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1. Erratum à : Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients [Nephrol. & Therap. 17 (1) (2021) 42–49]

Author: Mickaël Bobot, Laurent Zieleskiewicz, Noémie Jourde-Chiche, Clarissa Von Kotze, Manon Ebersolt, Bertrand Dussol, Marion Sallée, Sophie Chopinet, Yvon Berland, Philippe Brunet, Thomas Robert, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Nephrology, [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2022

2. Localized versus systemic granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry

Author: Claire de Moreuil, Olivier Aumaître, Pascal Godmer, Alexis Régent, François Maurier, Christian Pagnoux, Luc Mouthon, Bernard Bonnotte, Xavier Puéchal, Michele Iudici, Chahéra Khouatra, Noémie Jourde-Chiche, Marc Ruivard, François Lifermann, Benjamin Terrier, Claire Blanchard-Delaunay, Antoine Néel, Eric Hachulla, Pascal Cohen, Delphine S. Courvoisier, Thomas Le Gallou, Jean-François Viallard, Alain Le Quellec, Achille Aouba, Loïc Guillevin, Thomas Quemeneur, Alexandre Karras, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Vasculitis, medicine.medical_specialty, Cyclophosphamide, Subglottic stenosis, [SDV]Life Sciences [q-bio], Context (language use), macromolecular substances, vasculitis, Antibodies, Antineutrophil Cytoplasmic, stomatognathic system, Rheumatology, Recurrence, Internal medicine, medicine, Humans, Pharmacology (medical), Registries, Sinusitis, Retrospective Studies, ddc:616, Lung, granulomatosis with polyangiitis, business.industry, medicine.disease, Otitis, medicine.anatomical_structure, Granulomatosis with polyangiitis, medicine.symptom, business, ANCA-associated vasculitis, medicine.drug
Abstract: Objective To describe the main features at diagnosis and evolution over time of patients with localized granulomatosis with polyangiitis (L-GPA) compared with those of systemic GPA (S-GPA). Methods EULAR definitions of L-GPA, i.e. upper and/or lower respiratory tract involvement, and S-GPA were applied to patients from the French Vasculitis Study Group Registry. L-GPA and S-GPA patients’ characteristics at diagnosis and long-term outcomes were analysed and compared. Results Among the 795 Registry patients, 79 (10%) had L-GPA. Their main clinical manifestations were rhinitis, lung nodules, sinusitis and otitis. L-GPA vs S-GPA patients at diagnosis, respectively, were younger, more frequently had saddle nose deformity or subglottic stenosis and were less often PR3-ANCA–positive. L-GPA vs S-GPA induction therapy less frequently included CYC but more often a combination of MTX and glucocorticoids; 64% of MTX-treated patients experienced disease progression within 18 months post-diagnosis. L- and S-GPA patients’ estimated relapse-free–survival probabilities, relapse rates and refractory disease rates at each time point were comparable, but L-GPA patients had more frequent ENT and lung relapses, and higher overall survival rates (P Conclusions The relapse risks of L-GPA and S-GPA were similar, but relapse patterns differed and L-GPA overall survival rate was higher. About one-quarter of L-GPA patients developed S-GPA over time, but without end-stage organ involvement.
Published: 2022

3. Comparative study of granulomatosis with polyangiitis subsets according to ANCA status: data from the French Vasculitis Study Group Registry

Author: Xavier Puéchal, Michele Iudici, Christian Pagnoux, Pascal Cohen, Mohamed Hamidou, Achille Aouba, François Lifermann, Marc Ruivard, Olivier Aumaître, Bernard Bonnotte, Francois Maurier, Thomas Le Gallou, Eric Hachulla, Alexandre Karras, Chahéra Khouatra, Noémie Jourde-Chiche, Jean-François Viallard, Claire Blanchard-Delaunay, Pascal Godmer, Alain Le Quellec, Thomas Quéméneur, Claire de Moreuil, Luc Mouthon, Benjamin Terrier, Loïc Guillevin, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geneva University Hospitals and Geneva University, University of Toronto, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], and CHU Pontchaillou [Rennes]
Subjects: Male, granulomatosis with polyangiitis, Myeloblastin, [SDV]Life Sciences [q-bio], Immunology, autoimmunity, urologic and male genital diseases, Antibodies, Antineutrophil Cytoplasmic, respiratory tract diseases, Rheumatology, immune system diseases, Humans, Immunology and Allergy, Female, autoimmune diseases, Registries, cardiovascular diseases, systemic vasculitis, skin and connective tissue diseases, Retrospective Studies
Abstract: ObjectiveTo investigate whether antineutrophil cytoplasm antibody (ANCA)-negative and myeloperoxidase (MPO)-ANCA–positive granulomatosis with polyangiitis (GPA) differ from proteinase-3 (PR3)-ANCA–positive GPA.MethodsDiagnostic characteristics and outcomes of newly diagnosed French Vasculitis Study Group Registry patients with ANCA-negative, MPO-ANCA–positive or PR3-ANCA–positive GPA satisfying American College of Rheumatology criteria and/or Chapel Hill Conference Consensus Nomenclature were compared.ResultsAmong 727 GPA, 62 (8.5%) were ANCA-negative, 119 (16.4%) MPO-ANCA–positive and 546 (75.1%) PR3-ANCA–positive. ANCA-negative patients had significantly (pConclusionsBased on this large cohort, ANCA-negative versus ANCA-positive patients more frequently had limited disease but similar RFS and OS. MPO-ANCA–positive patients had similar RFS but lower OS due to their older age. PR3-ANCA–positive GPA patients’ RFS was lower than those of the two other subsets combined but that difference did not persist when comparing only PR3 versus MPO-ANCA–positive patients.
Published: 2022

4. Presence of specific SARS-COV2 antibodies in hemodialysis patients and their caregivers after the first wave of COVID-19

Author: Thomas Robert, Guillaume Lano, Noémie Resseguier, Mickaël Bobot, Dammar Bouchouareb, Stéphane Burtey, Xavier de Lamballerie, Jean Dhorne, Bertrand Dussol, Ariane Duval, Julien Faraut, Toscane Fourié, Philippe Giaime, Mourad Hallah, Dominique Jaubert, Océane Jéhel, Tristan Legris, Stéphane Liotatis, Valérie Moal, Laetitia Ninove, Nathalie Pedinielli, Marion Pelletier, Manon Romeu-Giannoli, Mariela Saba, Marion Sallée, Laurent Samson, Adriana Saveanu, Violaine Scarfoglière, Pascale Sebahoun, Romain Vial, Clarissa Von Kotze, Philippe Brunet, Gaëtan Lebrun, Stanislas Bataille, Noémie Jourde-Chiche, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité des Virus Emergents (UVE), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, Caregivers, Renal Dialysis, SARS-CoV-2, Seroepidemiologic Studies, COVID-19, Humans, Prospective Studies, Antibodies, Viral
Abstract: Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020. SARS-COV2 seroprevalence was evaluated by a rapid serological test (BIOSYNEX) in HD patients and caregivers, and the presence or not of anti-SARS-COV2 neutralizing or non-neutralizing antibodies in patients was also determined by ELISA and seroneutralization. In June 2020, 451 HD patients and 238 caregivers were included. Overall SARS-COV2 seroprevalence was 8.4% (patients) and 6.7% (caregivers), and was 87.1% (patients) and 90.0% (caregivers) in participants with a previously documented SARS-COV2 infection. Overall seroprevalence reached 13.8% (patients) and 12.6% (caregivers) following the second epidemic wave. During the follow-up, 38 (8.4%) patients died (9 of COVID-19). Among the 44 (10.6%) patients who became infected, only two were seropositive at M0. The levels of anti-SARS-COV2 antibodies decreased over time in patients and caregivers. The BIOSYNEX test showed 82.9% sensitivity and 97.7% specificity. Prevalence of anti-SARS-COV2 antibodies was low in HD patients and caregivers after the first epidemic wave but rose after the second wave. A rapid serological test showed good performances and could be useful for future monitoring of anti-SARS-COV2 antibodies.
Published: 2022

5. Bartonella and Coxiella infections presenting as systemic vasculitis: case series and review of literature

Author: Christophe Rodriguez, Olivier Fain, Alexandre Cez, Noémie Jourde-Chiche, Maxime Beydon, Benjamin Terrier, Xavier Puéchal, Cédric Rafat, Carole Philipponnet, Dan Levy, Antoine Dossier, Nicolas Dupin, Alexandre Karras, Inès Aureau, Loïc Guillevin, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, 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), Service de Néphrologie et Dialyses [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 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 médecine interne [CHU Saint-Antoine], CHU Saint-Antoine [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), CHU Clermont-Ferrand, AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Strasbourg, and Centre hospitalier de Pau
Subjects: Bartonella, Vasculitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, 030204 cardiovascular system & hematology, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, 0302 clinical medicine, Glomerulonephritis, Coxiella, Rheumatology, Bartonella Infections, hemic and lymphatic diseases, medicine, Rheumatoid factor, Endocarditis, Humans, Pharmacology (medical), cardiovascular diseases, Cryoglobulinemic vasculitis, Retrospective Studies, 030203 arthritis & rheumatology, Infectious disease, biology, business.industry, ANCA, medicine.disease, biology.organism_classification, bacterial infections and mycoses, Cryoglobulinemia, 3. Good health, Immunology, bacteria, business, Bartonella Infection, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Systemic vasculitis
Abstract: Objectives Coxiella and Bartonella spp. display particular tropism for endothelial or endocardial tissues and an abnormal host response to infections with induced autoimmunity. We aimed, through a case series combined with a comprehensive literature review, to outline characteristics of Coxiella and Bartonella infections presenting as systemic vasculitis. Methods We retrospectively included cases of definite Coxiella and Bartonella infections presenting with vasculitis features and performed a comprehensive literature review. Results Six cases of Bartonella infections were added to 18 cases from literature review. Causative pathogens were mainly B. henselae. Bartonella infection mimicked ANCA-associated vasculitis in 83% with PR3-ANCA and presented as cryoglobulinaemic vasculitis in 8%. GN was present in 92%, and 88% had endocarditis. Complement fractions were low in 82% and rheumatoid factor positive in 85%. Kidney biopsies showed cell proliferation, mostly crescentic, with pauci-immune GN in 29%. Outcome was favourable, with the use of antibiotics alone in one-third. Five cases of Coxiella infections were added to 16 from literature review. Sixteen had small-vessel vasculitides, mainly cryoglobulinaemia vasculitis in 75%. One patient had polyarteritis nodosa-like vasculitis and four large-vessel vasculitis. Outcome was good except for one death. A highly sensitive next generation sequencing analysis on three Coxiella- and two Bartonella-related vasculitides biopsies did not find any bacterial DNA. Conclusion Coxiella and Bartonella are both able to induce vasculitis but display distinct vasculitis features. Bartonella mimics PR3-ANCA-associated vasculitis in the setting of endocarditis, whereas Coxiella may induce vasculitis involving all vessel sizes.
Published: 2021

6. Impact of aging on phenotype and prognosis in IgA vasculitis

Author: Stanislas Faguer, Noémie Le Gouellec, François Maurier, Bertrand Lioger, Patrice Cacoub, Noémie Jourde-Chiche, Sébastien Sanges, Christian Lavigne, Benjamin Terrier, Julie Goutte, Geoffrey Urbanski, Zahir Amoura, Aurélie Hummel, Evangeline Pillebout, Sophie Deriaz, Loic Raffray, Alban Deroux, Alexandra Audemard-Verger, Elisabeth Diot, Guillaume Moulis, Nicole Feirreira-Maldent, Johan Chanal, François Maillot, A. Baldolli, Loïc Guillevin, Jean-François Augusto, Eric Thervet, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LUNAM Université [Nantes Angers Le Mans], Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Biomarqueurs d’urgence et de réanimation (GRC 14 - BIOSFAST), Sorbonne Université (SU), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Ambroise Paré [AP-HP], Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Vasculaire [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Plateforme Histologie, Immunomarquage et Microdissection laser [Institut Cochin] (HistIM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Immunoglobulin A, Adult, Male, Vasculitis, medicine.medical_specialty, Aging, Henoch-Schonlein purpura, Disease, 03 medical and health sciences, IgA vasculitis, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Aged, Retrospective Studies, 030203 arthritis & rheumatology, biology, business.industry, Age Factors, Retrospective cohort study, Middle Aged, medicine.disease, renal involvement, Purpura, 030104 developmental biology, Phenotype, Quartile, age, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biology.protein, outcome, Kidney Failure, Chronic, Female, prognosis, medicine.symptom, business, Henoch–Schönlein purpura
Abstract: Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P 6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
Published: 2021

7. Unsupervised clustering analysis of data from an online community to identify lupus patient profiles with regards to treatment preferences

Author: Julien Mancini, Laurent Chiche, Damien Testa, Lise Radoszycki, Noémie Jourde-Chiche, Pasquale Varriale, Carenity [Paris] (Else Care), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Européen [Fondation Ambroise Paré - Marseille], Service Biostatistique et Technologies de l’Information et de la Communication [AP-HM Hôpital de la Timone] (BioSTIC), and Malbec, Odile
Subjects: Adult, Male, medicine.medical_specialty, treatment preferences, [SDV]Life Sciences [q-bio], online community, Affect (psychology), Medication Adherence, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Therapeutic Adherence, Rheumatology, systemic lupus erythematosus, Surveys and Questionnaires, medicine, Cluster Analysis, Humans, Lupus Erythematosus, Systemic, 030212 general & internal medicine, Intensive care medicine, Aged, 030203 arthritis & rheumatology, Autoimmune disease, Clinical Trials as Topic, Internet, Systemic lupus erythematosus, business.industry, Social Support, Patient Preference, lupus, Middle Aged, medicine.disease, Online community, [SDV] Life Sciences [q-bio], Pharmaceutical Preparations, therapeutic adherence, Female, France, Unsupervised clustering, business, Attitude to Health, Social Media
Abstract: Objective Lupus is a chronic complex autoimmune disease. Non-adherence to treatment can affect patient outcomes. Considering patients’ preferences into medical decisions may increase acceptance to their medication. The PREFERLUP study used unsupervised clustering analysis to identify profiles of patients with similar treatment preferences in an online community of French lupus patients. Methods An online survey was conducted in adult lupus patients from the Carenity community between August 2018 and April 2019. Multiple Correspondence Analysis (MCA) was used with three unsupervised clustering methods (hierarchical, kmeans and partitioning around medoids). Several indicators (measure of connectivity, Dunn index and Silhouette width) were used to select the best clustering algorithm and choose the number of clusters. Results The 268 participants were mostly female (96%), with a mean age of 44.3 years 83% fulfilled the American College of Rheumatology (ACR) self-reported diagnostic criteria for systemic lupus erythematosus. Overall, the preferred route of administration was oral (62%) and the most important feature of an ideal drug was a low risk of side-effects (32%). Hierarchical clustering identified three clusters. Cluster 1 (59%) comprised patients with few comorbidities and a poor ability to identify oncoming flares; 84% of these patients desired oral treatments with limited side-effects. Cluster 2 (13%) comprised younger patients, who had already participated in a clinical trial, were willing to use implants and valued the compatibility of treatments with pregnancy. Cluster 3 (28%) comprised patients with a longer lupus duration, poorer control of the disease and more comorbidities; these patients mainly valued implants and injections and expected a reduction of corticosteroid intake. Conclusions Different profiles of lupus patients were identified according to their drug preferences. These clusters could help physicians tailor their therapeutic proposals to take into account individual patient preferences, which could have a positive impact on treatment acceptance and then adherence. The study highlights the value of data acquired directly from patient communities.
Published: 2021

8. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre

Author: Claire Pouteil-Noble, Steven Grangé, Claire Presne, Ygal Benhamou, Agnès Veyradier, Paul Coppo, Arnaud François, Véronique Frémeaux-Bacchi, Dominique Guerrot, Noémie Jourde Chiche, François Provôt, Jean-Philippe Coindre, Maximilien Grall, Alexandre Karras, Florence Daviet, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, Centre Hospitalier Le Mans (CH Le Mans), Hospices Civils de Lyon (HCL), 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), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, Nephrology, Blood transfusion, medicine.medical_treatment, 030204 cardiovascular system & hematology, Kidney Function Tests, urologic and male genital diseases, Deoxycytidine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Medicine, Coagulation, thrombotic disorders and therapies, Cancer and thrombosis, Gemcitabineinduced thrombotic microangiopathy, Remission Induction, Acute kidney injury, Acute Kidney Injury, Middle Aged, Eculizumab, Gemcitabine-induced thrombotic microangiopathy, Haemolysis, 3. Good health, Renal Replacement Therapy, Treatment Outcome, Cancer and thrombosis, 030220 oncology & carcinogenesis, Female, France, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Thrombotic microangiopathy, Urology, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Internal medicine, Humans, Blood Transfusion, Renal replacement therapy, thrombotic disorders and therapies, Coagulation, Thrombotic Microangiopathies, business.industry, Research, Recovery of Function, medicine.disease, Gemcitabine, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Diseases of the genitourinary system. Urology, Complement Inactivating Agents, RC870-923, business, Packed red blood cells
Abstract: Background Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). Methods This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. Results Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2–22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, P 2 respectively in the eculizumab group and in the control group. Conclusions These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.
Published: 2021

9. IgA Vasculitis With Underlying Liver Cirrhosis: A French Nationwide Case Series of 20 Patients

Author: Ines Elhani, Evangeline Pillebout, Antoine Hankard, Matthieu Groh, Sophie Greillier, Benjamin Terrier, François Vrtovsnik, Adrien Bigot, Noémie Jourde-Chiche, Hubert de Boysson, Loic Raffray, Alexandra Audemard-Verger, Geoffrey Urbanski, Isabelle Ollivier, Achille Aouba, Georges-Philippe Pageaux, Nabil Belfeki, François Maillot, Service de rhumatologie, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Foch [Suresnes], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Liver Cirrhosis, Vasculitis, 0301 basic medicine, medicine.medical_specialty, Cirrhosis, Henoch-Schonlein purpura, Immunology, Alcohol abuse, Autoimmune hepatitis, liver, Gastroenterology, 03 medical and health sciences, Liver disease, IgA vasculitis, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Immunology and Allergy, Aged, Retrospective Studies, business.industry, cirrhosis, Middle Aged, medicine.disease, Immunoglobulin A, 3. Good health, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, 030211 gastroenterology & hepatology, alcohol, Viral hepatitis, business
Abstract: ObjectiveImmunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis.MethodsWe conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS).ResultsTwenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, P < 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, P = 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, P = 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12–84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV.ConclusionWe report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse.
Published: 2021

10. Urinary Peptides as Potential Non-Invasive Biomarkers for Lupus Nephritis: Results of the Peptidu-LUP Study

Author: Maxence, Tailliar, Joost P, Schanstra, Tim, Dierckx, Benjamin, Breuil, Guillaume, Hanouna, Nicolas, Charles, Jean-Loup, Bascands, Bertrand, Dussol, Alain, Vazi, Laurent, Chiche, Justyna, Siwy, Stanislas, Faguer, Laurent, Daniel, Eric, Daugas, Noémie, Jourde-Chiche, On Behalf Of The Groupe Coopératif Sur le Lupus Rénal Gclr, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), 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), Université Catholique de Louvain = Catholic University of Louvain (UCL), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Aix Marseille Université (AMU), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM-TRANSFERT [Paris] (IT), Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: PREDICTION, ERYTHEMATOSUS, [SDV]Life Sciences [q-bio], non-invasive, kidney biopsy, lcsh:Medicine, PROGRESSION, DIAGNOSIS, CLASSIFICATION, VALIDATION, Article, Medicine, General & Internal, proteomics, systemic lupus erythematosus, General & Internal Medicine, lupus nephritis, Science & Technology, lcsh:R, CAPILLARY-ELECTROPHORESIS, peptidomics, KIDNEY-DISEASE, MASS-SPECTROMETRY, urine, RENAL-DISEASE, classification, biomarker, prognosis, Life Sciences & Biomedicine, prognosi
Abstract: Background: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design: Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery (n = 42) and an independent validation (n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated. ispartof: JOURNAL OF CLINICAL MEDICINE vol:10 issue:8 ispartof: location:Switzerland status: published
Published: 2021

11. Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice

Author: Alexandrine Foucault-Bertaud, Richard Bachelier, Panagiotis Kavvadas, Maja T. Lindenmeyer, Ahmad Joshkon, Nathalie Bardin, Ahmed Abed, Noémie Jourde-Chiche, Clemens D. Cohen, Christos E. Chadjichristos, Florence Authier, Françoise Dignat-George, Stéphane Burtey, Magali Genest, Aurélie S. Leroyer, Marcel Blot-Chabaud, Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Contextes, Variation, Usages : Groupe de Recherche en linguistique des langues germaniques et scandinaves de Paris-Sorbonne (CoVariUs), Université Paris-Sorbonne (UP4), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-BSV1-0019,READ,CD146 et JAMs dans le contrôle de l'intégrité des junctions endothéliales : des bases moléculaires aux maladies inflammatoires rénales.(2011), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians University [Munich] (LMU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Chadjichristos, Christos, Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ludwig Maximilian University [Munich] (LMU), and Leroyer, Aurelie
Subjects: 0301 basic medicine, mice, [SDV]Life Sciences [q-bio], Kidney Glomerulus, Inflammation, CD146 Antigen, 030204 cardiovascular system & hematology, urologic and male genital diseases, Experimental glomerulonephritis, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gene Knockout Techniques, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, Fibrosis, Drug Discovery, Internal Medicine, Animals, Medicine, Proteinuria, business.industry, Monocyte, fibrosis, Endothelial Cells, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Up-Regulation, [SDV] Life Sciences [q-bio], Disease Models, Animal, Intercellular Junctions, 030104 developmental biology, medicine.anatomical_structure, inflammation, Immunology, monocyte, CD146, medicine.symptom, proteinuria, business
Abstract: International audience; CD146 is an endothelial junctional adhesion molecule, which expression is increased in human glomerular diseases. However, the pathological significance of this overexpression remains unknown. Induction of glomerulonephritis in mice, by using nephrotoxic serum, showed that CD146 expression was highly induced within damaged glomeruli and was associated with renal inflammation and fibrosis. Interestingly, 2 weeks after glomerulonephritis induction, CD146 knockout mice showed preserved renal function as proteinuria and blood urea nitrogen levels were significantly lower compared with wild-type littermates. Furthermore, renal structure was considerably conserved, since crescents formation, tubular dilation, monocyte and lymphocyte infiltration, and interstitial renal fibrosis were highly reduced. Colocalization with markers for different types of glomerular cells showed that CD146 expression was mainly increased within the injured endothelium of the glomerular tuft. Consequently, we generated a new transgenic strain in which CD146 was specifically deleted in the vascular endothelium. Similarly to CD146 knockout, these mice showed preservation of renal structure and function after the induction of glomerulonephritis compared with wild-type animals. These data show that endothelial CD146 plays a major role in glomerulonephritis and may represent a novel therapeutic target to reduce glomerular damage and the progression of renal disease.
Published: 2021

12. Kidney biopsy in very elderly patients: indications, therapeutic impact and complications

Author: Pierre Gobert, Éric Magnant, David Verhelst, Julia Torrents, Yannick Knefati, Mickaël Bobot, Noémie Jourde-Chiche, Stanislas Bataille, Stéphane Burtey, Laurent Daniel, Valérie Masson, Philippe Giaime, Julien Santini, Bertrand Dussol, Mathilde Fedi, Philippe Brunet, G. Lebrun, Julien Mancini, Malbec, Odile, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Privé de Provence [Aix-en-Provence] (HPP), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Polyclinique des fleurs, Clinique Bouchard - ELSAN [Marseille], Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Male, Nephrology, medicine.medical_specialty, Survival, Biopsy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Kidney biopsy, Nephrotic syndrome, Kidney, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glomerulonephritis, Hypertensive Nephropathy, Internal medicine, medicine, Pathology, Humans, 030212 general & internal medicine, Acute tubular necrosis, Dialysis, Retrospective Studies, Aged, 80 and over, Creatinine, business.industry, Research, Age Factors, Acute kidney injury, Retrospective cohort study, Advanced age, medicine.disease, Diseases of the genitourinary system. Urology, 3. Good health, Treatment, [SDV] Life Sciences [q-bio], Proteinuria, chemistry, Adverse events, Female, RC870-923, business, Elderly patient
Abstract: Background Few data is available on the risk/benefit balance of native kidney biopsy (KB) in very elderly patients. Methods Multicenter retrospective cohort study in the Aix-Marseille area: the results of KB and medical charts of all patients over 85 years biopsied between January 2010 and December 2018 were reviewed. Results 104 patients were included. Median age was 87 years. Indications for KB were: acute kidney injury (AKI) in 69.2% of patients, nephrotic syndrome (NS) with AKI in 13.5%, NS without AKI in 12.5%, and proteinuria in 4.8%. Median serum creatinine was 262 μmol/L, 21% of patients required dialysis at the time of KB. Significant bleeding occurred in 7 (6.7%) patients, requiring blood cell transfusion in 4 (3.8%), and radiological embolization in 1 (1%). The most frequent pathological diagnoses were: non-diabetic glomerular diseases (29.8%, including pauci-immune crescentic glomerulonephritis in 9.6%), hypertensive nephropathy (27.9%), acute interstitial nephritis (16.3%), renal involvement of hematological malignancy (8.7%), and acute tubular necrosis (6.7%). After KB, 51 (49%) patients received a specific treatment: corticosteroids (41.3%), cyclophosphamide (6.7%), rituximab (6.7%), bortezomib (3.8%), other chemotherapies (3.8%). Median overall survival was 31 months. Conclusions KB can reveal a diagnosis with therapeutic impact even in very elderly patients. Severe bleeding was not frequent in this cohort, but KB may have not been performed in more vulnerable patients.
Published: 2021

13. Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort

Author: Noémie Jourde-Chiche, Jean-Jacques Grob, Philippe Berbis, Stéphane Burtey, Marion Sallée, C. Gaudy, Stéphane Honoré, Julien Mancini, Claire Stein, Philippe Brunet, M. Pelletier, 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM], Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service Pharmacie [Hôpital de la Timone - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), and Dupuis, Christine
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Pembrolizumab, Antibodies, Monoclonal, Humanized, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, melanoma, Medicine, Humans, anti-PD1, education, Adverse effect, Retrospective Studies, Transplantation, education.field_of_study, business.industry, Incidence (epidemiology), Acute kidney injury, Receptors, Death Domain, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Nivolumab, acute kidney injury, Nephrology, 030220 oncology & carcinogenesis, Cohort, immune checkpoints inhibitors, immune-related adverse events, business, Kidney disease
Abstract: Background Immune checkpoints inhibitors have transformed the prognosis of advanced melanoma but are associated with immune-related adverse events (irAEs). We evaluated the incidence, risk factors and causes of acute kidney injury (AKI) in a monocentric real-life cohort of patients treated with anti-programmed death receptor-1 (anti-PD1) antibodies for advanced melanoma. Methods Retrospective collection of medical charts and comprehensive analysis of lab results from patients treated with nivolumab or pembrolizumab for advanced melanoma between 2014 and 2018 was carried out. AKI was defined by Kidney Disease Improving Global Outcomes criteria, and causes were determined by chart review. Overall survival, survival without AKI and impact of AKI on survival were analysed. Risk factors for death and for AKI were identified. Results Two hundred and thirty-nine patients were included. Forty-one (17%) had at least one episode of AKI. Independent risk factors for AKI were treatment with renin–angiotensin–aldosterone system inhibitors (RAASi), pre-existing chronic kidney disease (CKD) and cumulated doses of anti-PD1. The main cause of AKI was prerenal, and only eight patients (3.3%) developed acute interstitial nephritis; 8% of patients developed CKD. The median overall survival was 13.4 months and was not affected by AKI. In multivariate analysis, the overall mortality was lower in overweight and obese patients and higher in patients treated with proton-pump inhibitors (PPI) or corticosteroids. Conclusions AKI is common in patients treated with anti-PD1 for advanced melanoma but is mostly prerenal and favoured by the use of RAASi; renal irAE is rare. PPI and corticosteroids were associated with poor survival in this population, while overweight/obesity was protective.
Published: 2021

14. Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy

Author: Laurent Daniel, Julia Torrents, Christine Zandotti, Stéphane Burtey, Noémie Jourde-Chiche, Mickaël Bobot, Yannick Knefati, Olivier Moranne, Maëlis Kauffmann, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Assistance Publique - Hôpitaux de Marseille (APHM), and Lucas, Nelly
Subjects: Male, 0301 basic medicine, Nephrology, Biopsy, Lupus nephritis, Parvovirus B19, Antibodies, Viral, Kidney, lcsh:RC870-923, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Glomerulonephritis, Seroepidemiologic Studies, Parvovirus B19, Human, Prevalence, Minimal change disease, Aged, 80 and over, Systemic lupus erythematosus, medicine.diagnostic_test, Incidence, Acute Kidney Injury, Middle Aged, 3. Good health, medicine.anatomical_structure, Female, Research Article, Adult, medicine.medical_specialty, Adolescent, Glomerulonephritis, Membranoproliferative, Erythema Infectiosum, Young Adult, 03 medical and health sciences, Primary infection, Internal medicine, medicine, Humans, Thrombotic microangiopathy, Viremia, Aged, business.industry, Nephrosis, Lipoid, Kidney Tubular Necrosis, Acute, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 030104 developmental biology, Immunoglobulin M, Immunoglobulin G, DNA, Viral, Hemolytic-Uremic Syndrome, business, 030217 neurology & neurosurgery, Kidney disease
Abstract: Background The seroprevalence of human Parvovirus B19 (PVB19) is 70–85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. Methods Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017–2018. Results The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. Conclusion PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.
Published: 2020

15. Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19

Author: Thomas Robert, Mélanie Velier, Raphael Cauchois, Guillaume Lano, Philippe Brunet, Clara Degioanni, Laurent Papazian, Florence Daviet, Léa Pietri, Marie Koubi, Gilles Kaplanski, Yael Berda, Christophe Guervilly, Françoise Dignat-George, Sami Hraiech, Evelyne Abdili, Stéphane Burtey, Romaric Lacroix, Laurent Arnaud, Noémie Jourde-Chiche, Florence Sabatier, Hôpital Nord [CHU - APHM], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Aix-Marseille University Institut National de la Sante et de la Recherche Medicale (Inserm) European CommissionAssistance Publique-Hopitaux de Marseille, and Prémilleux, Annick
Subjects: Adult, Male, 0301 basic medicine, circulating endothelial cells, Endothelium, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, law.invention, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, law, In vivo, Intensive care, Cell Adhesion, Humans, Immunology and Allergy, Medicine, Chronic exertional compartment syndrome, Aged, Retrospective Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, Brief Report, COVID-19, Retrospective cohort study, Middle Aged, endothelial injury, medicine.disease, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, AcademicSubjects/MED00290, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Cytokine, Immunology, Female, Endothelium, Vascular, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.
Published: 2020

16. Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort

Author: Khaled Gaha, Mickaël Bobot, Magued Nakhla, Tristan Legris, Marion Sallée, Pascale Halin, Julie Moussi-Frances, Thomas Robert, Valérie Moal, Philippe Rieu, Isabelle Kazes, Eric Canivet, Alain Wynckel, Alexandre Debrumetz, R. Vial, M. Pelletier, Guilhem Cavaille, Natacha Noël, Pascal Bindi, Guillaume Lano, Philippe Brunet, Stéphane Burtey, Bénédicte Levy, Janette Mansour, Stanislas Bataille, Bertrand Gondouin, Marion Gully, Antoine Braconnier, Noémie Jourde-Chiche, Violaine Scarfoglière, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM), Association Dialyse Provence Corse, Centre Hospitalier de Verdun Saint-Mihiel, Centre Hospitalier de Laon (CH Laon), hopital, Centre Hospitalier de Charleville-Mezières, CH de Troyes, Association Regionale Promotion Dialyse Domicile ( ARPDD), 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), Prémilleux, Annick, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Maison Blanche, Clinique Bouchard - ELSAN [Marseille], Association des dialysés Provence-Corse (ADPC), Centre hospitalier Troyes (CH Troyes), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: lymphocytes, medicine.medical_specialty, hydroxychloroquine, BLOCKADE, medicine.medical_treatment, OUTBREAK, [SDV]Life Sciences [q-bio], Population, 030232 urology & nephrology, HEMODIALYSIS-PATIENTS, Disease, CORONAVIRUS DISEASE 2019, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Epidemiology, medicine, 030212 general & internal medicine, education, Dialysis, Transplantation, education.field_of_study, OUTCOMES, angiotensin II receptor blockers, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, COVID-19, Intensive care unit, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV] Life Sciences [q-bio], Nephrology, Cohort, dialysis, Hemodialysis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: BackgroundCoronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD).MethodsWe conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality.ResultsAmong the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses.ConclusionsCOVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.
Published: 2020

17. Sera From Patients With Minimal Change Disease Increase Endothelial Permeability to Sodium

Author: Manon Carre, Richard Bachelier, Nathalie Bardin, Karim Fallague, Françoise Dignat-George, Florence Daviet, Manon Laforêt, Stéphane Burtey, Marcel Blot-Chabaud, Stéphane Poitevin, Noémie Jourde-Chiche, Muriel G. Blin, Aurélie S. Leroyer, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Leroyer, Aurelie, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Prémilleux, Annick
Subjects: Endothelial permeability, Sodium, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, chemistry.chemical_element, 030204 cardiovascular system & hematology, Pharmacology, lcsh:RC870-923, Alimentation, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Research Letter, Medicine, Minimal change disease, Marseille, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Agriculture, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV] Life Sciences [q-bio], chemistry, Nephrology, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; E dema is the main symptom of nephrotic syndrome associated to minimal change disease (MCD). Besides the increase in glomerular permeability, possibly induced by a circulating permeability factor, 1 an increase in systemic vascular permeability could participate in the constitution of edema. This study was conducted to evaluate the permeability of endothelial cells (EC) exposed to serum from nephrotic patients with MCD, to low-or high-molecularweight molecules, by trans-or paracellular transport.
Published: 2020

18. Accumulation of protein-bound uremic toxins: the kidney remains the leading culprit in the gut-liver-kidney axis

Author: Stéphane Burtey, Noémie Jourde-Chiche, 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, education, 030232 urology & nephrology, Renal function, Kidney, urologic and male genital diseases, Culprit, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Dialysis, Toxins, Biological, Uremia, urogenital system, business.industry, Metabolism, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Renal Elimination, Liver, Nephrology, Uremic toxins, business, Kidney disease
Abstract: International audience; Protein-bound uremic toxins (PBUTs) accumulate in chronic kidney disease (CKD) and are poorly removed by dialysis. Gryp et al. demonstrated that fecal bacteria from patients with CKD do not produce more PBUTs than do those from healthy controls and that the accumulation of PBUTs, as CKD progresses, is mainly due to their reduced renal elimination by glomerular filtration and tubular secretion. This work underlines the importance of studying the metabolism of PBUTs along the diet-gut-liver-kidney axis. Copyright (C) 2020, International Society of Nephrology.
Published: 2020

19. Paradoxical association between blood modular interferon signatures and quality of life in patients with systemic lupus erythematosus

Author: Frédérique Retornaz, Philippe Halfon, Mickaël Bobot, Noémie Jourde-Chiche, Stéphane Burtey, Laurent Chiche, Elisabeth Whalen, Stéphanie Gentile, Julie Seguier, Elisabeth Jouve, Damien Chaussabel, Bertrand Dussol, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Gérontologique Départemental de Marseille (CGD 13), Systems Immunology Laboratory, Benaroya Research Institute, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Benaroya Research Institute [Seattle] (BRI), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Qatar University
Subjects: Male, 0301 basic medicine, Multivariate analysis, Health Status, [SDV]Life Sciences [q-bio], Lupus nephritis, 0302 clinical medicine, Quality of life, systemic lupus erythematosus, Interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, Lupus Erythematosus, Systemic, Medicine, Pharmacology (medical), transcriptomic analysis, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, interferon, Middle Aged, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, SF-36, Population, Young Adult, 03 medical and health sciences, Rheumatology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Association (psychology), education, Aged, 030203 arthritis & rheumatology, business.industry, Gene Expression Profiling, medicine.disease, Mental health, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cross-Sectional Studies, 030104 developmental biology, quality of life, Interferons, business
Abstract: Objectives Blood transcriptomic IFN signature is a hallmark of SLE. The impaired health-related quality of life (HRQOL) observed in SLE is poorly related to disease activity. The aim of this study was to test how IFN signatures were associated with HRQOL in SLE patients. Methods Among consecutive patients, blood transcriptomic profiles were analysed with a modular framework comprising 3 IFN modules: M1.2, M3.4 and M5.12. Disease activity was evaluated by the SLEDAI score, and HRQOL was assessed with the SF-36 questionnaire, which includes eight domains: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (MH) and physical component summary and mental component summary scores. Results A total of 57 SLE patients were evaluated, among whom 27 (47%) were clinically quiescent, 30 (53%) were flaring, and 19 (33%) had active lupus nephritis. All SF-36 domains were altered in SLE patients compared with the general French population (P < 0.0001). In multivariate analysis, taking into account flares, age, ethnicity, smoking and renal severity, social functioning was independently associated with the IFN score (P = 0.027). Analyses restrained to quiescent patients (n = 27) yielded greater associations between social functioning and the three IFN modules, and between MH and M3.4. Considering all quiescent visits (n = 51), the IFN score was independently correlated with social functioning (P = 0.022) and MH (P = 0.038). Conclusion This unexpected paradoxical association between IFN signature and some specific HRQOL domains argues against a pivotal role of IFNs in the persistently altered HRQOL of SLE patients.
Published: 2019

20. toxins Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease

Author: Noémie Jourde-Chiche, Laetitia Dou, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), and HAL AMU, Administrateur
Subjects: medicine.medical_specialty, Health, Toxicology and Mutagenesis, lcsh:Medicine, Inflammation, Review, 030204 cardiovascular system & hematology, Kidney, Toxicology, medicine.disease_cause, AGEs, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, endothelial dysfunction, 03 medical and health sciences, 0302 clinical medicine, Polyol pathway, Glycation, Internal medicine, medicine, Animals, Humans, Diabetic Nephropathies, Endothelial dysfunction, Progenitor cell, glucose, 030304 developmental biology, 0303 health sciences, polyols, business.industry, lcsh:R, Endothelial Cells, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, diabetic kidney disease, 3. Good health, Endocrinology, Albuminuria, Glomerular Filtration Barrier, medicine.symptom, business, Oxidative stress
Abstract: International audience; Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation end products (AGEs), a group of modified proteins and/or lipids that become glycated after exposure to sugars, and glucose metabolites produced via the polyol pathway. These glucose-related endothelio-toxins notably induce an alteration of the glomerular filtration barrier by increasing the permeability of glomerular endothelial cells, altering endothelial glycocalyx, and finally, inducing endothelial cell apoptosis. The glomerular endothelial dysfunction results in albuminuria. In addition, high glucose and by-products impair the endothelial repair capacities by reducing the number and function of endothelial progenitor cells. In this review, we summarize the mechanisms of renal endothelial toxicity of high glucose/glucose by-products, which encompass changes in synthesis of growth factors like TGF-β and VEGF, induction of oxidative stress and inflammation, and reduction of NO bioavailability. We finally present potential therapies to reduce endothelial dysfunction in diabetic kidney disease.
Published: 2019

21. Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors

Author: Sophie Limou, Véronique Frémeaux-Bacchi, Noémie Jourde-Chiche, Fadi Fakhouri, David Ribes, Alice Le Clech, François Provôt, Ludivine Lebourg, Moglie Le Quintrec, Alexandre Karras, Jean-Michel Halimi, Paula Vieira-Martins, Eric Rondeau, Noémie Simon-Tillaux, Steven Grangé, Yahsou Delmas, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Translational ImmunoGenetic in AutoImmunity and Transplantation (Team 5 - U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Immunotherapy in Transplantation And Autoimmunity (Team 3 - U1064 Inserm - CRTI), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, medicine.medical_specialty, Thrombotic microangiopathy, medicine.medical_treatment, 030232 urology & nephrology, Disease, urologic and male genital diseases, Gastroenterology, Organ transplantation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, complement, Dialysis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Eculizumab, medicine.disease, 3. Good health, thrombotic microangiopathy, 030104 developmental biology, Nephrology, Cohort, hemolytic uremic syndrome, Pancreatitis, eculizumab, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease, medicine.drug
Abstract: International audience; Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). The frequency of complement gene rare variants was similar in patients with secondary HUS (5%) and in healthy individuals (6% and 8% in French and European controls, respectively). At diagnosis, 40% of patients required dialysis and 18% had neurological manifestations. Fifty percent of patients received plasmatherapy and 35% were treated with eculizumab. Haematological and complete renal remission was achieved in 80% and 24% of patients, respectively. Thirty-nine percent of patients progressed to chronic kidney disease (stages 3-4) and an additional 37% reached end-stage renal disease. Eleven percent of patients died, most often from complications of the underlying cause of HUS. Only one patient experienced an HUS relapse. Patients treated with eculizumab presented with more severe HUS and were more likely to require dialysis at the time of diagnosis as compared to patients not treated with eculizumab. Rates of hematological remission, chronic kidney disease (stages 3-4), and end-stage renal disease were similar in the two groups. Secondary HUS is an acute nonrelapsing form of HUS, not related to complement dysregulation. The efficacy of eculizumab in this setting is not yet established.
Published: 2019

22. Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy

Author: Jack F.M. Wetzels, Anne-Els van de Logt, Christine Payré, Gian Marco Ghiggeri, Noémie Jourde-Chiche, Pierre Ronco, Jennie Lonnbro-Widgren, Joana Justino, Christelle Zaghrini, Gérard Lambeau, Barbara Seitz-Polski, Laurence H. Beck, Emma Rigby, Christophe Mariat, Zhao Cui, Jenny Nyström, Guillaume Dolla, Caroline J. Booth, Hanna Debiec, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut Laue-Langevin (ILL), ILL, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radboud University Medical Center [Nijmegen], Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Renal Division [Beijing, China], Peking University First Hospital [China]-Peking University Institute of Nephrology [China], Department of Nephrology [Nijmegen, The Netherlands], Radboud University Medical Centre [Nijmegen, The Netherlands], Divisione di Nefrologia, Istituto G.Gaslini, Nestlé France, CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Fondation Maladies Rares LAM-RD_20170304, National Research AgencyANR-17-CE17-0012-01, SIGNALIFE ANR-11-LABX-0028-01, Fondation de la Recherche Medicale DEQ20180339193, FDT201805005509, (PLA2R1 autoantibodies in Membranous Nephropathy in Kidney Transplantation Programme), PRAM-KT PHRC2011-A01302-39, European Research Council ERC-2012 ADG_ 20120314, 2012-305608 Dutch Kidney Foundation, 17PhD12, R01 DK097053, European Project: 322947,EC:FP7:ERC,ERC-2012-ADG_20120314,OSAI(2013), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-17-CE17-0012,MNaims,Dissection moléculaire de la glomérulonéphrite extramembraneuse liée à PLA2R1: vers l'identification de nouveaux biomarqueurs cliniques(2017), CCSD, Accord Elsevier, and Membranous nephropathy : a model for solving organ-specific auto-immunity (OSAI) - OSAI - - EC:FP7:ERC2013-05-01 - 2018-04-30 - 322947 - VALID
Subjects: Male, 0301 basic medicine, Time Factors, Biopsy, 030232 urology & nephrology, clinical outcome, Glomerulonephritis, Membranous, Gastroenterology, 0302 clinical medicine, Medicine, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Middle Aged, 3. Good health, Titer, Treatment Outcome, Nephrology, Cohort, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, ELISA, Drug Monitoring, Immunosuppressive Agents, Adult, medicine.medical_specialty, Enzyme-Linked Immunosorbent Assay, Malignancy, Sensitivity and Specificity, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Western blot, Membranous nephropathy, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, sex, Aged, Autoantibodies, Retrospective Studies, Thrombospondin, business.industry, Receptors, Phospholipase A2, Autoantibody, membranous nephropathy, medicine.disease, HEK293 Cells, 030104 developmental biology, Feasibility Studies, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], Thrombospondins, business, Biomarkers, malignancy
Abstract: International audience; Autoantibodies against phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) are emerging as biomarkers to classify membranous nephropathy (MN) and to predict outcome or response to treatment. Anti-THSD7A autoantibodies are detected by Western blot and indirect immunofluorescence test (IIFT). Here, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) optimized for quantitative detection of anti-THSD7A autoantibodies. Among 1012 biopsy-proven MN patients from 6 cohorts, 28 THSD7A-positive patients were identified by ELISA, indicating a prevalence of 2.8%. By screening additional patients, mostly referred because of PLA2R1-unrelated MN, we identified 21 more cases, establishing a cohort of 49 THSD7A-positive patients. Twenty-eight patients (57%) were male, and male patients were older than female patients (67 versus 49 years). Eight patients had a history of malignancy, but only 3 were diagnosed with malignancy within 2 years of MN diagnosis. We compared the results of ELISA, IIFT, Western blot, and biopsy staining, and found a significant correlation between ELISA and IIFT titers. Anti-THSD7A autoantibodies were predominantly IgG4 in all patients. Eight patients were double positive for THSD7A and PLA2R1. Levels of anti-THSD7A autoantibodies correlated with disease activity and with response to treatment. Patients with high titer at baseline had poor clinical outcome. In a subgroup of patients with serial titers, persistently elevated anti-THSD7A autoantibodies were observed in patients who did not respond to treatment or did not achieve remission. We conclude that the novel anti-THSD7A ELISA can be used to identify patients with THSD7A-associated MN and to monitor autoantibody titers during treatment.
Published: 2019

23. Endothelium structure and function in kidney health and disease

Author: Vincent Pernin, Claire Rigothier, Gilles Kaplanski, Jeremy Bellien, Pierre-André Jarrot, Lubka T. Roumenina, Marion Sallée, Stéphane Burtey, Dominique Guerrot, Moglie Le Quintrec, Véronique Frémeaux-Bacchi, Laetitia Dou, Noémie Jourde-Chiche, Fadi Fakhouri, Marie Frimat, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Immunotherapy in Transplantation And Autoimmunity (Team 3 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pharmacologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Lapeyronie [Montpellier] (CHU), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service d'immunologie biologique [Hôpital Européen Georges Pompidou [APHP], 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), 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 Paris Cité (UPCité), Service de Néphrologie [Rouen], INSERM., Assistance Publique-Hôpitaux de Paris (AP-HP)-Programme Hospitaliser de Recherche Clinique (PHRC) AOM08198., Association pour l'Information et la Recherche sur les maladies rénales Génétiques., The French Society of Nephrology., A grant from Appel d'Offre de Recherche Clinique (AORC) 2011-A01347., Assistance Publique-Hôpitaux de Marseille (AP-HM)-PHRC grant 2012-A00217-36., ANR-15-CE15-0001,INFLACOMP,Inflammation et lésions endothéliales induites par le Complément et l'hémolyse(2015), European Project, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Lille Inflammation Research International Center (LIRIC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médecine interne et immunologie clinique [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Bioingénierie tissulaire (BIOTIS), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-École pratique des hautes études (EPHE), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Sorbonne Universités, Université Paris Descartes - Paris 5 (UPD5), The research was supported by grants from theAgence Nationale de la Recherche (ANR) JCJC–INFLACOMP2015–2018 (ANR-15-CE15-0001, to L.T.R.), INSERM (toL.T.R.), EU FP7 grant 2012–305608 (EURenOmics, to V.F.-B.), Assistance Publique-Hôpitaux de Paris (AP-HP)-Programme Hospitaliser de Recherche Clinique (PHRC)AOM08198 (to V.F.-B.), Association pour l'Information et laRecherche sur les maladies rénales Génétiques (AIRG) (toV.F.-B.), the French Society of Nephrology (to V.F.-B.), a grantfrom Appel d'Offre de Recherche Clinique (AORC) 2011-A01347 (to G.K.), and Assistance Publique-Hôpitaux deMarseille (AP-HM)-PHRC grant 2012-A00217-36 (to G.K.)., Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie [Rouen], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Le Bihan, Sylvie, Inflammation et lésions endothéliales induites par le Complément et l'hémolyse - - INFLACOMP2015 - ANR-15-CE15-0001 - AAPG2015 - VALID, and EU FP7 grant 2012–305608 - INCOMING
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Endothelium, Angiogenesis, [SDV]Life Sciences [q-bio], TO-MESENCHYMAL TRANSITION, 030232 urology & nephrology, Kidney, urologic and male genital diseases, ANTIBODY-MEDIATED REJECTION, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, COMPLEMENT FACTOR-H, Podocyte, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Renal fibrosis, Medicine, Humans, DONOR-SPECIFIC ANTIBODIES, PROTEASE-ACTIVATED RECEPTOR-2, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, ANTIENDOTHELIAL CELL ANTIBODIES, Endothelial Cells, NEUTROPHIL EXTRACELLULAR TRAPS, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Nephrology, Renal physiology, Glomerular Filtration Barrier, cardiovascular system, HEMOLYTIC-UREMIC SYNDROME, Kidney Diseases, RENAL VASCULAR DYSFUNCTION, business, GROWTH-FACTOR RECEPTOR, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract: International audience; The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, which is also fenestrated, transports reabsorbed components and participates in epithelial cell function. The endothelium of large and small vessels supports the renal vasculature. These renal endothelia are protected by regulators of thrombosis, inflammation and complement, but endothelial injury (for example, induced by toxins, antibodies, immune cells or inflammatory cytokines) or defects in factors that provide endothelial protection (for example, regulators of complement or angiogenesis) can lead to acute or chronic renal injury. Moreover, renal endothelial cells can transition towards a mesenchymal phenotype, favouring renal fibrosis and the development of chronic kidney disease. Thus, the renal endothelium is both a target and a driver of kidney and systemic cardiovascular complications. Emerging therapeutic strategies that target the renal endothelium may lead to improved outcomes for both rare and common renal diseases.
Published: 2019

24. Prognostic Factors in Anti-glomerular Basement Membrane Disease: A Multicenter Study of 119 Patients

Author: Cindy Marques, Julien Carvelli, Lucie Biard, Stanislas Faguer, François Provôt, Marie Matignon, Jean-Jacques Boffa, Emmanuelle Plaisier, Alexandre Hertig, Maxime Touzot, Olivier Moranne, Xavier Belenfant, Djillali Annane, Thomas Quéméneur, Jacques Cadranel, Hassan Izzedine, Nicolas Bréchot, Patrice Cacoub, Alexis Piedrafita, Noémie Jourde-Chiche, David Saadoun, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, CHU Tenon [AP-HP], AURA Paris - Plaisance, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Raymond Poincaré [AP-HP], Gestionnaire, Hal Sorbonne Université, Service de rhumatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Immunologie - Immunopathologie - Immunothérapie (I3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] (DHU i2B ), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint Louis [APHP]-Institut national du cancer [Boulogne] (INCA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital de Rangueil, CHU Toulouse [Toulouse], CIC - Toulouse (CIC 1436 - CHU de Toulouse/Inserm/UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Pierre-Paul Riquet [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Hôpital Universitaire Carémeau [Nîmes], AP-HP Hôpital Raymond Poincaré [Garches], CHU Tenon [APHP], Service de médecine chirurgicale intensive [CHU Pitié-Salpêtrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares[CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Sorbonne Université (SU)-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), 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 Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière]
Subjects: Male, 0301 basic medicine, anti-glomerular basement membrane disease, Goodpasture's disease, glomerulonephritis, vasculitis, outcome, mortality, medicine.medical_treatment, urologic and male genital diseases, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Immunologie, Immunology and Allergy, Medicine, Original Research, hémorragie, Acute kidney injury, Middle Aged, Prognosis, 3. Good health, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, maladie rénale, France, medicine.drug, lcsh:Immunologic diseases. Allergy, Adult, medicine.medical_specialty, Cyclophosphamide, [SDV.IMM] Life Sciences [q-bio]/Immunology, pronostic, Immunology, 03 medical and health sciences, Internal medicine, Humans, Renal replacement therapy, Aged, Retrospective Studies, Mechanical ventilation, business.industry, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Kidney Failure, Chronic, Plasmapheresis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:RC581-607, business, Dyslipidemia, 030215 immunology
Abstract: International audience; We report the overall and renal outcome in a French nationwide multicenter cohort of 119 patients with anti-glomerular basement membrane (anti-GBM) disease. Sixty-four patients (54%) had an exclusive renal involvement, 7 (6%) an isolated alveolar hemorrhage and 48 (40%) a combined renal and pulmonary involvement. Initial renal replacement therapy (RRT) was required in 78% of patients; 82% received plasmapheresis, 82% cyclophosphamide, and 9% rituximab. ANCA positive (28%) patients were older (70 vs. 47 years, p < 0.0001), less frequently smokers (26 vs. 54%, p = 0.03), and had less pulmonary involvement than ANCA- patients. The 5 years overall survival was 92%. Risk factors of death (n = 11, 9.2%) were age at onset [HR 4.10 per decade (1.89–8.88) p = 0.003], hypertension [HR 19.9 (2.52–157 0.2) p = 0.005], dyslipidemia [HR 11.1 (2.72–45) p = 0.0008], and need for mechanical ventilation [HR 5.20 (1.02–26.4) p = 0.047]. The use of plasmapheresis was associated with better survival [HR 0.29 (0.08–0.98) p = 0.046]. At 3 months, 55 (46%) patients had end-stage renal disease (ESRD) vs. 37 (31%) ESRD-free and 27 (23%) unevaluable with follow-up < 3 months. ESRD patients were older, more frequently female and had a higher serum creatinine level at presentation than those without ESRD. ESRD-free survival was evaluated in patients alive without ESRD at 3 months (n = 37) using a landmark approach. In conclusion, this large French nationwide study identifies prognosis factors of renal and overall survival in anti-GBM patients.
Published: 2019

25. Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells

Author: Bertrand Gondouin, Françoise Dignat-George, Omar Kheroua, Kamel Eddine El Mecherfi, Nathalie McKay, Tawfik Addi, Stéphane Burtey, Alix de Macedo, Noémie Jourde-Chiche, Claire Cerini, Stéphane Poitevin, Laetitia Dou, Philippe Brunet, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Oran 1 Ahmed Ben Bella [Oran], Université Mohamed Boudiaf de M'sila, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Saint-Joseph [Marseille], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Association des dialysés Provence-Corse (ADPC), DIGNAT-GEORGE, Françoise, and Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: Male, 0301 basic medicine, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], 010501 environmental sciences, Toxicology, Indole-3 acetic acid, 01 natural sciences, Umbilical vein, chemistry.chemical_compound, Chronic kidney disease, Basic Helix-Loop-Helix Transcription Factors, heterocyclic compounds, Prospective Studies, RNA, Small Interfering, Promoter Regions, Genetic, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Aryl hydrocarbon receptor, Aged, 80 and over, biology, NF-kappa B, food and beverages, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Gene Knockdown Techniques, Female, Signal transduction, Nuclear factor kappa-B, Signal Transduction, Adult, P50, p38 mitogen-activated protein kinases, Uremic toxins, Thromboplastin, Young Adult, 03 medical and health sciences, Tissue factor, Human Umbilical Vein Endothelial Cells, Humans, Renal Insufficiency, Chronic, Transcription factor, Aged, 0105 earth and related environmental sciences, Indoleacetic Acids, Molecular biology, 030104 developmental biology, Receptors, Aryl Hydrocarbon, chemistry, biology.protein, Indole-3-acetic acid
Abstract: International audience; Chronic kidney disease (CKD) is associated with high risk of thrombosis. Indole-3 acetic acid (IAA), an indolic uremic toxin, induces the expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVEC) via the transcription factor aryl hydrocarbon receptor (AhR). This study aimed to understand the signaling pathways involved in AhR-mediated TF induction by IAA. We incubated human endothelial cells with IAA at 50 mu M, the maximal concentration found in patients with CKD. IAA induced TF expression in different types of human endothelial cells: umbilical vein (HUVEC), aortic (HAoEC), and cardiac-derived microvascular (HMVEC-C). Using AhR inhibition and chromatin immunoprecipitation experiments, we showed that TF induction by IAA in HUVEC was controlled by AhR and that AhR did not bind to the TF promoter. The analysis of TF promoter activity using luciferase reporter plasmids showed that the NF-B site was essential in TF induction by IAA. In addition, TF induction by IAA was drastically decreased by an inhibitor of the NF-B pathway. IAA induced the nuclear translocation of NF-B p50 subunit, which was decreased by AhR and p38MAPK inhibition. Finally, in a cohort of 92 CKD patients on hemodialysis, circulating TF was independently related to serum IAA in multivariate analysis. In conclusion, TF up-regulation by IAA in human endothelial cells involves a non-genomic AhR/p38 MAPK/NF-B pathway. The understanding of signal transduction pathways related to AhR thrombotic/inflammatory pathway is of interest to find therapeutic targets to reduce TF expression and thrombotic risk in patients with CKD.
Published: 2019

26. Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

Author: Julien Mancini, Pascale Poullin, Joëlle Micallef, Florence Daviet, Marion Sallée, Paul Coppo, Aurélie Grandvuillemin, Franck Rouby, Noémie Jourde-Chiche, Renaud Sabatier, Steven Grangé, Véronique Frémeaux-Bacchi, Bertrand Pourroy, Stéphane Burtey, Florence Duffaud, Julie Moussi-Frances, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Centre régional de pharmacovigilance de Marseille [CHU de Marseille], CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d\'hémaphérèse, Hôpital de la Conception, APHM, Marseille, France, Service d'hémaphérèse, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service Pharmacie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de réanimation médicale [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Saint-Antoine [APHP], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), and Prémilleux, Annick
Subjects: Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, Thrombotic microangiopathy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], chemotherapy, 030226 pharmacology & pharmacy, Gastroenterology, Deoxycytidine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, Dialysis, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Pharmacology, adverse drug reactions, business.industry, Thrombotic Microangiopathies, Acute kidney injury, Retrospective cohort study, Original Articles, Eculizumab, Middle Aged, medication safety, medicine.disease, Gemcitabine, 3. Good health, [SDV] Life Sciences [q-bio], acute kidney injury, pharmacovigilance, Female, Fresh frozen plasma, France, business, medicine.drug
Abstract: International audience; Aims Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA). Methods From 1998 to 2015, all cases of G-TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results G-TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m(-2). Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new-onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion This large cohort confirms the severity of G-TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
Published: 2018

27. HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome

Author: Patrick Blanco, Maarten Limper, Jamilya Khizroeva, Pier Luigi Meroni, Olivier Lambotte, Nadine Magy-Bertrand, Loic Sentilhes, Raquel Ferrer-Oliveras, Pieter Van Paasen, Jan Willem Cohen Tervaert, Marie Noelle Ungeheuer, Enrique Esteve-Valverde, Katrien Devreese, Ricard Cervera, Laura Andreoli, A. Djokovic, Emmanuel Andrès, Antonia Caligaro, Jean Sibilia, Daniel Henrion, Angela Tincani, Guillaume Mahé, Jose Omar Latino, N. Stanisavljevic, Sebastián Udry, Patrick Saulnier, Ljudmila Stojanovich, Şule Apraş Bilgen, Bernard Imbert, Cédric Landron, Damien Sène, Karina de Leeuw, Céline Fassot, Fatma Said, Boris Bienvenu, Laura Damian, Florence Perrinet, Jaume Alijotas-Reig, Francesca Pregnolato, Alban Godon, Estibaliz Lazaro, Thierry Martin, Viktoria Bitsadze, Laurent Arnaud, Laurent Loufrani, Gilles Pernod, Alexander Makatsariya, Gilberto Pires da Rosa, Noémie Jourde-Chiche, Pierre Yves Jeandel, Elisabeta Candrea, Maria Orietta Borghi, Milena Hasan, Jean Marie Chretien, Crina Sinescu, Cristina Belizna, Mathilde Versini, Pascale Jeannin, Thomas Le Gallou, Fréderic Tollis, Marc Antoine Pistorius, Loukman Omarjee, Valentina Canti, Mohamed Hamidou, Achile Aouba, György Nagy, Ova Shovman, Sébastien Abad, Levent Kilic, Teresa Delross, Howard Amital, Lai-Shan Tam, Zahir Amoura, Christian Muchardt, Amelia Ruffatti, Laurent Chiche, Patrick Jego, Emmanuelle Dernis, Maria Favaro, Miri Blank, Romain Lubin, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Paris 13 (UP13), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vall d'Hebron University Hospital [Barcelona], Sackler Faculty of Medicine, Tel Aviv University (TAU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Brescia, CHU Strasbourg, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hacettepe University = Hacettepe Üniversitesi, Hôpital Saint-Joseph [Marseille], Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical University, Moscow, Russia., Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli Studi di Padova = University of Padua (Unipd), University of Medicine and Pharmacy, Luliu-Hatieganu, Hôpital Européen [Fondation Ambroise Paré - Marseille], Maastricht University [Maastricht], University of Alberta, Universitatea Babeş-Bolyai [Cluj-Napoca], Centre Hospitalier du Mans, Ghent University Hospital, University of Belgrade [Belgrade], Althaia Healthcare Network of Manresa, Barcelona, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Cardiovascular Functions In Vitro (CARFI), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), CHU Grenoble, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical University, Moscow, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hospital Carlos G. Durand, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], University Medical Center Groningen [Groningen] (UMCG), University Medical Center [Utrecht], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Semmelweis University [Budapest], Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hospital de São João [Porto], Hôpital La Rabta [Tunis], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Université de Médecine Carol Davila, The Chinese University of Hong Kong [Hong Kong], Diaverum Dialysis Center, Angers, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Arnault Tzanck, Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), The HIBISCUS study is funded for its French part of the trial by the Ministery of Health, France in 2015 (PHRC N PAPIRUS)., The investigators are very grateful to Professor Y Shoenfeld for the scientific revision of the design and very valuable remarks. The investigators are also grateful to the patients, patients' association, collaborators and networks involved in the trial and to the research staff at all participating hospitals., Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Tel Aviv University [Tel Aviv], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Universita degli Studi di Padova, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Centre de Recherche Translationnelle (CRT), Institut Pasteur [Paris], Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Jean Minjoz, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches et Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: ANTICOAGULANT, Pediatrics, Additional Therapy, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, RECOMMENDATIONS, COMPLEMENT, 0302 clinical medicine, Pregnancy, An international multicenter trial on Hydroxychloroquine for the secondary prevention of relapses in primary antiphospholipid syndrome is launched, Antiphospholipid syndrome, Immunology and Allergy, PREGNANT PATIENTS, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Secondary prevention, Anticoagulant, Pregnancy Outcome, Take home messages, WOMEN, 3. Good health, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.drug, Hydroxychloroquine, Primary antiphospholipid syndrome, medicine.medical_specialty, medicine.drug_class, Immunology, Relapse rate, Relapse rate in antiphospholipid syndrome (APS) is high despite standard current therapies, 53 centers from 16 countries participate to this international trial, Orphan drug, 03 medical and health sciences, Survival rate in this population is 90.1% at 10 years and 65% at 15 years, There is a need for additional or alternative therapies in this disease, hydroxychloroquine, primary antiphospholipid syndrome, secondary prevention, medicine, MANAGEMENT, Humans, DRUGS, 030203 arthritis & rheumatology, business.industry, Thrombosis, Delivery, Obstetric, medicine.disease, ANTIBODIES, RISK-FACTORS, business
Abstract: International audience; The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS [2, 3].Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16].Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency.Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial.This trial consists in two parts: a retrospective and a prospective study.The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
Published: 2018

28. Autoantibodies targeting ficolin-2 in systemic lupus erythematosus patients with active nephritis

Author: Evelyne Gout, Jean-Yves Cesbron, Françoise Sarrot-Reynauld, Alban Deroux, Nicole M. Thielens, Laurence Bouillet, Nathalie Bardin, Chantal Dumestre-Pérard, Sophie Colliard, Mélanie Fougere, Noémie Jourde-Chiche, Giovanna Clavarino, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Grenoble Alpes (UGA), Centre recherche en CardioVasculaire et Nutrition (C2VN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), and Thomas, Frank
Subjects: Adult, Male, 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lupus nephritis, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, Severity of Illness Index, Serology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, systemic lupus erythematosus, immune system diseases, Lectins, Biopsy, Prevalence, medicine, ficolin-2, Humans, Lupus Erythematosus, Systemic, skin and connective tissue diseases, Autoantibodies, 030203 arthritis & rheumatology, lupus nephritis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Systemic lupus erythematosus, medicine.diagnostic_test, anti-ficolin-2 antibodies, business.industry, Biopsy, Needle, Autoantibody, biomarkers, Middle Aged, medicine.disease, Immunohistochemistry, 3. Good health, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antibodies, Antinuclear, Immunology, Biomarker (medicine), [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Nephritis, Anti-SSA/Ro autoantibodies
Abstract: Objective Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease characterized by production of various autoantibodies. The aim of this study was to investigate the presence of anti-ficolin-2 antibodies in SLE patients and to evaluate the association between the levels of these autoantibodies, clinical manifestations, and disease activity. Methods This is a comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE patients were further divided into two groups, with “low disease activity” (SLEDAI score ≤ 4, n = 88) and with “high disease activity” (SLEDAI score > 4, n = 77). Clinical manifestations were defined according to the physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy. Detection of anti-ficolin-2 antibodies was performed by ELISA. Results Levels of the anti-ficolin-2 autoantibodies were significantly higher in SLE patients as compared to healthy subjects and associated with the SLEDAI score. They were found positive in 61/165 (37%) SLE patients. Presence of anti-ficolin-2 antibodies was significantly related only to renal involvement, with a very high prevalence (86%) of anti-ficolin-2 antibodies in SLE patients with active LN. Patients with active proliferative LN had significantly more positive anti-ficolin-2 antibodies than those with non-proliferative LN. The combination of anti-ficolin-2, anti-ficolin-3 and anti-C1q demonstrated a very high specificity (98%) for the diagnosis of active LN. Conclusion Our results support the usefulness of anti-ficolin-2 as a complementary serological biomarker for the diagnosis of active lupus with renal manifestation. This article is protected by copyright. All rights reserved.
Published: 2018

29. Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

Author: Marion Sallée, Tawfik Addi, Stéphane Burtey, Françoise Dignat-George, Claire Cerini, Philippe Brunet, A. Duval-Sabatier, Michael S. Denison, Bertrand Gondouin, Stéphane Poitevin, Laetitia Dou, Nathalie McKay, Noémie Jourde-Chiche, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, urologic and male genital diseases, 0302 clinical medicine, Risk Factors, Cause of Death, Basic Helix-Loop-Helix Transcription Factors, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Whole blood, Aged, 80 and over, Mice, Knockout, biology, respiratory system, Middle Aged, Phenotype, female genital diseases and pregnancy complications, Nephrectomy, 3. Good health, Treatment Outcome, Nephrology, Cardiovascular Diseases, Female, Adult, medicine.medical_specialty, Mice, 129 Strain, 03 medical and health sciences, Renal Dialysis, Internal medicine, medicine.artery, Cell Line, Tumor, medicine, Cytochrome P-450 CYP1A1, Animals, Humans, Renal Insufficiency, Chronic, Transcription factor, Aged, Aorta, business.industry, Aryl hydrocarbon receptor, medicine.disease, respiratory tract diseases, Mice, Inbred C57BL, Repressor Proteins, Disease Models, Animal, 030104 developmental biology, Endocrinology, Receptors, Aryl Hydrocarbon, Case-Control Studies, biology.protein, business, Indican, Kidney disease
Abstract: Patients with chronic kidney disease (CKD) are exposed to uremic toxins and have an increased risk of cardiovascular disease. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AHR). These toxins induce a vascular procoagulant phenotype. Here we investigated AHR activation in patients with CKD and in a murine model of CKD. We performed a prospective study in 116 patients with CKD stage 3 to 5D and measured the AHR-Activating Potential of serum by bioassay. Compared to sera from healthy controls, sera from CKD patients displayed a strong AHR-Activating Potential; strongly correlated with eGFR and with the indoxyl sulfate concentration. The expression of the AHR target genes Cyp1A1 and AHRR was up-regulated in whole blood from patients with CKD. Survival analyses revealed that cardiovascular events were more frequent in CKD patients with an AHR-Activating Potential above the median. In mice with 5/6 nephrectomy, there was an increased serum AHR-Activating Potential, and an induction of Cyp1a1 mRNA in the aorta and heart, absent in AhR –/– CKD mice. After serial indoxyl sulfate injections, we observed an increase in serum AHR-AP and in expression of Cyp1a1 mRNA in aorta and heart in WT mice, but not in AhR –/– mice. Thus, the AHR pathway is activated both in patients and mice with CKD. Hence, AHR activation could be a key mechanism involved in the deleterious cardiovascular effects observed in CKD.
Published: 2018

30. Hemodialysis vascular graft as a focus of persistent Q fever

Author: Pierre-Edouard Fournier, Didier Raoult, Eric Guedj, Vincent Ernest, Yvon Berland, Raafat Boustani, Cindy Perron, Serge Cammilleri, Stéphane Burtey, Valérie Moal, Noémie Jourde-Chiche, M. Pelletier, Mathilde Fedi, Clarissa Von Kotze, Philippe Brunet, Philippe Amabile, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of nuclear medicine aphm Timone, Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), HOPITAL DE MANOSQUE, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Département de Médecine Nucléaire [AP-HM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Université Bordeaux Segalen - Bordeaux 2, Service de médecine nucléaire [Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: DNA, Bacterial, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Prosthesis-Related Infections, COXIELLA-BURNETII, Vascular graft infection, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030106 microbiology, Q fever, DIAGNOSIS, Gastroenterology, Serology, 03 medical and health sciences, Renal Dialysis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Positron Emission Tomography Computed Tomography, Internal medicine, INFECTION, medicine, Humans, Chronic fever, ComputingMilieux_MISCELLANEOUS, biology, business.industry, General Medicine, Middle Aged, Coxiella burnetii, biology.organism_classification, medicine.disease, bacterial infections and mycoses, 3. Good health, Treatment Outcome, Infectious Diseases, Hemodialysis, Hypermetabolism, bacteria, Female, Vascular Grafting, France, Complication, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Vascular graft
Abstract: International audience; Vascular access infection is a frequent complication in hemodialysis patients. We report the second case worldwide of a prosthetic hemodialysis vascular graft infection by Coxiella burnetii, with intense hypermetabolism on PET-CT, Q fever serology consistent with persistent infection, and positive C. burnetii DNA in the blood and removed vascular graft.
Published: 2018

31. Uro-and nephrotoxic effects of drugs of abuse: Literature review and pharmaco-epidemiological survey in France and in the Marseille area

Author: Marion Sallée, Bertrand Dussol, Marion Gully, Vanessa Pauly, Bertrand Gondouin, Fanny Romain, Michel Spadari, Stéphane Burtey, Julie Moussi-Frances, Liselotte Pochard, Joëlle Micallef, Elisabeth Frauger, Noémie Jourde-Chiche, Laurent Daniel, 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 Pharmacologie Clinique [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service de Santé Publique et d'Information Médicale (SSPIM), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Laboratoire d'Anatomopathologie [Aix-Marseille], and Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: Vasculitis, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Drug abuse, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Acute kidney injury, 03 medical and health sciences, 0302 clinical medicine, Glomerulonephritis, Nephrology, Chronic kidney disease, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; A great diversification of drugs of abuse has been observed in recent years, both in the populations using them and in the types of drugs. Although dependency and psychiatric disorders associated with the abuse of these substances is well known, somatic complications, uro-nephrotoxicity in particular, are less recognized. We propose here an overview of the products used by drugs abusers in France, through the analysis of the national pharmaco-epidemiological study Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse (OPPIDUM). Among the 5003 patients who participated in this survey, 84% were on prescribed psychoactive substances, with indicators of abuse in 28% of cases; more than half of these patients had also been using drugs of abuse (mainly cannabis) in the previous week. We then describe the main urological and renal toxicities of these drugs, in particular of heroin, cocaine, cannabis, ecstasy, LSD, amphetamine, new designer drugs, ketamine and opiate substitution treatment. We finally present a pharmaco-epidemiological survey of patients hospitalized for drugs complications in nephrology at the university hospital of Marseille. Between 2000 and 2015, 22 patients aged 18 to 57 years were hospitalized for renal adverse effects of drugs of abuse, such as glomerulonephritides, focal segmental glomerulosclerosis, acute kidney injury or chronic kidney disease. The somatic complications of drugs participate in their dangerousness and should be a red flag. They should be systematically reported to the addictovigilance national network to allow the improvement of information given to the patients and the medical community, and to adapt the prevention and risk reduction policies.; L’abus de substances psychoactives (SPA) s’est diversifié ces dernières années, tant au niveau des populations concernées que des produits consommés. Si la dépendance et les troubles psychiatriques liés à la consommation de ces substances sont généralement connus, les complications somatiques, en particulier uro-néphrologiques, le sont moins. Nous proposons tout d’abord dans cette revue un état des lieux des SPA consommées par les usagers de drogue en France, à partir des données de l’étude nationale pharmaco-épidémiologique OPPIDUM (Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse). Parmi les 5003 patients interrogés, 84 % étaient consommateurs d’au moins une SPA médicamenteuse, avec des indicateurs d’abus dans 28 % des cas, et plus de la moitié avaient consommé une SPA non médicamenteuse (principalement du cannabis) la semaine précédente. Nous décrivons ensuite les complications urologiques et néphrologiques des principales SPA, telles que l’héroïne, la cocaïne, le cannabis, l’ecstasy, le LSD, les amphétamines, les nouveaux produits de synthèse, la kétamine et les médicaments de substitution aux opiacés. Nous présentons enfin une enquête pharmaco-épidémiologique concernant les patients hospitalisés en néphrologie adulte au CHU de Marseille pour des complications liées à l’abus de SPA. Entre 2000 et 2015, 22 patients âgés de 18 à 57 ans ont été hospitalisés pour des complications néphrologiques des SPA, telles que glomérulonéphrite aiguë, hyalinose segmentaire et focale, insuffisance rénale aiguë ou chronique. Les complications somatiques liées à l’usage des SPA participent à leur dangerosité et peuvent avoir une valeur d’alerte. Il est important que les professionnels de santé signalent au centre d’addictovigilance de leur territoire les complications sanitaires liées à l’usage des SPA, afin d’optimiser l’information donnée aux patients et aux professionnels de santé et d’adapter des programmes de prévention et de réduction des risques.
Published: 2017

32. Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge

Author: Philippe Halfon, Patrick Blanco, Marie Kostine, Estibaliz Lazaro, Frédérique Retornaz, Caroline Charpin, Noémie Jourde-Chiche, Christophe Richez, Denis Arniaud, Laurent Chiche, C. Stavris, Département de Rhumatologie, CHU Bordeaux [Bordeaux]-Université de Bordeaux (UB), Hôpital Européen de Marseille (HEM), Hôpital du Haut-L'Evêque, Hôpital Européen [Fondation Ambroise Paré - Marseille], Hôpital Saint-Joseph [Marseille], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Autoimmunity, medicine.disease_cause, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, Neoplasms, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Enzyme Inhibitors, Adverse effect, Cancer, business.industry, Melanoma, Gastroenterology, Antibodies, Monoclonal, Cell Cycle Checkpoints, Immunotherapy, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Immunology, Adenocarcinoma, Opportunistic, business, Adjuvant, Checkpoint inhibitors
Abstract: International audience; With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists. Within irAEs, we propose to individualize the induced autoimmunity by the term "Opportunistic Autoimmunity Secondary to Cancer Immunotherapy" (OASI). The aims of this article are (1) to present the different available checkpoint inhibitors and the OASIs reported with these treatments and (2) to propose practical recommendations for diagnosis, pre-therapeutic assessment and management of OASIs. The need for predictive biomarkers of OASIs occurrence will also be discussed.
Published: 2017

33. Clinical and Genetic Spectrum of Bartter Syndrome Type 3

Author: 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
Subjects: 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.
Published: 2017

34. French translation of the clinical practice guideline on management of patients with diabetes and chronic kidney disease stage 3B or higher (eGFR<45mL/min/1.73 m2

Author: Jean-Jacques Boffa, Dominique Chauveau, Dominique Guerrot, Noémie Jourde-Chiche, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Translation (biology), Guideline, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Diabetes mellitus, Internal medicine, medicine, Chronic kidney disease stage 3B, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

35. Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

Author: R. Vial, Raj Purgus, Laurent Daniel, Tristan Legris, Noémie Jourde-Chiche, Sophie Alain, Christine Zandotti, Alexandre Decourt, Charleric Bornet, Valérie Moal, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), Fédération de Bactériologie-Virologie-Hygiène [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Unité pharmacie hospitalière [AP-HM Hôpital de la Conception], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], DIGNAT-GEORGE, Françoise, and Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: 0301 basic medicine, Foscarnet, Ganciclovir, Article Subject, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030106 microbiology, lcsh:Surgery, Salvage therapy, Case Report, Brincidofovir, 030230 surgery, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Management of Technology and Innovation, medicine, business.industry, virus diseases, Immunosuppression, lcsh:RD1-811, biochemical phenomena, metabolism, and nutrition, medicine.disease, 3. Good health, Transplantation, [SDV] Life Sciences [q-bio], chemistry, Immunology, business, Cidofovir, medicine.drug
Abstract: Background. Cytomegalovirus (CMV) antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome. Despite a large decrease in immunosuppression, CMV disease was not controlled and a salvage therapy with Brincidofovir (BCV), which is an oral lipid conjugate of cidofovir with limited nephrotoxicity, was attempted. Clinical and virological remission was observed after a 21-day course of BCV, despite mild and reversible liver toxicity. However, a new relapse could not be effectively cured by BCV due to a new mutation in the UL54 gene, which is known to confer resistance to cidofovir. A new course of foscarnet finally resulted in prolonged CMV remission. Herein, we present a review of foscarnet nephropathy cases in solid-organ transplanted patients. Conclusions. This unique case highlights the potential benefit of BCV use during resistant CMV infection, although mutations in the UL54 gene may limit its therapeutic efficacy. These findings need to be confirmed in clinical trials.
Published: 2017

36. A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren’s syndrome

Author: Stanislas Faguer, H. François, Alain Le Quellec, Guillaume Moulis, Laurent Chiche, Alexandre Karras, Philippe Remy, Xavier Mariette, Aurélie Hummel, Evguenia Krastinova, Perrine Jullien, Anne-Laure Fauchais, J.B. Fraison, Véronique Le Guern, Estibaliz Lazaro, R. Mesbah, Magali Jasiek, Noémie Jourde-Chiche, Emmanuelle Dernis, Benjamin Terrier, Sophie Ferlicot, Carole Cordonnier, Philippe Vanhille, Pierre Ronco, Eric Thervet, Raphaèle Seror, Nathalie Costedoat-Chalumeau, Eric Hachulla, Vannary Meas-Yedid, Laurent Daniel, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), Centre National de Référence Maladies Systémiques et Autoimmunes Rares, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CH Boulogne sur Mer, Hôpital de Rangueil, CHU Toulouse [Toulouse], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Dupuytren, Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Le Mans (CH Le Mans), Hôpital Purpan [Toulouse], CH Béziers, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Saint-Etienne, Hôpital Claude Huriez [Lille], CHU Lille, CHU Saint-Eloi, CHU Henri Mondor, CHU Necker - Enfants Malades [AP-HP], 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), CH Valenciennes, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Hôpital Bicêtre, No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript., The authors thank all the clinicians and pathologists who participated in the REINSS study: C. Agard, A. Audemard, S. Bally, J.J. Boffa, D. Le Thi Huong-Boutin, P. Cacoub, P. Cathebras, G. Choukroun, E. Daugas, J.G. Fuzibet, C. Garrouste, M. Hamidou, P.Y. Hatron, D. Joly, J.E. Kahn, B. Knebelmann, T. Kofman, B. Laurent-Pilonchery, C. Lavigne, G. Le Guenno, T. Lobbedez, J. Schmidt, C. Sordet, A. Barbier-Dupas, A. Guillaudeau, A. Moreau, B. Ambrosetti, B. Mougenot, B. Mac-Gregor, C. Deminiere, C. Guilbeau-Frugier, C. Mussini, D. Droz, D. Desvaux-Belghiti, F. Comoz, H. Perrochia, H. Beaufils, J. Verine, L.H. Noel, J.P. Duong Van Huyen, A. Modesto, L. Marcellin, M. Mignon-Conte, D. Nochy, N. Patey-Mariaud De Serre, P. Rouvier, S. Lepreux, V. Algagnac-Oskman, M.-C. Copin, B. Gosselin, B. Delisle, F. Paraf, I. Brocheriou, J.-P. Saint-Are, J.-L. Kermeny, P. Callard., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Henri Mondor [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Biopsy, T-Lymphocytes, Kidney Glomerulus, Plasma cell, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Adrenal Cortex Hormones, Medicine, Pharmacology (medical), tubulointerstitial nephritis, 030212 general & internal medicine, Renal Insufficiency, Cryoglobulins, Aged, 80 and over, B-Lymphocytes, medicine.diagnostic_test, biology, Middle Aged, 3. Good health, medicine.anatomical_structure, Sjogren's Syndrome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antibodies, Antinuclear, Rituximab, Female, Renal biopsy, France, Antibody, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Plasma Cells, primary Sjögren’s syndrome, Renal function, cryoglobulinaemia, Nephropathy, 03 medical and health sciences, Young Adult, Rheumatology, Internal medicine, Humans, Aged, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Plasmacytosis, medicine.disease, biology.protein, Nephritis, Interstitial, business
Abstract: International audience; Objective. Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment. Methods. We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling AmericanEuropean Consensus Group criteria or enlarged AmericanEuropean Consensus Group criteria, and with biopsy-proven renal involvement. Results. A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of
Published: 2017

37. Acute pancreatitis as a cause of mortality in pediatric systemic lupus erythematosus: Results of a multiple cause-of-death analysis in France

Author: Mireille Eb, Noémie Jourde-Chiche, Grégoire Rey, Brigitte Bader-Meunier, Laurent Chiche, Sarah Malaekah, Frederique Retornaz, Alexandre Belot, Hôpital Européen [Fondation Ambroise Paré - Marseille], Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Physiopathologie de l'Endothelium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'immuno-hématologie 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), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre d'épidémiologie sur les causes médicales de décès (CépiDc), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 030203 arthritis & rheumatology, medicine.medical_specialty, Lupus erythematosus, business.industry, [SDV]Life Sciences [q-bio], MEDLINE, Multiple cause of death, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Rheumatology, medicine, Acute pancreatitis, Pancreatitis, 030211 gastroenterology & hepatology, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

38. Introducing a New Dimension to Molecular Disease Classifications

Author: Noémie Jourde-Chiche, Laurent Chiche, Damien Chaussabel, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Européen [Fondation Ambroise Paré - Marseille], and Sidra Medical and Research Center
Subjects: 0301 basic medicine, INTERFERON, BLOOD, [SDV]Life Sciences [q-bio], Molecular Disease, Disease, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Medicine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, skin and connective tissue diseases, Molecular Biology, SIGNATURES, Autoimmune disease, business.industry, TRANSCRIPTIONAL REPERTOIRE ANALYSES, medicine.disease, 3. Good health, 030104 developmental biology, Treatment modality, Immunology, Molecular Medicine, Pediatric SLE, business, 030217 neurology & neurosurgery
Abstract: International audience; Systemic lupus erythematosus (SLE) is an autoimmune disease presenting with a wide range of clinical manifestations. A recent study in Cell has uncovered distinct molecular classes of pediatric SLE patients. The approach employed is remarkable in that it may enable alignment of molecular classifications of disease with the development and selection of novel treatment modalities.
Published: 2016

39. Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis

Author: Philippe Halfon, Laurent Chiche, Xavier Puéchal, Nathalie Bardin, Emmanuel Andrès, Vincent Vuiblet, Baptiste Hervier, Daniel Bertin, Laurent Daniel, Noémie Jourde-Chiche, Jean-Loup Pennaforte, Pierre-André Jarrot, Zahir Amoura, Bertrand Dussol, Eric Rondeau, Gilles Kaplanski, Benjamin Terrier, Mohamed Hamidou, Eric Daugas, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen [Fondation Ambroise Paré - Marseille], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Service de médecine interne [CHU Pitié-Salpétrière], Université Pierre et Marie Curie - Paris 6 (UPMC), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Bichat - Claude Bernard, CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU), Hôpital Civil de Strasbourg, Héritages et Constructions dans le Texte et l'Image (HCTI), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO)-Université de Brest (UBO), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [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), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [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 Tenon [AP-HP], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vascular research center of Marseille ( VRCM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ), Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Matrice extracellulaire et dynamique cellulaire - UMR 7369 ( MEDyC ), Université de Reims Champagne-Ardenne ( URCA ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ) -Centre National de la Recherche Scientifique ( CNRS ), Aix Marseille Université ( AMU ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Héritages et Constructions dans le Texte et l'Image ( HCTI ), Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Maison des Sciences de l'Homme de Bretagne-Institut Brestois des Sciences de l'Homme et de la Société ( IBSHS ), Université de Brest ( UBO ) -Université de Brest ( UBO ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO)-Université de Brest (UBO)-Université de Bretagne Sud (UBS)-Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université de la Méditerranée - Aix-Marseille 2 - Aix Marseille Université (AMU), Hôpital Européen Marseille, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Pitié-Salpêtrière [APHP], Laboratoire d'Anatomopathologie [Aix-Marseille], Assistance Publique - Hôpitaux de Marseille (APHM) - Hôpital de la Timone [CHU - APHM] (TIMONE) - CHU Marseille, Matrice extracellulaire et dynamique cellulaire (MEDyC), Université de Reims Champagne-Ardenne (URCA) - Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie [APHM-Hôpital de la Conception, Marseille], Assistance Publique - Hôpitaux de Marseille (APHM) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [APHP] - Université Paris Descartes - Paris 5 (UPD5), CHU Tenon [APHP] - Assistance publique - Hôpitaux de Paris (AP-HP), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), CHU Angers - Hôtel-Dieu de Nantes - Hôpital Laennec - Faculté de Médecine d'Angers - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS) - CHU Nantes, Hôpital Robert Debré - CHU Reims, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat - Claude Bernard [Paris] - Université Paris Diderot - Paris 7 (UPD7), Aix Marseille Université (AMU) - Assistance Publique - Hôpitaux de Marseille (APHM) - Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Institut Cochin, Université Sorbonne Paris Cité (USPC) - Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Université de Brest (UBO), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN ( NICN ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Male, ANCA-ASSOCIATED VASCULITIS, Pathology, Anti-nuclear antibody, Biopsy, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Lupus nephritis, Kidney, Gastroenterology, Neutrophil extracellular traps, DISEASE, Glomerulonephritis, 0302 clinical medicine, immune system diseases, Lupus Erythematosus, Systemic, 10. No inequality, skin and connective tissue diseases, SJOGRENS-SYNDROME, medicine.diagnostic_test, Incidence, Overlap syndrome, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], ANTINUCLEAR ANTIBODY, Population Surveillance, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, CLINICAL-IMPLICATIONS, France, CRESCENTIC GLOMERULONEPHRITIS, Vasculitis, Research Article, Adult, medicine.medical_specialty, Adolescent, Antineutrophil cytoplasmic antibody-associated vasculitis, Observational Study, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, GRANULOPOIESIS SIGNATURES, CLASSIFICATION, Young Adult, 03 medical and health sciences, Internal medicine, NETTING NEUTROPHILS, medicine, Humans, Immune response, NEPHRITIS, Retrospective Studies, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, Lupus erythematosus, [ SDV ] Life Sciences [q-bio], business.industry, medicine.disease, Antineutrophil cytoplasmic autoantibodies, business
Abstract: Supplemental Digital Content is available in the text, The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options.
Published: 2016

40. An interactive web application for the dissemination of human systems immunology data

Author: Damien Chaussabel, Anna Bjork, Scott R. Presnell, Dimitry Popov, Noémie Jourde-Chiche, Darawan Rinchai, Elizabeth Whalen, Olivia Vargas, Cate Speake, Laurent Chiche, David Anderson, Brad Zeitner, Charlie Quinn, Kelly Domico, Michael Mason, Systems Immunology Laboratory, Benaroya Research Institute, Sidra Medical and Research Center, Aix Marseille Université (AMU), Department of Internal Medicine and Infectious Diseases, and European Hospital
Subjects: EXPRESSION, Source code, Bioinformatics, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Statistics as Topic, Immunology, BIOLOGY, Context (language use), Data type, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, User-Computer Interface, 0302 clinical medicine, Knowledge extraction, Landing page, Web application, Humans, TRANSCRIPTIONAL SIGNATURE, Transcriptomics, 030304 developmental biology, media_common, Medicine(all), 0303 health sciences, Internet, Biochemistry, Genetics and Molecular Biology(all), business.industry, Systems Biology, Research, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Visualization, Databases as Topic, INFLUENZA, 030220 oncology & carcinogenesis, Data Interpretation, Statistical, Immune System, CELLS, ONSET, [SDV.IMM]Life Sciences [q-bio]/Immunology, The Internet, business, Software, CIRCUITS
Abstract: Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators’ interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.
Published: 2015

41. The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Author: Selim Aractingi, Denis Jullien, Antoine Petit, François Maurier, Isabelle Guichard, Leonardo Astudillo, Pascal Godmer, Béatrice Flageul, Luc Mouthon, Clotilde Martel, Martine Bagot, Véronique Frémeaux-Bacchi, Florence Cordoliani, Adrien Bigot, Géraldine Jeudy, Noémie Jourde-Chiche, Didier Bessis, Benjamin Terrier, Alban Deroux, Mikael Ebbo, Sara Melboucy-Belkhir, Nicolas Dupin, Bernard Simorre, C. Morice, Laurent Machet, Emmanuel Héron, Marie Jachiet, C. Abasq, Alain Le Quellec, Marie-Sylvie Doutre, P. Belenotti, Christian Lavigne, Marie-Alice Macher, Loïc Guillevin, Laurence Bouillet, Thierry Zenone, Eric Hachulla, CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Toulouse [Toulouse], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Lille Nord de France (COMUE), CIC Quinze-Vingts, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Marseille, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), AP-HP Hôpital universitaire Robert-Debré [Paris], CHU Limoges, Hôpital Jean Verdier [Bondy], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Centre hospitalier de Valence, Physiopathologie vasculaire : interactions cellulaires, signalisation et vieillissement, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Hôpital Jean Verdier [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), 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)-Hôpital Cochin [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Constitutional symptoms, Immunology, Azathioprine, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, medicine, Immunology and Allergy, Livedo reticularis, 030203 arthritis & rheumatology, Angioedema, business.industry, Hydroxychloroquine, medicine.disease, Dermatology, 3. Good health, Surgery, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Etiology, Rituximab, medicine.symptom, business, Vasculitis, medicine.drug
Abstract: International audience; OBJECTIVE:Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.METHODS:We conducted a French nationwide retrospective study that included 57 patients with chronic urticaria, histologic leukocytoclastic vasculitis, and hypocomplementemia. We assessed clinical and laboratory data and evaluated the patients' cutaneous and immunologic responses to therapy. We evaluated treatment efficacy by measuring the time to treatment failure.RESULTS:Urticarial lesions were typically more pruritic than painful and were associated with angioedema in 51% of patients, purpura in 35%, and livedo reticularis in 14%. Extracutaneous manifestations included constitutional symptoms (in 56% of patients) as well as musculoskeletal involvement (in 82%), ocular involvement (in 56%), pulmonary involvement (in 19%), gastrointestinal involvement (in 18%), and kidney involvement (in 14%). Patients with HUV typically presented with low C1q levels and normal C1 inhibitor levels, in association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine or colchicine seemed to be as effective as corticosteroids as first-line therapy. In patients with relapsing and/or refractory disease, rates of cutaneous and immunologic response to therapy seemed to be higher with conventional immunosuppressive agents, in particular, azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. Finally, a cutaneous response to therapy was strongly associated with an immunologic response to therapy.CONCLUSION:HUV represents an uncommon systemic and relapsing vasculitis with various manifestations, mainly, musculoskeletal and ocular involvement associated with anti-C1q antibodies, which were found in approximately half of the patients. The best strategy for treating HUV has yet to be defined.
Published: 2015

42. The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid

Author: Stéphane Burtey, Bertrand Gondouin, Noémie Jourde-Chiche, Philippe Brunet, Karim Fallague, Laetitia Dou, Raymond Calaf, Stéphane Poitevin, Bertrand Dussol, Claire Cerini, Bernard Mallet, Marion Sallée, Françoise Dignat-George, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dou, Laetitia
Subjects: Male, 030232 urology & nephrology, medicine.disease_cause, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, chemistry.chemical_compound, 0302 clinical medicine, heterocyclic compounds, Endothelial dysfunction, Aged, 80 and over, 2. Zero hunger, 0303 health sciences, food and beverages, General Medicine, Middle Aged, Malondialdehyde, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Cardiovascular Diseases, Nephrology, Female, medicine.symptom, Signal Transduction, Adult, medicine.medical_specialty, Inflammation, Proinflammatory cytokine, Young Adult, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Human Umbilical Vein Endothelial Cells, medicine, Humans, Renal Insufficiency, Chronic, Aged, Uremia, 030304 developmental biology, Indoleacetic Acids, business.industry, Cholesterol, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Oxidative Stress, Basic Research, Endocrinology, chemistry, Cyclooxygenase 2, Endothelium, Vascular, Reactive Oxygen Species, business, Indole-3-acetic acid, Oxidative stress
Abstract: International audience; In CKD, uremic solutes may induce endothelial dysfunction, inflammation, and oxidative stress, leading to increased cardiovascular risk. We investigated whether the uremic solute indole-3 acetic acid (IAA) predicts clinical outcomes in patients with CKD and has prooxidant and proinflammatory effects. We studied 120 patients with CKD. During the median study period of 966 days, 29 patients died and 35 experienced a major cardiovascular event. Kaplan-Meier analysis revealed that mortality and cardiovascular events were significantly higher in the higher IAA group (IAA>3.73 mu M) than in the lower IAA group (IAA
Published: 2015

43. Plasma Xanthine Oxidase Activity Is Predictive of Cardiovascular Disease in Patients with Chronic Kidney Disease, Independently of Uric Acid Levels

Author: Noémie Jourde-Chiche, Claire Cerini, Laetitia Dou, Anderson Loundou, Bertrand Gondouin, Yvon Berland, Bertrand Dussol, Sophie Morange, Régis Guieu, Marion Sallée, Stéphane Burtey, Philippe Brunet, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Physiopathologie de l'Endothelium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, 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), Assistance Publique - Hôpitaux de Marseille (APHM), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Xanthine Oxidase, Antioxidant, medicine.medical_treatment, Kaplan-Meier Estimate, urologic and male genital diseases, medicine.disease_cause, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, End stage renal disease, chemistry.chemical_compound, Adenosine deaminase, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, Renal Insufficiency, Chronic, Xanthine oxidase, Aged, Aged, 80 and over, Super oxide dismutase, biology, business.industry, Middle Aged, medicine.disease, 3. Good health, Uric Acid, Oxidative Stress, Endocrinology, chemistry, Cardiovascular Diseases, Purines, biology.protein, Uric acid, Female, business, Oxidation-Reduction, Oxidative stress, Kidney disease, Follow-Up Studies
Abstract: Background: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Oxidative stress seems to play a pivotal role in this process, and purine metabolism may be involved in CKD-related oxidative stress. Xanthine oxidase (XO) is an enzyme involved in purine metabolism and is also responsible for the production of reactive oxygen species. Methods: This prospective study aimed to analyze the relation between plasma dosages of molecules involved in redox balance, purine metabolism and cardiovascular events in patients with non-diabetic CKD stages 3-5 or on chronic hemodialysis (HD). CKD (n = 51) and HD (n = 50) patients were compared to matched healthy controls (n = 38) and followed-up for 3 years. Results: Both CKD and HD patients had decreased plasma levels of antioxidants (selenium, zinc, vitamin C). HD patients had decreased levels of the antioxidant enzyme superoxide dismutase and increased levels of oxidation products (ischemia-modified albumin, malondialdehyde [MDA]). The following substrates and enzymes involved in purine metabolism were increased in the HD cohort: adenosine, adenosine deaminase and the pro-oxidant XO. XO activity was negatively correlated with super oxide dismutase and positively with MDA. Interestingly, XO activity was an independent predictor of cardiovascular events in CKD and HD patients, regardless of uric acid levels. Uric acid was not predictive of events. Conclusion: This highlights a possible role of XO itself in CKD-related cardiovascular disease (CVD) and raises the hypothesis that beneficial effects observed with XO inhibitors on CVD in CKD may also be due to the reduction of oxidative stress.
Published: 2015

44. Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway

Author: Romaric Lacroix, Laurent Arnaud, Raymond Vanholder, Laetitia Dou, Françoise Dignat-George, Anneleen Pletinck, Raymond Calaf, Stéphane Poitevin, Claire Cerini, Stéphane Burtey, A. Duval-Sabatier, Bertrand Gondouin, Noémie Jourde-Chiche, Philippe Brunet, Marion Sallée, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Nephrology Section [Ghent], Ghent University Hospital, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Umbilical Veins, 030204 cardiovascular system & hematology, Polymerase Chain Reaction, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Benzoquinones, RNA, Small Interfering, Receptor, Cells, Cultured, Aged, 80 and over, 0303 health sciences, biology, Middle Aged, Up-Regulation, 3. Good health, medicine.anatomical_structure, Nephrology, Female, medicine.symptom, Signal Transduction, Adult, medicine.medical_specialty, Endothelium, Lactams, Macrocyclic, Inflammation, In Vitro Techniques, Dioxins, Peripheral blood mononuclear cell, Thromboplastin, 03 medical and health sciences, Tissue factor, Downregulation and upregulation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Aged, 030304 developmental biology, Indoleacetic Acids, Microarray analysis techniques, Aryl hydrocarbon receptor, Endocrinology, Receptors, Aryl Hydrocarbon, Tissue Array Analysis, Case-Control Studies, Leukocytes, Mononuclear, biology.protein, Endothelium, Vascular, Indican
Abstract: International audience; In chronic kidney disease (CKD), uremic solutes accumulate in blood and tissues. These compounds probably contribute to the marked increase in cardiovascular risk during the progression of CKD. The uremic solutes indoxyl sulfate and indole-3-acetic acid (IAA) are particularly deleterious for endothelial cells. Here we performed microarray and comparative PCR analyses to identify genes in endothelial cells targeted by these two uremic solutes. We found an increase in endothelial expression of tissue factor in response to indoxyl sulfate and IAA and upregulation of eight genes regulated by the transcription factor aryl hydrocarbon receptor (AHR). The suggestion by microarray analysis of an involvement of AHR in tissue factor production was confirmed by siRNA inhibition and the indirect AHR inhibitor geldanamycin. These observations were extended to peripheral blood mononuclear cells. Tissue factor expression and activity were also increased by AHR agonist dioxin. Finally, we measured circulating tissue factor concentration and activity in healthy control subjects and in patients with CKD (stages 3-5d), and found that each was elevated in patients with CKD. Circulating tissue factor levels were positively correlated with plasma indoxyl sulfate and IAA. Thus, indolic uremic solutes increase tissue factor production in endothelial and peripheral blood mononuclear cells by AHR activation, evoking a `dioxin-like' effect. This newly described mechanism of uremic solute toxicity may help understand the high cardiovascular risk of CKD patients.
Published: 2013

45. Determination of uremic solutes in biological fluids of chronic kidney disease patients by HPLC assay

Author: Bertrand Gondouin, Pascal Rathelot, Françoise Dignat-George, Pierre Verhaeghe, David Bergé-Lefranc, Àngel Argilés, Noémie Jourde-Chiche, Cecile Genovesio, Philippe Charpiot, Laetitia Dou, Philippe Brunet, Sophie Morange, Claire Cerini, Raymond Calaf, Laboratoire de chimie de coordination ( LCC ), Centre National de la Recherche Scientifique ( CNRS ), Vascular research center of Marseille ( VRCM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ), Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Institut méditerranéen de biodiversité et d'écologie marine et continentale ( IMBE ), Centre National de la Recherche Scientifique ( CNRS ) -Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université ( AMU ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ), CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Institut de Chimie Radicalaire ( ICR ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Physiopathologie de l'Endothelium, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ), Département de Recherche en Ingéniérie des Véhicules pour l'Environnement ( DRIVE ), Université de Bourgogne ( UB ), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Recherche en Ingéniérie des Véhicules pour l'Environnement (DRIVE), Université de Bourgogne (UB), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Clinical Biochemistry, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Sulfuric Acid Esters, Biochemistry, High-performance liquid chromatography, [ CHIM ] Chemical Sciences, Analytical Chemistry, 03 medical and health sciences, Cresols, 0302 clinical medicine, Hplc assay, Phenols, Biological fluids, medicine, [CHIM]Chemical Sciences, Humans, Hplc method, education, Chromatography, High Pressure Liquid, Aged, Uremia, education.field_of_study, Chromatography, Indoleacetic Acids, Phenol, Chemistry, Healthy subjects, Cell Biology, General Medicine, Middle Aged, medicine.disease, Indoxyl Sulfate, Kidney Failure, Chronic, Female, Indican, Kidney disease
Abstract: International audience; During chronic kidney disease (CKD), solutes called uremic solutes, accumulate in blood and tissues of patients. We developed an HPLC method for the simultaneous determination of several uremic solutes of clinical interest in biological fluids: phenol (Pol), indole-3-acetic acid (3-IAA), p-cresol (p-C), indoxyl sulfate (3-INDS) and p-cresol sulfate (p-CS). These solutes were separated by ion-pairing HPLC using an isocratic flow and quantified with a fluorescence detection. The mean serum concentrations of 3-IAA, 3-INDS and p-CS were 2.12, 1.03 and 13.03 mu M respectively in healthy subjects, 3.21, 17.45 and 73.47 mu M in non hemodialyzed stage 3-5 CKD patients and 5.9, 81.04 and 120.54 mu M in hemodialyzed patients (stage 5D). We found no Pol and no p-C in any population. The limits of quantification for 3-IAA, 3-INDS, and p-CS were 0.83, 0.72, and 3.2 mu M respectively. The within-day CVs were between 1.23 and 3.12% for 3-IAA, 0.98 and 2% for 3-INDS, and 1.25 and 3.01% for p-CS. The between-day CVs were between 1.78 and 5.48% for 3-IAA, 1.45 and 4.54% for 3-INDS, and 1.19 and 6.36% for p-CS. This HPLC method permits the simultaneous and quick quantification of several uremic solutes for daily analysis of large numbers of samples. (C) 2011 Elsevier B.V. All rights reserved.
Published: 2011

46. Does Uremia Cause Vascular Dysfunction?

Author: A. Duval-Sabatier, Stéphane Burtey, Claire Cerini, Philippe Brunet, Bertrand Gondouin, Àngel Argilés, Noémie Jourde-Chiche, Laetitia Dou, Françoise Dignat-George, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Vascular smooth muscle, 030232 urology & nephrology, Inflammation, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Muscle, Smooth, Vascular, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Von Willebrand factor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Vascular Diseases, Vascular Calcification, Uremia, Neointimal hyperplasia, biology, business.industry, Vascular disease, General Medicine, medicine.disease, 3. Good health, Endocrinology, chemistry, Nephrology, Plasminogen activator inhibitor-1, biology.protein, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Asymmetric dimethylarginine
Abstract: International audience; Vascular dysfunction induced by uremia has 4 main aspects. (1) Atherosclerosis is increased. Intima-media thickness is increased, and animal studies have established that uremia accelerates atherosclerosis. Uremic toxins are involved in several steps of atherosclerosis. Leukocyte activation is stimulated by guanidines, advanced glycation end products (AGE), p-cresyl sulfate, platelet diadenosine polyphosphates, and indoxyl sulfate. Endothelial adhesion molecules are stimulated by indoxyl sulfate. Migration and proliferation of vascular smooth muscle cells (VSMC) are stimulated by local inflammation which could be triggered by indoxyl sulfate and AGE. Uremia is associated with an increase in von Willebrand factor, thrombomodulin, plasminogen activator inhibitor 1, and matrix metalloproteinases. These factors contribute to thrombosis and plaque destabilization. There is also a decrease in nitric oxide (NO) availability, due to asymmetric dimethylarginine (ADMA), AGE, and oxidative stress. Moreover, circulating endothelial microparticles (EMP) are increased in uremia, and inhibit the NO pathway. EMP are induced in vitro by indoxyl sulfate and p-cresyl sulfate. (2) Arterial stiffness occurs due to the loss of compliance of the vascular wall which induces an increase in pulse pressure leading to left ventricular hypertrophy and a decrease in coronary perfusion. Implicated uremic toxins are ADMA, AGE, and oxidative stress. (3) Vascular calcifications are increased in uremia. Their formation involves a transdifferentiation process of VSMC into osteoblast-like cells. Implicated uremic toxins are mainly inorganic phosphate, as well as reactive oxygen species, tumor necrosis factor and leptin. (4) Abnormalities of vascular repair and neointimal hyperplasia are due to VSMC proliferation and lead to severe reduction of vascular lumen. Restenosis after coronary angioplasty is higher in dialysis than in nondialysis patients. Arteriovenous fistula stenosis is the most common cause of thrombosis. Uremic toxins such as indoxyl sulfate and some guanidine compounds inhibit endothelial proliferation and wound repair. Endothelial progenitor cells which contribute to vessel repair are decreased and impaired in uremia, related to high serum levels of beta(2)- microglobulin and indole-3 acetic acid. Overall, there is a link between kidney function and cardiovascular risk, as emphasized by recent meta-analyses. Moreover, an association has been reported between cardiovascular mortality and uremic toxins such as indoxyl sulfate, pcresol and p-cresyl sulfate. Copyright (C) 2011 S. Karger AG, Basel
Published: 2011

47. Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients

Author: Raymond Calaf, Philippe Charpiot, Noémie Jourde-Chiche, Laurence Camoin-Jau, Àngel Argilés, Stéphane Robert, Laetitia Dou, Claire Cerini, Françoise Dignat-George, Philippe Brunet, Florence Sabatier, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Myeloid, Homocysteine, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, CD34, Context (language use), Antigens, CD34, Apoptosis, 030204 cardiovascular system & hematology, Biology, Endothelial progenitor cell, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Antigens, CD, Renal Dialysis, Internal medicine, medicine, Humans, AC133 Antigen, Endothelial dysfunction, Progenitor cell, Aged, Glycoproteins, Uremia, Indoleacetic Acids, Stem Cells, Endothelial Cells, Hematology, Middle Aged, medicine.disease, 3. Good health, Endocrinology, medicine.anatomical_structure, chemistry, Immunology, Kidney Failure, Chronic, Female, Peptides, beta 2-Microglobulin
Abstract: International audience; Background: Patients suffering from chronic kidney diseases (CKD) exhibit cardiovascular diseases and profound endothelial dysfunction. CKD patients have reduced numbers of endothelial progenitor cells, but little is known about the factors influencing these numbers. Objectives: Among these factors, we hypothesized that uremic toxins and vascular injury affect endothelial progenitor cells. Patients/methods: Thirty-eight hemodialysis patients were investigated and compared with 21 healthy controls. CD34+CD133+ immature progenitors, CD34+KDR+ endothelial progenitors cells (EPC) and myeloid EPC (mEPC) were counted in peripheral blood. Levels of uremic toxins beta(2)-microglobulin, indole-3 acetic acid, indoxylsulfate, p-cresylsulfate and homocysteine were measured. Vascular injury was assessed in hemodialysis (HD) patients by measuring aortic pulse wave velocity and plasma levels of endothelial microparticles. In vitro experiments were performed to study the effect of uremic toxins on apoptosis of progenitor cells. Results and conclusions: CD34+CD133+ immature progenitor cell number was negatively correlated with the levels of uremic toxins beta(2)-microglobulin and indole-3 acetic acid. In vitro, indole-3 acetic acid induced apoptosis of CD133+ cells. These data indicate uremic toxins have a deleterious role on progenitor cells, early in the differentiation process. Moreover, mEPC number was positively correlated with markers of vascular injury-pulse wave velocity and endothelial microparticle levels. This suggests that vascular lesions could stimulate progenitor cell mobilization, even in a context of reduced EPC induced by CKD. In conclusion, uremic toxins and vascular injury appear to affect endothelial progenitor cell biology in CKD.
Published: 2009

48. Protein-Bound Toxins-Update 2009

Author: Raymond Vanholder, Françoise Dignat-George, Philippe Brunet, Claire Cerini, Laetitia Dou, Noémie Jourde-Chiche, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Nephrology Section [Ghent], Ghent University Hospital, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Homocysteine, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Phenylacetic acid, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Peritoneal dialysis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glycation, Renal Dialysis, Medicine, Humans, Phenols, Toxins, Biological, business.industry, Albumin, Activated charcoal, chemistry, Biochemistry, Nephrology, Free fraction, Kidney Diseases, business, Protein Binding
Abstract: International audience; Protein-bound uremic retention solutes constitute a group whose common characteristic is their difficult removal by dialysis. In 2003, the EUTox group described 25 protein-bound solutes. They comprised six advanced glycation end products (AGE), four phenols (including p-cresol), six indoles (including indoxylsulfate), two hippurates, three polyamines, and two peptides, homocysteine and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). As then, three new compounds have been added to the list: phenylacetic acid, dinucleoside polyphosphates, and IL-18. During the last years, protein-bound compounds have been identified as some of the main toxins involved in vascular lesions of chronic kidney disease. The removal of these solutes by conventional hemodialysis (HD) is low because only the free fraction of the solute is available for diffusion. The increase in the convective part with hemodiafiltration improves the performance of depuration but convection only applies to the free fraction and its benefit is limited. One possibility to improve the removal of a protein-bound solute would be to stimulate its dissociation from the binding protein. This could be obtained in experiments by setting the dialysate flow rate and the dialyzer mass transfer area coefficient (KoA) at much higher levels than the plasma flow rate, or by adding to the dialysate a sorbent such as activated charcoal or albumin. In the future, specific adsorbents may be developed. Today, the only possibility is to use approaches such as daily HD and long HD which could allow better equilibration between extravascular and vascular compartments and consequently result in greater removal of protein-bound compounds.
Published: 2009

49. The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells

Author: Françoise Dignat-George, Philippe Brunet, Noémie Jourde-Chiche, Yvon Berland, Laetitia Dou, Claire Cerini, Valérie Faure, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Nephrologie- Nephrology and renal transplantation Centre, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Mitochondrial ROS, Xanthine Oxidase, Antioxidant, Endothelium, Nitric Oxide Synthase Type III, medicine.medical_treatment, 030232 urology & nephrology, Nitric Oxide Synthase Type II, 030204 cardiovascular system & hematology, medicine.disease_cause, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, RNA, Messenger, Xanthine oxidase, Cells, Cultured, Uremia, Oxidase test, Base Sequence, Endothelial Cells, NADPH Oxidases, Hematology, Glutathione, Oxidative Stress, medicine.anatomical_structure, chemistry, Biochemistry, Apocynin, Reactive Oxygen Species, Indican, Oxidative stress
Abstract: International audience; Background: Endothelial dysfunction and oxidative stress are matters of concern in patients with chronic renal failure (CRF). Uremic solutes retained in these patients could be involved in these processes. Notably, the protein-bound uremic solute indoxyl sulfate induces endothelial dysfunction in vitro, and has shown pro-oxidant effects. Objective: To demonstrate that indoxyl sulfate is a potential mediator of oxidative stress in endothelial cells in vitro. Methods: Indoxyl sulfate-induced oxidative stress in human umbilical vein endothelial cells (HUVEC) was studied by measuring reactive oxygen specie (ROS) production by cytofluorimetry, by analyzing the involvement of the pro-oxidative enzymes NAD(P)H oxidase, xanthine oxidase, and NO synthase, and by measuring the levels of the non-enzymatic antioxidant glutathione. Results: We showed that indoxyl sulfate induced a significant production of ROS in HUVEC, with or without human serum albumin. We then investigated the role of pro-oxidative enzymes and measured the levels of the antioxidant glutathione. The NAD(P)H oxidase inhibitors, DPI, and apocynin, inhibited ROS production, whereas inhibitors of xanthine oxidase, NO synthase, and mitochondrial ROS had no effect. Interestingly, indoxyl sulfate strongly decreased the levels of glutathione, one of the most active antioxidant systems of the cell. In addition, the ROS production mediated by indoxyl sulfate was inhibited by the antioxidants vitamin C, vitamin E, and NAC. Conclusion: The uremic solute indoxyl sulfate enhances ROS production, increases NAD(P)H oxidase activity, and decreases glutathione levels in endothelial cells. Thus, indoxyl sulfate induces oxidative stress by modifying the balance between pro- and antioxidant mechanisms in endothelial cells.
Published: 2007

50. Étude Psy-LUP : conséquences psycho-sociales du lupus érythémateux systémique

Author: Manet, Cécile, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), and Noémie Jourde-Chiche
Subjects: Lupus érythémateux systémique, [SDV]Life Sciences [q-bio], Qualité de vie, Participation sociale, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectifs : la participation sociale (PS) est définie comme "l'implication dans des situations de la vie réelle". Le lupus érythémateux systémique (LES) a un impact négatif significatif sur la PS des patients. Cette étude visait à identifier les déterminants de la PS chez les patients atteints de LES. Méthodes : une évaluation par méthodes mixtes de 100 patients adultes atteints de LES inclus dans la cohorte transversale multicentrique PsyLUP. Les participants ont rempli les questionnaires standardisés suivants : Échelle de participation évaluant la PS, Short Form-36 (SF-36) et Lupus-QOL, Questionnaire de soutien social de Sarason (SSQ), Indice de satisfaction des couples, Inventaire de la perspective temporelle de Zimbardo (ZTPI) et Bref Questionnaire de Perception de Maladie (B-IPQ). Une analyse de régression linéaire multiple descendante a été menée pour identifier les facteurs prédictifs de la PS parmi les facteurs cliniques et démographiques, les domaines de la QDV et les autres facteurs psychosociaux. Résultats : quatre-vingt-douze femmes et huit hommes ont été inclus. L'âge médian était de 41 ans (19-76), la durée moyenne de la maladie de 14 ans (±10), 29/100 patients avaient une PS réduite. Leur satisfaction de couple, leur orientation temporelle et leurs représentations de la maladie étaient impactées, ainsi que tous les domaines du SF-36 et du Lupus-QOL. Dans la régression linéaire multivariée, les prédicteurs cliniques et socio-démographiques de l'altération de la PS étaient le sexe, le tabagisme, l’ostéoporose fracturaire et les anticorps anti-cardiolipine, tandis que l'atteinte hématologique, l'emploi et le traitement anti-ostéoporotique étaient protecteurs. Parmi les domaines Lupus-QoL, "santé physique" (p=0,001), "planification" (p
Published: 2023

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