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1. Among CMV‐positive renal transplant patients receiving non‐T‐cell depleting induction, the absence of CMV disease prevention is a safe strategy: A retrospective cohort of 372 patients

Author: Cécile Vigneau, Yannick Le Meur, Emmanuel Oger, Diego Cantarovich, Nolwenn Lorcy, Hugoline Boulay, Antoine Thierry, Agnès Duveau, Philippe Gatault, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Graft Rejection, medicine.medical_specialty, T-Lymphocytes, [SDV]Life Sciences [q-bio], T cell, valganciclovir, Cytomegalovirus, kidney transplantation, 030230 surgery, medicine.disease_cause, Antiviral Agents, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, CMV disease prevention, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Humans, Medicine, Ganciclovir, Kidney transplantation, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), virus diseases, Retrospective cohort study, Valganciclovir, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Infectious Diseases, medicine.anatomical_structure, Renal transplant, Cytomegalovirus Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: International audience; Cytomegalovirus (CMV) is the most common opportunistic pathogen affecting renal transplant recipients, especially in the first months. CMV-seropositive renal transplant recipients (CMV R+) are at intermediate risk for CMV disease, but this risk is enhanced among CMV R+ receiving T-cell depleting induction, compared to CMV R+ receiving non-depleting induction. In this second group, data in favour of prophylactic antiviral treatment with valganciclovir to reduce CMV disease is sparse. In this retrospective and multicentric trial, we included 372 CMV R+ transplanted between January 2012 and April 2015 and receiving non-depleting induction. During the first year following transplantation, CMV disease occurred in 5/222 patients (2.25%) in the prophylaxis group and 9/150 (6%) in the no-prophylaxis group (difference + 3.7; 95%CI - 0.5 to 8; p=0.002 for non-inferiority). The incidence of allograft rejection and other infectious diseases was similar between the 2 groups. Graft and patient survival were similar at the end of follow-up. In conclusion, the absence of prophylaxis did not appear to have a deleterious effect for CMV diseases among CMV R+ receiving non-depleting induction.
Published: 2021

2. Comprehensive molecular characterization of a heavy chain deposition disease case

Author: Maria Victoria Ayala, Christophe Sirac, Michel Cogné, Sébastien Bender, Arnaud Jaccard, Vincent Javaugue, Frank Bridoux, Amélie Bonaud, Guy Touchard, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie CHU Poitiers, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)
Subjects: 0301 basic medicine, Clone (cell biology), [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Plasma cell, Biology, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Online Only Articles, ComputingMilieux_MISCELLANEOUS, Kidney pathology, Kidney metabolism, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Molecular biology, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Monoclonal, Heavy Chain Deposition Disease, Nephrotic syndrome
Abstract: We herein report the complete characterization of the monoclonal Ig fragments produced by the plasma cell clone in a 65-year-old patient with a typical heavy chain deposition disease (HCDD).[1][1]–[3][2] The patient was referred for nephrotic syndrome and the main biological parameters are
Published: 2018

3. Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study

Author: Bertrand Arnulf, Jean Michel Goujon, Dominique Nochy, Vincent Audard, Arnaud Jaccard, Camille Cohen, Mohamed Belmouaz, Jean Paul Fermand, Christophe Sirac, Mathilde Nouvier, François Provôt, Sébastien Bender, Bertrand Knebelmann, Guy Touchard, Florent Joly, Viviane Gnemmi, Frank Bridoux, Vincent Javaugue, Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chromatin Assembly, Nuclear Domains, Virus [Lyon], Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Néphrologie Transplantation, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou], 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)-Université Paris Descartes - Paris 5 (UPD5), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Service de néphrologie - hémodialyse et transplantation rénale, Service d'hématologie adulte [Hôpital de Saint Louis], 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), Service de Néphrologie CHU Poitiers, Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, 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)-Université Paris Descartes - Paris 5 (UPD5), CHU Saint Louis [APHP], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
Subjects: Male, medicine.medical_specialty, Immunology, 030232 urology & nephrology, Paraproteinemias, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Immunoglobulin light chain, Biochemistry, Gastroenterology, Nephropathy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Antineoplastic Combined Chemotherapy Protocols, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine, Humans, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Aged, Kidney, business.industry, Acute kidney injury, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Middle Aged, medicine.disease, Prognosis, 3. Good health, Survival Rate, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, Monoclonal, Female, Immunoglobulin Light Chains, Kidney Diseases, business, Immunoglobulin Heavy Chains, Monoclonal gammopathy of undetermined significance, Monoclonal Immunoglobulin Deposition Disease, Follow-Up Studies
Abstract: Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of B-cell clonal disorders, defined by Congo red negative–deposits of monoclonal light chain (LCDD), heavy chain (HCDD), or both (LHCDD). MIDD is a systemic disorder with prominent renal involvement, but little attention has been paid to the description of extrarenal manifestations. Moreover, mechanisms of pathogenic immunoglobulin deposition and factors associated with renal and patient survival are ill defined. We retrospectively studied a nationwide cohort of 255 patients, with biopsy-proven LCDD (n = 212) (including pure LCDD [n = 154], LCDD with cast nephropathy (CN) [n = 58]), HCDD (n = 23), or LHCDD (n = 20). Hematological diagnosis was monoclonal gammopathy of renal significance in 64% and symptomatic myeloma in 34%. Renal presentation was acute kidney injury in patients with LCCD and CN, and chronic glomerular disease in the other types, 35% of whom had symptomatic extrarenal (mostly hepatic and cardiac) involvement. Sequencing of 18 pathogenic LC showed high isoelectric point values of variable domain complementarity determining regions, possibly accounting for tissue deposition. Among 169 patients who received chemotherapy (bortezomib-based in 58%), 67% achieved serum free light chain (FLC) response, including very good partial response (VGPR) or above in 52%. Renal response occurred in 62 patients (36%), all of whom had achieved hematological response. FLC response ≥ VGPR and absence of severe interstitial fibrosis were independent predictors of renal response. This study highlights an unexpected frequency of extrarenal manifestations in MIDD. Rapid diagnosis and achievement of deep FLC response are key factors of prognosis.
Published: 2019

4. Animal models of monoclonal immunoglobulin-related renal diseases

Author: Jiamin Teng, Frank Bridoux, Elba A. Turbat-Herrera, Michel Cogné, Vincent Javaugue, Maria Victoria Ayala, Nelson Leung, Guillermo A. Herrera, Guy Touchard, Sébastien Bender, Christophe Sirac, Paul W. Sanders, Vecihi Batuman, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie CHU Poitiers, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Paraproteinemias, Lymphoproliferative disorders, Immunoglobulins, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Plasma cell, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine, Animals, B cell, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Kidney, biology, business.industry, Monoclonal immunoglobulin, Antibodies, Monoclonal, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Nephrology, Immunology, Monoclonal, biology.protein, Kidney Diseases, Antibody, business
Abstract: The renal deposition of monoclonal immunoglobulins can cause severe renal complications in patients with B cell and plasma cell lymphoproliferative disorders. The overproduction of a structurally unique immunoglobulin can contribute to the abnormal propensity of monoclonal immunoglobulins to aggregate and deposit in specific organs. A wide range of renal diseases can occur in multiple myeloma or monoclonal gammopathy of renal significance, including tubular and glomerular disorders with organized or unorganized immunoglobulin deposits. The development of reliable experimental models is challenging owing to the inherent variability of immunoglobulins and the heterogeneity of the pathologies they produce. However, although imperfect, animal models are invaluable tools to understand the molecular pathogenesis of these diseases, and advances in creating genetically modified animals might provide novel approaches to evaluate innovative therapeutic interventions. We discuss the strategies employed to reproduce human monoclonal immunoglobulin-induced kidney lesions in animal models, and we highlight their advantages and shortcomings. We also discuss how these models have affected the management of these deposition diseases and might do so in the future. Finally, we discuss hypotheses that explain some limitations of the various models, and how these models might improve our understanding of other nephropathies without immunoglobulin involvement that have similar pathogenic mechanisms.
Published: 2018

5. Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an Alarmin

Author: Jean-Marc Gombert, Antoine Thierry, Jean-Michel Goujon, Sandra Sena, Aurélie Robin, André Herbelin, Jean-Philippe Girard, Sébastien Giraud, Thierry Hauet, Maroua Ferhat, Guy Touchard, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie - hémodialyse et transplantation rénale, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers
Subjects: 0301 basic medicine, Neutrophils, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Inflammation, Kidney, Neutrophil Activation, 03 medical and health sciences, Interferon-gamma, Mice, 0302 clinical medicine, medicine, Alarmins, Animals, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Innate immune system, Renal ischemia, business.industry, Interleukin-17, General Medicine, Dendritic Cells, Interleukin-33, Interleukin-1 Receptor-Like 1 Protein, Interleukin-12, Immunity, Innate, Interleukin 33, Transplantation, Killer Cells, Natural, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Basic Research, Gene Expression Regulation, Nephrology, Reperfusion Injury, Immunology, Cytokines, medicine.symptom, Cell activation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Inflammation is a prominent feature of ischemia-reperfusion injury (IRI), which is characterized by leukocyte infiltration and renal tubular injury. However, signals that initiate these events remain poorly understood. We examined the role of the nuclear alarmin IL-33 in tissue injury and innate immune response triggered by experimental kidney ischemia-reperfusion. In wild-type mice, we found that IL-33 was constitutively expressed throughout the kidney in peritubular and periglomerular spaces, mainly by microvascular endothelial cells, from which it was released immediately during IRI. Compared with wild-type mice, mice lacking IL-33 (IL-33(Gt/Gt)) exhibited reductions in early tubular cell injury and subsequent renal infiltration of IFN-γ/IL-17A–producing neutrophils, with preservation of renal functions. This protection associated with decreased renal recruitment of myeloid dendritic cells, natural killer (NK) cells, and invariant natural killer T (iNKT) cells, the latter of which were reported as deleterious in IRI. Increases in the level of circulating IL-12, a key IL-33 cofactor, and the expression of ST2, an IL-33–specific receptor, on the surface of iNKT cells preceded the IL-33– and iNKT cell–dependent phase of neutrophil infiltration. Furthermore, IL-33 directly targeted iNKT cells in vitro, inducing IFN-γ and IL-17A production. We propose that endogenous IL-33 is released as an alarmin and contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Our findings show a novel molecular mediator contributing to innate immune cell recruitment induced by renal ischemia-reperfusion and may provide therapeutic insights into AKI associated with renal transplantation.
Published: 2018

6. Warfarin-related nephropathy induced by three different vitamin K antagonists: analysis of 13 biopsy-proven cases

Author: Léonard Golbin, Cécile Vigneau, Jean-Michel Halimi, Nathalie Rioux-Leclercq, P. Siohan, Guy Touchard, Eric Thervet, Alexandre Hertig, Theophile Sawadogo, Thierry Frouget, Nathan Lagoutte, Elie Zagdoun, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CH de Lorient, Service de Néphrologie CH Quimper, Service de Néphrologie CH QUIMPER, Centre Hospitalier Mémorial France États-Unis de Saint-Lô (CH Saint-Lô), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Department of Nephrology and Hemodialysis, Centre Hospitalier Mémorial France Etats-Unis, Saint-Lô, France., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: medicine.medical_specialty, warfarin-related nephropathy, medicine.medical_treatment, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, renal biopsy, Internal medicine, medicine, Dialysis, Acute tubular necrosis, Transplantation, medicine.diagnostic_test, business.industry, urogenital system, drug nephrotoxicity, Warfarin, Acute kidney injury, medicine.disease, 3. Good health, vitamin k antagonists, Endocrinology, acute kidney injury, Nephrology, Cardiovascular Disease and CKD, Renal biopsy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Kidney disease
Abstract: International audience; Background: Acute kidney injury (AKI) with renal tubular obstruction by red blood cell casts (RBCC) has been described in patients treated with warfarin and is known as warfarin-related nephropathy (WRN). Methods: To determine whether other vitamin K antagonists (VKA) cause WRN, we retrospectively collected and analyzed the clinical and histological data of 13 patients treated with different VKA (seven with fluindione, four with warfarin and two with acenocoumarol) in seven French hospitals. Results: They all developed gross hematuria following overanticoagulation complicated by severe AKI (median serum creatinine concentration = 693 μmol/L). Histological analysis of the kidney biopsies highlighted the presence of intratubular RBCC and acute tubular necrosis in all patients and of an underlying kidney disease in 12 patients. WRN was suspected in patients treated with warfarin; however, the initial diagnosis was incorrect in six of the nine patients treated with other VKA. Nine patients progressed to chronic kidney disease, one fully recovered renal function, two died and one still needs dialysis. Conclusions: This is the first report of AKI caused by fluindione. In agreement with the recent publication on AKI in two patients treated with dabigatran, we suggest that the term 'anticoagulant-related nephropathy' is more appropriate than WRN. Gross hematuria in patients with an underlying kidney disease and treated with VKA requires rapid control of the international normalized ratio and renal function monitoring.
Published: 2017

7. Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naive patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III)

Author: Pierre Morel, Arnaud Jaccard, Dania Mohty, Margarette Macro, Christopher P. Venner, Jean Luc Pellegrin, Estibaliz Lazaro, David Lavergne, Olivier Decaux, Murielle Roussel, Julian D. Gillmore, Ashutosh D. Wechalekar, Parameswaran Hari, Raymond L. Comenzo, Frank Bridoux, Philip N. Hawkins, Patrick Mercié, CHU Limoges, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et maladies infectieuses, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de cardiologie [CHU Limoges], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine Interne [Rennes], CHU Pontchaillou [Rennes], Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, medicine.medical_specialty, Cyclophosphamide, 030204 cardiovascular system & hematology, Dexamethasone, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, AL amyloidosis, Humans, Medicine, Immunoglobulin Light-chain Amyloidosis, Survival rate, Lenalidomide, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Articles, Amyloidosis, Hematology, medicine.disease, Boronic Acids, 3. Good health, Surgery, Regimen, Cardiac amyloidosis, Pyrazines, 030220 oncology & carcinogenesis, Female, Cardiomyopathies, business, medicine.drug, Primary systemic amyloidosis
Abstract: International audience; Bortezomib is an active agent in AL amyloidosis and responses to this drug in combination with cyclophosphamide and dexamethasone are both rapid and deep. Here we present an international, multicenter series of 60 patients with Mayo Clinic stage III cardiac amyloidosis to assess the impact of this regimen in improving outcomes in this poor-risk group. The median follow-up for the entire cohort is 11.8 months. The overall response rate was 68%. In a landmark analysis, examining patients who survived more than 3 months, the overall response rate was 86%. A cardiac response was seen in 32% of patients. The estimated 1-year survival rate for the whole cohort was 57% and 24 patients (40%) died while on therapy. Although unable to save the poorest risk patients, the combination of bortezomib, cyclophosphamide and dexamethasone can achieve a high number of hematologic and cardiac responses, likely improving overall survival and justifying a prospective trial.
Published: 2014

8. Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy

Author: Kelhia Sendeyo, Mario Ollero, Catherine Rucker-Martin, Franck Bridoux, Shao-yu Zhang, Dominique Desvaux, Qingfeng Fan, Georges Guellaen, Philippe Lang, Khedidja Bouachi, André Pawlak, Vincent Audard, Pierre Ronco, Elodie Gouadon, Djillali Sahali, Inserm U955, équipe 21, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, Département de pathologie [Mondor], Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported in part by an Avenir Program from INSERM, a grant from the French Kidney Foundation and Association pour l'Utilisation du Rein Artificiel (AURA)., Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Guellaen, Georges, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, 030232 urology & nephrology, Protein Serine-Threonine Kinases, urologic and male genital diseases, Glomerulonephritis, Membranous, Article, Podocyte, 03 medical and health sciences, Heymann Nephritis, 0302 clinical medicine, Membranous nephropathy, Downregulation and upregulation, Heavy proteinuria, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Adaptor Proteins, Signal Transducing, 0303 health sciences, Proteinuria, business.industry, Podocytes, urogenital system, medicine.disease, 3. Good health, Up-Regulation, Death-Associated Protein Kinases, medicine.anatomical_structure, Nephrology, Immunology, Calcium-Calmodulin-Dependent Protein Kinases, Cyclosporine, Synaptopodin, medicine.symptom, business, Apoptosis Regulatory Proteins, Carrier Proteins, Nephrotic syndrome
Abstract: Membranous nephropathy (MN) is a glomerular disease characterized by a nephrotic syndrome without infiltration of inflammatory cells or proliferation of resident cells. Although the cause of the disease is unknown, the primary pathogenic mechanism responsible for the accumulation of immune deposits on the outer aspect of the glomerular basement membrane involves the generation of autoantibodies against antigen targets expressed at the membrane surface of podocyte. The molecular mechanisms of nephrotic proteinuria, which reflects a profound disorder of podocyte function, remain unclear. We show here that induction of c-mip in passive type Heymann nephritis (PHN) coincides with the occurrence of proteinuria. c-mip expression is not detectable in the glomeruli of PHN rats receiving a single dose of anti-megalin polyclonal antibody, yet the immune complexes are readily present but without triggering of proteinuria. Rats reinjected with anti-megalin develop a few days later heavy proteinuria concomitantly with c-mip overproduction in podocytes. We show that overexpression of c-mip is associated with downregulation of synaptopodin in human MN, PHN rats and c-mip transgenic mice, while the abundance of death-associated protein kinase (DAPK) and integrin linked kinase (ILK) is increased. Finally, cyclosporine treatment reduces significantly proteinuria in PHN rats, concomitantly with downregulation of c-mip abundance in podocytes. These results suggest that c-mip plays an active role in podocyte disorders of MN.
Published: 2013
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9. A lack of significant effect of POR*28 allelic variant on tacrolimus exposure in kidney transplant recipients

Author: Cécile Vigneau, Antoine Thierry, Isabelle Etienne, Anne-Elizabeth Heng, Xavier Vuillemin, Mathias Büchler, Bruno Moulin, Jean-Philippe Rerolle, Christophe Legendre, Gabriel Choukroun, Jean-François Subra, Philippe Beaune, Nicolas Pallet, Eric Thervet, Bruno Hurault de Ligny, Marie-Anne Loriot, Charlotte Colosio, Anne-Sophie Jannot, 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), Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Néphrologie et Transplantation, CHU Strasbourg, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Pharmacologie des Immunosuppresseurs et de la Transplantation ( PIST ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université d'Angers ( UA ) -CHU Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Graft Rejection, Male, medicine.medical_specialty, Genotype, CYP3A, [SDV]Life Sciences [q-bio], Population, chemical and pharmacologic phenomena, Biology, 030226 pharmacology & pharmacy, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Cytochrome P-450 Enzyme System, Polymorphism (computer science), Internal medicine, medicine, Cytochrome P-450 CYP3A, Humans, Pharmacology (medical), Prospective Studies, CYP3A5, education, Alleles, Pharmacology, education.field_of_study, [ SDV ] Life Sciences [q-bio], Genetic Variation, Middle Aged, Kidney Transplantation, Transplant Recipients, Calcineurin, Transplantation, stomatognathic diseases, Endocrinology, 030220 oncology & carcinogenesis, Immunology, Female, Immunosuppressive Agents
Abstract: International audience; BACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxydoreductase (POR) which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least one allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (Co). The objective of this study is to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts Tacrolimus (Tac) pharmacokinetics. METHODS: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac Co) 10 days after transplantation. We have also measured the association between POR*28 and the Tac Co, and adjusted Tac Co (Tac Co/Tac dose) over time using generalized mixed linear models. RESULTS: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac Co (Co 10-15 ng/ml) according to the POR*28 genotype (p=0.8). The mean Tac Co at day 10 in the POR*1/*1 group was 15.3±9.7 ng/ml compared with 15.7±7.8 ng/ml in the POR*1/*28 group and 14.2 ±6.8 ng/ml, in the POR*28/*28 group, p=0.8. The adjusted Tac Co was not associated with POR*28 genotype over time (random effects model, p=0.9). When restricted to KTR expressing CYP3A5, POR*28 gentoype did not impact the proportion of individuals within the Tac Co target range neither the adjusted Tac Co (random effects model, p=0.1). CONCLUSIONS: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target Co
Published: 2016

10. Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study

Author: Vincent Vuiblet, Guy Touchard, Marie Essig, Jean-Claude Aldigier, Antoine Thierry, Yann Lemeur, Vincent Javaugue, Bruno Hurault de Ligny, Ramzi Abou-Ayache, Isabelle Etienne, Charlotte Laurent, Frank Bridoux, Nicolas Bouvier, Elise Gand, Charlotte Colosio, Jean-Philippe Rerolle, Laure Ecotiere, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Sciences Pour l'Oenologie (SPO), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de néphrologie - hémodialyse et transplantation rénale, Université Montpellier 1 (UM1)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Graft Rejection, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Renal function, Azathioprine, Cyclosporins, 030230 surgery, Pharmacology, Risk Assessment, Mycophenolic acid, Statistics, Nonparametric, Nephropathy, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Prospective Studies, Prospective cohort study, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Immunosuppression Therapy, Transplantation, business.industry, Graft Survival, Immunosuppression, Middle Aged, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Survival Analysis, 3. Good health, Treatment Outcome, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Follow-Up Studies
Abstract: Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).
Published: 2016

11. Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype

Author: B. Moulin, Cécile Vigneau, Mathias Büchler, B. Hurault de Ligny, Y. Le Meur, Isabelle Etienne, E. Thervet, Marie-Anne Loriot, Gabriel Choukroun, E. Bailly, Anne-Elisabeth Heng, Antoine Thierry, Philippe Beaune, Charlotte Colosio, Nicolas Pallet, C. Legendre, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Néphrologie et Transplantation, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de néphrologie adultes [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), Jonchère, Laurent, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), CHRU Tours, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT ), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Graft Rejection, Male, immunosuppressant, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, translational research/science, kidney transplantation/nephrology, immunosuppression/immune modulation, Pharmacology, Kidney Function Tests, 030226 pharmacology & pharmacy, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Risk Factors, Cytochrome P-450 CYP3A, Immunology and Allergy, Medicine, Tissue Distribution, Pharmacology (medical), genetics, Prospective Studies, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, Prospective cohort study, Kidney transplantation, Incidence (epidemiology), Graft Survival, Middle Aged, Prognosis, 3. Good health, surgical procedures, operative, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, pharmacokinetics/pharmacodynamics, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.medical_specialty, Genotype, Renal function, chemical and pharmacologic phenomena, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, clinical research/practice, Tacrolimus, calcineurin inhibitor: tacrolimus, 03 medical and health sciences, patient survival, Internal medicine, Humans, Dosing, CYP3A5, Transplantation, Dose-Response Relationship, Drug, business.industry, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, medicine.disease, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Pharmacogenetics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Kidney Failure, Chronic, business, Follow-Up Studies
Abstract: International audience; Pretransplantation adaptation of the daily dose of tacrolimus to CYP3A5 genotype is associated with improved achievement of target trough concentration (C0 ), but whether this improvement affects clinical outcomes is unknown. In the present study, we have evaluated the long-term clinical impact of the adaptation of initial tacrolimus dosing according to CYP3A5 genotype: the transplantation outcomes of the 236 kidney transplant recipients included in the Tactique study were retrospectively investigated over a period of more than 5 years. In the Tactique study, patients were randomly assigned to receive tacrolimus at either a fixed dosage or a dosage determined by their genotype, and the primary efficacy end point was the proportion of patients for whom tacrolimus C0 was within target range (10-15 ng/ml) at day 10. Our results indicate that the incidence of biopsy proven acute rejection and graft survival were similar between the control and the adapted tacrolimus dose groups, as well as between the patients who achieve the tacrolimus C0 target ranges earlier. Parients death, cancer, cardiovascular events and infections were also similar, and renal function did not change. We conclude that optimization of initial tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes.
Published: 2016

12. Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation

Author: Bruno Moulin, Joseph Rivalan, Matthias Büchler, Anne-Elisabeth Heng, Johnny Sayegh, Pierre-François Weestel, Bruno Hurault de Ligny, Renaud Snanoudj, Dominique Bertrand, Yvon Lebranchu, Antoine Thierry, Jean-Philippe Rerolle, Philippe Gatault, Bénédicte Sautenet, Charlotte Colosio, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Reims (CHU Reims), Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dyalise et transplantation, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Department of Kidney Transplantation CHU Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Francois Rabelais [Tours], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de Néphrologie, Immunologie clinique, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Service de Néphrologie et d’Immunologie Clinique, and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Graft Rejection, Male, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Kaplan-Meier Estimate, 030230 surgery, 0302 clinical medicine, target of rapamycin-inhibitors, Cause of Death, Prospective Studies, Prospective cohort study, Kidney transplantation, immunosuppression, Statistics, Graft Survival, Immunosuppression, clinical trial, Middle Aged, 3. Good health, Survival Rate, surgical procedures, operative, Treatment Outcome, Cyclosporine, Female, Drug, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Urology, Renal function, Risk Assessment, Drug Administration Schedule, Statistics, Nonparametric, Dose-Response Relationship, 03 medical and health sciences, medicine, Humans, Nonparametric, Survival rate, Immunosuppression Therapy, Sirolimus, Transplantation, Analysis of Variance, Dose-Response Relationship, Drug, business.industry, human leukocyte antigen-antibody posttransplantation, medicine.disease, Kidney Transplantation, Surgery, Regimen, business, Follow-Up Studies
Abstract: International audience; We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.
Published: 2015

13. Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN

Author: Mohamad, Zaidan, Benjamin, Terrier, Agnieszka, Pozdzik, Thierry, Frouget, Nathalie, Rioux-Leclercq, Christian, Combe, Sébastien, Lepreux, Aurélie, Hummel, Laure-Hélène, Noël, Isabelle, Marie, Bruno, Legallicier, Arnaud, François, Antoine, Huart, David, Launay, Gilles, Kaplanski, Frank, Bridoux, Philippe, Vanhille, Raifah, Makdassi, Jean-François, Augusto, Philippe, Rouvier, Alexandre, Karras, Chantal, Jouanneau, Marie-Christine, Verpont, Patrice, Callard, Fabrice, Carrat, Olivier, Hermine, Jean-Marc, Léger, Xavier, Mariette, Patricia, Senet, David, Saadoun, Pierre, Ronco, Isabelle, Brochériou, Patrice, Cacoub, Emmanuelle, Plaisier, Thierry, Zénone, CHU Necker - Enfants Malades [AP-HP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [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), Department of Nephrology - Dialysis and Renal Transplantation, Hôpital Erasmes, Laboratory of Experimental Nephrology - Department of Biochimie, Université Libre de Bruxelles [Bruxelles] (ULB), Service de néphrologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre de compétences des microangiopathies thrombotiques, Université Bordeaux Segalen - Bordeaux 2, Centre de recherche Croissance et signalisation (UMR_S 845), 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 d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [Rouen], Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de Médecine Interne et d'Immunologie clinique, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et néphrologie, CH Valenciennes, Université d'Angers - Faculté de médecine (UA UFR Médecine), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA), Service de Néphrologie et Hémodialyse [CHU HEGP], 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), 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 [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), CHU Saint-Antoine [APHP], Centre de référence des mastocytoses, Service d'Hématologie Adulte, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre d'Immunologie et de Maladies Infectieuses (CIMI), 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), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Immunologie - Immunopathologie - Immunothérapie (I3), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Sorbonne Universités, Service de Néphrologie et Dialyses [CHU Tenon], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] ( DHU - I2B ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Libre de Bruxelles [Bruxelles] ( ULB ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Laboratoire d'Immunologie ( EA 2686 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -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, Université d'Angers - Faculté de médecine ( UA UFR Médecine ), Université d'Angers ( UA ) -CHU Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département de santé publique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), 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-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie - Immunopathologie - Immunothérapie ( I3 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Anatomopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université libre de Bruxelles (ULB), Service de néphrologie [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne [CHU Rouen], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), CHU Tenon [AP-HP], CHU Saint-Antoine [AP-HP], Centre de référence des mastocytoses (CEREMAST), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)
Subjects: Male, medicine.medical_specialty, Pathology, Cyclophosphamide, Glomerulonephritis, Membranoproliferative, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Lymphoproliferative disorders, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, medicine, Humans, Cause of death, Retrospective Studies, 030203 arthritis & rheumatology, Proteinuria, [ SDV ] Life Sciences [q-bio], business.industry, General Medicine, membranoproliferative GN, Middle Aged, medicine.disease, Prognosis, Cryoglobulinemia, 3. Good health, Lymphoma, Regimen, Nephrology, histopathology, Rituximab, Female, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death
Published: 2015

14. Strategies to model AL amyloidosis in mice

Author: Corinne Lacombe, Arnaud Jaccard, Michel Cogné, Guy Touchard, Sébastien Bender, Christophe Sirac, Franck Bridoux, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Laboratoire d'immunologie [CHU Poitiers]
Subjects: MESH: DNA Primers, NLM, Transgene, Lymphoproliferative disorders, Disease, MESH: Base Sequence, Biology, Immunoglobulin light chain, Polymerase Chain Reaction, Mass Spectrometry, law.invention, Mice, 03 medical and health sciences, 0302 clinical medicine, law, Internal Medicine, medicine, AL amyloidosis, Animals, MESH: Amyloidosis, MESH: Animals, MESH: Mice, Severe complication, Polymerase chain reaction, DNA Primers, 030304 developmental biology, MESH: Mass Spectrometry, 0303 health sciences, Base Sequence, [CHIM.ORGA]Chemical Sciences/Organic chemistry, MESH: Polymerase Chain Reaction, Amyloidosis, medicine.disease, 3. Good health, Transgenesis, Disease Models, Animal, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Disease Models, Animal
Abstract: International audience; Monoclonal immunoglobulin (Ig) deposition in AL amyloidosis is a severe complication of lymphoproliferative disorders. Research on this disease suffers from the lack of animal models, as they could allow for the testing of new innovative therapeutic strategies. We are trying to develop a transgenic animal model for this disease by overexpressing Ig light chain (LC) sequences cloned from AL amyloidosis patients. After several unsuccessful attempts using additional transgenesis due to low LC expression, we currently are following a strategy of targeted insertion of human LC sequences in the mouse endogenous kappa LC locus. We describe here the first data from this ‘knock-in’ model and propose future prospects to increase the rates of free LC and mimic the human disease. Absence of amyloid deposits in such models would raise the possibility of a resistance to AL amyloidosis in mice and question the feasibility of a reliable animal model for this disease.
Published: 2011
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15. Renal transplantation in light chain amyloidosis: coming out of the cupboard

Author: Franck Bridoux, Jean-Paul Fermand, Pierre Ronco, Julian D. Gillmore, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH: Immunoglobulin Light Chains, medicine.medical_specialty, 030204 cardiovascular system & hematology, Immunoglobulin light chain, MESH: Kidney Transplantation, 03 medical and health sciences, 0302 clinical medicine, medicine, Coming out, AL amyloidosis, MESH: Amyloidosis, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, Transplantation, MESH: Humans, business.industry, Amyloidosis, medicine.disease, Dermatology, Cupboard, Nephrology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Stem Cell Transplantation, business
Abstract: International audience
Published: 2011

16. The Alarmin Concept Applied to Human Renal Transplantation: Evidence for a Differential Implication of HMGB1 and IL-33

Author: Jean-Philippe Girard, Guy Touchard, Antoine Thierry, Sébastien Giraud, Thierry Hauet, Aurélie Robin, Virginie Ameteau, Anne Barra, Franck Bridoux, André Herbelin, Jean-Marc Gombert, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'immunologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie - hémodialyse et transplantation rénale, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: [SDV]Life Sciences [q-bio], lcsh:Medicine, Umbilical vein, Cohort Studies, 0302 clinical medicine, Molecular Cell Biology, Renal Transplantation, Prospective Studies, HMGB1 Protein, lcsh:Science, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Cellular Stress Responses, White Cells, 0303 health sciences, Kidney, Multidisciplinary, biology, Hematology, Middle Aged, Flow Cytometry, Cell Hypoxia, Innate Immunity, medicine.anatomical_structure, Transplant Surgery, Nephrology, Reperfusion Injury, Medicine, Research Article, Adult, medicine.medical_specialty, Urinary system, Enzyme-Linked Immunosorbent Assay, chemical and pharmacologic phenomena, Real-Time Polymerase Chain Reaction, HMGB1, Statistics, Nonparametric, 03 medical and health sciences, Internal medicine, Human Umbilical Vein Endothelial Cells, medicine, Humans, Immunoassays, Biology, Aged, 030304 developmental biology, Transplantation, business.industry, Interleukins, lcsh:R, Immunity, Immunologic Subspecialties, Interleukin-33, medicine.disease, Kidney Transplantation, Immunity, Innate, TLR2, Endocrinology, Immunology, Immunologic Techniques, biology.protein, lcsh:Q, Clinical Immunology, Surgery, business, Reperfusion injury, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been identified as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. We analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme-linked immunosorbent assay, in a cohort of 26 deceased renal transplant recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to those before treatment. Moreover, both serum and urinary IL-33 (but not HMGB1) increase was positively correlated with cold ischemia time, from 30 min to 3 days post-transplantation. In vitro, human umbilical vein endothelial cells subjected to hypoxia conditions released both HMGB-1 and IL-33, while only the latter was further increased upon subsequent re-oxygenation. Finally, we postulate that leukocytes from renal recipient patients are targeted by both HMGB1 and IL-33, as suggested by increased transcription of their respective receptors (TLR2/4 and ST2L) shortly after transplantation. Consistent with this view, we found that iNKT cells, an innate-like T cell subset involved in IRI and targeted by IL-33 but not by HMGB1 was activated 1 hour post-transplantation. Altogether, these results are in keeping with a potential role of IL-33 as an innate-immune mediator during kidney IRI in humans.
Published: 2014

17. Associations between polymorphisms in target, metabolism, or transport proteins of mycophenolate sodium and therapeutic or adverse effects in kidney transplant patients

Author: Nicolas Picard, Antoine Thierry, Guy Touchard, Pierre Marquet, Jean-Baptiste Woillard, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Grants from Roche and Novartis, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers
Subjects: Graft Rejection, Male, Pharmacology, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, General Pharmacology, Toxicology and Pharmaceutics, Genetics (clinical), Kidney transplantation, pharmacogenetics, education.field_of_study, Leukopenia, Hazard ratio, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, Multidrug Resistance-Associated Protein 2, 3. Good health, 030220 oncology & carcinogenesis, Molecular Medicine, Female, medicine.symptom, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Population, Lower risk, Polymorphism, Single Nucleotide, Mycophenolic acid, Article, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, education, Molecular Biology, Genetic Association Studies, Proportional Hazards Models, Proportional hazards model, business.industry, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Transplantation, adverse effects, mycophenolate sodium, BPAR, business, Carrier Proteins
Abstract: International audience; OBJECTIVES: Different associations between single nucleotide polymorphisms (SNPs) in cellular target, metabolism enzymes or transport proteins, and biopsy-proven acute rejection (BPAR) or adverse events have been reported in transplant patients receiving mycophenolate mofetil. This work aimed to study these in patients on enteric-coated mycophenolate sodium (EC-MPS). PATIENTS AND METHODS: The study included 189 renal transplant patients from the DOMINOS trial. Fifteen SNPs in IMPDH2, IMPDH1, ABCC2, SLCO1B3, UGT1A8, UGT1A9, UGT2B7, CYP2C8, HUS1, and IL12A were genotyped in all patients. Associations between SNPs and the first event of BPAR or diarrhea were investigated using multivariate logistic regressions. Associations between SNPs and leukopenia or anemia at nine different visits between days 0 and 190 after transplantation were studied using time-dependent Cox proportional hazards regression models. RESULTS: Multivariate analyses showed that the CYP2C8 rs11572076 wild-type genotype was associated significantly with a lower risk of leukopenia [GG vs. GA: hazard ratio (95% confidence interval) 0.14 (0.03, 0.59), P=0.00783]. Higher EC-MPS doses and the UGT2B7 c.-840 G>A variant allele were associated with an increased risk of anemia [EC-MPS per unit dose increase: 1.004 (1.003, 1.005), P
Published: 2014

18. Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey

Author: Jean-Marc Léger, Fabrice Carrat, P. Belenotti, Luc de Saint-Martin, Isabelle Marie, P. Rullier, Franck Bridoux, Guillaume Le Guenno, Thierry Zenone, Olivier Hermine, Xavier Mariette, Emmanuelle Plaisier, Benjamin Terrier, Antoine Huart, Thomas Quemeneur, Patrice Cacoub, Adeline Lacraz, Fabrice Bonnet, Olivier Hinschberger, Estibaliz Lazaro, Jean-Emmanuel Kahn, Elisabeth Diot, Patricia Senet, David Launay, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: Vasculitis, medicine.medical_specialty, Cyclophosphamide, Immunology, Early Relapse, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Immunology and Allergy, In patient, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, Gastrointestinal tract, business.industry, Remission Induction, medicine.disease, 3. Good health, Purpura, Cryoglobulinemia, Mixed cryoglobulinemia, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, France, medicine.symptom, business, Follow-Up Studies, medicine.drug
Abstract: Objective Although in most patients induction therapy leads to complete or partial remission, relapses in patients with non-infectious mixed cryoglobulinemia vasculitis (CryoVas) remain a major problem. We aimed to identify predictors of early relapses occurring within the first 12 months of treatment in such patients. Methods Patients included in the French CryoVas survey exhibiting complete/partial clinical remission and followed-up for at least 12 months after induction therapy (n = 145) were analyzed for predictors of early relapses. Results Forty out of 145 patients (28%) experienced early relapse. Relapses occurred after a median time of 9.5 months after induction therapy (3–12) and involved skin (75%), joints and peripheral nerve (28% each), kidneys (25%) and gastrointestinal tract (5%). Baseline factors associated with an early relapse were purpura [HR 3.35 (1.02–10.97), P = 0.046], cutaneous necrosis [HR 4.46 (1.58–12.57), P = 0.005] and articular involvement [HR 2.20 (1.00–4.78), P = 0.048]. The only factor negatively associated with an early relapse during follow-up was the achievement of complete immunological response [HR 0.07 (0.01–0.51), P = 0.009]. The use of corticosteroids plus rituximab or cyclophosphamide tended to be associated negatively with early relapse [HR 0.43 (0.17–1.08), P = 0.07]. Conclusion In patients with non-infectious CryoVas, main predictors of early relapses after initial remission are purpura, articular involvement, and cutaneous necrosis. The absence of complete immunological response during follow-up was associated with early relapse. These findings may help in adapting future treatment strategies.
Published: 2014

19. How I treat monoclonal gammopathy of renal significance (MGRS)

Author: Fermand, Jean-Paul, Bridoux, Franck, Kyle, Robert A, Kastritis, Efstathios, Weiss, Brendan M, Cook, Mark A, Drayson, Mark T, Dispenzieri, Angela, Leung, Nelson, Renseigné, Non, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Pathology, medicine.medical_specialty, MESH: Cryoglobulinemia, Immunology, 030232 urology & nephrology, Paraproteinemias, Biochemistry, Immunoglobulin Light-chain Amyloidosis, 03 medical and health sciences, 0302 clinical medicine, MESH: Paraproteinemias, MESH: B-Lymphocytes, medicine, Humans, MESH: Amyloidosis, Kidney transplantation, Multiple myeloma, MESH: Fanconi Syndrome, Kidney, B-Lymphocytes, MESH: Kidney Diseases, MESH: Humans, business.industry, Cell Biology, Hematology, Amyloidosis, medicine.disease, Fanconi Syndrome, 3. Good health, medicine.anatomical_structure, Cryoglobulinemia, 030220 oncology & carcinogenesis, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Kidney Diseases, business, Monoclonal gammopathy of undetermined significance, Monoclonal Immunoglobulin Deposition Disease, Kidney disease
Abstract: Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable of injuring the kidney resulting in permanent damage. Except for immunoglobulin light chain amyloidosis with heart involvement in which death can be rapid, treatment of MGRS is often indicated more to preserve kidney function and prevent recurrence after kidney transplantation rather than the prolongation of life. Clinical trials are rare for MGRS-related kidney diseases, except in immunoglobulin light chain amyloidosis. Treatment recommendations are therefore based on the clinical data obtained from treatment of the clonal disorder in its malignant state. The establishment of these treatment recommendations is important until data can be obtained by clinical trials of MGRS-related kidney diseases.
Published: 2013

20. Long-term kidney disease outcomes in fibrillary glomerulonephritis: a case series of 27 patients

Author: Stéphanie Ragot, Vincent Javaugue, Jean-Michel Goujon, Franck Bridoux, Alexandre Karras, François Glowacki, Brigitte Mcgregor, Guy Touchard, Corinne Lacombe, Pierre Aucouturier, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Centre de Recherche Saint-Antoine (CR Saint-Antoine), and Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)
Subjects: Nephrology, Male, Pathology, Time Factors, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Renin-Angiotensin System, 0302 clinical medicine, Glomerulonephritis, MESH: Aged, 80 and over, MESH: Renin-Angiotensin System, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Middle Aged, MESH: Glomerulonephritis, 3. Good health, Treatment Outcome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Renal function, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Retrospective Studies, MESH: Humans, business.industry, Fibrillary Glomerulonephritis, MESH: Time Factors, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, business, Nephrotic syndrome, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: Fibrillary glomerulonephritis (GN) is a rare disorder with poor renal prognosis. Therapeutic strategies, particularly the use of immunosuppressive drugs, are debated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 27 adults with fibrillary GN referred to 15 nephrology departments in France between 1990 and 2011 were included. All patients were given renin-angiotensin system blockers and 13 received immunosuppressive therapy, including rituximab (7 patients) and cyclophosphamide (3 patients). OUTCOMES & MEASUREMENTS: Clinical and histologic features of patients and kidney disease outcome. Renal response was defined as a >50% decrease in 24-hour proteinuria with
Published: 2013

21. C3 glomerulopathy in adults: monoclonal gammopathy should be considered

Author: Frank Bridoux, Guy Touchard, Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Université de Poitiers
Subjects: Male, 030203 arthritis & rheumatology, Pathology, medicine.medical_specialty, MESH: Humans, business.industry, MESH: Complement C3, Complement C3, 030204 cardiovascular system & hematology, medicine.disease, MESH: Glomerulonephritis, MESH: Male, 03 medical and health sciences, Monoclonal gammopathy, Glomerulonephritis, 0302 clinical medicine, Nephrology, Glomerulopathy, Humans, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2013

22. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey

Author: Isabelle Marie, Jean-Marc Léger, Estibaliz Lzaro, Xavier Mariette, Adeline Lacraz, Thomas Quemeneur, Olivier Hermine, Franck Bridoux, Olivier Hinschberger, P. Rullier, Jean-Emmanuel Kahn, Fabrice Carrat, Patrice Cacoub, Thierry Zenone, Christian Pagnoux, P. Belenotti, Fabrice Bonnet, Patricia Senet, Luc de Saint Martin, Guillaume Le Guenno, Antoine Huart, Aurélie Hummel, Evguenia Krastinova, Elisabeth Diot, Benjamin Terrier, Emmanuelle Plaisier, David Launay, Immunologie - Immunopathologie - Immunothérapeutique (I3), 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), Service de Médecine Interne, 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), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Médecine Interne (MARSEILLE - Med Int), Assistance Publique - Hôpitaux de Marseille (APHM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Département de Médecine Interne (VALENCIENNES - Med Int), CH Valenciennes, Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Département de Médecine Interne (MULHOUSE - Med Int), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service de Médecine Interne B, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Bretonneau, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Médecine Interne (VALENCE - Med Int), Centre hospitalier de Valence, Cytokines, hématopoïèse et réponse immune (CHRI), 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 Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [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), Remodelage et Reparation du Tissu Renal, Service de médecine interne [CHU Pitié-Salpétrière], 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), Biologie et thérapeutique des pathologies immunitaires (BTPI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Brest (UBO), Centre Hospitalier Universitaire Estaing, CHU Estaing, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Rouen, Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Médecine Interne ( MARSEILLE - Med Int ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Département de Médecine Interne ( VALENCIENNES - Med Int ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire d'Immunologie ( EA 2686 ), Département de Médecine Interne ( MULHOUSE - Med Int ), Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Médecine Interne ( VALENCE - Med Int ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Biologie et thérapeutique des pathologies immunitaires ( BTPI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, MESH : Retrospective Studies, [SDV]Life Sciences [q-bio], MESH : Aged, 030232 urology & nephrology, Kaplan-Meier Estimate, medicine.disease_cause, Severity of Illness Index, 0302 clinical medicine, Epidemiology, Immunology and Allergy, MESH : Female, MESH: Data Collection, MESH: Aged, MESH : Prognosis, MESH: Middle Aged, Data Collection, Mortality rate, MESH: Vasculitis, Middle Aged, Prognosis, 3. Good health, MESH : Vasculitis, Cryoglobulinemia, Area Under Curve, Female, MESH : Severity of Illness Index, MESH : Data Collection, Vasculitis, medicine.medical_specialty, MESH: Genetic Diseases, Inborn, MESH: Cryoglobulinemia, MESH : Male, Hepatitis C virus, Immunology, Renal function, General Biochemistry, Genetics and Molecular Biology, MESH: Prognosis, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, MESH : Genetic Diseases, Inborn, Rheumatology, Internal medicine, MESH: Severity of Illness Index, Severity of illness, medicine, Humans, MESH : Middle Aged, In patient, MESH: Kaplan-Meier Estimate, Aged, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, Genetic Diseases, Inborn, Retrospective cohort study, MESH: Retrospective Studies, medicine.disease, MESH : Cryoglobulinemia, MESH: Male, Surgery, MESH: Area Under Curve, MESH : Area Under Curve, business, MESH: Female
Abstract: International audience; BACKGROUND: Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. METHODS: The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. RESULTS: After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate 65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.
Published: 2013

23. Post-transplantation lymphoproliferative disorder after kidney transplantation: report of a nationwide French registry and the development of a new prognostic score

Author: Sophie Caillard, Raphael Porcher, François Provot, Jacques Dantal, Sylvain Choquet, Antoine Durrbach, Emmanuel Morelon, Valérie Moal, Benedicte Janbon, Eric Alamartine, Claire Pouteil Noble, Delphine Morel, Nassim Kamar, Matthias Buchler, Marie France Mamzer, Marie Noelle Peraldi, Christian Hiesse, Edith Renoult, Olivier Toupance, Jean Philippe Rerolle, Sylvie Delmas, Philippe Lang, Yvon Lebranchu, Anne Elisabeth Heng, Jean Michel Rebibou, Christiane Mousson, Denis Glotz, Joseph Rivalan, Antoine Thierry, Isabelle Etienne, Marie Christine Moal, Laetitia Albano, Jean François Subra, Nacera Ouali, Pierre François Westeel, Michel Delahousse, Robert Genin, Bruno Hurault de Ligny, Bruno Moulin, Service de néphrologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Biostatistiques, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [APHP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Transplantation Medicine, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Centre de cytométrie en flux (CCF), Université Jean Monnet [Saint-Étienne] (UJM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Reims Champagne-Ardenne (URCA), Service de transplantation rénale, Hôpital Foch [Suresnes], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité Transversale d'Allergologie, Néphrologie et Immunologie Clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Pasteur [Nice] (CHU), Service de Néphrologie et Transplantation, CHU Strasbourg, Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre commun de Cytométrie en Flux (CCCF), Université Jean Monnet - Saint-Étienne (UJM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Marquet, Pierre, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Pontchaillou [Rennes]-Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Cancer Research, MESH: Registries, 030230 surgery, MESH: Kidney Transplantation, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, Postoperative Complications, MESH: Risk Factors, Risk Factors, hemic and lymphatic diseases, MESH: Postoperative Complications, Prospective Studies, Registries, Young adult, Prospective cohort study, Kidney transplantation, MESH: Aged, education.field_of_study, MESH: Middle Aged, MESH: Follow-Up Studies, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, Prognosis, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, surgical procedures, operative, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, Cohort, Female, France, Adult, medicine.medical_specialty, Adolescent, Population, Lymphoproliferative disorders, MESH: Multivariate Analysis, MESH: Prognosis, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Intensive care medicine, education, Survival rate, Survival analysis, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Adult, medicine.disease, Kidney Transplantation, Survival Analysis, MESH: Prospective Studies, MESH: Male, Lymphoproliferative Disorders, MESH: France, Multivariate Analysis, business, MESH: Female, Follow-Up Studies
Abstract: Purpose Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years. Patients and Methods A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses. Results Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 μmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high–risk recipients. Conclusion This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.
Published: 2013

24. Specific impairment of proximal tubular cell proliferation by a monoclonal κ light chain responsible for Fanconi syndrome

Author: Christelle Oblet, Franck Bridoux, Jean-Claude Aldigier, Chahrazed El Hamel, Michel Cogné, Brice Laffleur, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Université de Limoges (UNILIM)
Subjects: medicine.medical_specialty, Tubular atrophy, 030232 urology & nephrology, Immunoglobulin light chain, Kidney Tubules, Proximal, 03 medical and health sciences, Immunoglobulin kappa-Chains, 0302 clinical medicine, Internal medicine, medicine, Humans, Multiple myeloma, Cells, Cultured, 030304 developmental biology, Cell Proliferation, 0303 health sciences, Transplantation, Cell growth, business.industry, Fanconi syndrome, medicine.disease, Fanconi Syndrome, Endocrinology, Nephrology, Apoptosis, Renal physiology, Monoclonal, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Atrophy, business
Abstract: International audience; Background Fanconi syndrome (FS) is a rare renal disorder featuring proximal tubule dysfunction that may occur following tubular reabsorption of a monoclonal light chain (LC), in patients with multiple myeloma. FS may precede the recognition of multiple myeloma by several years. In most cases, crystalline inclusions of monoclonal κ LCs are observed within the lysosomes of proximal tubular cells (PTCs) and probably participate in their functional alteration. Methods To investigate the mechanism implicated in proximal tubule dysfunction, we compared the effects of κ LC-CHEB obtained from a patient with myeloma-associated FS to those of control κ LC-BON obtained from a patient without evidence of FS, on the viability and proliferation of two different PTC lines. Results Our data suggest that the tubular atrophy in myeloma-associated FS does not result from increased apoptosis of PTCs, but from their impaired capacity to proliferate and renew. Indeed, in vitro incubation of cultured PTCs with physiological amounts of the nephrotoxic κ LC-CHEB was sufficient to cause a depression in DNA synthesis and in cell proliferation. This effect was observed neither with control κ LC-BON nor in the absence of κ LC. Conclusions The reduced turnover of PTCs may affect tubular repair and regeneration. In addition, the reduced proliferation of myeloma cells producing the same monoclonal κ LC might explain the frequent association of FS with smoldering multiple myeloma.
Published: 2012

25. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant

Author: Leung, Nelson, Bridoux, Franck, Hutchison, Colin A, Nasr, Samih H, Cockwell, Paul, Fermand, Jean-Paul, Dispenzieri, Angela, Song, Kevin W, Kyle, Robert A, Renseigné, Non, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Pathology, medicine.medical_specialty, Immunology, Paraproteinemias, 030232 urology & nephrology, Renal function, MESH: Antineoplastic Agents, Alkylating, Monoclonal Gammopathy of Undetermined Significance, Biochemistry, MESH: Kidney Transplantation, 03 medical and health sciences, 0302 clinical medicine, MESH: Paraproteinemias, medicine, Humans, Antineoplastic Agents, Alkylating, Multiple myeloma, Kidney transplantation, Kidney, MESH: Kidney Diseases, MESH: Humans, business.industry, Cell Biology, Hematology, medicine.disease, Kidney Transplantation, 3. Good health, medicine.anatomical_structure, MESH: Kidney Failure, Chronic, 030220 oncology & carcinogenesis, MESH: Monoclonal Gammopathy of Undetermined Significance, Monoclonal, Disease Progression, Kidney Failure, Chronic, [SDV.IMM]Life Sciences [q-bio]/Immunology, Kidney Diseases, MESH: Disease Progression, Clone (B-cell biology), business, Monoclonal gammopathy of undetermined significance, Monoclonal Immunoglobulin Deposition Disease
Abstract: Multiple myeloma is the most frequent monoclonal gammopathy to involve the kidney; however, a growing number of kidney diseases associated with other monoclonal gammopathies are being recognized. Although many histopathologic patterns exist, they are all distinguished by the monoclonal immunoglobulin (or component) deposits. The hematologic disorder in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with multiple myeloma. Unfortunately, due to the limitations of the current diagnostic schema, they are frequently diagnosed as MGUS. Because treatment is not recommended for MGUS, appropriate therapy is commonly withheld. In addition to end-stage renal disease, the persistence of the monoclonal gammopathy is associated with high rates of recurrence after kidney transplantation. Preservation and restoration of kidney function are possible with successful treatment targeting the responsible clone. Achievement of hematologic complete response has been shown to prevent recurrence after kidney transplantation. There is a need for a term that properly conveys the pathologic nature of these diseases. We think the term monoclonal gammopathy of renal significance is most helpful to indicate a causal relationship between the monoclonal gammopathy and the renal damage and because the significance of the monoclonal gammopathy is no longer undetermined.
Published: 2012

26. Fanconi syndrome and chronic kidney disease in paroxysmal nocturnal hemoglobinuria: effect of eculizumab therapy

Author: Nathalie Quellard, Sébastien Delbès, Edouard Randriamalala, Simohamed Belmouaz, Eric Moumas, Guy Touchard, Franck Bridoux, Fannie Leroy, Estelle Desport, Brigitte Dreyfus, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Carrion, Claire
Subjects: Male, Hemoglobinuria, Paroxysmal, 030232 urology & nephrology, Gastroenterology, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Fanconi Syndrome, MESH: Aged, Kidney, MESH: Middle Aged, MESH: Hemoglobinuria, Paroxysmal, 05 social sciences, General Medicine, Middle Aged, Eculizumab, 3. Good health, medicine.anatomical_structure, Nephrology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Kidney Diseases, Hemoglobinuria, medicine.drug, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Renal function, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Internal medicine, 0502 economics and business, medicine, Humans, Aged, MESH: Kidney Diseases, MESH: Humans, business.industry, MESH: Chronic Disease, Fanconi syndrome, Fanconi Syndrome, medicine.disease, MESH: Male, Endocrinology, MESH: Antibodies, Monoclonal, Humanized, Hemosiderin, Chronic Disease, Paroxysmal nocturnal hemoglobinuria, 050211 marketing, business, MESH: Female, Kidney disease
Abstract: International audience; The association of Fanconi syndrome (FS) and chronic kidney disease (CKD) has been rarely described during the course of paroxysmal nocturnal hemoglobinuria (PNH). We report 2 patients with PNH and CKD associated with proximal tubule dysfunction, which manifested as full-blown FS in one case. In both patients, abnormal iron load within the kidneys was demonstrated by magnetic resonance imaging, which correlated with diffuse and numerous hemosiderin inclusions within proximal tubular cells. After 12 months, eculizumab treatment resulted in significant decrease in the kidney iron load in both cases. Glomerular filtration rate improved in one case and was stabilized in the other, in whom pretreatment kidney biopsy had shown severe extensive interstitial fibrosis. However, symptoms of proximal tubular dysfunction persisted in both patients. These data suggest that hemosiderin deposition in proximal tubules is probably an important mechanism involved in the development of FS, an under recognized and early manifestation of CKD in PNH. Prolonged treatment with eculizumab may improve long-term renal function in PNH patients with CKD.
Published: 2012

27. Optimizing treatment strategies in myeloma cast nephropathy: rationale for a randomized prospective trial

Author: Franck Bridoux, Jean-Paul Fermand, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP]
Subjects: MESH: Immunoglobulin Light Chains, medicine.medical_specialty, medicine.medical_treatment, MESH: Acute Kidney Injury, 030232 urology & nephrology, Urology, MESH: Multiple Myeloma, MESH: Prognosis, law.invention, Kidney Tubules, Proximal, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, Randomized controlled trial, Renal Dialysis, law, MESH: Kidney Tubules, Proximal, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, MESH: Renal Dialysis, Myeloma cast nephropathy, Prospective cohort study, Multiple myeloma, Randomized Controlled Trials as Topic, Chemotherapy, MESH: Humans, Plasma Exchange, Bortezomib, business.industry, Acute Kidney Injury, MESH: Plasma Exchange, Prognosis, medicine.disease, MESH: Glomerulonephritis, 3. Good health, Surgery, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Randomized Controlled Trials as Topic, Nephrology, 030220 oncology & carcinogenesis, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin Light Chains, Multiple Myeloma, Complication, business, medicine.drug
Abstract: International audience; Renal failure is a frequent complication of multiple myeloma (MM) that strongly affects patient survival. Although a variety of renal diseases may be observed in MM, myeloma cast nephropathy (MCN), a tubulo-interstitial disorder related to precipitation of a monoclonal light chain (LC) within tubular distal lumens, is the main cause of severe and persistent renal failure. To date, the respective frequency and initial evolution of renal disorders associated with monoclonal LC in MM remain poorly defined. Treatment of MCN relies on urgent symptomatic measures and rapid introduction of chemotherapy to reduce the production of monoclonal LC. The introduction of novel chemotherapy regimens based on the association of bortezomib with dexamethasone is likely to have improved the prognosis of MM patients with renal failure. In addition, the combination of novel agents with efficient removal of circulating LC through high cut-off hemodialysis membrane may further increase renal response rate. However, the impact on patient and renal outcomes of these potential therapeutic advances has not been evaluated in prospective studies. The randomized trials EuLITE in the UK and Germany and MYRE in France should help to answer these issues. MYRE is a randomized controlled phase III trial (NCT01208818) that aims to better define the epidemiology and typology of inaugural renal failure in MM and to optimize therapy of MCN patients with and without dialysis-dependent renal failure.
Published: 2012

28. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome

Author: Franck Bridoux, Elisabeth Cassuto, Valérie Chatelet, Mathieu Jablonski, Nassim Kamar, Chantal Loirat, Eric Rondeau, Georges Mourad, Michel Delahousse, Christiane Mousson, Bruno Moulin, Arnaud Lionet, Véronique Frémeaux-Bacchi, Julien Zuber, M. Le Quintrec, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: Graft Rejection, Male, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, medicine.disease_cause, Gastroenterology, MESH: Kidney Transplantation, 0302 clinical medicine, MESH: Risk Factors, Recurrence, Risk Factors, Immunology and Allergy, Pharmacology (medical), Atypical Hemolytic Uremic Syndrome, MESH: Aged, Mutation, MESH: Middle Aged, MESH: Genetic Testing, Graft Survival, MESH: Complement C3, MESH: Complement Factor B, Complement C3, Middle Aged, Prognosis, 3. Good health, MESH: Complement Factor H, MESH: Hemolytic-Uremic Syndrome, MESH: Young Adult, Complement Factor H, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Complement Factor B, Adult, medicine.medical_specialty, Thrombotic microangiopathy, MESH: Mutation, MESH: Graft Survival, Adolescent, MESH: Antigens, CD46, MESH: Complement System Proteins, MESH: Graft Rejection, Complement factor I, Complement factor B, MESH: Prognosis, Membrane Cofactor Protein, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Genetic Testing, Gene, Aged, Retrospective Studies, MESH: Adolescent, Transplantation, MESH: Humans, business.industry, MESH: Biological Markers, Fibrinogen, MESH: Adult, MESH: Retrospective Studies, Complement System Proteins, medicine.disease, Kidney Transplantation, MESH: Male, MESH: Recurrence, Calcineurin, MESH: Fibrinogen, Immunology, Hemolytic-Uremic Syndrome, Alternative complement pathway, business, MESH: Female, Biomarkers
Abstract: International audience; Atypical hemolytic and uremic syndrome (aHUS) is a severe disease strongly associated with genetic abnormalities in the complement alternative pathway. In renal posttransplantation, few data are available on recurrence risk and graft outcome according to genetic background in aHUS patients. The aim of this study was to identify risk factors for recurrence and transplant outcome and, in particular, the role of complement gene abnormalities. We retrospectively studied 57 aHUS patients who had received 71 renal transplants. A mutation in complement gene was identified in 39 (68%), in factor H (CFH), factor I (CFI), membrane cofactor-protein (MCP), C3 and factor B (CFB). At 5 years, death-censored graft survival was 51%. Disease recurrence was associated with graft loss (p = 0.001). Mutations in complement genes were associated with higher risk of recurrence (p = 0.009). Patients with CFH or gain of function (C3, CFB) mutations had a highest risk of recurrence. M-TOR inhibitor was associated with significant risk of recurrence (p = 0.043) but not calcineurin inhibitor immunosuppressive treatment (p = 0.29). Preemptive plasmatherapy was associated with a trend to decrease recurrence (p = 0.07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence-related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies.
Published: 2012

29. Five-year results of a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation: the SPIESSER study

Author: Laetitia Finzi, Olivier Toupance, Antoine Thierry, P. Le Pogamp, Renaud Snanoudj, Mathias Büchler, B. Hurault de Ligny, Jean-François Subra, B. Moulin, Jean-Philippe Rerolle, P.-F. Weestel, Yvon Lebranchu, Isabelle Etienne, P. Deteix, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), service de néphrologie et transplantation, Centre Hospitalier Universitaire de Reims (CHU Reims), Service de dyalise et transplantation, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et transplantation rénale, Hospices Civils de Lyon (HCL), Service de Néphrologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de néphrologie, CHU Clermont-Ferrand, Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], ClinSearch, Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de néphrologie et immunologie clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Bretonneau-Université de Tours-CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Reims ( CHU Reims ), Université de Picardie Jules Verne ( UPJV ) -CHU Amiens-Picardie, Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), service de néphrologie et transplantation rénale, CHU Caen, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Hospices Civils de Lyon ( HCL ), Université d'Angers ( UA ) -CHU Angers, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Marquet, Pierre, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, Urology, Renal function, 030230 surgery, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Adverse effect, Sirolimus, Transplantation, business.industry, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Kidney Transplantation, 3. Good health, Surgery, Discontinuation, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Calcineurin, Regimen, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Cyclosporine, Female, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, Follow-Up Studies, medicine.drug
Abstract: International audience; Calcineurin inhibitors improve acute rejection rates and short-term graft survival in renal transplantation, but their continuous use may be deleterious. We evaluated the 5-year outcomes of sirolimus (SRL) versus cyclosporine (CsA) immunosuppressive treatment. This observational study was an extension of the SPIESSER study where deceased donor kidney transplant recipients were randomized before transplantation to a SRL- or CsA-based regimen and followed up 1 year. Data from 131 (63 SRL, 68 CsA) out of 133 patients living with a functional graft at 1 year were collected retrospectively at 5 years posttransplant. Seventy percent of CsA patients versus 54% of SRL patients were still on the allocated treatment at 5 years (p = 0.091), most discontinuations in each group being due to safety issues. In intent-to-treat, mean MDRD eGFR was higher with SRL: 54.2 versus 45.3 mL/min with CsA (p = 0.019); SRL advantage was greater in on-treatment analyses. There were no differences for patient survival (p = 0.873), graft survival (p = 0.121) and acute rejection (p = 0.284). Adverse events were more frequent with SRL (80% vs. 60%, p = 0.015). Results confirmed the high SRL discontinuation rate due to adverse events. Nevertheless, a benefit was evidenced on renal function in patients (more than 50%) still on treatment at 5 years.
Published: 2012

30. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey

Author: Antoine Huart, Estibaliz Lazaro, P. Belenotti, Olivier Hermine, David Launay, Guillaume Le Guenno, Thierry Zenone, Adeline Lacraz, Patrice Cacoub, Evguenia Krastinova, Franck Bridoux, Patricia Senet, P. Rullier, Elisabeth Diot, Xavier Mariette, Luc de Saint-Martin, Thomas Quemeneur, Isabelle Marie, Emmanuelle Plaisier, Benjamin Terrier, Fabrice Carrat, Fabrice Bonnet, Olivier Hinschberger, Jean-Emmanuel Kahn, Jean-Marc Léger, Immunologie - Immunopathologie - Immunothérapeutique (I3), 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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Médecine Interne (MARSEILLE - Med Int), Assistance Publique - Hôpitaux de Marseille (APHM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Médecine Interne (VALENCIENNES - Med Int), CH Valenciennes, Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire Estaing, CHU Estaing, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service de Médecine Interne B, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Médecine Interne, Hôpital Bretonneau, Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Médecine Interne (VALENCE - Med Int), Centre hospitalier de Valence, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytokines, hématopoïèse et réponse immune (CHRI), 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 neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Remodelage et Reparation du Tissu Renal, Service de médecine interne [CHU Pitié-Salpétrière], Biologie et thérapeutique des pathologies immunitaires (BTPI), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), 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 ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Médecine Interne ( MARSEILLE - Med Int ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Département de Médecine Interne ( VALENCIENNES - Med Int ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire d'Immunologie ( EA 2686 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Médecine Interne ( VALENCE - Med Int ), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Biologie et thérapeutique des pathologies immunitaires ( BTPI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université de Brest (UBO)-Université de Brest (UBO), CHU Clermont-Ferrand, Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [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 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Male, MESH: Combined Modality Therapy, MESH : Retrospective Studies, [SDV]Life Sciences [q-bio], MESH : Aged, Arthritis, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, MESH: Antibodies, Monoclonal, Cohort Studies, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, MESH : Female, MESH: Data Collection, MESH: Cohort Studies, MESH : Algorithms, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Data Collection, MESH: Vasculitis, Antibodies, Monoclonal, Hematology, Middle Aged, Connective tissue disease, Combined Modality Therapy, 3. Good health, MESH : Vasculitis, MESH : Infection, Treatment Outcome, Cryoglobulinemia, MESH : Antibodies, Monoclonal, Rituximab, Female, medicine.symptom, MESH : Data Collection, Vasculitis, MESH: Infection, Algorithms, medicine.drug, medicine.medical_specialty, MESH: Cryoglobulinemia, MESH : Male, Immunology, MESH : Cohort Studies, MESH: Algorithms, MESH : Treatment Outcome, Infections, MESH : Adrenal Cortex Hormones, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH : Middle Aged, Aged, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH: Retrospective Studies, Cell Biology, Skin ulcer, medicine.disease, MESH : Cryoglobulinemia, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Regimen, Peripheral neuropathy, MESH: Antibodies, Monoclonal, Murine-Derived, business, MESH : Combined Modality Therapy, MESH: Female
Abstract: Data on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials.
Published: 2012

31. Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin

Author: Jean-Michel Goujon, Mathieu Boimard, Corinne Lacombe, Violaine Planté-Bordeneuve, Philip N. Hawkins, Monica Stoppini, Julie A. Vrana, Mark B. Pepys, Guy Touchard, Vittorio Bellotti, Riccardo Porcari, Thierry Maisonobe, Franck Bridoux, Sophie Valleix, Julian D. Gillmore, Ahmet Dogan, Martino Bolognesi, Jason D. Theis, Pierre Lozeron, Sofia Giorgetti, Marc Delpech, Catherine Lacroix, Stefano Ricagno, David H. Adams, Brigitte Nedelec, Palma Mangione, Laboratoire de Biochimie et Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'anatomopathologie, Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Ischémie - Reperfusion en transplatation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Male, MESH: Hydrogen-Ion Concentration, Proteome, MESH: Protein Structure, Quaternary, MESH : beta 2-Microglobulin, MESH : Diarrhea, MESH: Monitoring, Physiologic, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Genes, Dominant, 0303 health sciences, MESH: Middle Aged, biology, Amyloidosis, MESH: Infant, Newborn, Fibrillogenesis, MESH : Genes, Dominant, General Medicine, Middle Aged, MESH : Amyloidosis, Familial, Pedigree, MESH: Glass, MESH: Proteome, MESH: Diarrhea, Sjogren's Syndrome, MESH : Glass, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Protein folding, MESH: beta 2-Microglobulin, MESH : Scalp, Amyloidosis, Familial, Diarrhea, medicine.medical_specialty, Amyloid, MESH: Pedigree, MESH : Male, MESH : Proteome, MESH : Infant, Newborn, Fibril, MESH: Scalp, 03 medical and health sciences, MESH : Hydrogen-Ion Concentration, MESH : Protein Structure, Quaternary, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH: Fetal Blood, Protein Structure, Quaternary, 030304 developmental biology, MESH : Fetal Blood, MESH: Humans, Beta-2 microglobulin, business.industry, MESH : Humans, MESH : Monitoring, Physiologic, MESH: Electrodes, medicine.disease, MESH: Amyloidosis, Familial, In vitro, MESH: Male, Transthyretin, Endocrinology, MESH: Sjogren's Syndrome, MESH : Pedigree, biology.protein, MESH : Sjogren's Syndrome, beta 2-Microglobulin, business, MESH: Genes, Dominant, MESH: Female, 030217 neurology & neurosurgery, MESH : Electrodes
Abstract: International audience; We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.
Published: 2012

32. Identification of invariant natural killer T cells in porcine peripheral blood

Author: Jean-Marc Gombert, Antoine Thierry, S. Minouflet, Guy Touchard, Aurélie Robin, A Herbelin, Anne Barra, Thierry Hauet, Sébastien Giraud, Franck Bridoux, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hauet, Thierry
Subjects: Male, MESH: Immunophenotyping, Swine, CD3, Immunology, Cell, MESH: Flow Cytometry, Galactosylceramides, Statistics, Nonparametric, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Antigen, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Swine, 030304 developmental biology, 0303 health sciences, MESH: Statistics, Nonparametric, MESH: Cytokines, Innate immune system, General Veterinary, biology, MESH: Galactosylceramides, Flow Cytometry, Phenotype, In vitro, MESH: Male, Immunity, Innate, Cell biology, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, MESH: Natural Killer T-Cells, MESH: Antigens, CD1d, CD1D, biology.protein, Leukocytes, Mononuclear, Cytokines, Natural Killer T-Cells, MESH: Immunity, Innate, Antigens, CD1d, CD8, 030215 immunology
Abstract: International audience; The pig is a relevant preclinical model for numerous pathologies used to validate therapeutic strategies for translation to human. Although invariant natural killer T (iNKT) lymphocytes are a component of innate immunity implicated in many pathological processes, little is known on their characterization in swine. By addressing this issue using mouse α-galactosylceramide-loaded CD1d tetramers (α-GC-CD1dTT), which are commonly used to track iNKT cells, we were able to unequivocally identify CD3(+)α-GC-CD1dTT(+) cells in porcine peripheral blood, hereafter referred to as swine iNKT cells. These lymphocytes are enriched in CD4(-)CD8(+) and CD4(-)CD8(-) cells, harbor an activated-memory phenotype (SLA-DR(+)CD45RA(-)), express the intracellular promyelocytic-leukemia-zinc-finger (PLZF) transcription factor and are significantly enriched in IFN-γ-producing cells after in vitro activation in comparison with conventional T cells. Importantly, in presence of IL-2 and IL-15, the iNKT cell ligand α-GC induces selective expansion of CD3(+)α-GC-CD1dTT(+) cells, confirming the reactivity of swine iNKT cells against α-GC. When associated with α-GC, IL-33, an alarmin of IL-1 family recently described to target iNKT cells, leads to a greater expansion of CD3(+)α-GC-CD1dTT(+) cells than IL-2 and IL-15. Altogether, our results provide the first phenotypic and functional description of swine iNKT cells allowing to further study the critical role of iNKT cells in porcine models of organ injury.
Published: 2012

33. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma

Author: Hutchison, Colin A, Batuman, Vecihi, Behrens, Judith, Bridoux, Franck, Sirac, Christophe, Dispenzieri, Angela, Herrera, Guillermo A, Lachmann, Helen, Sanders, Paul W, Renseigné, Non, Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Division of Hematology, and Mayo Clinic Rochester
Subjects: Pathology, medicine.medical_specialty, 030232 urology & nephrology, Article, Light chain deposition disease, Nephropathy, Immunoglobulin Light-chain Amyloidosis, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Myeloma cast nephropathy, Multiple myeloma, Kidney, business.industry, Acute kidney injury, Acute Kidney Injury, medicine.disease, Bence Jones protein, 3. Good health, medicine.anatomical_structure, Nephrology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Multiple Myeloma, business
Abstract: International audience; Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains. These endogenous proteins can result in isolated proximal tubule cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (myeloma kidney). Less frequently, high levels of free light chains can lead to immunoglobulin light chain amyloidosis and light chain deposition disease, although these conditions are usually associated with insidious progression of renal failure rather than acute kidney injury. Unless there is rapid intervention, progressive and irreversible damage occurs, particularly interstitial fibrosis and tubular atrophy. Despite advances in our understanding of the pathogenesis of these processes there has been a gap in translating these achievements into improved patient outcomes. The International Kidney and Monoclonal Gammopathy Research Group was formed to address this need. In this Review, we discuss the mechanisms of disease and diagnostic approaches to patients with acute kidney injury complicating multiple myeloma.
Published: 2012

34. Renal transplantation in patients with AA amyloidosis nephropathy: results from a French multicenter study

Author: P. Le Pogamp, Nicolas Bouvier, Julien Zuber, Vincent Audard, Tomek Kofman, Julie Peltier, Laetitia Albano, Lionel Couzi, P. Lang, Claire Pouteil-Noble, Luc Frimat, A. Le Thuaut, Gabriel Choukroun, Nassim Kamar, Florence Canoui-Poitrine, Mathias Büchler, G. Couvrat, Christiane Mousson, Valérie Garrigue, Philippe Grimbert, Franck Bridoux, Michel Delahousse, Christophe Mariat, Evangeline Pillebout, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: Male, 030232 urology & nephrology, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Gastroenterology, MESH: Kidney Transplantation, 0302 clinical medicine, AA amyloidosis, Recurrence, Immunology and Allergy, Pharmacology (medical), Kidney transplantation, MESH: Treatment Outcome, Kidney, MESH: Middle Aged, Amyloidosis, Graft Survival, Middle Aged, 3. Good health, Treatment Outcome, medicine.anatomical_structure, Cardiovascular Diseases, MESH: Kidney Failure, Chronic, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Kidney Diseases, MESH: Infection, Adult, medicine.medical_specialty, MESH: Graft Survival, Urinary system, Infections, Nephropathy, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: Amyloidosis, MESH: Kaplan-Meier Estimate, Retrospective Studies, Transplantation, MESH: Kidney Diseases, MESH: Humans, business.industry, MESH: Cardiovascular Diseases, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, MESH: Male, Surgery, MESH: Recurrence, Kidney Failure, Chronic, business, MESH: Female, Kidney disease
Abstract: International audience; Although end-stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5- and 10-year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5- and 10- year graft survival censored for death between two groups. AA amyloidosis-transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1-year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.
Published: 2011

35. Long-term Impact of Subclinical Inflammation Diagnosed by Protocol Biopsy One Year After Renal Transplantation

Author: Jean-Michel Goujon, Luc Marcellin, Sandrine Girardot-Seguin, Guy Touchard, Arnaud François, Antoine Thierry, François Comoz, Marie-Christine Machet, Laure-Hélène Noël, Nathalie Rioux-Leclercq, Carole Cordonnier, Eric Thervet, Vincent Vuiblet, Ischémie - Reperfusion en transplatation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'anatomopathologie, Service d'Anatomopathologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytopathologie, CHU Amiens-Picardie, Service d'Anatomie et Cytologie Pathologique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de Pathologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Laboratoire Roche, Laboratoire Roche SAS, Roche SAS, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), CHRU Tours-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire d'anatomie pathologique, CHU Caen-Hôpital côte de nacre, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), and De Villemeur, Hervé
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Protocol biopsy, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Biopsy, 030232 urology & nephrology, Renal function, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Kidney, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, subclinical inflammation, Internal medicine, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Humans, Pharmacology (medical), [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, Kidney transplantation, Survival analysis, Subclinical infection, Inflammation, Transplantation, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Graft Survival, renal function, renal transplantation, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Transplantation, Survival Analysis, 3. Good health, Surgery, Sirolimus, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; The long-term impact of subclinical acute rejection (SCAR) on renal graft function remains poorly understood. Furthermore, the interpretation of borderline lesions is difficult and their incidence is variable. The aim of this study was to analyze the characteristics of subclinical inflammation (SCI) in protocol biopsies performed 1-year after renal transplantation. SCI was defined as the presence of borderline lesions or SCAR according to the Banff 2005 classification. The patients included were a subpopulation of the CONCEPT study in which patients were randomized 3 months after transplantation to receive either sirolimus (SRL) or cyclosporine A (CsA) in combination with mycophenolate mofetil. At 1 year, we observed SCI in 37 of the 121 patients observed with an evaluable biopsy. The incidence was more frequent in the SRL group (SRL 45.2% vs. CsA 15.3%). At 30 months , SCI was associated with a significantly lower level of estimated glomerular filtration rate (mean MDRD 50.8 [±13.3] vs. 57.7 [±16.3] mL/min/1.73 m(2) , p = 0.035). In conclusion, SCI at 1-year posttransplantation is associated with worsening renal function and is more frequent in SRL-treated patients. Therefore, evaluation of SCI may be a valuable tool to allow the optimization of immunosuppressive regimens.
Published: 2011

36. Glomerulonephritis with isolated C3 deposits and monoclonal gammopathy: a fortuitous association?

Author: Guy Touchard, Christine Fen Chong, Franck Bridoux, Nathalie Quellard, Jean-Marc Gombert, Estelle Desport, Corinne Lacombe, Véronique Frémeaux-Bacchi, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Epidemiology, C3 Glomerulonephritis, Glomerulonephritis, Membranoproliferative, Complement Pathway, Alternative, 030232 urology & nephrology, Plasma cell dyscrasia, Paraproteinemias, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, MESH: Paraproteinemias, Membranoproliferative glomerulonephritis, medicine, Humans, MESH: Glomerulonephritis, Membranoproliferative, Aged, Retrospective Studies, MESH: Aged, Transplantation, MESH: Middle Aged, MESH: Humans, business.industry, MESH: Complement C3, Glomerulonephritis, MESH: Adult, MESH: Retrospective Studies, Original Articles, Complement C3, MESH: Follow-Up Studies, Middle Aged, medicine.disease, MESH: Male, 3. Good health, Nephrology, Monoclonal, Properdin, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, MESH: Complement Pathway, Alternative, Nephrotic syndrome, MESH: Female, Monoclonal gammopathy of undetermined significance, Follow-Up Studies
Abstract: International audience; BACKGROUND AND OBJECTIVES: Glomerular deposition of monoclonal Ig has been exceptionally described as the cause of membranoproliferative glomerulonephritis, through activation of the complement alternative pathway (CAP). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively studied six adults with monoclonal gammopathy and glomerulonephritis (GN) characterized by isolated C3 deposits. RESULTS: All patients presented with hematuria, associated with chronic renal failure and proteinuria in five patients, three of whom had nephrotic syndrome. Five patients had monoclonal gammopathy of undetermined significance and one had smoldering myeloma. The serum monoclonal IgG (κ four of six, λ two of six) was associated with light chain (LC) proteinuria in five patients. Four patients had low serum C3 and/or factor B levels. C4, factor H (CFH), and I protein levels were normal in five of five patients; none had detectable C3NeF. IgG anti-CFH activity was positive in one case. No mutations in CFH, CFI, and MCP genes were identified in four of four patients. Deposits were intramembranous, subepithelial, and mesangial by electron microscopy, and stained positive for C3 (six of six), properdin, and CFH (two of two) but negative for Ig LC and heavy chains, C4, and C1q (6/6) by immunofluorescence. Five patients progressed to end-stage renal disease over a median period of 47 months, despite chemotherapy in four patients. In one patient, monoclonal λLC deposits were observed on a follow-up kidney biopsy after 4 years. CONCLUSIONS: GN with isolated glomerular C3 deposits might represent an unusual complication of plasma cell dyscrasia, related to complement activation through an autoantibody activity of the monoclonal Ig against a CAP regulator protein.
Published: 2011

37. Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF-four-year results of the Postconcept study

Author: Isabelle Etienne, Pierre-François Westeel, Thierry Frouget, Yvon Lebranchu, B. Hurault de Ligny, Jean-Philippe Rerolle, Etienne Thervet, Antoine Thierry, Sandrine Girardot-Seguin, Bruno Moulin, Olivier Toupance, Mathias Büchler, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de dyalise et transplantation, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), service de néphrologie et transplantation, CHU Strasbourg, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Roche SAS, Centre Hospitalier Universitaire de Reims (CHU Reims), Marquet, Pierre, Service de néphrologie et immunologie clinique, Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de néphrologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours, 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 Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Tours-CHRU Tours, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Picardie Jules Verne ( UPJV ) -CHU Amiens-Picardie, service de néphrologie et transplantation rénale, CHU Caen, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Centre Hospitalier Universitaire de Reims ( CHU Reims )
Subjects: Male, 030232 urology & nephrology, 030230 surgery, Kidney Function Tests, urologic and male genital diseases, MESH: Cyclosporine, MESH: Kidney Transplantation, 0302 clinical medicine, Chronic allograft nephropathy, Immunology and Allergy, Medicine, MESH : Female, Pharmacology (medical), MESH : Immunosuppressive Agents, MESH : Graft Survival, education.field_of_study, Proteinuria, MESH: Middle Aged, Graft Survival, Middle Aged, MESH : Adult, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH : Survival Rate, 3. Good health, Survival Rate, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Kidney Failure, Chronic, MESH: Kidney Function Tests, Cyclosporine, Female, MESH: Immunosuppressive Agents, medicine.symptom, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, MESH: Survival Rate, MESH: Graft Survival, MESH : Male, Population, Urology, Renal function, MESH : Kidney Failure, Chronic, Nephrotoxicity, 03 medical and health sciences, MESH : Cyclosporine, Humans, MESH : Middle Aged, education, Sirolimus, Transplantation, MESH: Humans, business.industry, MESH : Sirolimus, MESH : Humans, MESH : Kidney Function Tests, MESH: Adult, medicine.disease, Kidney Transplantation, MESH: Male, Surgery, Calcineurin, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Kidney Failure, Chronic, MESH : Kidney Transplantation, MESH: Sirolimus, business, MESH: Female
Abstract: International audience; Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months. Renal function (Cockcroft and Gault) was significantly better at month 48 (M48) in the SRL group both in the intent-to-treat population (ITT): 62.6 mL/min/1.73 m(2) versus 57.1 mL/min/1.73 m(2) (p = 0.013) and in the on-treatment population (OT): 67.5 mL/min/1.73 m(2) versus 57.4 mL/min/1.73 m(2) (p = 0.002). Two biopsy proven acute rejection episodes occurred after M12 in each group. Graft and patient survival were comparable (graft survival: 97.4 vs. 100%; patient survival: 97.4 vs. 97.6%, respectively). The incidence of new-onset diabetes was numerically increased in the SRL group (7 vs. 2). In OT, three cancers occurred in the SRL group versus nine in the CsA group and mean proteinuria was increased in the SRL group (0.42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation.
Published: 2011

38. Spectrum of mutations in Gitelman syndrome

Author: Annabelle Venisse, Diana Kahila, Claire Rigothier, Bernard Grisart, Bruno Moulin, Marie-Christine Vantyghem, Ivan Tack, Anne-Paule Gimenez-Roqueplo, Franck Bridoux, Jean-Philippe Haymann, Olivier Devuyst, Hubert Nivet, Rosa Vargas-Poussou, Laurence Dubourg, Eva Riveira-Munoz, Anne Blanchard, Karin Dahan, Michel Godin, Pascal Houillier, Huguette Debaix, Bertrand Dussol, Robert J. Unwin, Xavier Jeunemaitre, Service de néphrologie - hémodialyse et transplantation rénale, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Physiology, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Klinik für Nephrologie, UniversitätsSpital, Division of Nephrology, UCL Medical School, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), University of Zürich [Zürich] (UZH)-Zurich Center for Integrative Human Physiology, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), 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), Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, 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), 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) (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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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)
Subjects: Male, MESH : Molecular Sequence Data, MESH : Retrospective Studies, Receptors, Drug, Gene Dosage, 030232 urology & nephrology, MESH: Base Sequence, MESH : Child, Preschool, medicine.disease_cause, MESH: Gitelman Syndrome, MESH: Gene Dosage, MESH : Chloride Channels, 0302 clinical medicine, MESH : Child, MESH: Child, Missense mutation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Solute Carrier Family 12, Member 3, MESH : Female, MESH : Gene Dosage, Child, Gene Rearrangement, Genetics, 0303 health sciences, Mutation, MESH: Middle Aged, Symporters, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, MESH : Adult, 3. Good health, Nephrology, MESH: Young Adult, Child, Preschool, MESH : Symporters, MESH: Solute Carrier Family 12, Member 3, MESH : Gitelman Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, MESH : Sensitivity and Specificity, Gitelman Syndrome, Adult, MESH: Symporters, MESH: Mutation, Adolescent, MESH: Gene Rearrangement, MESH : Male, Molecular Sequence Data, Non-allelic homologous recombination, MESH : Young Adult, MESH : Solute Carrier Family 12, Member 3, Biology, Sensitivity and Specificity, Gene dosage, Young Adult, 03 medical and health sciences, Chloride Channels, MESH: Receptors, Drug, MESH : Adolescent, MESH : Genetic Testing, medicine, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Genetic Testing, Multiplex ligation-dependent probe amplification, Allele, Alleles, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Receptors, Drug, MESH: Alleles, MESH: Child, Preschool, MESH: Chloride Channels, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, Gene rearrangement, MESH : Gene Rearrangement, Gitelman syndrome, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, Basic Research, MESH : Genetic Predisposition to Disease, MESH : Base Sequence, MESH : Alleles, MESH: Female
Abstract: International audience; Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.
Published: 2011

39. Renal Impairment in Multiple Myeloma: Time Is of the Essence

Author: Colin A. Hutchison, Frank Bridoux, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)
Subjects: MESH: Immunoglobulin Light Chains, Cancer Research, Pathology, 030232 urology & nephrology, MESH: Multiple Myeloma, Glomerulus (kidney), Bioinformatics, MESH: Kidney Transplantation, MESH: Paraproteinemias, 0302 clinical medicine, MESH: Renal Insufficiency, MESH: Glomerulonephritis, Membranoproliferative, ComputingMilieux_MISCELLANEOUS, Multiple myeloma, MESH: Treatment Outcome, MESH: Fanconi Syndrome, MESH: Aged, MESH: Middle Aged, MESH: Hemoglobinuria, Paroxysmal, MESH: Complement C3, MESH: Follow-Up Studies, medicine.anatomical_structure, Oncology, MESH: Kidney Failure, Chronic, 030220 oncology & carcinogenesis, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Infection, medicine.medical_specialty, MESH: Graft Survival, Time to treatment, Renal function, Endocytosis, Nephropathy, 03 medical and health sciences, MESH: Severity of Illness Index, medicine, MESH: Amyloidosis, MESH: Kaplan-Meier Estimate, Cathepsin, MESH: Kidney Diseases, MESH: Humans, business.industry, MESH: Chronic Disease, MESH: Time Factors, MESH: Cardiovascular Diseases, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, MESH: Recurrence, MESH: Glomerular Filtration Rate, MESH: Antibodies, Monoclonal, Humanized, MESH: Tumor Markers, Biological, MESH: Complement Pathway, Alternative, business, MESH: Female
Abstract: TO THE EDITOR: The recently published consensus statement fromtheInternationalMyelomaWorkingGroup 1 onthemanagement of renal impairment in patients with multiple myeloma provides a much needed overview of the topic. Unfortunately, however, the consensus statement fails to emphasis two key concepts: first, time to treatment, and second, consideration of the severity of renal impairment. As stated in the article, 1 when patients with multiple myeloma presentwithasevereacutekidneyinjury,itismostcommonlyaresult of cast nephropathy, often with a preceding trigger. This tubulointerstitial disorder is a direct consequence of the high monoclonal free lightchain(FLC)levelspresentinthepatient’ssera.Immunoglobulin FLCs, as a result of their low molecular weight, are freely filtered through the glomerulus. They are then reabsorbed in the proximal tubule through endocytosis, which is mediated by the tandem receptorsmegalinandcubilinthatarelocalizedontheapicalbrushborder. FLCs are then additionally processed in the endolysosomal compartment of the proximal tubular cell, where they are degraded by lysosomal enzymes, namely cathepsin B. 2
Published: 2011

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