, Michel Broyer, Nabil Mohsin, Marie-Alice Macher, Nicole Philip, Véronique Baudouin, Damian Brackman, Chantal Loirat, Marina Charbit, Maud Dehennault, Claude Guyot, Pierre Bataille, Mariet Elting, Georges Deschenes, Andrea Gropman, Geneviève Guest, Marie-France Gagnadoux, Philippe Nicoud, Pierre Cochat, Bruno Ranchin, Albert Bensman, Anne-Marie Guerrot, Bertrand Knebelmann, Ilmay Bilge, Danièle Bruno, Stéphane Burtey, Caroline Rousset Rouvière, Valérie Caudwell, Denis Morin, Hélène Dollfus, Anne Maisin, Christian Hamel, Eric Bieth, Sophie Gie, Judith Goodship, Gwenaelle Roussey, Hermine La Selve, Hubert Nivet, Lucie Bessenay, Mathilde Caillez, Jean Bernard Palcoux, Stéphane Benoît, Philippe Dubot, Marc Fila, Fabienne Giuliano, Daouya Iftene, Michele Kessler, Theresa Kwon, Anine Lahoche, Audrey Laurent, Anne-Laure Leclerc, David Milford, Thomas Neuhaus, Sylvie Odent, Philippe Eckart, Dominique Chauveau, Patrick Niaudet, Horacio Repetto, Sophie Taque, Alexandra Bruel, Alexandra Noel-Botte, Emma Allain Launay, Lisa Allard, Dany Anlicheau, Anne-Laure Adra, Arnaud Garnier, Arvind Nagra, Remy Baatard, Justine Bacchetta, Banu Sadikoglu, Christine Barnerias, Anne Barthelemy, Lina Basel, Nader Bassilios, Hedi Ben Maiz, Fatma Ben Moussa, Faïza Benmati, Romain Berthaud, Aurélia Bertholet, Dominique Blanchier, Jean Jacques Boffa, Karim Bouchireb, Ihab Bouhabel, Zakaria Boukerroucha, Guylhène Bourdat-Michel, Odile Boute, Karine Brochard, Roseline Caumes, Siham Chafai Elalaoui, Bernard Chamontin, Marie Caroline Chastang, Christine Pietrement, Christine Richer, Christophe Legendre, Karin Dahan, Fabienne Dalla-Vale, Damien Thibaudin, Maxime Dauvergne, Salandre Davourie, Martin Debeukelaer, Jean Daniel Delbet, Constantinos Deltas, Denis Graber, Nadège Devillars, Boucar Diouf, Martine Doco Fenzy, Jean-Luc André, Dominique Joly, Alan Fryer, Laetitia Albano, Elisabeth Cassuto, Aline Pincon, Ana Medeira, Annabelle Chaussenot, Anne Mensire-Marinier, Francois Bouissou, Stephane Decramer, Armand Bottani, Aurélie Hummel, Alexandre Karras, Avi Katz, Christine Azema, Bénédicte Janbon, Bernard Roussel, Claude Bonniol, Christiophe Mariat, Gérard Champion, Deborah Chantreuil, Nicolas Chassaing, Christiane Mousson, Christine Baudeau, Delphine Hafdar Cuntz, Cyril Mignot, Laurene Dehoux, Didier Lacombe, Thierry Hannedouche, Elodie Mérieau, Emmanuelle Charlin, Eric Gauthier, Florent Plasse, Stanislas Faguer, Fanny Lebas, Florence Demurger, Francesco Emma, François Cartault, Geneviève Dumont, Nathalie Godefroid, Vincent Guigonis, Sophie Hillaire, Jaap Groothoff, Jan Dudley, Noémie Jourde-Chiche, Khalil El Karoui, Saoussen Krid, Krier Coudert, Larbi Bencheick, Laurent Yver, Marie-Pierre Lavocat, Le Monies De Sagazan, Valerie Leroy, Lise Thibaudin, Liz Ingulli, Lorraine Gwanmesia, Lydie Burglen, Marie-Hélène Saïd-Menthon, Marta Carrera, Mathilde Nizon, Catherine Melander, Michel Foulard, Monique Blayo, Jacques Prinseau, Nadine Jay, Nathalie Brun, Nicolas Camille, François Nobili, Olivier Devuyst, Ouafa Ben Brahim, Paloma Parvex, Laurence Perrin Sabourin, Philippe Blanc, Philippe Vanhille, Pierre Galichon, Sophie Pierrepont, Vincent Planquois, Gwenaelle Poussard, Claire Pouteil Noble, Radia Allal, Raphaelle Bernard, Raynaud Mounet, Rémi Cahen, Renaud Touraine, Claire Rigothier, Amélie Ryckewaert, Mathieu Sacquepee, Salima El Chehadeh, Charlotte Samaille, Shuman Haq, Ari Simckes, Stéphanie Lanoiselée, Stephanie Tellier, Jean-François Subra, Sylvie Cloarec, Julie Tenenbam, Thomas Lamy, Valérie Drouin Garraud, Huguette Valette, Vanina Meyssonnier, Rosa Vargas-Poussou, Yves Snajer, Sandrine Durault, Emmanuelle Plaisier, Etienne Berard, Fadi Fakhouri, Ferielle Louillet, Paul Finielz, Michel Fischbach, Bernard Foliguet, Hélène Francois-Pradier, Florentine Garaix, Marion Gerard, Gianfranco Rizzoni, Brigitte Gilbert, Denis Glotz, Astrid Godron Dubrasquet, Jean-Pierre Grünfeld, Guillaume Bollee, Michelle Hall, Sverker Hansson, Damien Haye, Hélène Taffin, Friedhelm Hildebrandt, Maryvonne Hourmand, Hümya Kayserili, Ivan Tack, Marie Line Jacquemont, Jennifer Fabre-Teste, Cliff Kashtan, Kkoen Van Hoeck, Alexandre Klein, Yannick Knefati, Nine Knoers, Martin Konrad, Alain Lachaux, Isabelle Landru, Gilbert Landthaler, Philippe Lang, Patrick Le Pogamp, Tristan Legris, Catherine Didailler, Thierry Lobbedez, Loïc de Parscau, Lucile Pinson, Hervé Maheut, Marc Duval-Arnould, Marlène Rio, Marie-Claire Gubler, Pierre Merville, Guillaume Mestrallet, Maite Meunier, Karine Moreau, Jérôme Harambat, Graeme Morgan, Georges Mourad, Niksic Stuber, Odile Boespflug-Tanguy, Olivier Dunand, Olivier Niel, Nacera Ouali, Paolo Malvezzi, Pauline Abou Jaoude, Solenne Pelletier, Julie Peltier, M.B. Petersen, Philippe Michel, Philippe Rémy, Jean-Baptiste Philit, Valérie Pichault, Thierry Billette de Villemeur, Bernard Boudailliez, Bruno Leheup, Claire Dossier, Djamal-Dine Djeddi, Yves Berland, Bruno Hurault de Ligny, Susan Rigden, Christophe Robino, Annick Rossi, Sabine Sarnacki, Messaoud Saidani, Albane Brodin Sartorius, Elise Schäfer, Sztriha Laszlo, Marie-Christine Thouret, Angélique Thuillier-Lecouf, Howard Trachtman, Claire Trivin, Michel Tsimaratos, Rita Van Damme-Lombaerts, Marjolaine Willems, Michel Youssef, Ariane Zaloszyc, Alexis Zawodnik, and Marie-Julia Ziliotis
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Nephrology - Abstract
Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.
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- 2023
3. Anti-Factor B Antibodies and Acute Postinfectious GN in Children
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Ferielle Louillet, Guillaume Mestrallet, Aram G. Gyulkhandanyan, Amélie Ryckewaert, Bruno O. Villoutreix, Véronique Frémeaux-Bacchi, Magali Devriese, Paula Vieira Martins, Olivia Boyer, Caroline Rousset-Rouvière, Elodie Merieau, Morgane Mignotet, Lubka T. Roumenina, Tania Robe-Rybkine, Eric Thervet, Maria A. Miteva, Sophie Chauvet, J. Hogan, Tim Ulinski, and Romain Berthaud
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Male ,Complement factor B ,Nephritic syndrome ,Glomerulonephritis ,Glomerulopathy ,medicine ,Humans ,Child ,Complement Activation ,Autoantibodies ,Retrospective Studies ,Complement C3 Nephritic Factor ,business.industry ,Editorials ,Autoantibody ,Complement C3 ,General Medicine ,medicine.disease ,C3-convertase ,Complement system ,Nephrology ,Child, Preschool ,Immunology ,Alternative complement pathway ,Female ,France ,business ,Complement Factor B - Abstract
Background The pathophysiology of the leading cause of pediatric acute nephritis, acute postinfectious GN, including mechanisms of the pathognomonic transient complement activation, remains uncertain. It shares clinicopathologic features with C3 glomerulopathy, a complement-mediated glomerulopathy that, unlike acute postinfectious GN, has a poor prognosis. Methods This retrospective study investigated mechanisms of complement activation in 34 children with acute postinfectious GN and low C3 level at onset. We screened a panel of anticomplement protein autoantibodies, carried out related functional characterization, and compared results with those of 60 children from the National French Registry who had C3 glomerulopathy and persistent hypocomplementemia. Results All children with acute postinfectious GN had activation of the alternative pathway of the complement system. At onset, autoantibodies targeting factor B (a component of the alternative pathway C3 convertase) were found in a significantly higher proportion of children with the disorder versus children with hypocomplementemic C3 glomerulopathy (31 of 34 [91%] versus 4 of 28 [14%], respectively). In acute postinfectious GN, anti-factor B autoantibodies were transient and correlated with plasma C3 and soluble C5b-9 levels. We demonstrated that anti-factor B antibodies enhance alternative pathway convertase activity in vitro, confirming their pathogenic effect. We also identified crucial antibody binding sites on factor B, including one correlated to disease severity. Conclusions These findings elucidate the pathophysiologic mechanisms underlying acute postinfectious GN by identifying anti-factor B autoantibodies as contributing factors in alternative complement pathway activation. At onset of a nephritic syndrome with low C3 level, screening for anti-factor B antibodies might help guide indications for kidney biopsy to avoid misdiagnosed chronic glomerulopathy, such as C3 glomerulopathy, and to help determine therapy.
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- 2020
4. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study
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Véronique Frémeaux-Bacchi, Christiane Mousson, Emma Allain Launay, David Ribes, François Provôt, Simon Ville, Aurélie Le Thuaut, Claire Presne, Anne-Laure Sellier-Leclerc, Aurélie Hummel, Ferielle Louillet, Leila Tricot, Marc Fila, Quentin Raimbourg, Stéphane Bally, Fadi Fakhouri, Eric Rondeau, Ariane Zaloszyc, Moglie Le Quintrec, Djamal Djeddi, William Hanf, Guillaume Favre, Annie Lahoche, Valérie Châtelet, Sophie Caillard, Chantal Loirat, Jean-Philippe Coindre, Claire Pouteil-Noble, Yahsou Delmas, Olivia Boyer, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Hospices Civils de Lyon (HCL), Centre Hospitalier Le Mans (CH Le Mans), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine] (Cnr-mat), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Centre Hospitalier Alpes Léman (CHAL), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Foch [Suresnes], Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), AP-HP Hôpital universitaire Robert-Debré [Paris], Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immunology ,030232 urology & nephrology ,Renal function ,Disease ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,urologic and male genital diseases ,Biochemistry ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Atypical hemolytic uremic syndrome ,medicine ,Humans ,Prospective Studies ,Child ,Dialysis ,Atypical Hemolytic Uremic Syndrome ,business.industry ,Infant, Newborn ,Infant ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,Eculizumab ,Prognosis ,medicine.disease ,3. Good health ,Discontinuation ,Survival Rate ,Complement Inactivating Agents ,Withholding Treatment ,Child, Preschool ,Female ,business ,BLOOD Commentary ,Follow-Up Studies ,Kidney disease ,medicine.drug - Abstract
The optimal duration of eculizumab treatment in patients with atypical hemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicenter open-label study to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean treatment duration, 16.5 months). Twenty-eight patients (51%) had rare variants in complement genes, mostly in MCP (n = 12; 22%), CFH (n = 6; 11%), and CFI (n = 6; 10%). At eculizumab discontinuation, 17 (30%) and 4 patients (7%) had stage 3 and 4 chronic kidney disease, respectively. During follow-up, 13 patients (23%; 6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female sex and presence of a rare variant in a complement gene were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during a previous episode of acute aHUS was not. In addition, increased sC5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers with a complement gene rare variant, both by log-rank test and in multivariable analysis. Of the 13 relapsing patients, all of whom restarted eculizumab, 11 regained their baseline renal function and 2 had a worsening of their preexisting chronic kidney disease, including 1 patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment. This trial was registered at www.clinicaltrials.gov as #NCT02574403.
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- 2021
5. Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function
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Marie-Josèphe Tête, Matthias Hansen, Florie Lammens, Tobias Schäfer, Albert Bensman, Alexandra Cambier, Tobias B. Huber, Christoph J. Mache, Elisa Kuhn, Christian Brix Folsted Andersen, Corinne Isnard-Bagnis, Tarunveer S. Ahluwalia, Günter Klaus, Mathilda Bedin, Fabienne Jabot-Hanin, Julien Hogan, Laure Villoing-Gaudé, Timo Wagner, Patrick Nitschke, Carole Tournant, Marcus R. Benz, Maik Grohmann, Markus Gödel, Aude Servais, Corinne Antignac, Cécile Vigneau, Ferielle Louillet, Christine Bole-Feysot, Véronique Baudouin, Iseline Bouteau, Lars Pape, Kay Latta, Carsten Bergmann, Yong Li, Vincent Morinière, Saoussen Krid, Olivier Gribouval, Olivia Boyer, Bruno Ranchin, Anna Köttgen, Matias Simons, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], School of Software (THSS), Tsinghua University [Beijing], Néphropathies héréditaires et rein en développement (UMR_S 983), CHU Necker - Enfants Malades [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de Néphrologie Rhumatologie Dermatologie, HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'urologie, néphrologie et transplantation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Department of Pediatric Kidney, Hannover Medical School [Hannover] (MHH)-Children's Hospital, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Service de Génétique Médicale [CHU Necker], Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Plateforme de bioinformatique, Université Paris Descartes - Paris 5 (UPD5), IT University of Copenhagen, NNF18OC0052457, Novo Nordisk Fonden, KO 3598/5-1,KIDGEM SFB1140 246781735, Deutsche Forschungsgemeinschaft, ANR-10-IAHU-01,ANR-14-ACHN-0013, Agence Nationale de la Recherche, 01GM1515C, Federal Ministry or Education and Research, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Tsinghua University [Beijing] (THU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), IT University of Copenhagen (ITU), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), and ANR-14-ACHN-0013,NEPHROFLY,Utilisation de Drosophila melanogaster pour étudier les maladies génétiques du rein(2014)
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Male ,0301 basic medicine ,Nephrology ,medicine.medical_specialty ,Anemia, Megaloblastic ,[SDV]Life Sciences [q-bio] ,Renal function ,Receptors, Cell Surface ,Kidney ,urologic and male genital diseases ,Gastroenterology ,Kidney Tubules, Proximal ,03 medical and health sciences ,0302 clinical medicine ,Focal segmental glomerulosclerosis ,Malabsorption Syndromes ,Internal medicine ,Chronic kidney disease ,medicine ,Genetics ,Albuminuria ,Humans ,Alport syndrome ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Proteinuria ,business.industry ,urogenital system ,Vitamin B 12 Deficiency ,General Medicine ,medicine.disease ,Cubilin ,female genital diseases and pregnancy complications ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Female ,Clinical Medicine ,medicine.symptom ,business ,Nephrotic syndrome ,Genetic diseases - Abstract
International audience; BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).
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- 2020
6. Metabolic causes of nonimmune hydrops fetalis: A next-generation sequencing panel as a first-line investigation
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Annie Laquerrière, Bénédicte Sudrié-Arnaud, Raphaël Lanos, Laetitia Trestard, Ferielle Louillet, Sophie Coutant, Florent Marguet, Stéphane Marret, Abdellah Tebani, Sophie Patrier, Soumeya Bekri, Eric Verspyck, Myriam Vezain, Foudil Lamari, Pascal Chambon, Maria Fuller, Hélène Dranguet, Françoise Broux, Anne-Claire Brehin, Isabelle Tournier, Françoise Charbonnier, Jelena Martinovic, Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Normandie Université (NU), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), SA Pathology [Adelaide, SA, Australia], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Clinique du Belvédère, Service de gynécologie et obstétrique [CHU Rouen], and Département de Pathologie [CHU Rouen]
- Subjects
Adult ,Polyhydramnios ,0301 basic medicine ,Amniotic fluid ,Clinical Biochemistry ,Prenatal diagnosis ,Genomics ,Inborn errors of metabolism ,Disease ,030105 genetics & heredity ,Bioinformatics ,Biochemistry ,Inherited metabolic diseases ,Young Adult ,03 medical and health sciences ,Pregnancy ,Hydrops fetalis ,medicine ,Humans ,Non-immune hydrops fetalis ,Retrospective Studies ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,Precision medicine ,Biochemistry (medical) ,Computational Biology ,Barth syndrome ,Retrospective cohort study ,Sequence Analysis, DNA ,General Medicine ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,medicine.disease ,3. Good health ,030104 developmental biology ,Next-generation sequencing ,Female ,business ,Metabolism, Inborn Errors - Abstract
Purposes Hydrops fetalis is a life-threatening fetal condition, and 85% of all cases are classified as nonimmune hydrops fetalis (NIHF). Up to 15% of NIHF cases may be due to inborn errors of metabolism (IEM), but a large proportion of cases linked to metabolic disorders remains undiagnosed. This lack of diagnosis may be related to the limitations of conventional biological procedures, which involve sequential investigations and require multiple samples and steps. In addition, this approach is time consuming. We have developed a next-generation sequencing (NGS) panel to investigate metabolic causes of NIHF, ascites, and polyhydramnios associated to another fetal abnormality. Methods The hydrops fetalis (HydFet) panel was designed to cover the coding regions and flanking intronic sequences of 41 genes. A retrospective study of amniotic fluid samples from 40 subjects was conducted. A prospective study was subsequently initiated, and six samples were analyzed using the NGS panel. Results Five IEM diagnoses were made using the HydFet panel (Niemann-Pick type C (NPC), Barth syndrome, HNF1Β deficiency, GM1 gangliosidosis, and Gaucher disease). This analysis also allowed the identification of 8p sequence triplication in an additional case. Conclusion NGS combined with robust bioinformatics analyses is a useful tool for identifying the causative variants of NIHF. Subsequent functional characterization of the protein encoded by the altered gene and morphological studies may confirm the diagnosis. This paradigm shift allows a significant improvement of IEM diagnosis in NIHF.
- Published
- 2018
7. Confirmation and further delineation of the SMG9‐deficiency syndrome, a rare and severe developmental disorder
- Author
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Jean-François Deleuze, Tristan Hazelzet, Anne-Marie Guerrot, Alice Goldenberg, Jean-Baptiste Leca, François Lecoquierre, Alexandra Chadie, Marc Muraine, Olivier Quenez, Thierry Frebourg, Claire Gayet, Ferielle Louillet, M. Brasseur-Daudruy, Pascale Saugier-Veber, Gaël Nicolas, Anne Boland, Sophie Coutant, Mariette Renaux-Petel, Clémentine Dumant-Forest, Antoine Bonnevalle, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'imagerie médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Service d'ophtalmologie [Rouen], Normandie Université (NU)-Hôpital Charles-Nicolle, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Charles Nicolle [Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
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Pediatrics ,medicine.medical_specialty ,Deficiency syndrome ,Heart malformation ,Developmental Disabilities ,education ,Heart defect ,Context (language use) ,macromolecular substances ,SMG9 ,Feeding difficulty ,Consanguinity ,03 medical and health sciences ,Genetics ,nonsense mediated decay ,Humans ,Medicine ,Genetic Predisposition to Disease ,Global developmental delay ,Alleles ,Genetic Association Studies ,Genetics (clinical) ,Exome sequencing ,030304 developmental biology ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,Homozygote ,030305 genetics & heredity ,Intracellular Signaling Peptides and Proteins ,Brain ,Syndrome ,medicine.disease ,Pedigree ,3. Good health ,Developmental disorder ,Phenotype ,Child, Preschool ,Mutation ,Female ,business ,heart and brain malformation - Abstract
Introduction SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. Methods We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. Results Our patient presented with a syndromic association of severe global developmental delay and diverse malformations, including cleft lip and palate, facial dysmorphic features, brain abnormalities, heart defect, growth retardation, and severe infections. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous. Conclusions We confirm that bi-allelic truncating SMG9 variants cause a severe developmental syndrome including brain and heart malformations associated with facial dysmorphic features, severe growth and developmental delay with or without ophthalmological abnormalities, severe feeding difficulties, and life-threatening infections.
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- 2019
8. Treatment and outcome of congenital nephrotic syndrome
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Véronique Baudouin, Ariane Zaloszyc, Maud Dehennault, Sandra Bérody, Vincent Morinière, Elodie Merieau, Bernard Boudaillez, Rémi Salomon, Christine Pietrement, Adrien May, Laurence Heidet, Hugues Flodrops, Marie-Alice Macher, Loïc De Parscau, Rachel Vieux, Françoise Monceaux, Justine Bacchetta, Marc Fila, Arnaud Garnier, Caroline Rousset-Rouvière, Ferielle Louillet, J. Tenenbaum, Jérôme Harambat, Olivier Dunand, Olivier Gribouval, Olivia Boyer, Tim Ulinski, Sophie Taque, Gwenaelle Roussey, Patrick Niaudet, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Pediatrics ,medicine.medical_specialty ,Nephrotic Syndrome ,medicine.medical_treatment ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Nephrectomy ,LEHA ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Cumulative incidence ,Congenital nephrotic syndrome ,Dialysis ,Retrospective Studies ,Transplantation ,business.industry ,Incidence ,Infant, Newborn ,Infant ,Membrane Proteins ,medicine.disease ,3. Good health ,Survival Rate ,Treatment Outcome ,Nephrology ,Mutation ,Disease Progression ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,France ,Hemodialysis ,business ,Nephrotic syndrome ,Kidney disease - Abstract
Background Recommendations for management of Finnish-type congenital nephrotic syndrome (CNS) followed by many teams include daily albumin infusions, early bilateral nephrectomy, dialysis and transplantation. We aimed to assess the treatment and outcome of patients with CNS in France. Methods We conducted a nationwide retrospective study on 55 consecutive children born between 2000 and 2014 treated for non-infectious CNS. Results The estimated cumulative incidence of CNS was 0.5/100 000 live births. The underlying defect was biallelic mutations in NPHS1 (36/55, 65%), NPHS2 (5/55, 7%), PLCE1 (1/55, 2%), heterozygous mutation in WT1 (4/55, 7%) and not identified in nine children (16%). Fifty-three patients (96%) received daily albumin infusions from diagnosis (median age 14 days), which were spaced and withdrawn in 10 patients. Twenty children (35%) were managed as outpatients. Thirty-nine patients reached end-stage kidney disease (ESKD) at a median age of 11 months. The overall renal survival was 64% and 45% at 1 and 2 years of age, respectively. Thirteen children died during the study period including four at diagnosis, two of nosocomial catheter-related septic shock, six on dialysis and one after transplantation. The remaining 13 patients were alive with normal renal function at last follow-up [median 32 months (range 9-52)]. Renal and patient survivals were longer in patients with NPHS1 mutations than in other patients. The invasive infection rate was 2.41/patient/year. Conclusions Our study shows: (i) a survival free from ESKD in two-thirds of patients at 1 year and in one-half at 2 years and (ii) a significant reduction or even a discontinuation of albumin infusions allowing ambulatory care in a subset of patients. These results highlight the need for new therapeutic guidelines for CNS patients.
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- 2019
9. Be aware of Shiga-toxin 2f-producing Escherichia coli: case report and false-negative results with certain rapid molecular panels
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Alice Dufougeray, Patricia Mariani-Kurkdjian, Aurélie Cointe, André Birgy, Ferielle Louillet, Alice Pascault, Stéphane Bonacorsi, Université de Paris (UP), Service de Néphrologie pédiatrique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de Microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
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Male ,0301 basic medicine ,Microbiology (medical) ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,medicine.disease_cause ,Shiga Toxin ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,030212 general & internal medicine ,False Negative Reactions ,Escherichia coli ,Escherichia coli Infections ,Shiga-Toxigenic Escherichia coli ,biology ,business.industry ,Escherichia coli Proteins ,Shiga toxin ,General Medicine ,3. Good health ,Infectious Diseases ,Child, Preschool ,Hemolytic-Uremic Syndrome ,biology.protein ,business ,Multilocus Sequence Typing - Abstract
We report a hemolytic uremic syndrome (HUS) case due to Stx2f-producing E. coli illustrating the diagnostic difficulty of this Shiga-toxin subtype. Clinicians should be aware of limits of certain rapid molecular panels that are increasingly being used and may play a role in underestimating the global burden of such infections.
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- 2020
10. Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease
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Annie Lahoche, Françoise Broux, Ferielle Louillet, Vincent Morinière, Olivia Boyer, Amélie Ryckenwaert, Hanitra Randrianaivo, Elodie Merieau, Said Lebbah, Stéphane Decramer, Marie-Pierre Audrézet, Djalila Mekahli, Sandrine Maestri, Laurence Heidet, Carine Abel, Christine Corbiere, Georges Deschênes, Claude Férec, Ines Ouertani, Rémi Salomon, Sylvie Cloarec, Emilie Cornec-Le Gall, Michel Fischbach, Véronique Baudouin, Chiara Visconti, Ariane Zaloszyc, Gwenaelle Roussey, and Lucie Bessenay
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,TRPP Cation Channels ,Adolescent ,DNA Mutational Analysis ,Autosomal dominant polycystic kidney disease ,Mothers ,Receptors, Cell Surface ,Disease ,urologic and male genital diseases ,Ultrasonography, Prenatal ,Fathers ,Young Adult ,03 medical and health sciences ,Internal medicine ,Polycystic kidney disease ,Humans ,Medicine ,Child ,Aged ,Hepatocyte Nuclear Factor 1-beta ,Retrospective Studies ,Cystic kidney ,Genetics ,PKD1 ,urogenital system ,business.industry ,Infant ,General Medicine ,Middle Aged ,Polycystic Kidney, Autosomal Dominant ,medicine.disease ,HNF1B ,female genital diseases and pregnancy complications ,Pedigree ,030104 developmental biology ,Endocrinology ,Nephrology ,Child, Preschool ,Mutation ,Mutation (genetic algorithm) ,Mutation testing ,Kidney Failure, Chronic ,Female ,Brief Communications ,business - Abstract
Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.
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- 2016
11. Clinical and Genetic Spectrum of Bartter Syndrome Type 3
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Maria Mileva, Sandrine Lemoine, Christiane Mousson, Elsa Seys, Rosa Vargas-Poussou, Mathilde Cailliez, Gwenaëlle Roussey-Kesler, Aurélia Bertholet-Thomas, Paul Cozette, Theresa Kwon, Anne Blanchard, Guylhène Bourdat-Michel, Pauline Krug, Jean Sébastien Borde, Jacques Teulon, Christophe Simian, Laurence Dubourg, Robert Novo, Isabelle Vrillon, Bertrand Knebelmann, Brigitte Llanas, Djamal Djeddi, Dominique Chaveau, Stephen B. Walsh, Olga Andrini, François Nobili, Jean Daniel Delbet, Marc Fila, Georges Deschênes, Mathilde Keck, Ferielle Louillet, Lamisse Mansour-Hendili, Elodie Merieau, Stéphane Decramer, Noémie Jourde-Chiche, Marie-Pierre Lavocat, Pierre-Yves Courand, Luisa Mota-Vieira, Guillaume Bobrie, Pediatric Nephrology Unit, American Memorial Hospital, Reims University Hospital, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [Hôpital Croix- Rousse, HCL] (Centre d'excellence de la Société européenne d'hypertension artérielle), Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Génétique, Union nationale des coopératives d’élevage et d’insémination animale (UNCEIA), Unité de Néphrologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence des Maladies Rénales Rares Néphrogones, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Nephrology Unit, Clinique du Vert Galant, Tremblay-en-France, Nephrology Unit, Centre hospitalier de Saintonge, Saintes, Centre Hospitalo-Universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Pediatric Nephrology Unit, Centre Hospitalier du Pays d'Aix, Nephrology Unit, Centre Hospitalier du Pays d'Aix, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Métabolomique et maladies métaboliques, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Pédiatrie médicale et médecine de l'adolescent [Amiens], CHU Amiens-Picardie, Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Department of Pediatrics, Centre Hospitalier Pierre Oudot de Bourgoin-Jallieu, Bourgoin-Jallieu, Molecular Genetics and Pathology Unit, Hospital of Divino Espirito Santo of Ponta Delgada, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de néphrologie pédiatrique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Aeronautical and Automotive Engineering, Loughborough University, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Santé Lyon Est - Louis Léopold Ollier, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Union Nationale des Coopératives Agricoles d'Elevage et d'Insémination Animale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Unité d'hypertension artérielle, Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de nephrologie pédiatrique, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - Faculté de Médecine Paris Centre (UP Médecine Paris Centre), Université de Paris (UP), Service de Génétique [AP-HP Hôpital Européen Georges Pompidou, Paris], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de pédiatrie néonatale et réanimation - neuropédiatrie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Lyon, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte [CHU-Necker] (MARHEA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,[SDV]Life Sciences [q-bio] ,Nonsense mutation ,030232 urology & nephrology ,Bartter syndrome ,urologic and male genital diseases ,Hypocalciuria ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Tubulopathy ,Clinical Research ,Internal medicine ,Genotype ,medicine ,Humans ,Child ,Genetic Association Studies ,ComputingMilieux_MISCELLANEOUS ,Retrospective Studies ,CLCNKB ,biology ,business.industry ,Bartter Syndrome ,Infant ,General Medicine ,Gitelman syndrome ,medicine.disease ,3. Good health ,Bartter's syndrome ,030104 developmental biology ,Endocrinology ,Nephrology ,Child, Preschool ,Mutation ,biology.protein ,Female ,medicine.symptom ,business - Abstract
Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.
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- 2017
12. 06Adverse effects of rituximab used in children with idiopathic nephrotic syndrome. A multicentric retrospective study
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Ferielle Louillet, R. Novo, Elodie Merieau, Roman Klifa, François Nobili, Olivier Dunand, Gérard Champion, F. Laliève, Ariane Zaloszyc, Olivia Boyer, V. Lefranc, S. Crepin, Etienne Bérard, N. Jay, Sophie Taque, Justine Bacchetta, Djamal Djeddi, J.D. Delbet, D. Postil, Gwenaelle Roussey, C. Samaille, S. Tellier, L. De Parscaud, E. Cousin, Brigitte Llanas, Christine Pietrement, C. Rousset, M. Cailliez, C. Bahans, L. Ichay, Paloma Maria Parvex, and Vincent Guigonis
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Pediatrics ,medicine.medical_specialty ,business.industry ,Hemodynamics ,Retrospective cohort study ,Disease ,Idiopathic Nephrotic Syndrome ,Alternative treatment ,Relative risk ,Pediatrics, Perinatology and Child Health ,medicine ,Rituximab ,business ,Adverse effect ,medicine.drug - Abstract
Introduction Rituximab (RTX) is an effective alternative treatment for severe idiopathic nephrotic syndrome in children. Nevertheless, the actual indication of RTX within the therapeutic strategy remains controversial, given the lack of data on the safety of this treatment in this setting. Objective To retrospectively collect and describe all severe and significant adverse effects that had occurred in children treated with RTX for idiopathic nephrotic syndrome. Patients and methods All participating centres within the SNP network were asked to fill an online database for all their patients treated with RTX for INS. Data were collected from the patients’ medical charts. Severe or significant adverse effects were defined as follow: any event that led to (i) a vital risk, (ii) a hospitalization or a prolongation of hospitalization, (iii) the occurrence of sequelae or (iiii) the interruption of RTX therapy. Results Twenty-three centres participated to the study. In total, 196 cases were collected on October 10th. The mean age at diagnosis was 4.7 (± 3.2) years. The mean duration of disease was 7.5 (± 4.3) years when RTX was first used. The mean follow-up was 3.2 (± 2.5) years and 1.5 (± 1.7) years since the first and the last infusion of RTX respectively. Adverse effects were reported in 6.6% of cases during the infusion (dyspnea = 6, cardiac arrhythmia = 1, hemodynamic instability = 1, others = 7), and in 13.1% of cases after the infusion (in relation with neutropenia = 6, low IgM = 3, low IgG = 6, infectious disorder = 14, cardiac = 2, liver = 1, kidney = 1, digestive = 2, neurological = 2, others = 6, several complications can be present in the same patient). The main consequences of these adverse effects were: non-planned hospitalizations (n = 30), modifications or interruptions of RTX treatment (n = 6), significant invalidity (n = 3). A single adverse effect led to a life-threatening situation. Conclusion Adverse effects were reported in 18.9% of these 196 patients treated by RTX for INS. RTX treatment was interrupted or modified in 6 cases. Only 4 adverse effects led to severe consequences (either life threatening event or significant invalidity). These results will help to evaluate the benefit/risk ratio or RTX for INS in children. This is an ongoing study, therefore results can be different when they will be presented during the meeting.
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- 2017
13. Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants
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Christèle Gras-Le Guen, Sandra Biscardi, Karen Milcent, Gisèle Nissack, Loïc de Pontual, Philippe Babe, Christelle Vauloup-Fellous, I. Badier, François Dubos, Vincent Gajdos, Elisabeth Marc, Jean Bouyer, Claire Poulalhon, Andreea Madalina Dumitrescu, Christine Laguille, Alexis Mosca, S. Faesch, Ferielle Louillet, and Hélène Le Hors
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Calcitonin ,Male ,medicine.medical_specialty ,Urinalysis ,Fever ,Calcitonin Gene-Related Peptide ,Population ,Gastroenterology ,Procalcitonin ,03 medical and health sciences ,Leukocyte Count ,0302 clinical medicine ,Predictive Value of Tests ,030225 pediatrics ,Internal medicine ,Medicine ,Blood test ,Humans ,Blood culture ,030212 general & internal medicine ,Prospective Studies ,Protein Precursors ,education ,education.field_of_study ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Area under the curve ,Infant, Newborn ,Infant ,Bacterial Infections ,Surgery ,C-Reactive Protein ,ROC Curve ,Predictive value of tests ,Area Under Curve ,Pediatrics, Perinatology and Child Health ,Female ,business ,Emergency Service, Hospital ,Biomarkers - Abstract
Importance The procalcitonin (PCT) assay is an accurate screening test for identifying invasive bacterial infection (IBI); however, data on the PCT assay in very young infants are insufficient. Objective To assess the diagnostic characteristics of the PCT assay for detecting serious bacterial infection (SBI) and IBI in febrile infants aged 7 to 91 days. Design, Setting, and Participants A prospective cohort study that included infants aged 7 to 91 days admitted for fever to 15 French pediatric emergency departments was conducted for a period of 30 months (October 1, 2008, through March 31, 2011). The data management and analysis were performed from October 1, 2011, through October 31, 2014. Main Outcomes and Measures The diagnostic characteristics of the PCT assay, C-reactive protein (CRP) concentration, white blood cell (WBC) count, and absolute neutrophil cell (ANC) count for detecting SBI and IBI were described and compared for the overall population and subgroups of infants according to the age and the duration of fever. Laboratory test cutoff values were calculated based on receiver operating characteristic (ROC) curve analysis. The SBIs were defined as a pathogenic bacteria in positive culture of blood, cerebrospinal fluid, urine, or stool samples, including bacteremia and bacterial meningitis classified as IBIs. Results Among the 2047 infants included, 139 (6.8%) were diagnosed as having an SBI and 21 (1.0%) as having an IBI (11.0% and 1.7% of those with blood culture (n = 1258), respectively). The PCT assay offered an area under the curve (AUC) of ROC curve similar to that for CRP concentration for the detection of SBI (AUC, 0.81; 95% CI, 0.75-0.86; vs AUC, 0.80; 95% CI, 0.75-0.85; P = .70). The AUC ROC curve for the detection of IBI for the PCT assay was significantly higher than that for the CRP concentration (AUC, 0.91; 95% CI, 0.83-0.99; vs AUC, 0.77; 95% CI, 0.65-0.89; P = .002). Using a cutoff value of 0.3 ng/mL for PCT and 20 mg/L for CRP, negative likelihood ratios were 0.3 (95% CI, 0.2-0.5) for identifying SBI and 0.1 (95% CI, 0.03-0.4) and 0.3 (95% CI, 0.2-0.7) for identifying IBI, respectively. Similar results were obtained for the subgroup of infants younger than 1 month and for those with fever lasting less than 6 hours. Conclusions and Relevance The PCT assay has better diagnostic accuracy than CRP measurement for detecting IBI; the 2 tests perform similarly for identifying SBI in febrile infants aged 7 to 91 days.
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- 2015
14. Infection-related hospitalizations after kidney transplantation in children: Incidence, risk factors and cost
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Julien Hogan, Marie-Alice Macher, Etienne Bérard, Rémi Salomon, Anne-Laure Sellier-Leclerc, Ferielle Louillet, C. Pietrement, and C. Couchoud
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Nephrology ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Databases, Factual ,Urinary system ,030232 urology & nephrology ,030230 surgery ,Infections ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Child ,Kidney transplantation ,Cause of death ,Respiratory tract infections ,business.industry ,Proportional hazards model ,Incidence ,Risk of infection ,Incidence (epidemiology) ,Health Care Costs ,medicine.disease ,Kidney Transplantation ,Hospitalization ,Transplantation ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,France ,business - Abstract
Introduction Post-transplant infection-related hospitalisations have increased over time in children after renal transplantation. We attempt to describe those hospitalisations in a cohort of paediatric renal transplant recipients, to study the risk factors of infections and to evaluate the additional cost of those hospitalisations. Material and methods Patients under 20 years receiving a kidney transplant in France between 2008 and 2013 were screened from the National medico-administrative Hospital Discharge database and a probabilistic matching was performed with the National Renal Transplant Database. Costs’ calculation was based on the Public Health Care Tariff. We used Cox regression to study the risk factors of hospitalisation. To assess the evolution of the risk with time, we calculated the instantaneous risk of hospitalisation per month for all infections and by type of infection. Results Among 593 patients, 660 hospitalisations in 260 patients were identified; median follow-up time was 34.7 [14.7–53.2] months. The first cause of hospitalisation was UTI, incidence rate of 16.6 per 100 patient–years (py) followed by viral infections (15.6/100 py) including 128 digestive infections, 70 respiratory tract infections and 47 hospitalizations related to herpes viruses. Risk factors of hospitalisation were a younger age [HR 0.95 (0.92–0.97) per year], HLA mismatches [HR 1.14 (1.01–1.28) per mismatch] and the use of Cyclosporine rather than tacrolimus [HR 0.72 (0.54–0.95)]. Female gender, uropathy and cold ischemia time were specific risk factors of UTI. Instantaneous risk of infection decreased with time but CMV infection displayed a peak at the end of the prophylaxis. Total cost of infection-related hospitalisations was 1600k € (933 €/py) for 3529 days of hospitalisation. Conclusion This study points out the high burden of infection in paediatric transplanted patients, especially the youngest ones in terms of quality of life and health cost and highlights possible ways of improvement for clinical practice.
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- 2017
15. Acute renal cortical necrosis due to acquired antiprotein S antibodies
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Marie-Françoise Hurtaud-Roux, Hadji Djaffar, Brigitte Llanas, Solène Evrard, Georges Deschênes, Theresa Kwon, Ferielle Louillet, Véronique Baudouin, and Anis Larakeb
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Male ,Nephrology ,medicine.medical_specialty ,Pathology ,Protein S Deficiency ,Necrosis ,Anemia ,medicine.medical_treatment ,Kidney ,Protein S ,Chickenpox ,Renal cortical necrosis ,Internal medicine ,medicine ,Humans ,Protein S deficiency ,Enoxaparin ,Glucocorticoids ,Autoantibodies ,Ultrasonography ,biology ,business.industry ,Anticoagulants ,Infant ,Plasmapheresis ,medicine.disease ,Magnetic Resonance Imaging ,Treatment Outcome ,medicine.anatomical_structure ,Pulse Therapy, Drug ,Pediatrics, Perinatology and Child Health ,biology.protein ,Kidney Cortex Necrosis ,medicine.symptom ,business - Abstract
Although varicella is a common disease of childhood, renal complications are quite rare. We report here the interesting case of a-22 month-old boy exhibiting renal cortical necrosis related to an acquired protein S deficiency following varicella. Ten days after the vesicle eruption appearance, he presented with ecchymosed heels, oligoanuric kidney failure, anemia [hemoglobin (Hb) 78 g/L], schizocytosis (2.5%), but normal platelet count. Kidney sonography and magnetic resonance imaging evoked renal cortical necrosis. All together, these features suggested acquired protein S deficiency secondary to varicella. Strikingly, it was confirmed by a dramatic decrease in protein S plasma activity and a huge increase in immunoglobulin (Ig)G antibodies against protein S in the plasma. Anticoagulation therapy in addition with plasmapheresis and steroid pulses allowed a dramatic decrease in the antibodies against protein S and recovery of normal protein S activity. Undelayed diagnosis and treatment did not avoid kidney insufficiency but prevented life-threatening complications. In the light of this case report, protein S deficiency due to antibody inhibition should be carefully monitored anytime in the context of varicella when kidney insufficiency or necrosis occurs.
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- 2009
16. CO-58 – Syndrome néphrotique congénital: une étude multicentrique française
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Olivia Boyer, G. Rousset, Sophie Taque, S. Pierrepont, Véronique Baudouin, L de Parscau, Adrien May, Marc Fila, Caroline Rousset-Rouvière, B. Boudaillez, Hugues Flodrops, Tim Ulinski, R. Vieux, Maud Dehennault, Corinne Antignac, Laurence Heidet, Ferielle Louillet, Olivier Dunand, Ariane Zaloszyc, Patrick Niaudet, Christine Pietrement, J. Baccheta, Rémi Salomon, Sandra Bérody, Elodie Merieau, Arnaud Garnier, J. Tenenbaum, and Jérôme Harambat
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Pediatrics, Perinatology and Child Health - Published
- 2015
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