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1. Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD

Author

Natalia Alencar de Pinho, Jean Kaboré, Maurice Laville, Marie Metzger, Céline Lange, Christian Jacquelinet, Christian Combe, Denis Fouque, Luc Frimat, Carol Ayav, Bruce M. Robinson, Tilman Drueke, Ziad A. Massy, Bénédicte Stengel, Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaétan Lebrun, Eric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, Guy Lambrey, Jean Philippe Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Séverine Martin, Isabelle Landru, Eric Thervet, Philippe Lang, Xavier Belenfant, Pablo Urena, Carlos Vela, Dominique Chauveau, Viktor Panescu, Christian Noel, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, François Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Arbor Research Collaborative for Health, Hôpital Ambroise Paré [AP-HP], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agence Nationale de la Recherche, ANR Agence Nationale de la Recherche, ANR, The CKD-REIN study is funded by the Agence Nationale de la Recherche through the 2010 «Cohortes-Investissements d’Avenir » program (ANR) and by the 2010 national Programme Hospitalier de Recherche Clinique . CKD-REIN is also supported through a public–private partnership with Amgen , Fresenius Medical Care , and GlaxoSmithKline (GSK) since 2012, Lilly France since 2013, Otsuka Pharmaceutical since 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Sanofi-Genzyme from 2012 to 2015, and Vifor Fresenius and AstraZeneca , since 2018. Inserm Transfert set up and has managed this partnership since 2011., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Urinary system, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Excretion, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Interquartile range, Internal medicine, medicine, salt, 10. No inequality, education, sodium, education.field_of_study, business.industry, potassium, blood pressure, medicine.disease, 3. Good health, Blood pressure, Quartile, Nephrology, Albuminuria, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract

Introduction In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., Graphical abstract

Published
2020
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2. First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Author

Tschopp, Jonathan, LHuillier, Arnaud G., Mombelli, Matteo, Mueller, Nicolas J., Khanna, Nina, Garzoni, Christian, Meloni, Dario, Papadimitriou‐Olivgeris, Matthaios, Neofytos, Dionysios, Hirsch, Hans H., Schuurmans, Macé M., Müller, Thomas, Berney, Thierry, Steiger, Jürg, Pascual, Manuel, Manuel, Oriol, Delden, Christian, Amico, Patrizia, Aubert, John‐David, Banz, Vanessa, Beldi, Guido, Benden, Christian, Berger, Christoph, Binet, Isabelle, Bochud, Pierre‐Yves, Branca, Sanda, Bucher, Heiner, Carell, Thierry, Catana, Emmanuelle, Chalandon, Yves, Geest, Sabina, Rougemont, Olivier, Dickenmann, Michael, Duchosal, Michel, Elkrief, Laure, Fehr, Thomas, Ferrari‐Lacraz, Sylvie, Soccal, Paola Gasche, Gaudet, Christophe, Giostra, Emiliano, Golshayan, Déla, Hadaya, Karine, Halter, Jörg, Hauri, Dimitri, Heim, Dominik, Hess, Christoph, Hillinger, Sven, Hirsch, Hans H, Hofbauer, Günther, Huynh‐Do, Uyen, Immer, Franz, Klaghofer, Richard, Koller, Michael, Laesser, Bettina, Laube, Guido, Lehmann, Roger, Lovis, Christian, Majno, Pietro, Marti, Hans‐Peter, Martin, Pierre Yves, Martinelli, Michele, Meylan, Pascal, Mueller, Nicolas J, Müller, Antonia, Müllhaupt, Beat, Passweg, Jakob, Posfay‐Barbe, Klara, Rick, Juliane, Roosnek, Eddy, Rosselet, Anne, Rothlin, Silvia, Ruschitzka, Frank, Schanz, Urs, Schaub, Stefan, Schnyder, Aurelia, Schuurmans, Macé, Seiler, Christian, Sprachta, Jan, Stampf, Susanne, Steinack, Carolin, Stirnimann, Guido, Toso, Christian, Van Delden, Christian, Venetz, Jean‐Pierre, Villard, Jean, Wick, Madeleine, Wilhelm, Markus, Yerly, Patrick, University of Zurich, Swiss Transplant Cohort Study (STCS), Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P.G., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Laube, G., Lehmann, R., Lovis, C., Majno, P., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., Meylan, P., Mueller, N.J., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Seiler, C., Sprachta, J., Stampf, S., Steinack, C., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., and Yerly, P.

Subjects
Male, 10255 Clinic for Thoracic Surgery, Comorbidity, 030230 surgery, Infection and infectious agents/ Viral, Organ transplantation, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Postoperative Complications, Epidemiology, Immunology and Allergy, Medicine, Pharmacology (medical), Prospective Studies, Prospective cohort study, ddc:616, Infectious disease, education.field_of_study, ddc:618, ddc:617, Incidence, Clinical research/ practice, Middle Aged, 3. Good health, Survival Rate, 10209 Clinic for Cardiology, Female, medicine.symptom, 10178 Clinic for Pneumology, Coronavirus Infections, infectious [Complication], infectious, infection and infectious agents, infection and infectious agents - viral, infectious disease [Aged, Betacoronavirus, Coronavirus Infections/epidemiology, Disease Transmission, Infectious/prevention & control, Follow-Up Studies, Humans, Organ Transplantation/methods, Pandemics, Pneumonia, Viral/epidemiology, Postoperative Complications/epidemiology, Survival Rate/trends, Switzerland/epidemiology, Transplant Recipients, clinical research/ practice, complication], Switzerland, Cohort study, medicine.medical_specialty, Nausea, Population, Pneumonia, Viral, Infection and infectious agents, 610 Medicine & health, Brief Communication, 03 medical and health sciences, Internal medicine, Disease Transmission, Infectious, education, Survival rate, Aged, Transplantation, business.industry, SARS-CoV-2, COVID-19, Organ Transplantation, medicine.disease, 10032 Clinic for Oncology and Hematology, business
Abstract

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%) and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.

Published
2020

3. Management of allergy transfer upon solid organ transplantation

Author

Muller, Yannick D, Vionnet, Julien, Beyeler, Franziska, Eigenmann, Philippe, Caubet, Jean-Christoph, Villard, Jean, Berney, Thierry, Scherer, Kathrin, Spertini, Francois, Fricker, Michael P, Lang, Claudia, Schmid-Grendelmeier, Peter, Benden, Christian, Lombard, Pascale Roux, Aubert, Vincent, Immer, Franz, Pascual, Manuel, Harr, Thomas, Amico, Patrizia, Aubert, John-David, Banz, Vanessa, Beldi, Guido, Berger, Christoph, Binet, Isabelle, Bochud, Pierre-Yves, Branca, Sanda, Bucher, Heiner, Carell, Thierry, Catana, Emmanuelle, Chalandon, Yves, de Geest, Sabina, de Rougemont, Olivier, Dickenmann, Michael, Duchosal, Michel, Elkrief, Laure, Fehr, Thomas, Ferrari-Lacraz, Sylvie, Garzoni, Christian, Soccal, Paola Gasche, Gaudet, Christophe, Giostra, Emiliano, Golshayan, Dela, Hadaya, Karine, Halter, Joerg, Hauri, Dimitri, Heim, Dominik, Hess, Christoph, Hillinger, Sven, Hirsch, Hans H, Hofbauer, Guenther, Huynh-Do, Uyen, Klaghofer, Richard, Koller, Michael, Laesser, Bettina, Laube, Guido, Lehmann, Roger, Lovis, Christian, Majno, Pietro, Manuel, Oriol, Marti, Hans-Peter, Martin, Pierre Yves, Martinelli, Michele, Meylan, Pascal, Morel, Philippe, Mueller, Nicolas J, Mueller, Antonia, Mueller, Thomas, Muellhaupt, Beat, Yerly, Patrick, Passweg, Jakob, Posfay-Barbe, Klara, Rick, Juliane, Roosnek, Eddy, Rosselet, Anne, Rothlin, Silvia, Ruschitzka, Frank, Schanz, Urs, Schaub, Stefan, Schnyder, Aurelia, Seiler, Christian, Sprachta, Jan, Stampf, Susanne, Steiger, Juerg, Stirnimann, Guido, Toso, Christian, Van Delden, Christian, Venetz, Jean-Pierre, Wick, Madeleine, Wilhelm, Markus, Swiss Transplant Cohort Study, Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Gasche Soccal, P., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Laube, G., Lehmann, R., Lovis, C., Majno, P., Manuel, O., Marti, H.P., Yves Martin, P., Martinelli, M., Meylan, P., Morel, P., Mueller, N.J., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Seiler, C., Sprachta, J., Stampf, S., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, Muller, Yannick D, Gasche-Soccal, Paola Marina Alessandra, Posfay Barbe, Klara, and Lovis, Christian

Subjects
Allergy, diagnostic techniques and imaging, IgE, Immunoglobulin E, allergy transfer, anaphylaxis, immunosuppression, management, solid organ transplantation, allergy, business/management, clinical decision-making, clinical research/practice, guidelines, immunoglobulin E, immunosuppression/immune modulation, organ transplantation in general, patient safety, 10255 Clinic for Thoracic Surgery, 2747 Transplantation, medicine.medical_treatment, 030230 surgery, INCREASE, Cohort Studies, 0302 clinical medicine, Solid organ transplantation, Immunology and Allergy, Medicine, 2736 Pharmacology (medical), Pharmacology (medical), LUNG TRANSPLANTATION, ddc:616, Kidney, ddc:618, biology, ddc:617, PEANUT ALLERGY, 10177 Dermatology Clinic, Immunosuppression, practice, Management, clinical decision‐making, medicine.anatomical_structure, B-CELLS, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, 10178 Clinic for Pneumology, Brief Communications, Life Sciences & Biomedicine, Anaphylaxis, medicine.medical_specialty, 610 Medicine & health, Brief Communication, 03 medical and health sciences, Internal medicine, Humans, Peanut Hypersensitivity, Allergy transfer, business, Retrospective Studies, Transplantation, Lung, Science & Technology, immune modulation, business.industry, Organ Transplantation, medicine.disease, clinical research, 10036 Medical Clinic, 10032 Clinic for Oncology and Hematology, biology.protein, ASTHMA, Surgery, IMMUNOGLOBULIN-E
Abstract

Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and management of these cases. Based on a review of 577 consecutive deceased donors from the Swisstransplant Donor‐Registry, 3 cases (0.5%) of fatal anaphylaxis were identified, 2 because of peanut and 1 of wasp allergy. The sera of all 3 donors and their 10 paired recipients, prospectively collected before and after transplantation for the Swiss Transplant Cohort Study, were retrospectively processed using a commercial protein microarray fluorescent test. As early as 5 days posttransplantation, newly acquired peanut‐specific IgE were transiently detected from 1 donor to 3 recipients, of whom 1 liver and lung recipients developed grade III anaphylaxis. Yet, to define how allergy testing should be performed in transplant recipients and to better understand the impact of immunosuppressive therapy on IgE sensitization, we prospectively studied 5 atopic living‐donor kidney recipients. All pollen‐specific IgE and >90% of skin prick tests remained positive 7 days and 3 months after transplantation, indicating that early diagnosis of donor‐derived IgE sensitization is possible. Importantly, we propose recommendations with respect to safety for recipients undergoing solid‐organ transplantation from donors with a history of fatal anaphylaxis., Based on the Swisstransplant donor registry, the Swiss‐Transplant‐Cohort‐Study, and a prospective analysis on allergy maintenance in atopic recipients, this study makes new recommendations for the management of allergy transfer upon solid organ transplantation, emphasizing the poor effect of immunosuppression on IgE sensitization and the need of early allergological investigation in the donor and respective recipients.

Published
2020

4. Use of induction therapy in pediatric heart transplant recipients in Switzerland - Analysis of the Swiss national database

Author

M. Schweiger, T. Erdil, S. Di Bernardo, C. Balmer, M. Yildiz, A. Kadner, Patrizia Amico, Andres Axel, John-David Aubert, Vanessa Banz, Beckmann Sonja, Guido Beldi, Christoph Berger, Ekaterine Berishvili, Isabelle Binet, Pierre-Yves Bochud, Sanda Branca, Heiner Bucher, Thierry Carrel, Emmanuelle Catana, Yves Chalandon, Sabina De Geest, Olivier De Rougemont, Michael Dickenmann, Joëlle Lynn Dreifuss, Michel Duchosal, Thomas Fehr, Sylvie Ferrari-Lacraz, Christian Garzoni, Paola Gasche Soccal, Christophe Gaudet, Déla Golshayan, Nicolas Goossens, Karine Hadaya, Jörg Halter, Dominik Heim, Christoph Hess, Sven Hillinger, Hans Hirsch, Patricia Hirt, Günther Hofbauer, Uyen Huynh-Do, Franz Immer, Michael Koller, Mirjam Laager, Bettina Laesser, Roger Lehmann, Alexander Leichtle, Christian Lovis, Oriol Manuel, Hans-Peter Marti, Pierre Yves Martin, Michele Martinelli, Valérie McLin, Katell Mellac, Aurélia Merçay, Karin Mettler, Nicolas Mueller, Antonia Müller, Thomas Müller, Ulrike Müller-Arndt, Beat Müllhaupt, Mirjam Nägeli, Graziano Oldani, Manuel Pascual, Klara Posfay-Barbe, Juliane Rick, Anne Rosselet, Simona Rossi, Silvia Rothlin, Frank Ruschitzka, Urs Schanz, Stefan Schaub, Aurelia Schnyder, Macé Schuurmans, Thierry Sengstag, Federico Simonetta, Katharina Staufer, Susanne Stampf, Jürg Steiger, Guido Stirniman, Ueli Stürzinger, Christian Van Delden, Jean-Pierre Venetz, Jean Villard, Julien Vionnet, Madeleine Wick, Markus Wilhlem, Patrick Yerly, Chalandon, Yves, University of Zurich, and Schweiger, M

Subjects
Graft Rejection, medicine.medical_specialty, 10255 Clinic for Thoracic Surgery, 2747 Transplantation, medicine.medical_treatment, Immunology, 610 Medicine & health, Induction therapy, Pediatric heart transplantation, Diabetes mellitus, Internal medicine, Interleukin-2 receptor antagonis, Immunology and Allergy, Medicine, Humans, Polyclonal antibodies, 10220 Clinic for Surgery, Renal replacement therapy, Child, Retrospective Studies, ddc:616, 2403 Immunology, Transplantation, business.industry, Background data, Significant difference, Induction Chemotherapy, medicine.disease, 10036 Medical Clinic, Median time, 10032 Clinic for Oncology and Hematology, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, Chronic renal failure, Heart Transplantation, National database, business, Immunosuppressive Agents, Switzerland
Abstract

Background: Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes. Method: This is a retrospective national database analysis of children

Published
2021

5. Apheresis in Adult With Refractory Idiopathic Nephrotic Syndrome on Native Kidneys

Author

Christophe Mariat, Jean-Michel Halimi, Vincent Audard, Christiane Mousson, Fatouma Touré, Olivier Moranne, Noémie Jourde-Chiche, Lise Marie Pouteau, Lacraz Adeline, Alexandre Cez, Cyril Garrouste, Yahsou Delmas, Léa Moret, Bertrand Knebelman, Alexandre Ganea, Jean François Subra, Olivier Fritz, Myriam Dao, Johan Noble, Charlotte Laurent, Aurélie Hummel, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Limoges, Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Rouen, Normandie Université (NU), Centre Hospitalier de la Côte Basque (CHCB), CHU Bordeaux [Bordeaux], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de La Rochelle (CHR), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Laval (CH Laval), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Trousseau [Tours], EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], 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), Hôpital Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Le CHCB, Centre Hospitalier de la Côte Basque, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Renal function, apheresis, 030204 cardiovascular system & hematology, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Refractory, Clinical Research, Internal medicine, minimal change nephrotic syndrome, medicine, Dialysis, focal segmental glomerulosclerosis, Proteinuria, business.industry, nephrotic syndrome, medicine.disease, Transplantation, Apheresis, Nephrology, medicine.symptom, business, Nephrotic syndrome
Abstract

Background Apheresis is the gold standard for idiopathic nephrotic syndrome (INS) relapse after transplantation, but it remains unknown whether such treatment is useful for adults with refractory INS on native kidneys. Methods This retrospective study included patients older than 16 years with biopsy-proven refractory (persistent nephrotic syndrome on corticosteroids plus at least 1 immunosuppressive drug) INS treated by apheresis and followed for at least 3 months. Results Between September 1997 and January 2020, 21 patients (focal segmental glomerulosclerosis: 12, minimal change nephrotic syndrome: 9, men: 67%, median age: 34 years) were identified. At last follow-up (12 months), 7 of 21 patients were in complete or partial remission. Remission was associated with older age (51 vs. 30 years, P = 0.05), lower proteinuria (3.9 vs. 7.3 g/d, P = 0.03), and lower estimated glomerular filtration rate (eGFR) (28.0 vs. 48.5 ml/min per 1.73 m2, P = 0.05) at apheresis. The need for dialysis before apheresis (odds ratio [OR] 22.0 [1.00–524], P = 0.026), age ≥50 years (OR: 22.6 [1.00–524], P = 0.006), a marked (>4.5 g/d) decrease in proteinuria (OR: 9.17 [1.15–73.2], P = 0.041), and a short (, Graphical abstract

Published
2021
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6. Pre-transplant donor-specific HLA antibodies and risk for poor first-year renal transplant outcomes: results from the Swiss Transplant Cohort Study

Author

Wehmeier, Caroline, Amico, Patrizia, Sidler, Daniel, Wirthmüller, Urs, Hadaya, Karine, Ferrari-Lacraz, Sylvie, Golshayan, Déla, Aubert, Vincent, Schnyder, Aurelia, Sunic, Kata, Schachtner, Thomas, Nilsson, Jakob, Schaub, Stefan, Swiss Transplant Cohort Study, Chalandon, Yves, and University of Zurich

Subjects
Graft Rejection, medicine.medical_specialty, Graft failure, Allograft failure, 10255 Clinic for Thoracic Surgery, Population, 610 Medicine & health, Allograft loss, DSA, Rejection, Cohort Studies, HLA Antigens, Isoantibodies, Internal medicine, Allograft survival, Medicine, Humans, Hla antibodies, 10035 Clinic for Nephrology, Prospective Studies, education, Retrospective Studies, ddc:616, Transplantation, education.field_of_study, business.industry, Graft Survival, Donor-specific HLA antibodies, Renal transplantation, Kidney Transplantation, Tissue Donors, body regions, surgical procedures, operative, Renal transplant, 10036 Medical Clinic, Cohort, 10032 Clinic for Oncology and Hematology, 10209 Clinic for Cardiology, business, Switzerland, Cohort study
Abstract

The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre-transplant donor-specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first-year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.73 m2 ) at one year. Two hundred and twenty-one (221/2215; 10%) transplants showed a poor first-year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First-year patient's death was rare (48/2215; 2%). There were no statistically significant differences between DSA-positive and DSA-negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA-positive transplants experienced more frequently rejection episodes, mainly antibody-mediated rejection (both P

Published
2021

7. Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

Author

Cécile Couchoud, Florian Bayer, Carole Ayav, Clémence Béchade, Philippe Brunet, François Chantrel, Luc Frimat, Roula Galland, Maryvonne Hourmant, Emmanuelle Laurain, Thierry Lobbedez, Lucile Mercadal, Olivier Moranne, Abdelhamid Abbassi, Alain Debure, Abdallah Guerraoui, Abdelatif Benmoussa, Abdelaziz Hamani, Abdelaziz Ziane, Abdelhamid Nefti, Abdelkader Hadj, Abderrahim El Amari, Abderrahmane Ghazali, Abo Bakr Abd El Fatah Mohamed, Achour Laradi, Adel Ben Ahmed, Adel Sahar, Adele Pillet, Adeline Lacraz, Adnan Moinat, Afshin Massoumi, Agathe Pardon, Agnes Caillette Beaudoin, Agnes Chapelet Debout, Agnes Mariot, Ahmed Rachi, Aida Afiani, Aime Remy Boula, Al Jalaby, Alain Cremault, Alain Fournier, Alain Jeanson, Alain Lyon, Alain Nony, Alain Robert, Alain Slingeneyer, Alanor Agnes Labatide, Albane Brodin Sartorius, Albert Bensman, Albert Fournier, Alex Ranlin, Alex Vido Sandor, Alexandra Colombo, Alexandra Duhem, Alexandra Stancu, Alexandre Dufay, Alexandre Dumoulin, Alexandre Ebel, Alexandre Klein, Alexandre Martin, Alexandre Mouneimne, Alexandre Seidowsky, Alfio De Martin, Alfredo Zannier, Ali Aizel, Ali Hafi, Ali Zineddine Diddaoui, Alim Heyani, Alina Mocanu, Alina Preda, Aline Hafi, Aline Talaszka, Alyette Duquesne, Amar Amaouche, Amel Ghemmour, Amelie Simon, Amina Skalli, Amine Boukadida, Amr Ekhlas Ragab Eid, Ana Fedorca, Anabelle Baillet, Anais Poyet, Ancuta Bouffandeau Giorgita, Anderson Ratsimbazafy, Andre Pruna, Angel Argiles, Angelo Testa, Ann Karolien Vandooren, Anne Jolivot, Anne Kolko Labadens, Anne Lataste, Anne Maisin, Anne Paris, Anne Sechet, Anne Wuillai, Anne Elisabeth Heng, Anne Gaelle Josse, Anne Helene Querard, Anne Helene Reboux, Anne Laure Adra, Anne Laure Faller, Anne Laure Leclerc, Anne Laure Poitou, Annie Lahoche Manucci, Antoine Jacquet, Antoine Pommereau, Antoine Thierry, Arezki Adem, Arielle Chapelet, Arnaud Del Bello, Arnaud Delezire, Arnaud Garnier, Arnaud Guerard, Arnaud Klisnick, Arnaud Lionet, Arnaud Roccabianca, Arnaud Stolz, Arthur Capdeville, Asma Allal, Assem Alrifai, Assetou Diarrassouba, Assia Djema, Assia Ferhat Carre, Astrid Godron Dubrasquet, Atman Haddj Elmrabet, Audrey Jegado, Aurelia Bertholet Thomas, Aurelie Davourie Salandre, Aurelie Pajot, Aurelien Lorthioir, Aurelien Tiple, Aurore Sury, Ayman Abokasem, Ayman Sarraj, Bachir Henaoui, Baher Chaghouri, Bassem Wehbe, Beatrice Ball, Beatrice Viron, Belkassem Issad, Benedicte Hodemon Corne, Benedicte Janbon, Benjamin Deroure, Benjamin Savenkoff, Benoit Jonon, Benoit Vendrely, Benyakoub Djelaleddine, Bernard Ohry, Bernard Painchart, Bernard Strullu, Bernard Temperville, Bertin Ebikili, Bertrand Hacq, Bertrand Morel, Bilal Aoun, Blanca Muniz, Bouchra Chlih, Brahim Amara, Brice Mayor, Brigitte Gilson, Brigitte Llanas, Brigitte Zins, Bruno Bourgeon, Bruno Coevoet, Bruno Guery, Bruno Legallicier, Bruno Paris, Bruno Ranchin, Bruno Seigneuric, Camelia Ghiciuc Dita, Camelia Prelipcean, Carine Achard Hottelart, Carine Diet, Carlos Frangie, Carlos Vela, Carmina Muresan, Carole Deprele, Caroline Araujo, Caroline Bidault, Caroline Creput, Caroline Delclaux, Caroline Du Halgouet, Caroline Favennec, Caroline Freguin, Caroline Gourraud Vercel, Caroline Mesguen, Caroline Ndomo Obama, Caroline Poitou, Caroline Preissig Dirhold, Caroline Roubiou, Catherine Albert, Catherine Bessin, Catherine De Marion Gaja, Catherine Godart, Catherine Lasseur, Catherine Leocardi, Catherine Lumbroso, Catherine Melander, Catherine Michel, Catherine Quere Maurouard, Catherine Rouannet, Catherine Taddei, Cathy Verove, Cecile Guiraud, Cecile Tafelin, Cecile Turc Baron, Cedric Formet, Cedric Pinier, Celia Lessore De Ste Foy, Celine Granolleras, Chaouki Bennini, Charles Cartou, Charles Chazot, Charlotte Jouzel, Cherif Badid, Christa Roubicek, Christel Viaud, Christelle Verrier, Christian Chuet, Christian Combe, Christian Dabot, Christian Duvic, Christian Emond, Christian Lagarde, Christian Lamotte, Christian Pain, Christiane Mousson, Christie Lorriaux, Christine Beauchamp, Christine Fumeron, Christine Le Gurun, Christine Leroy, Christine Pietrement, Christine Richer, Christophe Bouaka, Christophe Charasse, Christophe Goupy, Christophe Ridel, Cindy Castrale, Cindy Detourne, Clair Francois, Claire Presne, Claire Trivin, Clarissa Von Kotze, Claude Bernard, Claude Bonniol, Claude Desvergnes, Claude Raharivelina, Claudia Nistor, Claudine Gueret, Claudine Lloret, Claudine Saltiel, Clelia Rosati, Clementine Rabate, Corina Stanescu, Corinne Ferrandini, Corinne Guibergia, Corinne Lemoine, Corinne Passeron, Cynthia Kahil, Cyril Garrouste, Cyril Vo Van, Cyrille Jolimoy, Dalila Kesraoui, Damien Jolly, Damien Thibaudin, Dan Teboulle, Daniel Daubresse, Daniel Louvet, Daniel Rasamimanantsoa, Daniel Toledano, Daniela Babici, Daniela David, Daniela Dincu, Danielle Bruno, Delia May, Delphine Haussaire, Delphine Henriet Viprey, Denis Bugnon, Denis Fouque, Denis Morin, Derradji Nour, Diab Mohamed Mahmoud, Diana Istrati Cristescu, Didier Aguilera, Didier Coste, Didier Hamel, Didier Le Chapois, Didier Testou, Dilaver Erbilgin, Djamal Dahmane, Doan Bui Quang, Dominique Bertrand, Dominique Besnier, Dominique Blanchier, Dominique Briffa, Dominique Caux, Dominique Durand, Dominique Fleury, Dominique Guerrot, Dominique Hestin, Dominique Jaubert, Dominique Joly, Dominique Lombart, Dominique Pagniez, Dominique Pierre, Dominique Schohn, Donatien Ikonga, Dorina Visanica, Dorothee Bazin, Edouard Boury, Edouard Maksour, Ekoue Agbonon, Elarbi Harrami, Elena Marcu, Elena Tudorache, Elisabeth Caniot, Elisabeth Semjen, Elisabeth Tomkiewicz, Elise Scheidt, Elke Gaboriau, Elodie Lamouroux, Elsa Guiard, Elsa Martin Passos, Emerson Nsembani, Emilie Fache, Emilie Kalbacher, Emilie Pambrun, Emilie Pincon, Emma Allain Launay, Emmanuel Baron, Emmanuel Dupuis, Emmanuel Villar, Emmanuelle Charlin, Emmanuelle Hecquet, Emmanuelle Kohler, Emmanuelle Rosier, Enrique Figueroa, Eric Azoulay, Eric Canivet, Eric Daugas, Eric Gauthier, Eric Laruelle, Eric Le Guen, Eric Legrand, Eric Moumas, Eric Postec, Eric Prinz, Eric Renaudineau, Estelle Desport, Estelle Ricard Sutra, Etienne Berard, Etienne Ged, Etienne Robin, Eve Vilaine, Evelyne Bargas, Evelyne Mac Namara, François Combarnous, Fatima Yazbeck, Fabien Gerard, Fabien Metivier, Fabien Parazols, Fabien Soulis, Fabrice Garnier, Fadhila Pech Messaoudene, Fadi Haidar, Fanny Boullenger, Fanny Lepeytre, Fanny Leroy, Fares Frejate, Farid Bellahsene, Farid Bellhasene, Farid Saidani, Fatouma Toure, Faycal Kriaa, Fazia Nemmar, Fernando Vetromile, Florence Chalmin, Florence Lucats, Florence Sens, Florence Villemain, Florent Plasse, Fouad Lebhour, Francis Schillinger, Franck Berge, Franck Bourdon, Franck Bridoux, Franck Reynaud, Francois Babinet, Francois Basse, Francois Chantrel, Francois Clair, Francois Coulomb, Francois De Cornelissen, Francois Glowacki, Francois Marchal, Francois Maurice, Francois Nobili, Francois Pourreau, Francois Provot, Francois Roux Amani, Francoise Broux, Francoise Bulte, Francoise Heibel, Francoise Leonetti, Francoise Moussion Schott, Frank Le Roy, Frederic Besson, Frederic Lavainne, Frederic Tollis, Frederique Bocquentin, Frederique Meeus, Frederique Vecina, Friederike Von Ey, Gabriel Balit, Gabriel Choukroun, Gabriel Gruget, Gabriel Huchard, Gabriella Golea, Gabrielle Duneau, Gaelle Lefrancois, Gaelle Pelle, Gaetan Lebrun, Genevieve Dumont, Georges Brillet, Georges Deschenes, Georges Mourad, Georges Stamatakis, Geraldine Cazajous, Geraldine D'ythurbide, Geraldine Robitaille Wiart, Gerard Cardon, Gerard Champion, Gerard Deschodt, Gerard Mangenot, Gerard Motte, Gerard Schortgen, Ghada Boulahia, Ghassan Maakaroun, Ghylene Bourdat Michel, Gilbert Zanetta, Gilles Hufnagel, Gilles Messier, Giorgina Piccoli, Gregoire Couvrat Desvergnes, Guillaume Bobrie, Guillaume Bonnard, Guillaume Clement, Guillaume Jean, Guillaume Queffeulou, Guillaume Seret, Guillaume Vernin, Guy Delavaud, Guy Lambrey, Guy Rostoker, Gwenaelle Poussard, Gwenaelle Roussey Kesler, H. Leon, Habib Aboubekr, Hacene Boulechfar, Hacene Sekhri, Hadia Hebibi, Hadjira Benalia, Hafed Fessi, Hafsabhai Atchia, Haiat Bittar, Hakim Maiza, Hakim Mazouz, Hamid El Ali, Hammouche Bougrida, Hans Van Der Pijl, Hassan Lokmane, Hassane Izzedine, Hassen Adda, Helene De Preneuf, Helene Leray, Helene Philippot, Henri Boulanger, Henri Merault, Henri Renaud, Herve Bonarek, Herve Maheut, Hilaire Nzeyimana, Hocine Mehama, Hocine Zaidi, Hugo Weclawiak, Hugues Flodrops, Huseyin Karaaslan, Ibrahim Haskour, Ihssen Belhadj, Imad Almoubarak, Imad Haddad, Ines Castellano, Ines Ferrandiz, Ioana Daniliuc, Ioana Darie, Ioana Enache, Ionut Prunescu, Irenee Djiconkpode, Irina Shahapuni, Isabelle Bouchoule, Isabelle Devriendt, Isabelle Kazes, Isabelle Kolb, Isabelle Landru, Isabelle Poli, Isabelle Rey, Isabelle Segalen, Isabelle Selcer, Isabelle Vernier, Isabelle Vrillon, Ismahane Guenifi, J. Dominique Gheerbrandt, Jacky Potier, Jacques Becart, Jacques Cledes, Jacques Ducros, Jacques Duvic, Jacques Fourcade, Jacques Gaultier, Jacques Jurine, Jacques Lebleu, Jacques Ollier, Jacques Ibsen Charles, Jamal Yazji, Janette Mansour, Jean Arnautou, Jean Brocard, Jean Carolfi, Jean Montoriol, Jean Baptiste Gouin, Jean Bernard Palcoux, Jean Christophe Bendini, Jean Claude Aldigier, Jean Claude Alphonse, Jean Daniel Delbet, Jean Francois Bonne, Jean Francois Cantin, Jean Francois De Fremont, Jean Francois Dessassis, Jean Francois Subra, Jean Francois Valentin, Jean Francois Verdier, Jean Jacques Dion, Jean Jacques Haultier, Jean Jacques Montseny, Jean Louis Bacri, Jean Louis Bouchet, Jean Luc Mahe, Jean Marc Chalopin, Jean Marc Gabriel, Jean Marc Hurot, Jean Marc Lanau, Jean Marie Batho, Jean Marie Coulibaly, Jean Michel Hardin, Jean Michel Marc, Jean Michel Poux, Jean Michel Rebibou, Jean Michel Tivollier, Jean Noel Ottavioli, Jean Paul Faucon, Jean Paul Imiela, Jean Paul Jaulin, Jean Paul Masselot, Jean Paul Ortiz, Jean Philippe Bourdenx, Jean Philippe Devaux, Jean Philippe Hammelin, Jean Pierre Rivory, Jean Pierre Wauquier, Jean Rene Larue, Jean Rene Mondain, Jean Sebastien Borde, Jean Simon Virot, Jean Yves Bosc, Jedjiga Achiche, Jennifer Parasote, Jeremie Diolez, Jerome Harambat, Jerome Potier, Jerome Sampol, Jihad Mustel, Jean Jacques Lefevre, Jocelyne Maurizi, Joel Gamberoni, Joelle Claudeon, Joelle Terzic, Joffrey Rogol, Johnny Sayegh, Jorge Cardozo, Jose Brasseur, Jose Guiserix, Joseph Barsumau, Julie Albaret, Julie Beaume, Julie Sohier Attias, Julien Dehay, Julien Hogan, Julien Journet, Julien Ott, Juliette Baleynaud, Justine Bacchetta, Justine Faucher, Kamel Yousfi, Karim Dardim, Karine Clabault, Karine Moreau, Kedna Thomas, Khaled Sirajedine, Khalil Chedid, Khalil El Kaeoui, Khalil El Karoui, Khedidja Bouachi, Kheira Hue, Khuzama El Nasser, Kodso Akposso, Kristian Kunz, Krzysztof Bijak, Lilia Kihal, L. Rasoloarijaona, Laid Harbouche, Larbi Bencheikh, Larbie Lamriben, Latifa Hanafi, Laura Braun Parvez, Laure Champion, Laure Croze, Laure Eprinchard, Laure Patrier, Laurence Nicolet, Laurence Vrigneaud, Laurent Duflot, Leandre Mackaya, Leila Chenine, Leon Odry, Lili Taghipour Tamiji, Lilia Antri Bouzar, Liliane Ngango Nga Messi, Lionel Le Mouellic, Lise Mandart, Lise Weis, Lise Marie Pouteau, Lora Georgieva, Lorita Vitanova, Lotfi Chalabi, Luc Delvallez, Luc Fromentin, Luc Marty, Luc Monjot, Luciana Spataru, Lucie Bessenay, Lucie Boissinot, Lucie Wajsbrot, Lucien Rakoff, Ludivine Lebourg, Lydie Perez, Lyliane Lafage, Lynda Azzouz, Madeleine Dumoulin, Messaoud Ouziala, Maan Joseph, Mabrouk Brahimi, Maeva Wong Fat, Magalie Fort, Magued Nakhla, Mahdi Abtahi, Mahen Albadawy, Mahmoud Alouach, Mahmoud Mezghani, Maite Daroux, Maklouf Boukelmoune, Malek Dhib, Malik Touam, Malina Dubau, Mamadou Balde, Man Nguyen Khoa, Manfred Ismer, Manolie Mehdi, Manon Laforet, Marc Bouiller, Marc Eugene, Marc Fila, Marc Hazzan, Marc Kribs, Marc Ladriere, Marc Lebot, Marc Padilla, Marc Souid, Marcel Marraoui, Maren Burbach, Maria Manescu, Maria Eugenia Noguera Gonzalez, Mariana Revenco, Marianne Terrasse, Marie Essi, Marie Alice Macher, Marie Beatrice Nogier, Marie Cecile Cazin, Marie Christine Schweitzer Camoin, Marie Christine Thouret, Marie Claude Hannaert, Marie France Servel, Marie Helene Chabannier, Marie Jeanne Coudert Krier, Marie Noelle Catoliquot, Marie Paule Guillodo, Marie Sophie Gavard, Marie Xaviere Vairon Codaccioni, Marina Rabec, Marine Freist, Marion Gauthier, Marion Lemaire, Marion Mehrenberger, Marion Venot, Marios Pongas, Marlene Beaubrun Diant, Martial Levannier, Martine Bertaux, Mathieu Jablonski, Mathieu Sacquepee, Mathilde Dargelos, Mathilde Lemoine, Mathilde Tamain, Matthieu Monge, Matthieu Reberolle, Maud Cousin, Maud Francois, Maurice Baron, Maxime Hoffmann, Maxime Ingwiller, Maxime Touzot, Mederick Mohajer, Mehadji Maaz, Melanie Hanoy, Melanie Marroc, Melodie Cuny, Menno Van Der Straaten, Mf. Serveaux, Michel Basteri, Michel Fen Chong, Michel Hecht, Michel Massad, Michel Normand, Michel Olmer, Michel Tolani, Michel Tsimaratos, Michele Hemery, Michele Kessler, Miguel Esposito, Milad Shenouda, Mimi Kareche, Mina Khalili, Mirella Diaconita, Mohamad Khair Rifard, Mohamed Aladib, Mohamed Belmouaz, Mohamed Brahim, Mohamed Diouani, Mohamed Fodil Cherif, Mohamed Jamali, Mohamed Maghlaoua, Mohamed Meddeb, Mohamed Ramdane, Mohamed Rifaat, Mohamed Sharifull Islam, Mohamed Adnan Abbade, Mokhtar Amrandi, Mokhtar Chawki, Monica Ciobotaru, Monica Indrieis, Monique Chanas, Monique Hoarau, Monzer Tomeh, Moufida Bellou, Mouloud Bouzernidj, Mounia Ammor, Mounir Guergour, Mountassir Benzakour, Mourad Hachicha, Moussa Coulibaly, Mustafa Smati, Mustapha Al Morabiti, Mustapha Amirou, Myriam Isnard, Myriam Pastural, Myriam Pujo, Nourredine Boumendjel, Nabil Majbri, Nabila Goumri, Nadege Mingat, Nader Bassilios, Nadia Kerkeni, Nadia Sedrati, Nadia Soltani, Nadine Maroun, Nadine Neyrat, Nahn Luang, Najeh El Esper, Naji Ammar, Nasredine Ghali, Nasser Hamdini, Natacha Noel, Natacha Potelune, Nathalie Maisonneuve, Nathalie Pertuiset, Nathalie Raynal, Nathalie Vittoz, Nazim Terki, Nelly Castin, Nestor Nankeu, Nicolas Bouvier, Nicolas Keller, Nicolas Legros, Nicolas Peters, Nicolas Quirin, Nicole Lefrancois, Nicole Monnier, Nicole Rance, Niels Bruckmann, Noel Mertens, Nolwenn Lorcy, Olivia Gilbert, Olivier Coldefy, Olivier Drouineau, Olivier Dunand, Olivier Fritz, Olivier Imhoff, Olivier Kourilsky, Olivier Lavelle, Olivier Papin, Olivier Roques, Ophelie Le Maner, Oussamah Fikri Benbrahim, Pablo Antonio Erina Torres, Pablo Antonio Urena Torres, Paolo Malvezzi, Pascal Bindi, Pascal Cluzel, Pascal Fontanier, Pascal Wheatley, Pascale Depraetre, Pascale Dubosq, Pascale Halin, Pascale Sebahoun, Pascale Siohan, Pascale Testevuide, Patrice Deteix, Patrice Nolen, Patricia Hue, Patricia Lemarchand, Patrick Donnadieu, Patrick Fievet, Patrick Fohrer, Patrick Francais, Patrick Giraud, Patrick Hallonet, Patrick Henri, Patrick Michaut, Patrick Niaudet, Patrick Pauly, Patrick Thomas, Patrik Deleaval, Paul Finielz, Paul Stroumza, Paule Hardy Yverneau, Pauline Caillard, Pedro Palacin, Perrine Aubertin, Philippe Attias, Philippe Chauveau, Philippe Coindre, Philippe Coste, Philippe Dubot, Philippe Fournier, Philippe Hiernaux, Philippe Jousset, Philippe Lan Yue Wah, Philippe Lang, Philippe Le Cacheux, Philippe Martin Dupont, Philippe Michel, Philippe Mirgaine, Philippe Moriniere, Philippe Nicoud, Philippe Rieu, Philippe Rousseau, Philippe Sporer, Philippe Thorel, Philippe Vanhille, Philippe Vigeral, Philippe Zaoui, Pierre Bataille, Pierre Brignon, Pierre Filipozzi, Pierre Housset, Pierre Peyronnet, Pierre Ramperez, Pierre Vautrin, Pierre Alexandre Michel, Pierre Francois Westeel, Pierre Louis Carron, Pierre Yves Durand, Pierrot Parent, Piotr Seniuta, François Kuentz, Rabah Fraoui, Rachel Tetaz, Rachid Amaria, Rachid Bourouma, Rachid Djeffal, Rachida Nebbad, Radia Allal, Radu Dimulescu, Rafaat Boustani, Rafik Mesbah, Raifat Makdassi, Raji Diab, Raluca Puslenghea, Raoul Roura, Rateb Khayat, Raymond Azar, Raymond Frayssinet, Regine Monkam, Rehouni Boulahrouz, Remi Boudet, Renato Demontis, Renaud Gansey, Rene Cuvelier, Renee Schmitt, Reschad Noordally, Reynald Binaut, Rezkallah Latif, Richard Dufresne, Richard Montagnac, Richard Reade, Robert Genin, Robert Novo, Rocsana Fickl, Roger Dufresne, Roger Magnol, Roland Issautier, Romain Mortelette, Ronan Delaval, Ronan Lohro, Roseline M'barga, S. Beau, Clémentine Dupuis, Marie Jacques Vidil, Sabria Hacini, Said Dahmoune, Saliha Lekhal, Salima Ahriz Sakso, Salima Saksi, Salvatore Citarda, Samir Boubenider, Samuel Kassis, Sandra Verhille, Sandrine Genestier, Sandrine Muller, Saoussen Krid, Sarah Richter, Sebastien Delbes, Sebastien Mailliez, Sebastien Veillon, Sébastien Nony, Seddick Benarbia, Severine Beaudreuil, Sidi Ali Benyaghla, Simon Duquennoy, Simona Baluta, Simona Boncila, Sonia Mzoughi, Sonia Ribal, Sophie Acamer, Sophie Chauvet, Sophie Girerd, Sophie Ozenne, Sophie Parahy, Sophie Rubens Duval, Sophie Taque, Soraya Menouer, Soumaya Chargui, Stanislas Bataille, Stephane Barbier, Stephane Billion, Stephane Roueff, Stephane Torner, Stephane Jean Martin, Stephanie Coupel, Sylvie Cloarec, Sylvie Lavaud, Sylvie Leou, T. Chatelet, Tania Onesta, Tassadit Benhabib, Tayeb Bensalem, Theodora Dimulescu, Theophile Sawadogo, Thibault Dolley Hitze, Thierry Baranger, Thierry Boudemaghe, Thierry Hannedouche, Thierry Krummel, Thierry Milcent, Thomas Dervaux, Thomas Guincestre, Thomas Kofman, Thomas Raphael, Thomas Sadreux, Tim Ulinski, Tiphaine Guyon Roger, Tomas Serrato, Tomek Kofman, Tony Wong, Toufik Boubia, Ubald Assogba Gbindoun, Usama Khuzaie, Valerie Caudwell, Valerie Chatelet, Valerie Crougneau, Valerie De Precigout, Valerie Drouillat, Valerie Galantine, Valerie Granveau Hugot, Valerie Leroy, Veronique Boubia, Veronique Falque, Veronique Fournier, Veronique Queron, Veronique Viviani, Victor Gueuttin, Victor Panescu, Victorio Menoyo Calonge, Viet Nguyen, Vincent Allot, Vincent Delattre, Vincent Leduc, Vincent Pradier, Violaine Emal Aglae, Viorica Badulescu, Virginia Molina, Virginie Besson, Virginie Chaigne, Waddah Jaber, Wael Boudi, Wael El Haggan, Wen Qin Guillon, Wided Tabbi Aneni, William Hanf, Wladimir Kohn, Xavier Bellenfant, Xavier Moreau Gaudry, Yahsou Delmas, Yannick Knefati, Yannick Saingra, Yannick Tirolien, Youssef Mann, Yvan Brunak, Yves Dimitrov, Yves Doussy, Yves Tanter, Zaid Benabid, Zaara Soltani, Zacharia Boukerroucha, Zafer Takla, Zana Ramanantsialonina, Zara Dickson, Zead Tubail, Zoe Koochaki Pour, Zohra Boukhalfa, Zohra Jacquot, Agence de la biomédecine [Saint-Denis la Plaine], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Caen Normandie (UNICAEN), Normandie Université (NU), CALYDIAL Vienne, Partenaires INRAE, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Armand Trousseau [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM), Service de diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU 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 de Diabétologie [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodialysis, Home, Disease, MESH: COVID-19 / therapy, registry, Ambulatory Care Facilities, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Aged, 80 and over, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, 80 and over, Prevalence, covid, dialysis, epidemiology, mortality, Aged, Aged, 80 and over, COVID-19, Case-Control Studies, Critical Care, Female, France, Humans, Incidence, Middle Aged, Patient Acuity, Protective Factors, Registries, Renal Dialysis, SARS-CoV-2, Sex Factors, Hypoalbuminemia, MESH: France / epidemiology, education.field_of_study, Incidence (epidemiology), 3. Good health, MESH: COVID-19 / epidemiology, Nephrology, Hemodialysis, medicine.medical_specialty, Population, Lower risk, Article, 03 medical and health sciences, MESH: Sex Factors, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Renal Dialysis / statistics & numerical data, education, Dialysis, Vascular disease, business.industry, medicine.disease, Former Smoker, MESH: Critical Care / statistics & numerical data, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Home, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Hemodialysis, Home / statistics & numerical data
Abstract

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

Published
2020
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8. Preformed and de novo DSA are associated with T-cell-mediated rejection in pediatric liver transplant recipients requiring clinically indicated liver biopsy

Author

Jean Villard, Dominique Charles Belli, Barbara E. Wildhaber, Laëtitia Marie Petit, Vladimir L. Cousin, Anne-Laure Rougemont, Dominique Schluckebier, Valérie A. McLin, and Sylvie Ferrari-Lacraz

Subjects
Graft Rejection, Male, Biopsy, T-Lymphocytes, 030232 urology & nephrology, 030230 surgery, ddc:616.07, Gastroenterology, 0302 clinical medicine, T-cell, HLA Antigens, Isoantibodies, Medicine, Hla antibodies, Child, Donor-specific antibody, ddc:616, ddc:618, medicine.diagnostic_test, Mean fluorescence intensity, Graft survival, medicine.anatomical_structure, Liver, Child, Preschool, Liver biopsy, Female, medicine.medical_specialty, Mediated rejection, Adolescent, T cell, 03 medical and health sciences, Chart review, Internal medicine, Humans, In patient, Retrospective Studies, Transplantation, business.industry, Infant, Newborn, Infant, Liver Transplantation, body regions, Pediatrics, Perinatology and Child Health, business, Banff criteria, Biomarkers, Class II Antigens, Follow-Up Studies
Abstract

Despite growing interest about the impact of donor-specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single-center chart review of children (0-16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient- and donor-characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow-up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty-eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6-7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS.

Published
2020

9. Blood Purif

Author

Christine Germain, Philippe Chauveau, Carole Deprele, Christian Combe, Cécile Contin-Bordes, Valérie de Précigout, A Pommereau, Bruno Seigneuric, Cécile Courivaud, Antoine Bénard, Marine Douillet, Benjamin Taton, Adeline Lacraz, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Polymers, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Renal Dialysis, Internal medicine, medicine, MORPH3Eus, Humans, Polymethyl Methacrylate, Hepatitis B Vaccines, Polysulfone, Sulfones, Seroconversion, CD40 Antigens, Hepatitis B Antibodies, Dialysis, Aged, Aged, 80 and over, biology, business.industry, Membranes, Artificial, Hematology, General Medicine, Hepatitis B, Middle Aged, medicine.disease, 3. Good health, Vaccination, Titer, Treatment Outcome, chemistry, Nephrology, biology.protein, Kidney Failure, Chronic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Antibody, business
Abstract

Background: An altered immune response and decreased vaccine response are observed in patients with chronic renal failure. A preliminary study of 15 non-immunised patients, despite appropriate previous hepatitis B vaccination, showed a 60% seroconversion rate after 3 months of dialysis with a polymethylmethacrylate (PMMA) membrane. This response was associated with circulating soluble CD40 (CD40s) decrease, a natural inhibitor of the humoral immune response. The aim of the study is to confirm these results in a randomised study. Methods: We conducted a multicentre randomised intention-to-treat superiority clinical trial comparing polysulfone and a PMMA membrane in 2 parallel patient groups. The primary end point was the vaccine response rate, as defined by an anti-HBs antibodies titre of >10 IU/L, 1 month after the last vaccination with a double dose of Engerix B20®, performed at weeks 12, 16, 20, and 36. Results: Twenty-five patients were randomised and included in an intention-to-treat analysis. They were dialysed on polysulfone (n = 11) or PMMA (n = 14) for 40 weeks. Fifty percent of the PMMA patients versus 54.5% of the polysulfone patients achieved seroconversion (p = 1.00). The median anti-HBs antibody titre in responders at week 40 was 496 (92–750) versus 395 (43–572) UI/mL for PMMA and polysulfone, respectively (p = 0.46). The median CD40s titre at week 12 was 306 (193–448) versus 491 (281–515) pg/mL (p = 0.21). The CD40s median variation between week 0 and week 12 was 5 (–105 to 90) versus 64 (–63 to 123) pg/mL (p = 0.55). The CD40s level at week 12 in non-responders was slightly inferior to that of the responders: median 193 (168–331) versus 413 (281–512) pg/mL (p = 0.08). Conclusion: We did not observe a better vaccine response with the PMMA membrane compared to high-flux polysulfone. The PMMA membrane did not decrease the CD40s more than the polysulfone membrane probably because the titre was previously low in the 2 groups.

Published
2019
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10. High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation

Author

Urs Schanz, Jean Villard, Sylvie Ferrari-Lacraz, Tayfun Güngör, Alicia Sanchez-Mazas, Stéphane Buhler, Yves Chalandon, Grazia Nicoloso, Dominik Heim, Jose Manuel Nunes, Jakob Passweg, Jörg Halter, Helen Baldomero, Jean-Marie Tiercy, Gayathri Nair, Stravroula Massouridi-Levrat, University of Zurich, and Buhler, Stéphane

Subjects
Oncology, medicine.medical_specialty, Bone marrow transplantation, 2747 Transplantation, medicine.medical_treatment, 2720 Hematology, 610 Medicine & health, Hematopoietic stem cell transplantation, Human leukocyte antigen, Logistic regression, Article, 03 medical and health sciences, 0302 clinical medicine, ddc:590, Polymorphism (computer science), Transplant immunology, Internal medicine, medicine, ddc:616, Transplantation, business.industry, Haplotype, Correction, Hematology, medicine.disease, Graft-versus-host disease, medicine.anatomical_structure, 10036 Medical Clinic, 030220 oncology & carcinogenesis, Cohort, 10032 Clinic for Oncology and Hematology, Bone marrow, business, 030215 immunology
Abstract

HLA matching is a critical factor for successful allogeneic hematopoietic stem cell transplantation. For unrelated donor searches, matching is usually based on high-resolution typing at five HLA loci, looking for a 10/10 match. Some studies have proposed that further matching at the haplotype level could be beneficial for clinical outcome. In this study, we determined the phased haplotypes of 291 patients using family members and segregation analysis. The sum of ranks of the haplotypes carried by patients was used as a surrogate predictor of a successful unrelated donor search. The putative impact of haplotypes was then analyzed in a cohort of 211 recipients transplanted with 10/10 matched unrelated donors. A logistic regression analysis showed a highly significant effect of the haplotypes in the outcome of a search, but we did not find any significant effect on overall survival, graft versus host disease or relapse/progression following HSCT. This study provides useful data for the optimization of unrelated bone marrow donor searches, but does not confirm previous reports that matching at the haplotype level has a clinical impact following HSCT. Due to the extreme polymorphism of HLA genes, further studies are warranted to better understand the many factors at play.

Published
2018

11. Defective functional β-cell mass and Type 2 diabetes in the Goto-Kakizaki rat model

Author

Gregory Lacraz, Françoise Homo-Delarche, Bernard Portha, Jamileh Movassat, M-H Giroix, and M. Dolz

Subjects
endocrine system, geography, medicine.medical_specialty, geography.geographical_feature_category, Endocrinology, Diabetes and Metabolism, Type 2 Diabetes Mellitus, Inflammation, Type 2 diabetes, Biology, Islet, medicine.disease, biology.organism_classification, medicine.disease_cause, Neogenesis, medicine.anatomical_structure, Endocrinology, Internal medicine, Immunology, medicine, Epigenetics, medicine.symptom, Pancreas, Oxidative stress
Abstract

Increasing evidence indicates that decreased functional β-cell mass is the hallmark of Type 2 diabetes mellitus. Therefore, the debate focuses on the possible mechanisms responsible for abnormal islet microenvironment, decreased β-cell number, impaired β-cell function and their multifactorial etiologies. The information available on the Goto-Kakizaki/Par rat line, one of the best characterized animal models of spontaneous Type 2 diabetes mellitus, are reviewed in such a perspective. We propose that the defective β-cell mass and function in the Goto-Kakizaki/Par model reflect the complex interactions of multiple pathogenic players, including several independent loci containing genes responsible for some diabetic traits (but not decreased β-cell mass), gestational metabolic impairment inducing an epigenetic programming of the pancreas (decreased β-cell neogenesis), which is transmitted to the next generation, and loss of β-cell differentiation due to chronic exposure to hyperglycemia, inflammatory mediators, oxidative stress and perturbed islet microarchitecture.

Published
2018

12. Prevalence of atheromatous and non-atheromatous cardiovascular disease by age in chronic kidney disease

Author

Villain, Cédric, Metzger, Marie, Combe, Christian, Fouque, Denis, Frimat, Luc, Jacquelinet, Christian, Laville, Maurice, Briançon, Serge, Klein, Julie, Schanstra, Joost, Robinson, Bruce, Mansencal, Nicolas, Stengel, Bénédicte, Massy, Ziad, Hannedouche, T, Moulin, B., Klein, A, Bourdenx, J, Keller, A, Delclaux, C, Vendrely, B., Deroure, B, Lacraz, A, Lobbedez, T., Landru, I, Lang, P., Belenfant, X., Thervet, E., Urena, P, Delahousse, M, Vela, C, Essig, M, Sekhri, H, Smati, M, Jamali, M, Hacq, B, Panescu, V, Bellou, M, Kamar, Nassim, Noël, C., Glowacki, F., Maisonneuve, N, Azar, R., Hoffmann, M, Hourmant, M., Testa, A, Besnier, D., Choukroun, Gabriel, Lambrey, G, Burtey, Stéphane, Lebrun, G, Magnant, E, Juillard, L., Chazot, C, Zaoui, P, Kuentz, F, Hôpital Ambroise Paré [AP-HP], 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) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Agence de la biomédecine [Saint-Denis la Plaine], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Arbor Research Collaborative for Health, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], CKD REIN, and 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)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, Coronary artery disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Prevalence, medicine, Humans, Prospective Studies, cardiovascular diseases, Renal Insufficiency, Chronic, Aged, Aged, 80 and over, Transplantation, business.industry, valvular heart disease, Age Factors, Odds ratio, Middle Aged, medicine.disease, Plaque, Atherosclerotic, 3. Good health, Cardiovascular Diseases, Nephrology, Heart failure, Cohort, Albuminuria, Cardiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, business, Glomerular Filtration Rate, Kidney disease
Abstract

Background Although chronic kidney disease (CKD) and age are major risk factors for cardiovascular disease (CVD), little is known about the relative proportions of atheromatous and non-atheromatous CVD by age in CKD patients. Methods We used baseline data from the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort of 3033 patients (65% men) with CKD Stages 3–4 to study crude and adjusted associations between age, the estimated glomerular filtration rate (eGFR), atheromatous CVD (coronary artery disease, peripheral artery disease and stroke) and non-atheromatous CVD (heart failure, cardiac arrhythmia and valvular heart disease). Results Mean age was 66.8 and mean Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR was 32.9 mL/min/1.73 m2. In the Conclusions In this large cohort of CKD patients, both atheromatous and non-atheromatous CVD were highly prevalent and more frequent in older patients. In a given age group, the prevalence of atheromatous and non-atheromatous CVD was similar (except for a greater prevalence of non-atheromatous CVD after 85).

Published
2018
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13. Factors associated with immune hemolytic anemia after pediatric liver transplantation

Author

Jean Villard, Sophie Waldvogel, Valérie A. McLin, Nathalie Rock, Sylvie Ferrari-Lacraz, and Marc Ansari

Subjects
Hemolytic anemia, Male, medicine.medical_treatment, Evans syndrome, Autoimmunity, 030230 surgery, Liver transplantation, Pediatrics, Immune Hemolytic Anemia, 0302 clinical medicine, Postoperative Complications, Risk Factors, Outcome Assessment, Health Care, Autoimmune/diagnosis/epidemiology/etiology, Child, ddc:616, Univariate analysis, ddc:618, Incidence (epidemiology), Incidence, Postoperative Complications/diagnosis/epidemiology/etiology, Anemia, Child, Preschool, Female, medicine.medical_specialty, 03 medical and health sciences, Outcome Assessment (Health Care), Internal medicine, parasitic diseases, medicine, Humans, Preschool, Retrospective Studies, Transplantation, business.industry, Infant, medicine.disease, Liver Transplantation, body regions, Pediatrics, Perinatology and Child Health, Anemia, Hemolytic, Autoimmune, business, Complication, Hemolytic, 030215 immunology, Autoimmune, Follow-Up Studies
Abstract

Immune-mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single-center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune-mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL-1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV-negative recipients who received an organ from a CMV-positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post-LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV-negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL-1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.

Published
2018

14. Clinical and histological evolution after de novo donor-specific anti-human leukocyte antigen antibodies: A single centre retrospective study

Author

Jean Villard, Olivia Seyde, Karine Hadaya, Pierre-Yves Martin, Sylvie Ferrari-Lacraz, Yassine Bouatou, Solange Moll, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, Graduate School, and AII - Infectious diseases

Subjects
Nephrology, Graft Rejection, Male, medicine.medical_treatment, Biopsy, 030232 urology & nephrology, 030230 surgery, ddc:616.07, Kidney, lcsh:RC870-923, Gastroenterology, 0302 clinical medicine, HLA Antigens, Risk Factors, Kidney transplantation, Outcome, ddc:616, medicine.diagnostic_test, HLA-antibody post-transplantation, Graft Survival, Middle Aged, Tissue Donors, de novo DSA, Rituximab, Female, medicine.drug, Research Article, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Renal function, Antibodies, 03 medical and health sciences, Immunocompromised Host, Internal medicine, medicine, Humans, Retrospective Studies, business.industry, Renal pathology, Retrospective cohort study, Transplant glomerulopathy, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, Kidney Transplantation, body regions, Plasmapheresis, business
Abstract

Background Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) can be preformed or de novo (dn). Strategies to manage preformed DSA are well described, but data on the management and outcomes of dnDSA are lacking. Methods We performed a retrospective analysis of data from a single centre of the management and outcomes of 22 patients in whom a dnDSA was identified with contemporary and follow up biopsies. Results Evolution from baseline to follow up revealed a statistically significant loss of kidney function (estimated glomerular filtration rate: 45.9 ± 16.7 versus 37.4 ± 13.8 ml/min/1.73 m2; p = 0.005) and increase in the proportion of patients with transplant glomerulopathy (percentage with cg lesion ≥1: 27.2% vs. 45.4%; p = 0.04). Nine patients were not treated at the time of dnDSA identification, and 13 patients received various drug combinations (e.g., corticosteroids, plasmapheresis, thymoglobulins and/or rituximab). No significant pathological changes were observed for the various treatment combinations. Conclusion Our retrospective analysis of a small sample suggests that dnDSA should be considered a risk factor for the loss of kidney function independent of the baseline biopsy, and multidisciplinary evaluations of the transplant patient are a necessary requirement. Further confirmation in a multicentre prospective trial is required.

Published
2018

15. Clostridium difficile infection is associated with graft loss in solid organ transplant recipients

Author

Cusini, A, Béguelin, C, Stampf, S, Boggian, K, Garzoni, C, Koller, M, Manuel, O, Meylan, P, Mueller, NJ, Hirsch, HH, Weisser, M, Berger, C, van Delden, C, Achermann, R, Amico, P, Aubert, JD, Banz, V, Beldi, G, Benden, C, Binet, I, Bochud, PY, Bucher, H, Bühler, L, Carell, T, Catana, E, Chalandon, Y, de Geest, S, de Rougemont, O, Dickenmann, M, Duchosal, M, Elkrief, L, Fehr, T, Ferrari-Lacraz, S, Gasche Soccal, P, Gaudet, C, Giostra, E, Golshayan, D, Hadaya, K, Halter, J, Heim, D, Hess, C, Hillinger, S, Hofbauer, G, Huynh-Do, U, Immer, F, Klaghofer, R, Laesser, B, Lehmann, R, Lovis, C, Marti, HP, Martin, PY, Mohacsi, P, Morel, P, Mueller, U, Mueller-McKenna, H, Müller, A, Müller, T, Müllhaupt, B, Nadal, D, Pascual, M, Passweg, J, Rick, J, Roosnek, E, Rosselet, A, Rothlin, S, Ruschitzka, F, Schanz, U, Schaub, S, Schnyder, A, Seiler, C, Steiger, J, Stirnimann, G, Toso, C, Venetz, JP, Villard, J, Wick, M, Wilhelm, M, Yerly, P, Gasche-Soccal, Paola Marina Alessandra, University of Zurich, and van Delden, C

Subjects
Graft Rejection, Male, genetic structures, 2747 Transplantation, 10265 Clinic for Endocrinology and Diabetology, 030230 surgery, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Postoperative Complications, Risk Factors, Medicine, 2736 Pharmacology (medical), Immunology and Allergy, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, 610 Medicine & health, Prospective cohort study, ddc:616, Incidence, Hazard ratio, Graft Survival, Clostridium difficile, Middle Aged, Prognosis, Anti-Bacterial Agents, Diarrhea, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, Female, medicine.symptom, 10178 Clinic for Pneumology, Switzerland, Cohort study, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, Humans, Transplantation, business.industry, Clostridioides difficile, Case-control study, Organ Transplantation, Confidence interval, Transplant Recipients, 10036 Medical Clinic, Case-Control Studies, Clostridium Infections, business, Follow-Up Studies
Abstract

© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P =.02). These findings may help to improve the management of SOT recipients. ispartof: American Journal of Transplantation vol:18 issue:7 pages:1745-1754 ispartof: location:United States status: published

Published
2017

16. Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab

Author

Benjamin Clouzeau, Armel Reffet, Cécile Bordes, Hiba Bachir, P. Rolland, Christian Combe, Benoît Vendrely, Sophie Skopinski, Adeline Lacraz, Sébastien Helou, Brigitte Llanas, Hoang-Nam Bui, Didier Gruson, and Yahsou Delmas

Subjects
Adult, Diarrhea, Male, medicine.medical_specialty, Thrombotic microangiopathy, Renal function, Context (language use), Antibodies, Monoclonal, Humanized, Kidney, Gastroenterology, Disease Outbreaks, CLINICAL SCIENCE, chemistry.chemical_compound, haemolytic uraemic syndrome, Internal medicine, complement inhibition, Escherichia coli, medicine, Humans, Adverse effect, Escherichia coli Infections, Transplantation, Creatinine, Shiga-Toxigenic Escherichia coli, business.industry, Acute kidney injury, Middle Aged, Acute Kidney Injury, Eculizumab, medicine.disease, thrombotic microangiopathy, Treatment Outcome, chemistry, Nephrology, Child, Preschool, Hemolytic-Uremic Syndrome, Immunology, Female, eculizumab, France, medicine.symptom, business, medicine.drug
Abstract

Background An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab. Methods The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab. Results Among 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3-12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14-93) G/L; haemoglobin 6.6 (range 5-10.7) g/dL; LDH 1520 (range 510-2568) IU/L; creatinine 152 (range 48-797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0-4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab. Conclusions Early treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.

Published
2013
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17. Structural Basis of Bone Fragility in Young Subjects with Inflammatory Bowel Disease: A High-resolution pQCT Study of the SWISS IBD Cohort (SIBDC)

Author

Jessica Pepe, Serge Ferrari, Sylvie Ferrari-Lacraz, René Rizzoli, Pascal Juillerat, Osman Ratib, Sophie Zawadynski, François Herrmann, Thierry Chevalley, Pierre Michetti, and Dominique Charles Belli

Subjects
Male, Bone density, Bone fragility, Inflammatory bowel disease, Gastroenterology, Fractures, Bone, 0302 clinical medicine, Absorptiometry, Photon, Adrenal Cortex Hormones, Bone Density, Immunology and Allergy, Prospective Studies, Quantitative computed tomography, Prospective cohort study, Child, 610 Medicine & health, ddc:616, Bone mineral, ddc:618, medicine.diagnostic_test, Resolution (electron density), medicine.anatomical_structure, Cohort, 030211 gastroenterology & hepatology, Female, Disease Susceptibility, Switzerland, Peak bone mass, Adult, musculoskeletal diseases, medicine.medical_specialty, Adolescent, Urology, 030209 endocrinology & metabolism, ddc:616.0757, Bone and Bones, 03 medical and health sciences, Young Adult, IBD, bone, osteoporosis, Internal medicine, medicine, Humans, Tibia, business.industry, medicine.disease, Inflammatory Bowel Diseases, Surgery, Bone Diseases, Metabolic, Logistic Models, Case-Control Studies, ddc:618.97, Multivariate Analysis, Cortical bone, business, Tomography, X-Ray Computed
Abstract

BACKGROUND The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown. METHODS One hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures. RESULTS Clinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity. CONCLUSIONS Young patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.

Published
2017
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18. Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease

Author

Sheela Ramanathan, Yi-Guang Chen, Alfredo Menendez, Gregory Lacraz, Farnaz Ghobadi, Yuneivy Cepero-Donates, Marian Mayhue, Subburaj Ilangumaran, Sakina Orkhis, Volatiana Rakotoarivelo, and Marek Rola-Pleszczynski

Subjects
0301 basic medicine, medicine.medical_specialty, Chemokine, Immunology, Inflammation, CD8-Positive T-Lymphocytes, CCL2, Biochemistry, CCL5, 03 medical and health sciences, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, NAFLD, medicine, Journal Article, Animals, CXCL10, Immunology and Allergy, Liver X receptor, Molecular Biology, Mice, Knockout, Interleukin-15, biology, Receptors, Interleukin-15, Fatty liver, Hematology, medicine.disease, Dietary Fats, 3. Good health, Killer Cells, Natural, 030104 developmental biology, Endocrinology, Liver, Interleukin 15, 030220 oncology & carcinogenesis, Hepatocytes, biology.protein, Chemokines, medicine.symptom, Immunologic Memory
Abstract

Interleukin-15 (IL-15) is essential for the homeostasis of lymphoid cells particularly memory CD8(+) T cells and NK cells. These cells are abundant in the liver, and are implicated in obesity-associated pathogenic processes. Here we characterized obesity-associated metabolic and cellular changes in the liver of mice lacking IL-15 or IL-15Rα. High fat diet-induced accumulation of lipids was diminished in the livers of mice deficient for IL-15 or IL-15Rα. Expression of enzymes involved in the transport of lipids in the liver showed modest differences. More strikingly, the liver tissues of IL15-KO and IL15Rα-KO mice showed decreased expression of chemokines CCl2, CCL5 and CXCL10 and reduced infiltration of mononuclear cells. In vitro, IL-15 stimulation induced chemokine gene expression in wildtype hepatocytes, but not in IL15Rα-deficient hepatocytes. Our results show that IL-15 is implicated in the high fat diet-induced lipid accumulation and inflammation in the liver, leading to fatty liver disease.

Published
2016

19. Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto–Kakizaki (GK) rat

Author

S. Calderari, Nadim Kassis, Christophe Noll, Micheline Kergoat, M. Cornut, M.H. Giroix, Fabien Schmidlin, Jean-Louis Paul, Jean-Claude Irminger, Nathalie Janel, Josiane Coulaud, Gregory Lacraz, Philippe A. Halban, Françoise Homo-Delarche, Jan A. Ehses, Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of British Columbia (UBC), Merck Serono, Merck & Co. Inc, Laboratoire de Biochimie, 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-Sud - Paris 11 (UP11), ProdInra, Migration, and Université de Genève = University of Geneva (UNIGE)

Subjects
Blood Glucose, Male, Aging, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Diabetic Angiopathies/physiopathology, Type 2 diabetes, Hypercholesterolemia/physiopathology, 0302 clinical medicine, Pregnancy, Insulin-Secreting Cells, Insulin, ddc:576.5, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, geography.geographical_feature_category, Neovascularization, Pathologic, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Islet, 3. Good health, fetus, Islets of Langerhans/blood supply, Insulin-Secreting Cells/pathology, Disease Progression, Female, Beta cell, medicine.symptom, endocrine system, medicine.medical_specialty, dyslipidaemia, Hypercholesterolemia, 030209 endocrinology & metabolism, Inflammation, Biology, liver, programming, Endothelial activation, Islets of Langerhans, 03 medical and health sciences, Predictive Value of Tests, goto-kakizaki, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Genetic predisposition, Animals, Rats, Wistar, Diabetes Mellitus, Type 2/physiopathology, 030304 developmental biology, type 2 diabete, geography, Blood Glucose/metabolism, beta cell mass, Microangiopathy, cholesterol, Rats, Inbred Strains, Neovascularization, Pathologic/physiopathology, medicine.disease, Rats, Aging/metabolism, Disease Models, Animal, Endocrinology, Animals, Newborn, Diabetes Mellitus, Type 2, islet microangiopathy, Insulin/blood, Diabetic Angiopathies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; The adult non-obese Goto–Kakizaki (GK) rat model of type 2 diabetes, particularly females, carries in addition to hyperglycaemia a genetic predisposition towards dyslipidaemia, including hypercholesterolaemia. As cholesterol-induced atherosclerosis may be programmed in utero, we looked for signs of perinatal lipid alterations and islet microangiopathy. We hypothesise that such alterations contribute towards defective pancreas/islet vascularisation that might, in turn, lead to decreased beta cell mass. Accordingly, we also evaluated islet inflammation and endothelial activation in both prediabetic and diabetic animals. Blood, liver and pancreas were collected from embryonic day (E)21 fetuses, 7-day-old prediabetic neonates and 2.5-month-old diabetic GK rats and Wistar controls for analysis/quantification of: (1) systemic variables, particularly lipids; (2) cholesterol-linked hepatic enzyme mRNA expression and/or activity; (3) pancreas (fetuses) or collagenase-isolated islet (neonates/adults) gene expression using Oligo GEArray microarrays targeted at rat endothelium, cardiovascular disease biomarkers and angiogenesis, and/or RT-PCR; and (4) pancreas endothelial immunochemistry: nestin (fetuses) or von Willebrand factor (neonates). Systemic and hepatic cholesterol anomalies already exist in GK fetuses and neonates. Hyperglycaemic GK fetuses exhibit a similar percentage decrease in total pancreas and islet vascularisation and beta cell mass. Normoglycaemic GK neonates show systemic inflammation, signs of islet pre-microangiopathy, disturbed angiogenesis, collapsed vascularisation and altered pancreas development. Concomitantly, GK neonates exhibit elevated defence mechanisms. These data suggest an autoinflammatory disease, triggered by in utero programming of cholesterol-induced islet microangiopathy interacting with chronic hyperglycaemia in GK rats. During the perinatal period, GK rats show also a marked deficient islet vascularisation in conjunction with decreased beta cell mass.

Published
2011
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20. Diabetic GK/Par rat β-cells are spontaneously protected against H2O2-triggered apoptosis. A cAMP-dependent adaptive response

Author

Bernard Portha, Gregory Lacraz, Nadim Kassis, Jamileh Movassat, and Florence Figeac

Subjects
Male, medicine.medical_specialty, Programmed cell death, Physiology, Endocrinology, Diabetes and Metabolism, Population, Apoptosis, Type 2 diabetes, Biology, Rats, Mutant Strains, Proto-Oncogene Proteins c-myc, chemistry.chemical_compound, Insulin-Secreting Cells, Physiology (medical), Diabetes mellitus, Internal medicine, Cyclic AMP, medicine, Animals, Cyclin D1, Cyclic adenosine monophosphate, RNA, Messenger, Rats, Wistar, education, Cells, Cultured, chemistry.chemical_classification, Reactive oxygen species, education.field_of_study, Hydrogen Peroxide, Hypoxia-Inducible Factor 1, alpha Subunit, Oxidants, medicine.disease, Adaptation, Physiological, Adenosine, Rats, Disease Models, Animal, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Apoptosis Regulatory Proteins, Reactive Oxygen Species, Cell Division, Heme Oxygenase-1, medicine.drug
Abstract

The alteration of the β-cell population in the Goto-Kakizaki rat (GK/Par line), a model of spontaneous type 2 diabetes, has been ascribed to significantly decreased β-cell replication and neogenesis, while β-cell apoptosis is surprisingly not enhanced and remains in the normal range. To gain insight into the mechanisms by which those β-cells are protected from death, we studied ex vivo the apoptotic activity and the expression of a large set of pro/antiapoptotic and pro/antioxidant genes in GK/Par islet cells. This was done in vitro in freshly isolated islets as well as in response to culture conditions and calibrated reactive oxygen species (ROS) exposure (i.e., H2O2). We also investigated the intracellular mechanisms of the diabetic β-cell response to ROS, the role if any of the intracellular cAMP metabolism, and finally the kinetic of ROS response, taking advantage of the GK/Par rat normoglycemia until weaning. Our results show that the peculiar GK/Par β-cell phenotype was correlated with an increased expression of a large panel of antioxidant genes as well as pro/antiapoptotic genes. We demonstrate that such combination confers resistance to cytotoxic H2O2exposure in vitro, raising the possibility that at least some of the activated stress/defense genes have protective effects against H2O2-triggered β-cell death. We also present some evidence that the GK/Par β-cell resistance to H2O2is at least partly cAMP dependent. Finally, we show that such a phenotype is not innate but is spontaneously acquired after diabetes onset as the result of an adaptive response to the diabetic environment.

Published
2010
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21. Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues

Author

Subburaj Ilangumaran, Mathieu Vernier, André C. Carpentier, Marie-France Langlois, Sébastien M. Labbé, Denis Richard, Christophe Noll, Adel Schwertani, Marian Mayhue, Gregory Lacraz, Sheela Ramanathan, Julie Fradette, Marek Rola-Pleszczynski, Guillaume Grenier, Alfredo Menendez, Volatiana Rakotoarivelo, Gerardo Ferbeyre, Jana Stankova, and Université de Sherbrooke (UdeS)

Subjects
0301 basic medicine, Physiology, [SDV]Life Sciences [q-bio], Adipose tissue, lcsh:Medicine, Pathology and Laboratory Medicine, Biochemistry, Animal Cells, Immune Physiology, Brown adipose tissue, Adipocytes, Medicine and Health Sciences, lcsh:Science, Immune Response, ComputingMilieux_MISCELLANEOUS, Connective Tissue Cells, Innate Immune System, Multidisciplinary, Thermogenesis, Cell Differentiation, Lipids, medicine.anatomical_structure, Adipose Tissue, Physiological Parameters, Connective Tissue, Interleukin 15, Brown Adipose Tissue, Cytokines, Cellular Types, Anatomy, medicine.symptom, Stem cell, Research Article, medicine.medical_specialty, Immunology, Inflammation, Biology, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Internal medicine, Adipocyte Differentiation, medicine, Obesity, Body Weight, lcsh:R, Biology and Life Sciences, Skeletal muscle, Cell Biology, Molecular Development, Biological Tissue, 030104 developmental biology, Endocrinology, Immune System, lcsh:Q, Physiological Processes, Weight gain, Developmental Biology
Abstract

Objective IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. Methods Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. Results Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues. Conclusions Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.

Published
2016
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22. Lack of starvation-induced activation of AMP-activated protein kinase in the hypothalamus of the Lou/C rats resistant to obesity

Author

G Lacraz, Louis Hue, Bruno Guigas, I De Potter, Roland Favier, Nellie Taleux, Xavier Leverve, C Deransart, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Grenoble Institut des Neurosciences (GIN), Collaboration, and Deransart, Colin

Subjects
Leptin, Male, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), AMP-Activated Protein Kinases, MESH: Multienzyme Complexes, MESH: Neuropeptides, MESH: Eating, Eating, 0302 clinical medicine, AMP-activated protein kinase, MESH: Obesity, MESH: Animals, MESH: AMP-Activated Protein Kinases, Phosphorylation, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, biology, Chemistry, digestive, oral, and skin physiology, MESH: Adiponectin, MESH: Rats, Inbred Strains, Ghrelin, Hypothalamus, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adiponectin, Disease Susceptibility, medicine.drug, MESH: Enzyme Activation, medicine.medical_specialty, MESH: Rats, Blotting, Western, MESH: Disease Susceptibility, MESH: Ghrelin, Neuropeptide, MESH: Starvation, Protein Serine-Threonine Kinases, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, Species Specificity, Multienzyme Complexes, Internal medicine, Orexigenic, medicine, Animals, MESH: Species Specificity, MESH: Blotting, Western, Obesity, RNA, Messenger, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, MESH: RNA, Messenger, 030304 developmental biology, Leptin receptor, MESH: Phosphorylation, Neuropeptides, AMPK, Rats, Inbred Strains, MESH: Rats, Wistar, MESH: Leptin, MESH: Hypothalamus, MESH: Male, Rats, Enzyme Activation, Endocrinology, Starvation, biology.protein, 030217 neurology & neurosurgery
Abstract

International audience; OBJECTIVE: The AMP-activated protein kinase (AMPK) is involved in the control of food intake by the hypothalamus. The aim of this work was to investigate if modification of hypothalamic AMPK regulation could be related to the spontaneous food restriction of Lou/C rats, a strain resistant to obesity exhibiting a 40% reduction in caloric intake compared with their lean Wistar counterparts. DESIGN: Three-month-old male Lou/C rats were compared with age-matched male Wistar rats in both fed ad libitum and 24-h food deprivation state. MEASUREMENTS AND RESULTS: We first confirmed that starvation activated both isoforms of AMPK catalytic alpha subunits and enhanced the phosphorylation state of its downstream targets acetyl-CoA carboxylase and elongation factor 2 in the hypothalamus of Wistar rats. These changes were not observed in the hypothalamus of Lou/C rats. Interestingly, the starvation-induced changes in hypothalamic mRNA levels of the main orexigenic and anorexigenic neuropeptides were also blunted in the Lou/C rats. Analysis of the concentrations of circulating substrates and hormones known to regulate hypothalamic AMPK indicated that the starvation-induced changes in ghrelin, adiponectin and leptin were not observed in Lou/C rats. Furthermore, an increased phosphorylation state of signal transducer and activator of transcription 3 (STAT3), which admittedly mediates leptin signaling, was evidenced in the hypothalamus of the starved Lou/C rats, as well as modifications of expression of the leptin-sensitive genes suppressor of cytokine signaling-3 and stearoyl-coenzyme A desaturase 1. In addition, despite reduced leptin level in fed Lou/C rats, the phosphorylation state of hypothalamic STAT3 remained similar to that found in fed Wistar rats, an adaptation that could be explained by the concomitant increase in ObRb leptin receptor mRNA expression. CONCLUSION: Activation of hypothalamic AMPK by starvation, which stimulates food intake through changes in (an)orexigenic neuropeptides in the normal rats, was not observed in the spontaneously hypophagic Lou/C rats.

Published
2007
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23. Islet Structure and Function in the GK Rat

Author

Bernard Portha, Cécile Tourrel-Cuzin, M.H. Giroix, Magali Fradet, Audrey Chavey, Jamileh Movassat, Florence Figeac, Danièle Bailbé, Gregory Lacraz, Françoise Homo-Delarche, and M. N. Gangnerau

Subjects
endocrine system, geography, medicine.medical_specialty, geography.geographical_feature_category, endocrine system diseases, Insulin, medicine.medical_treatment, Type 2 Diabetes Mellitus, Type 2 diabetes, Biology, Islet, medicine.disease, biology.organism_classification, Neogenesis, Insulin oscillation, medicine.anatomical_structure, Endocrinology, Diabetes mellitus, Internal medicine, medicine, Pancreas
Abstract

Type 2 diabetes mellitus (T2D) arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand because of β-cell secretory dysfunction and/or decreased β-cell mass. Defining the nature of the pancreatic islet defects present in T2D has been difficult, in part because human islets are inaccessible for direct study. This review is aimed to illustrate to what extent the Goto–Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved to be a valuable tool offering sufficient commonalities to study this aspect. A comprehensive compendium of the multiple functional GK islet abnormalities so far identified is proposed in this perspective. The pathogenesis of defective β-cell number and function in the GK model is also discussed. It is proposed that the development of T2D in the GK model results from the complex interaction of multiple events: (i) several susceptibility loci containing genes responsible for some diabetic traits (distinct loci encoding impairment of β-cell metabolism and insulin exocytosis, but no quantitative trait locus for decreased β-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the offspring pancreas (decreased β-cell neogenesis and proliferation) transmitted over generations; and (iii) loss of β-cell differentiation related to chronic exposure to hyperglycaemia/hyperlipidaemia, islet inflammation, islet oxidative stress, islet fibrosis and perturbed islet vasculature.

Published
2014
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24. The spectrum of renal involvement in patients with inflammatory myopathies

Author

Alexandra Bruel, Olivier Benveniste, Philippe Rouvier, Anne Moreau, Evelyne Mac Namara, Raymond Azar, Adeline Lacraz, Thomas De Broucker, Jean-Marie Mussini, Mohamed Hamidou, Laurent Daniel, Maurice Laville, Brigitte MacGregor, David Buob, Etienne Dantan, Philippe Remy, Fadi Fakhouri, Eric Hachulla, Agathe Masseau, Grégoire Couvrat-Desvergnes, Philippe Carli, Baptiste Hervier, 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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, Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), LabEx TRANSPLANTEX [CHU de Nantes], Université de Nantes (UN), CHU Lille, CHU Henri Mondor, CH de Dunkerque, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Centre Hospitalier de Saint-Denis [Ile-de-France], Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Centre hospitalier universitaire de Nantes (CHU Nantes), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques

Subjects
Nephrology, Adult, Male, medicine.medical_specialty, Pathology, Biopsy, [SDV]Life Sciences [q-bio], Acute Kidney Injury/epidemiology/etiology, Kidney, urologic and male genital diseases, Acute Kidney Injury/epidemiology/*etiology, Polymyositis, Gastroenterology, France/epidemiology, Chronic/epidemiology/*etiology, Kidney/pathology, Internal medicine, medicine, Humans, Myositis/*complications/epidemiology, Original Study, Renal Insufficiency, Renal Insufficiency, Chronic, Acute tubular necrosis, Retrospective Studies, Aged, Kidney Diseases/epidemiology/pathology, Myositis, business.industry, urogenital system, Chronic/epidemiology/etiology, Acute kidney injury, General Medicine, Dermatomyositis, Acute Kidney Injury, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, medicine.anatomical_structure, Renal pathology, Kidney Diseases, Female, France, business, Kidney disease
Abstract

International audience; Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria \textgreater0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM.

Published
2014
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25. 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
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26. 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
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27. Matrix metalloproteinases and TIMP in acute respiratory distress syndrome

Author

S Lacraz, Laurent P. Nicod, Jean-Michel Dayer, Howard G. Welgus, Bara Ricou, and Peter M. Suter

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, ARDS, Time Factors, animal structures, Enzyme-Linked Immunosorbent Assay, Matrix Metalloproteinase Inhibitors, Lung injury, Critical Care and Intensive Care Medicine, Gastroenterology, Risk Factors, Fibrosis, Internal medicine, medicine, Humans, Protease Inhibitors, Collagenases, Glycoproteins, Respiratory Distress Syndrome, Lung, medicine.diagnostic_test, Respiratory distress, Interleukin-6, Multiple Trauma, business.industry, Septic shock, Respiratory disease, Tissue Inhibitor of Metalloproteinases, Middle Aged, medicine.disease, Shock, Septic, medicine.anatomical_structure, Bronchoalveolar lavage, Matrix Metalloproteinase 9, Case-Control Studies, Female, business, Bronchoalveolar Lavage Fluid
Abstract

To investigate the implication of extracellular matrix proteinases in acute respiratory distress syndrome (ARDS), we determined 92 kD gelatinase (92 G'ase) and its natural antagonist, the tissue inhibitor of metalloproteinases-1 (TIMP) in bronchoalveolar lavage fluid (BALF) and plasma of 33 intensive care unit (ICU) patients presenting with trauma or septic shock. Eleven of these patients developed short-course ARDS, nine developed prolonged ARDS, and 13 did not progress to ARDS. Ten non-ICU patients served as controls. During the early phase of disease, 92 G'ase in BALF of ICU patients was higher than in controls, but plasma levels were not different. TIMP was increased in BALF and plasma in ARDS as compared with those of patients at risk. The 92 G'ase/TIMP ratio in BALF remained elevated in late phases of prolonged ARDS. The high intrapulmonary levels of 92 G'ase in patients at risk and with ARDS may reflect increased turnover of extracellular matrix in acute lung injury. Increased TIMP may interfere with tissue repair and fibrosis by its inhibition of 92 G'ase. Interleukin-6 (IL-6) could be involved in enhanced local synthesis of TIMP. The balance between 92 G'ase and TIMP may play an important role in lung remodeling, which is characteristic of ARDS.

Published
1996
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28. 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
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29. Wound dehiscence and stump infection after lower limb amputation: risk factors and association with antibiotic use

Author

Wilson Belaieff, Nathalie Dunkel, Saziye Karaca, Mathieu Assal, Ilker Uçkay, Alain Lacraz, and Valentina Corni

Subjects
Male, medicine.medical_specialty, animal structures, Time Factors, digestive system, Amputation stumps, Amputation, Surgical, Lower limb amputation, Risk Factors, Internal medicine, Surgical Wound Dehiscence, Medicine, Surgical Wound Infection, Humans, Orthopedics and Sports Medicine, Antibiotic use, Antibiotic prophylaxis, Surgical Wound Infection/epidemiology, Aged, Retrospective Studies, ddc:616, ddc:617, business.industry, Wound dehiscence, Amputation Stumps, Surgical Wound Dehiscence/epidemiology, Retrospective cohort study, Antibiotic Prophylaxis, medicine.disease, Rheumatology, Surgery, body regions, surgical procedures, operative, Amputation/adverse effects, Antibiotic Prophylaxis/statistics & numerical data, Orthopedic surgery, Female, business
Abstract

Optimal duration of antibiotic prophylaxis following major lower limb amputation in preventing adverse stump outcomes is controversial.We assess the epidemiology and risk factors of wound dehiscence and stump infection after mid-thigh to transmetatarsal amputations with regard to antibiotic administration.Our retrospective observational study at the Geneva University Hospital (January 1995-June 2010) includes a total of 289 amputations in 270 adult patients (199 males; median age 70 years).Wound dehiscence and/or stump infection occurred in 47 (16.3%) and 63 (21.8%) patients with a median delay of 24 and 14 days, respectively. No clinical variable was significantly associated with stump infection. Diabetes and older age (80 years) were associated with dehiscence. Importantly, transcutaneous tissue oxygen tension (TcPO2) and duration of antibiotic administration showed no association with either outcome.The duration of antibiotic administration before or after surgery does not change the epidemiology of stump complications.

Published
2012

30. Early reduction of circulating homocysteine levels in Goto-Kakizaki rat, a spontaneous nonobese model of type 2 diabetes

Author

Danièle Bailbé, Jan A. Ehses, Bernard Portha, Jean-Louis Paul, Gregory Lacraz, Françoise Homo-Delarche, Christophe Noll, Josiane Coulaud, Nathalie Janel, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Endocrinology, Faculté de Pharmacie, Institut National de la Recherche Agronomique (INRA), Ministere de l'Enseignement superieur et de la Recherche, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, Homocysteine, HFS, Transsulfuration pathway, Type 2 diabetes, prediabetes, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Goto-Kakizaki rats, tHcy, STZ, Prediabetes, glutathione, 0303 health sciences, biology, Chemistry, Age Factors, GK, 3. Good health, Hcy, Molecular Medicine, Goto–Kakizaki rat, type 2 diabetes, DTNB, medicine.medical_specialty, Hyperhomocysteinemia, endocrine system, CBS, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, ZDF, medicine, GSH, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, Molecular Biology, 030304 developmental biology, Body Weight, homocysteine, medicine.disease, cystathionine beta synthase, Cystathionine beta synthase, Rats, Disease Models, Animal, Endocrinology, Diabetes Mellitus, Type 2, biology.protein, Insulin Resistance
Abstract

Diabetes mellitus is associated with increased risk for cardiovascular disorders, which are major causes of mortality in this disease. Hyperhomocysteinemia, defined by high plasma homocysteine levels, is an independent risk factor for the development of cardiovascular diseases. Type 2 diabetic patients have higher circulating homocysteine levels than healthy subjects and these levels are even higher in plasma of obese than nonobese diabetic patients. Homocysteine metabolism that has been studied in 2 animal models of type 2 diabetes with obesity led to conflicting data. The aim of the present study was to analyze homocysteine metabolism in a spontaneous nonobese model of type 2 diabetes, the Goto–Kakizaki rats at various successive and well characterized stages of the disease: during early postnatal normoglycemia, at the onset of hyperglycemia (around weaning), and during chronic mild hyperglycemia with progressive insulin resistance. Compared to age-matched Wistar controls, Goto–Kakizaki rats showed lower plasma levels of homocysteine and a falling trend in its major byproduct antioxidant, glutathione, from the prediabetic stage onwards. Concomitantly, Goto–Kakizaki rats exhibited increased liver activity of cystathionine beta synthase, which catalyzes the condensation of homocysteine with serine in the first step of the transsulfuration pathway. These results emphasize a strong association between homocysteine metabolism and insulin via the first step of the hepatic transsulfuration pathway in Goto–Kakizaki rats.

Published
2011
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31. Eculizumab in acute recurrence of thrombotic microangiopathy after renal transplantation

Author

Delphine Fumeaux, Karine Hadaya, Christian Toso, Sylvie Ferrari-Lacraz, Solange Moll, Pierre-Yves Martin, Jean Villard, and Françoise Boehlen

Subjects
medicine.medical_specialty, Thrombotic microangiopathy, Fulminant, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, ddc:616.07, Antibodies, Monoclonal, Humanized, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Recurrence, Internal medicine, Atypical hemolytic uremic syndrome, Immunology and Allergy, Medicine, Lupus Erythematosus, Systemic, Humans, Pharmacology (medical), Kidney transplantation, ddc:616, Transplantation, ddc:617, business.industry, Thrombotic Microangiopathies, Kidney Transplantation/adverse effects, Thrombotic Microangiopathies/drug therapy, Eculizumab, medicine.disease, Kidney Transplantation, Lupus Erythematosus, Systemic/complications, 3. Good health, Antibodies, Antiphospholipid/blood, Kidney Failure, Chronic/etiology, Antibodies, Monoclonal, Humanized/therapeutic use, Immunology, Paroxysmal nocturnal hemoglobinuria, Antibodies, Antiphospholipid, Kidney Failure, Chronic, Female, business, medicine.drug
Abstract

Renal thrombotic microangiopathy (TMA) is a severe complication of systemic lupus erythematosus (SLE), which is associated with the presence of antiphospholipid (aPL) antibodies. In its most fulminant form, TMA leads to a rapid and irreversible end-stage renal failure. Eculizumab, an anti-C5 monoclonal antibody, is a novel therapy of choice for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. Here, we report the case of a 27-year-old woman, known for SLE and end-stage renal disease due to fulminant TMA. Both aPL antibodies and antinucleosome antibodies were positive. The patient underwent a living-related kidney transplantation with immediate production of urine. Although serum creatinine was remaining high, a graft biopsy, performed on day 6, demonstrated a TMA recurrence. Despite a treatment with plasma exchange, the situation got worse and dialysis was started. Eculizumab treatment was subsequently administered and renal function improved rapidly. Three months after transplantation, serum creatinine was at 100 μmol/L, without proteinuria. This case illustrates the benefit of eculizumab therapy in a fulminant recurrence of TMA after kidney transplantation, resistant to classical therapy.

Published
2011

32. Regulation of Interleukin-1ra, Interleukin-1α, and Interleukin-1β Production by Human Alveolar Macrophages with Phorbol Myristate Acetate, Lipopolysaccharide, and Interleukin-4

Author

Jean-Michel Dayer, Rachel Chicheportiche, Christophe Baumberger, Sylvie Lacraz, Béatrice Galve-de Rochemonteix, and Laurent P. Nicod

Subjects
Lipopolysaccharides, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lipopolysaccharide, medicine.drug_class, medicine.medical_treatment, Blotting, Western, Clinical Biochemistry, Biology, chemistry.chemical_compound, Internal medicine, Macrophages, Alveolar, medicine, Humans, RNA, Messenger, Northern blot, Prostaglandin E2, Receptor, Molecular Biology, Cells, Cultured, Interleukin 4, Receptors, Interleukin-1, Interleukin, Cell Biology, Receptor antagonist, Molecular biology, Up-Regulation, Kinetics, Endocrinology, Cytokine, chemistry, Tetradecanoylphorbol Acetate, Interleukin-4, Interleukin-1, medicine.drug
Abstract

Human alveolar macrophages (AM) are antigen-presenting cells that have an important immune effector function in the lung. We have previously shown that AM produce a specific interleukin-1 (IL-1) inhibitor of 20 to 25 kD that blocks biologic activities of IL-1 alpha and IL-1 beta such as prostaglandin E2 production by fibroblasts. This inhibitor acts as a receptor antagonist (IL-1ra) by binding to the IL-1 receptor. We are now presenting evidence that the natural AM-derived IL-1ra is immunologically identical to IL-1ra cloned from human peripheral blood monocytes and shows a band at 20 kD compatible with the natural glycosylated IL-1ra. No constitutive expression of IL-1 mRNA was detected when analyzed by Northern blot immediately after bronchoalveolar lavage from six control patients. Comparison of in vitro kinetics of IL-1ra, IL-1 alpha, and IL-1 beta analyzed during culture in the presence or absence of phorbol myristate acetate revealed that their mRNA expression was asynchronous. IL-1 alpha and IL-1 beta mRNA were expressed after as little as 15 min, whereas IL-1ra mRNA was detectable only after 3 h in culture. The production of IL-1ra was measured by enzyme-linked immunosorbent assay and compared with that of IL-1 alpha and IL-1 beta. In freshly isolated AM (10(6)/ml), cell-associated IL-1ra was present in an average amount of 2.0 +/- 0.5 ng/ml, i.e., 25 and 100 times more than IL-1 alpha and IL-1 beta, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1993
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33. Inhibition of T cell-dependent and RANKL-dependent osteoclastogenic processes associated with high levels of bone mass in interleukin-15 receptor-deficient mice

Author

Sylvie Ferrari-Lacraz, Dominique D. Pierroz, Souad Djaafar, Rachel Chicheportiche, Xin Xiao Zheng, and S. Ferrari

Subjects
musculoskeletal diseases, medicine.medical_specialty, Bone density, Osteoclasts/*metabolism, T-Lymphocytes, T cell, Immunology, Blotting, Western, Osteoclasts, Receptors, Interleukin-15/genetics/*metabolism, Bone and Bones/*metabolism, Spleen/metabolism, Bone and Bones, Bone resorption, Bone remodeling, T-Lymphocytes/*metabolism, Mice, Rheumatology, Osteoclast, Bone Density, Internal medicine, medicine, Immunology and Allergy, Animals, Pharmacology (medical), ddc:610, Bone Resorption, Cells, Cultured, ddc:616, Mice, Knockout, biology, Receptors, Interleukin-15, Chemistry, Reverse Transcriptase Polymerase Chain Reaction, RANK Ligand, Cell Differentiation, Dendritic cell, medicine.anatomical_structure, Endocrinology, Interleukin 15, RANKL, ddc:618.97, RANK Ligand/genetics/*metabolism, biology.protein, Female, Bone Resorption/*metabolism, Spleen, Signal Transduction
Abstract

OBJECTIVE: T cell production of RANKL, interferon-gamma (IFNgamma), and other cytokines in inflammatory processes such as rheumatoid arthritis or secondary to conditions such as estrogen deficiency stimulates osteoclast activity, which leads to bone resorption and bone loss. The purpose of this study was to characterize the effects of interleukin-15 (IL-15), a master T cell growth factor whose role in bone remodeling remains unknown. METHODS: We used mice lacking the IL-15 receptor (IL-15Ralpha(-/-) ) to investigate the effects of IL-15 on osteoclast development, T cell and dendritic cell activation in vitro and in vivo, bone mass, and microarchitecture in intact and ovariectomized (OVX) mice. RESULTS: In wild-type (WT) animals, IL-15 and RANKL provided a costimulatory signal for osteoclast development. Spleens from IL-15Ralpha(-/-) mice contained few c-Kit+ osteoclast precursors, and the expression of NF-ATc1 and the osteoclastogenic response to RANKL were impaired. In addition, dendritic cell-dependent and T cell-dependent mechanisms of osteoclast activation, including RANKL and IFNgamma production, were impaired in IL-15Ralpha(-/-) mice. In turn, IL-15Ralpha(-/-) T cells failed to stimulate WT osteoclasts, whereas WT T cells failed to stimulate IL-15Ralpha(-/-) osteoclasts. Compared with WT mice, both intact and OVX IL-15Ralpha(-/-) mice had significantly greater bone mineral density and microarchitecture, including a higher trabecular bone volume fraction and cortical thickness. The numbers of osteoclasts on the bone surface as well as markers of bone turnover were significantly decreased in IL-15Ralpha(-/-) mice. CONCLUSION: In the absence of IL-15 signaling, several converging mechanisms of osteoclastogenesis are inhibited, both directly and indirectly, through T cells, which leads to a high bone mass phenotype. Targeting the IL-15 pathway may represent a novel therapeutic approach to treating primary and secondary osteoporosis.

Published
2010

34. Suppression of metalloproteinase biosynthesis in human alveolar macrophages by interleukin-4

Author

Howard G. Welgus, B Galve-de Rochemonteix, S Lacraz, C. Baumberger, Laurent P. Nicod, and Jean-Michel Dayer

Subjects
medicine.medical_specialty, medicine.medical_treatment, Gene Expression, In Vitro Techniques, Matrix metalloproteinase, Biology, Interferon-gamma, Internal medicine, Macrophages, Alveolar, medicine, Humans, Macrophage, RNA, Messenger, Glycoproteins, Metalloproteinase, Tumor Necrosis Factor-alpha, Lymphokine, Metalloendopeptidases, Tissue Inhibitor of Metalloproteinases, General Medicine, Macrophage Activation, Molecular biology, Microbial Collagenase, Endocrinology, Cytokine, Microbial collagenase, Interstitial collagenase, Tumor necrosis factor alpha, Interleukin-4, Research Article, Interleukin-1
Abstract

To study the interaction of lymphocytes and macrophages in the control of extracellular matrix turnover, we determined the effects of several soluble T cell products on mononuclear phagocyte production of metalloproteinases. Cytokines including IL-2, IL-4, IL-6, tumor necrosis factor alpha (TNF alpha), GM-CSF, and IFN-gamma were each tested for capacity to modulate macrophage metalloproteinase and tissue inhibitor of metalloproteinases (TIMP) expression. The addition of IL-4 to cells cultured under basal conditions caused a dose-dependent suppression in the release of 92-kD type IV collagenase without affecting TIMP production. 92-kD enzyme secretion was inhibited by 50% with 1-2 ng/ml of IL-4 and by 90% with 10 ng/ml of IL-4. When cells were first exposed to killed Staphylococcus aureus to induce metalloproteinase production, IL-4 potently blocked the stimulated release of both interstitial collagenase and 92-kD type IV collagenase, again without effect upon TIMP. Metabolic labeling experiments and Northern hybridizations demonstrated that IL-4 exerted its action at a pretranslational level. Furthermore, IL-4 possessed the capacity to inhibit metalloproteinase expression even in the relatively immature peripheral blood monocyte. As reported previously (Shapiro, S. D., E. J. Campbell, D. K. Kobayashi, and H. G. Welgus. 1990. J. Clin. Invest. 86:1204), IFN-gamma suppressed constitutive macrophage production of 92-kD type IV collagenase. Despite the frequent antagonism observed between IL-4 and IFN-gamma in other systems, the combination of these two agents lowered metalloproteinase biosynthesis dramatically, whereas IL-4 opposed the IFN-gamma-stimulated production of cytokines (IL-1 and TNF alpha). IL-6 had only minimal effect upon metalloproteinase production, but appeared to specifically augment TIMP release. In summary, cytokines released by activated T cells may profoundly reduce the capacity of the macrophage to mediate extracellular matrix degradation.

Published
1992
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35. Islet endothelial activation and oxidative stress gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat

Author

Bernard Portha, Jean-Claude Irminger, Christophe Noll, Mélanie Cornut, Josiane Coulaud, Gregory Lacraz, Nadim Kassis, Françoise Homo-Delarche, Nathalie Janel, M.H. Giroix, Micheline Kergoat, Marc Y. Donath, Jan A. Ehses, Anne Galinier, Jean-Louis Paul, and Fabien Schmidlin

Subjects
Male, endocrine system diseases, lcsh:Medicine, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease_cause, Antioxidants, 0302 clinical medicine, Fibrosis, Cardiovascular Disorders/Vascular Biology, ddc:576.5, Diabetes Mellitus, Experimental/metabolism, lcsh:Science, Regulation of gene expression, 0303 health sciences, Multidisciplinary, geography.geographical_feature_category, Chemistry, Islet, 3. Good health, Islets of Langerhans/cytology, Endothelial stem cell, Interleukin-1/metabolism, medicine.symptom, Research Article, medicine.medical_specialty, endocrine system, Antioxidants/metabolism, Inflammation, Models, Biological, Diabetes Mellitus, Experimental, Endothelial activation, Islets of Langerhans, 03 medical and health sciences, Internal medicine, medicine, Animals, Diabetes and Endocrinology/Type 2 Diabetes, Rats, Wistar, 030304 developmental biology, Pharmacology, geography, lcsh:R, Endothelial Cells, medicine.disease, Diabetes Mellitus, Type 2/metabolism, Rats, Interleukin 1 Receptor Antagonist Protein, Oxidative Stress, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, lcsh:Q, Endothelial Cells/cytology, Oxidative stress, Interleukin-1, Interleukin 1 Receptor Antagonist Protein/metabolism
Abstract

BACKGROUND:Inflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra). METHODOLOGY/PRINCIPAL FINDINGS:Gene expression was analyzed by quantitative RT-PCR on islets isolated from 10-week-old diabetic GK and control Wistar rats. Furthermore, GK rats were treated s.c twice daily with IL-1Ra (Kineret, Amgen, 100 mg/kg/day) or saline, from 4 weeks of age onwards (onset of diabetes). Four weeks later, islet gene analysis and pancreas immunochemistry were performed. Thirty-two genes were selected encoding molecules involved in endothelial cell activation, particularly fibrinolysis, vascular tone, OS, angiogenesis and also inflammation. All genes except those encoding angiotensinogen and epoxide hydrolase (that were decreased), and 12-lipoxygenase and vascular endothelial growth factor (that showed no change), were significantly up-regulated in GK islets. After IL-1Ra treatment of GK rats in vivo, most selected genes implied in endothelium/OS/immune cells/fibrosis were significantly down-regulated. IL-1Ra also improved islet vascularization, reduced fibrosis and ameliorated glycemia. CONCLUSIONS/SIGNIFICANCE:GK rat islets have increased mRNA expression of markers of early islet endothelial cell activation, possibly triggered by several metabolic factors, and also some defense mechanisms. The beneficial effect of IL-1Ra on most islet endothelial/OS/immune cells/fibrosis parameters analyzed highlights a major endothelial-related role for IL-1 in GK islet alterations. Thus, metabolically-altered islet endothelium might affect the beta-cell microenvironment and contribute to progressive type 2 diabetic beta-cell dysfunction in GK rats. Counteracting islet endothelial cell inflammation might be one way to ameliorate/prevent beta-cell dysfunction in type 2 diabetes.

Published
2009

36. IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat

Author

Bernard Portha, Françoise Homo-Delarche, Marc Y. Donath, F. Schmidlin, M-H. Giroix, M. Kergoat, Nadim Kassis, Jan A. Ehses, G. Lacraz, J. Coulaud, Jean-Claude Irminger, and University of Zurich

Subjects
Antigens, Differentiation, T-Lymphocyte, Chemokine, Myeloid Differentiation Factor 88/metabolism, medicine.medical_treatment, Interleukin-1beta, Interleukin-6/metabolism, 10265 Clinic for Endocrinology and Diabetology, Antigens, CD/biosynthesis, Mice, ddc:576.5, Diabetes Mellitus, Experimental/metabolism, Proinsulin, Multidisciplinary, geography.geographical_feature_category, biology, Biological Sciences, Islet, Cytokine, Antigens, Differentiation, Myelomonocytic/biosynthesis, 10076 Center for Integrative Human Physiology, Beta cell, medicine.symptom, Islets of Langerhans/metabolism, medicine.medical_specialty, Antigens, Differentiation, T-Lymphocyte/biosynthesis, Interleukin-1/antagonists & inhibitors/metabolism, Antigens, Differentiation, Myelomonocytic, Inflammation, 610 Medicine & health, Tetraspanin 25, Diabetes Mellitus, Experimental, Proinflammatory cytokine, Islets of Langerhans, Insulin resistance, Antigens, CD, Internal medicine, Macrophages/metabolism, medicine, Animals, Rats, Wistar, geography, 1000 Multidisciplinary, Hyperglycemia/pathology, Interleukin-6, Macrophages, medicine.disease, Diabetes Mellitus, Type 2/metabolism, Rats, Interleukin 1 Receptor Antagonist Protein, Endocrinology, Diabetes Mellitus, Type 2, Hyperglycemia, Myeloid Differentiation Factor 88, Interleukin-1beta/metabolism, biology.protein, 570 Life sciences, Interleukin-1, Inflammation/pathology, Interleukin 1 Receptor Antagonist Protein/metabolism
Abstract

Recent studies suggest an inflammatory process, characterized by local cytokine/chemokine production and immune cell infiltration, regulates islet dysfunction and insulin resistance in type 2 diabetes. However, the factor initiating this inflammatory response is not known. Here, we characterized tissue inflammation in the type 2 diabetic GK rat with a focus on the pancreatic islet and investigated a role for IL-1. GK rat islets, previously characterized by increased macrophage infiltration, displayed increased expression of several inflammatory markers including IL-1β. In the periphery, increased expression of IL-1β was observed primarily in the liver. Specific blockade of IL-1 activity by the IL-1 receptor antagonist (IL-1Ra) reduced the release of inflammatory cytokines/chemokines from GK islets in vitro and from mouse islets exposed to metabolic stress. Islets from mice deficient in IL-1β or MyD88 challenged with glucose and palmitate in vitro also produced significantly less IL-6 and chemokines. In vivo, treatment of GK rats with IL-1Ra decreased hyperglycemia, reduced the proinsulin/insulin ratio, and improved insulin sensitivity. In addition, islet-derived proinflammatory cytokines/chemokines (IL-1β, IL-6, TNFα, KC, MCP-1, and MIP-1α) and islet CD68 + , MHC II + , and CD53 + immune cell infiltration were reduced by IL-1Ra treatment. Treated GK rats also exhibited fewer markers of inflammation in the liver. We conclude that elevated islet IL-1β activity in the GK rat promotes cytokine and chemokine expression, leading to the recruitment of innate immune cells. Rather than being directly cytotoxic, IL-1β may drive tissue inflammation that impacts on both β cell functional mass and insulin sensitivity in type 2 diabetes.

Published
2009

37. Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark

Author

Jean Villard, Thierry Berney, Jose Oberholzer, Jacques Philippe, Sylvie Ferrari-Lacraz, Leo Buhler, Philippe Morel, and Nicola Marangon

Subjects
Oncology, Blood Glucose, Adult, medicine.medical_specialty, Time Factors, Hypoglycemic Agents/blood, medicine.medical_treatment, Islets of Langerhans Transplantation, Diabetes mellitus, Internal medicine, medicine, Immunology and Allergy, Hypoglycemic Agents, Insulin, Humans, Transplantation, Homologous, Pharmacology (medical), Postoperative Period, Pancreatic hormone, Immunosuppression Therapy, Transplantation, Type 1 diabetes, geography, geography.geographical_feature_category, ddc:617, Blood Glucose/metabolism, business.industry, Graft Survival, Immunosuppression, medicine.disease, Islet, Diabetes Mellitus, Type 1, Treatment Outcome, Metabolic control analysis, Diabetes Mellitus, Type 1/surgery, Immunology, Female, business, Insulin/blood
Abstract

Results of islet of Langerhans transplantation have markedly improved in recent years, but most patients still lose insulin independence in the long-term. We report herein the longest (over 11 years) case of insulin independence after allogeneic islet transplantation. The subject had a 27-year history of type 1 diabetes and received a single islet-after-kidney graft of 8800 islet equivalents (IEQ)/kg, pooled from 2 donors. Insulin was discontinued by 3 months posttransplant and the patient has remained off insulin ever since. Yearly follow-up studies have revealed normal metabolic control, including normal oral glucose tolerance test (OGTT). Reasons for success may involve choice of immunosuppression, low metabolic demand and low immune responsiveness as suggested by an excellent HLA matching and a high count of circulating regulatory T cells. This observation is so far an exceptional case, but clearly demonstrates the validity of the concept that long-term insulin independence after allogeneic islet transplantation is an achievable target.

Published
2009

38. The GK Rat Beta-Cell: A Prototype for the Diseased Human Beta-Cell in Type 2 Diabetes?

Author

M.H. Giroix, Micheline Kergoat, M. Dolz, D. Bailbé, Jamileh Movassat, M. N. Gangnerau, Cécile Tourrel-Cuzin, Gregory Lacraz, Bernard Portha, and Françoise Homo-Delarche

Subjects
endocrine system, medicine.medical_specialty, endocrine system diseases, 030209 endocrinology & metabolism, Inflammation, Type 2 diabetes, medicine.disease_cause, Biochemistry, Neogenesis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin-Secreting Cells, Diabetes mellitus, Internal medicine, medicine, Animals, Humans, Epigenetics, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, geography, geography.geographical_feature_category, biology, Life Sciences, biology.organism_classification, medicine.disease, Islet, Rats, Disease Models, Animal, Diabetes Mellitus, Type 2, Beta cell, medicine.symptom, Oxidative stress
Abstract

Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of type 2 diabetes (T2D) mellitus. Nowadays, the debate focuses on the possible mechanisms responsible for abnormal islet microenvironment, decreased beta-cell number, impaired beta-cell function, and their multifactorial aetiologies. This review is aimed to illustrate to what extend the Goto-Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved be a valuable tool offering sufficient commonalities to study these aspects. We propose that the defective beta-cell mass and function in the GK model reflect the complex interactions of multiple pathogenic players: (i) several independent loci containing genes responsible for some diabetic traits (but not decreased beta-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the pancreas (decreased beta-cell neogenesis and/or proliferation) which is transmitted to the next generation; and (iii) loss of beta-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammatory mediators, oxidative stress and to perturbed islet microarchitecture.

Published
2008
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39. Liver mitochondrial properties from the obesity-resistant Lou/C rat

Author

Xavier Leverve, Nellie Taleux, Stéphane Servais, Grégory Lacraz, Hervé Dubouchaud, Karine Couturier, Bruno Guigas, Brigitte Sibille, Dominique Letexier, Roland Favier, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie intégrative, cellulaire et moléculaire (PICM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hamant, Sarah, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Cytochrome, Endocrinology, Diabetes and Metabolism, Respiratory chain, Medicine (miscellaneous), Dehydrogenase, Mitochondria, Liver, Growth, MESH: Energy Intake, Mitochondrion, MESH: Eating, Ion Channels, Oxidative Phosphorylation, Eating, 0302 clinical medicine, MESH: Membrane Potential, Mitochondrial, MESH: Obesity, Uncoupling Protein 2, MESH: Animals, MESH: Oxygen Consumption, 2. Zero hunger, chemistry.chemical_classification, Membrane Potential, Mitochondrial, 0303 health sciences, Nutrition and Dietetics, biology, MESH: Mitochondrial Proteins, MESH: Reactive Oxygen Species, MESH: Rats, Inbred Strains, MESH: Dietary Fats, MESH: Hydrogen Peroxide, Disease Susceptibility, MESH: Mitochondria, Liver, medicine.medical_specialty, MESH: Rats, MESH: Disease Susceptibility, 030209 endocrinology & metabolism, Oxidative phosphorylation, Mitochondrial Proteins, 03 medical and health sciences, Oxygen Consumption, Species Specificity, MESH: Oxidative Phosphorylation, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cytochrome c oxidase, Animals, MESH: Species Specificity, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, Rats, Wistar, 030304 developmental biology, Reactive oxygen species, MESH: Growth, Rats, Inbred Strains, Hydrogen Peroxide, MESH: Rats, Wistar, Dietary Fats, MESH: Male, Reverse electron flow, Rats, Endocrinology, chemistry, MESH: Ion Channels, biology.protein, Energy Intake, Reactive Oxygen Species
Abstract

International audience; OBJECTIVE: The first objective was to evaluate the influence of caloric intake on liver mitochondrial properties. The second objective was aimed at determining the impact of increasing fat intake on these properties. DESIGN: Lou/C rats, displaying an inborn low caloric intake and resistant to diet-induced obesity, were compared to Wistar rats fed either ad libitum or pair-fed. An additional group of Lou/C rats were allowed to increase their fat intake by adjusting their diet from a standard high carbohydrate low-fat diet to a high-fat carbohydrate-free diet. MEASUREMENTS: Hydrogen peroxide (H(2)O(2)) generation, oxygen consumption rate (J(O(2))), membrane potential (DeltaPsi), activity of respiratory chain complexes, cytochrome contents, oxidative phosphorylation efficiency (OPE) and uncoupling protein 2 (UCP2) expression were determined in liver mitochondria. RESULTS: H(2)O(2) production was higher in Lou/C than Wistar rats with glutamate/malate and/or succinate, octanoyl-carnitine, as substrates. These mitochondrial features cannot be mimicked by pair-feeding Wistar rats and remained unaltered by increasing fat intake. Enhanced H(2)O(2) production by mitochondria from Lou/C rats is due to an increased reverse electron flow through the respiratory-chain complex I and a higher medium-chain acyl-CoA dehydrogenase activity. While J(O(2)) was similar over a large range of DeltaPsi in both strains, Lou/C rats were able to sustain higher membrane potential and respiratory rate. In addition, mitochondria from Lou/C rats displayed a decrease in OPE that cannot be explained by increased expression of UCP2 but rather to a slip in proton pumping by cytochrome oxidase. CONCLUSIONS: Liver mitochondria from Lou/C rats display higher reactive oxygen species (ROS) generation but to deplete upstream electron-rich intermediates responsible for ROS generation, these animals increased intrinsic uncoupling of cytochrome oxidase. It is likely that liver mitochondrial properties allowed this strain of rat to display higher insulin sensitivity and resist diet-induced obesity.

Published
2008
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40. Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease

Author

Gorki Antonio Carmona, Ulrich M. Vischer, Olivier Marcel Tschopp, François Herrmann, J. Vaucher, Pierre Hoffmeyer, and Alain Lacraz

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Arterial Occlusive Diseases, Single Center, Amputation, Surgical, Endocrinology, Diabetes mellitus, Epidemiology, Internal Medicine, medicine, Humans, Aged, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Leg, ddc:617, Vascular disease, Proportional hazards model, business.industry, Retrospective cohort study, General Medicine, Prognosis, medicine.disease, Diabetic Foot, Surgery, Amputation, ddc:618.97, Etiology, Female, France, business, Diabetic Angiopathies, Switzerland
Abstract

Summary Background Major amputation is a dreaded event with high mortality and morbidity. However, few studies have investigated the epidemiology of amputation in the elderly over time, in the face of evolving management and prevention efforts. Methods We undertook a retrospective study to determine the incidence rate, etiology and prognosis of major lower limb amputations (transtibial or higher) in elderly patients (> 65 years). Cases were identified over a 10-year period in the Geneva (Switzerland) area, where all amputations are performed in a single center and reliable demographic data are available. Results The rate of amputation varied from 1.8 to 11.4/10000 patients/year, increasing with age and male gender. Diabetes was present in 48% patients, and conferred a 10 times higher risk of amputation. Severe peripheral arterial disease (PAD) was present in > 94% patients. The prognosis remains poor, 47% patients had died after two years and only 53% patients could be equipped with a prosthetic limb. Over 10 years we found a progressive increase in age at amputation; this encouraging increase was mostly accounted for by diabetic patients (> 6 months per year). Conclusions The rate of amputation observed among elderly patients was low. Neither the rate nor the prognosis improved over the decade studied. However, the age at amputation increased by > 6 months/year, particularly in diabetic amputees, suggesting that current management successfully delays amputation. Amputations were almost exclusively performed for severe PAD. Further reduction in the rate of amputation will require progress in the prevention and management of PAD.

Published
2005

41. Malignant hypertension and interferon-beta: a case report

Author

A Lacraz, P Gosse, V Galantine, and S Rubin

Subjects
Ramipril, medicine.medical_specialty, business.industry, Renal artery stenosis, medicine.disease, Atenolol, Surgery, Irbesartan, Blood pressure, Hypertensive retinopathy, Bisoprolol, Internal medicine, Internal Medicine, medicine, Cardiology, Amlodipine, business, medicine.drug
Abstract

On 23 May 2012, a 41-year-old patient was admitted to hospital following a convulsive episode and severe hypertension. She had been treated for multiple sclerosis by interferon-beta since 2002. Her usual blood pressure (BP) values were unknown. She did not have any other cardiovascular risk factors. On admission to the emergency unit her BP was 220/140 mm Hg, and she was in a convulsive state. On initial evaluation, there was hemolysis, low serum potassium (3.2 mmol l−1), secondary hyperaldosteronism, and an elevation of cardiac, hepatic and pancreatic enzymes (Table 1). The electrocardiogram and the echocardiography were normal. There was no evidence of renal artery stenosis on Doppler echography, and adrenals, liver and pancreas were normal on computed tomography scan. Magnetic resonance imaging (MRI) of the brain showed ‘posterior regressive encephalopathy syndrome’ (PRES), and on fundal examination there was grade III hypertensive retinopathy. The patient was admitted to the intensive care unit and required intubatation and ventilation. Interferon-beta was stopped and she was given nicardipine IV to control BP, but the hemolysis persisted with worsening renal function. After extubation on 26 May she was started on bisoprolol. After the acute phase, the patient was transferred to the kidney unit on 05/06/2012. Blockers of the renin–angiotensin aldosterone system were titrated (progressive introduction of ramipril up to 10 mg per day followed by irbesartan up to 300 mg per day along with atenolol 100 mg per day). Amlodipine 10 mg was then administered reducing the BP below 140/90 mm Hg; all biologic parameters were normalized in 4 weeks (Table 1).

Published
2013
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42. Interleukin-15 in the Regulation of Obesity and Fatty Liver Disease

Author

Sheela Ramanathan, Gregory Lacraz, Yuneivy Cepar Donates, Marian Mayhue, Marie France Langois, Marek Rola Pleszczynski, and Subburaj Ilangumaran

Subjects
medicine.medical_specialty, Endocrinology, Hepatology, business.industry, Interleukin 15, Internal medicine, Fatty liver, medicine, Disease, medicine.disease, business, Obesity
Published
2014
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44. O8 Signes précoces de microangiopathie dans les îlots pancréatiques du rat GK, modèle spontané de diabète de type 2 (DT2)

Author

Josiane Coulaud, Jean-Claude Irminger, Gregory Lacraz, Françoise Homo-Delarche, M. Cornut, and M.H. Giroix

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract

Introduction La microangiopathie diabetique est reconnue au niveau renal et oculaire, mais pas encore au niveau de l'ilot bien qu'une reaction inflammatoire insulaire ait ete decelee chez des patients et divers modeles animaux de DT2. Chez le rat GK, l'inflammation insulaire progresse parallelement a l'hyperglycemie, qui debute au sevrage (28 j) et s'accompagne d'une alteration endotheliale et de fibrose insulaire. Les rats GK, surtout les femelles, presentent aussi une dyslipidemie. Or un lien entre perturbations metaboliques chez la mere gestante et hypertension, maladies cardiovasculaires et diabetes dans la descendance a ete etabli. Notre hypothese est que l'hyperlipidemie maternelle, associee a l'hyperglycemie, perturbe le developpement du pancreas endocrine chez le rat GK via la mise en place d'un processus de type microangiopathie/atherosclerose. Materiels et methodes Les ilots de rats males Wistar (temoins) et GK âges de 7 jours ont ete isoles. Par une double approche ( Affimetrix gene array et Oligo-GEAarray ® ) l'expression de genes en rapport avec la vascularisation (endothelium, angiogenese et maladies cardiovasculaires) a ete comparee dans les 2 groupes d'ilots. Resultats Les ilots des nouveau-nes GK (prediabetiques) 1) surexpriment des genes codant pour des facteurs proarteriosclereux : caspase 1, IL-15, IL-18, CXCL1, CXCL2, ICAM-1, fibronectine, carboxypeptidase-2 et angiotensinogene ; 2) sous-expriment des genes codant pour des molecules pro-angiogeniques : osteoprotegerine, neuropiline-1, eotaxine, PDGF-β, facteur tissulaire et neuropeptide Y, suggerant un defaut d'angiogenese ; 3) surexpriment les genes de molecules aux effets anti-arteriosclerose et vasoprotecteur : prostacycline synthetase et apolipoproteine A-1 ; 4) sous-expriment le gene de l'epoxyde hydrolase (EH) qui, en augmentant le taux des acides epoxyeicosatrienoiques, prolonge les effets vasodilateur, anti-inflammatoire, anti-oxydant et angiogenique d'autres facteurs. Le gene de l'EH est aussi sous-exprime dans le pancreas du rat GK au stade fœtal. Conclusion Chez le rat GK des processus pro-inflammatoires (proarteriosclereux) et anti-inflammatoires au niveau de l'endothelium insulaire sont en place des la periode perinatale. L'alteration vasculaire insulaire pourrait etre a l'origine du deficit precoce en cellules β pancreatiques observe chez ces animaux.

Published
2009
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47. Clinical Nephrology: primary and secondary glomerulonephritis

Author

Maria Stangou, Aki Kuroki, Magdalena Silska, Meg Jardine, Rosanna Coppo, Helen Liakou, Alessandra Grosso, Marco Di Girolamo, Masanori Ito, Domingo Hernández, H. Marco, Y. Arce, Kenji Ito, Paolo Lorusso, Cátia Pêgo, Marco Quaglia, Jacek Zachwieja, Heejung Choi, Salvatore Di Paolo, Domniki Ekonomidou, John Feehally, Ladislava Grcevska, Lidia Kozlovskaya, Hirotsugu Iwatani, Libor Vítek, Andrzej Blumczynski, Guido Ricchiuti, Jana Švarcová, Hala Kfoury, Marian Klinger, Rachele Gallo, Manoj R. Gumber, Eleni Rizopoulou, Timothy S. Johnson, Edgar Lorga, B. Laurent, Elisa Colombini, J.M. Llobet, Momir Polenakovic, Marta Kalousová, Elena Shakhnova, Caili Wang, Peter Heering, Rafid Tofik, Kentaro Ohtoshi, Elena Potencz, Nan Chen, Yaowen Xu, Grazia Vocino, N.L. Kozlovskaya, Alina Casian, Patricia Rullier, Sukran Gurses, Afroditi Pantzaki, Adamasco Cupisti, Bernardo Faria, Vladimir Nikolov, Alice C. Smith, Jakub Zavada, Eva Jancova, Anna Musielak, KyungHwan Jeong, Jessica N. Ivany, Adeline Lacraz, Eduardo B. Coelho, Junying Fan, Silvia Velciov, Tatsuya Shoji, Ju-Young Moon, Kazuo Kitamura, Masahiro Yamamoto, A. Jin Cho, Licia Peruzzi, Martina Giorgetti, Maria Svelto, Valentina Daprà, Natalia Meteleva, Katarzyna Lipkowska, Hong Ren, Jung Eun Lee, Christos Bantis, Panagiotis Patinakis, Himanshu V Patel, Noura AlOudah, Corina Vernic, Richard J. Johnson, Hiroyuki Komatsu, Gheorghe Gluhovschi, Young Tai Shin, Carla Lima, Anhar Ullah, Miltiadis Gerolymos, Gianna Mazzucco, Ilaria Cipollini, Stefan H. Jacobson, Katarzyna Koscielska-Kasprzak, Elena Kamyshova, Pavel Avdonin, Atsushi Yamauchi, Yuji Sato, Yasuhiro Date, Wladimir Szpirt, Eva Honsova, Niya Jia, Henrik Braunitzer, Hye Ryoun Jang, Polina Semenovylh, Yasuhiro Abe, Pankaj R Shah, Qianying Zhang, Larisa Bobrova, Josep M. Grinyó, Sérgio Lemos, Yoshimitsu Yamasaki, Hakan Yavas, Oktawia Mazanowska, Yoshitaka Rakugi, Tadao Akizawa, David Launay, Sang-Ho Lee, Grazia Tamma, R. Poveda, Kang Wook Lee, F.N. Vigotti, Pantelitsa Kalliakmani, Gyl Eanes Barros Silva, Ha Young Oh, Ji Yoon Jung, Florica Gadalean, Saori Nishio, Hargovind L Trivedi, Marten Trendelenburg, Nadia Sami, Yukihiro Wada, Christina Schwandt, Michalis Spartalis, Antoine Huart, Aurélie Hummel, Elisa Loiacono, Linghong Huang, Kostas Pliakos, Marios Papasotiriou, Nicoletta-Maria Kouri, Zdenka Hruskova, Jesus Garrido, Domniki Oikonomidou, M. Picazo, Jacek Manitius, Joachim Lundahl, George Efstratiadis, Alfons Segarra, Giovanni Sorbo, Ivan Topchii, Kamal K. Kaswan, Ole Torffvit, G. Daidola, Danuta Ostalska-Nowicka, Dimitrios Memmos, Valentina Panetta, Patrice Cacoub, YangGyoon Kim, Daniel Cioca, Manuela Bianciotto, Massimo Papale, Vladimira Bednarova, Naoto Katakami, Lina Muzi, Osman Z. Sahin, Javeria Peracha, Satoru Ogahara, Katrin Ivens, Shouichi Fujimoto, Ilona Kaszás, Giovanna Pasquariello, Demetris Christou, Jean-Emmanuel Kahn, Magdalena Grajewska, Xiaoxia Pan, Grazyna Odrowaz-Sypniewska, Arata Horii, Hiromi Rakugi, Elena Lazar, Helena Mareckova, Eliska Potlukova, Giuseppe Grandaliano, L. C. Rump, József Arányi, Dinesh Gera, Valeria T. Okino, Xiaonong Chen, Dong Seok Jang, Andrey Nesen, Dilek Gibyeli Genek, M. Diaz, Marcelina Zabinska, Ligia Petrica, Isabelle Marie, Dae Joong Kim, Pingyan Shen, Olivier Hinschberger, Sulra Lee, Virginia Trandafirescu, Ilona Dziemianko, Won Ik Jang, Ying Wang, Hiroshi Ohno, L. Besso, L. Colla, Dae Eun Choi, Natalia Tchebotareva, Gordana Petrusevska, Ryohei Yamamoto, Rifki Ersoy, Aida Afiani, Enyu Imai, Domenica Lasorsa, Paola Mattei, Maurizio Innocenti, Tânia Sousa, Xavier Fulladosa, Weiming Wang, Ágnes Haris, Maho Watanabe, Michael Walsh, Kálmán Polner, Shinji Fukuda, Annamaria D'Apollo, Atilla Uzum, Margherita Conrieri, Martin Lenicek, Valentina Galchinskaya, Yancun Li, Romana Rysava, Young Rok Ham, Joana Vidinha, Dorota Kaminska, Yoshitaka Isaka, Loredana Colla, Orhan Yucel, Irina Bobkova, Elen Almeida Romão, Beata Sulikowska, Jonathan Barratt, Carmen Vozmediano, ChunGyoo Ihm, Joan Torras, Cristiana Rollino, Itziar Navarro, Takao Saito, Funda Alkan Tasli, Kamal Goplani, Hidetoshi Ito, Frank Bridoux, Elisa Caramello, Mustafa Cirit, Alfred Warzywoda, Francesca M. Bosetti, Yoon-Goo Kim, Manuel Praga, Francois Berthoux, Fabrice Bonnet, Maria Teresa Rocchetti, M. Gomà, B. Svobodova, Zoltán Merán, Miguel Moysés Neto, Benjamin Terrier, Wen Zhang, Pinar Yeniay, Takao Koike, Kenichiro Iio, Olga Li, Lisa Mastrofrancesco, Mikhail Shvetsov, Reiko Hayaishi-Okano, Natalia Chebotareva, Francisco Rivera, Wooseong Huh, Giuseppe Paolo Segoloni, Magdalena Krajewska, Laura Morando, Osvaldo Merege Vieira Neto, Vladimir Tesar, Pauline Belenotti, Lise Thibaudin, Juan Manuel Lopez, Satu Sinikka Pesickova, Qiuhua Huang, Sigrid Lundberg, Christophe Mariat, K. Pinar Ozen, Tatiana Rudenko, Gheorghe Bozdog, Yingying Xie, Masao Kikuchi, Giovanna Valenti, Iva Gunnarsson, Abdulkareem Alsuwaida, Jan Penar, Bengt Rippe, Yoshiharu Tsubakihara, Xiao Li, Jolanta Soltysiak, Mohammed Alghonaim, Luc Saint-Martin, G.P. Segoloni, Loreto Gesualdo, Sufia Hussain, Hesham Mohey, Antonio Pasquariello, Sarah Chung, Francesco Quarello, Omran Bakoush, Miho Kimachi, Elena Khafizova, Roberta Camilla, Ida Valentina Suriano, Cristina Gluhovschi, M. Córica, Flaviu Bob, J. Ballarin, Hidenori Inohara, Maria Grazia Chiappini, Karen Molyneux, Eriko Kinugasa, Rosana Gelpi, Dimitrios S. Goumenos, Alessandro Amore, Piero Stratta, Ki Ryang Na, David Jayne, Liliane Ngango, Emmanuelle Plaisier, Anna Bottai, Antai Zheng, Aruna V. Vanikar, Rafał Donderski, Tae-Won Lee, Raffaella Cravero, Márcio Dantas, Yasuyuki Nagasawa, Giuliano Barsotti, Hiroaki Ogata, H. Hakan Yavas, Vaios Sigounas, and Fang Zhong

Subjects
Transplantation, medicine.medical_specialty, Primary (chemistry), Nephrology, business.industry, Internal medicine, medicine, Glomerulonephritis, Clinical nephrology, medicine.disease, business
Published
2011
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