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1. HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients

Author

Ann M. Moyer, Petra Mrázová, Guillaume Canaud, Jack F.M. Wetzels, Nadhir Yousfi, Maryvonne Hourmant, Christophe Legendre, Manish J. Gandhi, Vladimir Tesar, Mariam P. Alexander, Ondrej Viklický, Christiane Mousson, Hanna Debiec, Pierre Ronco, Philippe Rieu, Valérie Dubois, Anne-Els van de Logt, Paul Brenchley, Sylvain Guibert, Vincent Vuiblet, Charlène Levi, Patrick Hamilton, Armando Torres, Bruno Moulin, Eric Letouzé, Josep M. Cruzado, José Aurelio Ballarín Castan, Lena Berchtold, Gabriel Choukroun, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Geneva University Hospital (HUG), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Mayo Clinic [Rochester], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), Radboud University Medical Center [Nijmegen], University of Manchester [Manchester], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biospectroscopie Translationnelle - EA 7506 (BIOSPECT), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University of Barcelona, Universidad de La Laguna [Tenerife - SP] (ULL), Charles University [Prague] (CU), Institute for Clinical and Experimental Medicine (IKEM), Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Département de Néphrologie [CHU Necker], Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], 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, Oncology, medicine.medical_specialty, Linkage disequilibrium, recurrence, HLA-D, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Locus (genetics), Single-nucleotide polymorphism, Glomerulonephritis, Membranous, Polymorphism, Single Nucleotide, genetic risk score, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Internal medicine, medicine, Humans, genetics, PLA2R1, Alleles, Retrospective Studies, Genetic testing, next generation sequencing, medicine.diagnostic_test, business.industry, Donor selection, Receptors, Phospholipase A2, membranous nephropathy, Retrospective cohort study, medicine.disease, Kidney Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, Nephrology, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, transplantation
Abstract

Contains fulltext : 234032.pdf (Publisher’s version ) (Closed access) Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.

Published
2021

2. Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

Author

Bénédicte Janbon, Sophie Caillard, Isabelle Jollet, Elisabeth Cassuto, Elodie Bailly, Bruno Hurault de Ligny, Michel Delahousse, Marc Hazzan, Anne Devys, Antoine Thierry, Pierre Merville, Sophie Girerd, Renaud Snanoudj, Dany Anglicheau, Vincent Vuiblet, Nassim Kamar, Kahina Amokrane, Philippe Grimbert, Eric Rondeau, Gabriel Choukroun, Alexandre Hertig, Marie Metzger, Jean-Luc Taupin, Yann Le Meur, Christophe Legendre, Emmanuel Morelon, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, 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 Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Département de Néphrologie [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie [Amiens], CHU Amiens-Picardie-hôpital Sud, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Etablissement français du sang [Angers], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Foch [Suresnes], Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, 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), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)

Subjects
Adult, Graft Rejection, Male, 0301 basic medicine, Isoantigens, Allosensitization, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, kidney transplantation, Human leukocyte antigen, acute rejection, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA-DQ Antigens, immunosuppression minimization, Humans, Transplantation, Homologous, Medicine, Everolimus, education, Kidney transplantation, education.field_of_study, biology, Drug Substitution, business.industry, Histocompatibility Testing, Patient Selection, Graft Survival, Immunosuppression, Middle Aged, epitopes, medicine.disease, HLA mismatching, 3. Good health, 030104 developmental biology, Nephrology, Immunology, Cyclosporine, antibody-mediated rejection, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies
Abstract

International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.

Published
2019

3. Usefulness of morphometric image analysis with Sirius Red to assess interstitial fibrosis after renal transplantation from uncontrolled circulatory death donors

Author

Alyette Duquesne, Sophie Ferlicot, Charlotte Mussini, Antoine Durrbach, Katia Posseme, Myriam Dao, Hélène François, Catherine Guettier, Christelle Pouliquen, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], Hôpital Bicêtre, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], 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
Adult, Male, medicine.medical_specialty, Biopsy, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal graft, Urology, lcsh:Medicine, Diseases, 030230 surgery, Interstitial fibrosis, Graft function, Article, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Medical research, 0302 clinical medicine, Image Processing, Computer-Assisted, Humans, Medicine, lcsh:Science, Sirius Red, Kidney transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, business.industry, lcsh:R, Reproducibility of Results, Middle Aged, medicine.disease, Fibrosis, Kidney Transplantation, Circulatory death, Tissue Donors, Staining, [SDV] Life Sciences [q-bio], Transplantation, Treatment Outcome, chemistry, Blood Circulation, Female, lcsh:Q, business, Azo Compounds, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Early interstitial fibrosis (IF) correlates with long-term renal graft dysfunction, highlighting the need for accurate quantification of IF. However, the currently used Banff classification exhibits some limitations. The aim of our study was to precisely describe the progression of IF after renal transplantation using a new morphometric image analysis method relying of Sirius Red staining. The morphometric analysis we developed showed high inter-observer and intra-observer reproducibility, with ICC [95% IC] of respectively 0.75 [0.67–0.81] (n = 151) and 0.88 [0.72–0.95] (n = 21). We used this method to assess IF (mIF) during the first year after the kidney transplantation from 66 uncontrolled donors after circulatory death (uDCD). Both mIF and interstitial fibrosis (ci) according to the Banff classification significantly increased the first three months after transplantation. From M3 to M12, mIF significantly increased whereas Banff classification failed to highlight increase of ci. Moreover, mIF at M12 (p = 0.005) correlated with mean time to graft function recovery and was significantly associated with increase of creatininemia at M12 and at last follow-up. To conclude, the new morphometric image analysis method we developed, using a routine and cheap staining, may provide valuable tool to assess IF and thus to evaluate new sources of grafts.

Published
2020

4. Mise au point sur la maladie des anticorps anti-membrane basale glomérulaire ou syndrome de Goodpasture

Author

Emmanuelle Plaisier, Jacques Cadranel, David Saadoun, C. Marques, Patrice Cacoub, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, urologic and male genital diseases, Anti-Glomerular Basement Membrane Disease, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, Goodpasture's syndrome, Medicine, Rapidly progressive glomerulonephritis, Anti-neutrophil cytoplasmic antibody, Autoimmune disease, Basement membrane, business.industry, Gastroenterology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, business, Vasculitis
Abstract

Anti-glomerular basement membrane (anti-GBM) disease or Goodpasture's syndrome is a small vessel vasculitis affecting the capillary beds of kidneys and lungs. It is an autoimmune disease mediated by autoantibodies targeting the glomerular and alveolar basement membranes, leading to pneumorenal syndrome. It is a rare, monophasic and severe disease, associating rapidly progressive glomerulonephritis and alveolar hemorrhage. The presence of antineutrophil cytoplasmic antibodies (ANCA) is reported in 20 to 60% of cases. Management should be prompt and combine plasma exchange with systemic corticosteroids and immunosuppressive therapy by cyclophosphamide. The objective of this review is: 1) to describe the pathogenesis, clinical and histological features of the disease; 2) to characterize double-positive anti-GBM/ANCA patients; 3) to highlight the prognostic factors of renal and global survival, and 4) to focus on the treatment of anti-GBM disease.

Published
2020

5. The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

Author

Lazareth, Hélène, Henique, Carole, Lenoir, Olivia, Puelles, Victor G., Flamant, Martin, Bollée, Guillaume, Fligny, Cécile, Camus, Marine, Guyonnet, Lea, Millien, Corinne, Gaillard, François, Chipont, Anna, Robin, Blaise, Fabrega, Sylvie, Dhaun, Neeraj, Camerer, Eric, Kretz, Oliver, Grahammer, Florian, Braun, Fabian, Huber, Tobias B., Nochy, Dominique, Mandet, Chantal, Bruneval, Patrick, Mesnard, Laurent, Thervet, Eric, Karras, Alexandre, Le Naour, François, Rubinstein, Eric, Boucheix, Claude, Alexandrou, Antigoni, Moeller, Marcus J., Bouzigues, Cédric, Tharaux, Pierre-Louis, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris (AP-HP), Luxembourg Institute of Health (LIH), Systèmes Multi-Agents et Comportements (SMAC), Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille, Département de recherche translationnelle, Institut Curie, Plateforme Vecteurs Viraux et Transfert de Gènes [SFR Necker] (VVTG), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Renal Division, Freiburg University Medical Center, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Paul Brousse, Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'optique et biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire [PARCC - UMR-S U970], Institut Cochin [IC UM3 (UMR 8104 / U1016)], Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires [LRI - EA4062], Génétique moléculaire de la neurotransmission et des processus neurodégénératifs [LGMNPN], Luxembourg Institute of Health [LIH], Systèmes Multi-Agents et Comportements [SMAC], Plateforme Vecteurs Viraux et Transfert de Gènes [SFR Necker] [VVTG], Centre de Recherche des Cordeliers [CRC (UMR_S 872)], Hôpital Européen Georges Pompidou [APHP] [HEGP], Laboratoire d'optique et biosciences [LOB], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Université de Lille, Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'Optique et Biosciences (LOB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Department of Nephrology and Clinical Immunology [Aachen, Germany], Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University-RWTH Aachen University, Department of Medicine III [Hamburg, Germany] (Faculty of Medicine), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Department of Nephrology and Center for Inflammatory Diseases [Melbourne, VIC, Australia], Monash University [Melbourne], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Renal Medicine [Scotland, UK], Royal Infirmary of Edinburgh, Renal Division [Freiburg, Germany], Service de néphrologie et de transplantation rénale [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), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Modèles de Cellules Souches Malignes et Thérapeutiques, This work was supported by Institut National de Santé et de la Recherche Médicale (INSERM), research grants from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ ERC grant agreement n°107037), European Research Projects on Rare Diseases E-Rare-2 JTC 2011 from l’Agence Nationale de la Recherche (ANR) of France and the Freiburg Institute for Advanced Studies to P.-L.T. We thank National Health and Medical Research Council of Australia, the Humboldt Foundation and German Society of Nephrology for supporting VGP. We are grateful to Assistance Publique des Hôpitaux de Paris for supporting H.L. We thank the European Research Council for supporting C.H. and O.L. We thank Nano-K for supporting the Laboratoire d’Optique et de Biosciences at Ecole Polytechnique., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Ecole Centrale de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille-Centre National de la Recherche Scientifique (CNRS), Tharaux, Pierre-Louis, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH)-Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Service d'Urgences néphrologiques et transplantation rénale [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
Male, [SDV]Life Sciences [q-bio], Science, Focal segmental glomerulosclerosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Article, Tetraspanin 29, Mice, Glomerulonephritis, Cell Movement, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Humans, Cell migration, lcsh:Science, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Glomerulosclerosis, Focal Segmental, urogenital system, Epithelial Cells, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, female genital diseases and pregnancy complications, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Mechanisms of disease, embryonic structures, Disease Progression, Female, Kidney Diseases, lcsh:Q, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here we show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions., In both focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN), kidney injury is characterised by the invasion of glomerular tufts by parietal epithelial cells (PECs). Here Lazareth et al. identify the tetraspanin CD9 as a key regulator of PEC migration, and find its upregulation in FSGS and CGN contributes to kidney injury in both diseases.

Published
2019

6. The Case | Acute kidney injury associated with chronic myelomonocytic leukemia

Author

Eric Rondeau, Yosu Luque, Jérémy Pichon, Inna Mohamadou, Stéphane Gaudry, David Buob, Isabelle Brocheriou, Cédric Rafat, Marion Rabant, Service d'Urologie [CHU Pitié-Salpêtrière], 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), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de néphrologie et de transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], and Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP)

Subjects
medicine.medical_specialty, business.industry, 030232 urology & nephrology, Acute kidney injury, Chronic myelomonocytic leukemia, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Leukemia, Myelomonocytic, Chronic, Acute Kidney Injury, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, 3. Good health, Fanconi syndrome, 03 medical and health sciences, 0302 clinical medicine, Nephrology, proximal tubule, Internal medicine, medicine, Humans, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

7. B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab

Author

Karine Dahan, Tabassome Simon, Eva Languille, Michelle Rosenzwajg, Joana Hygino, Hanna Debiec, Pierre Ronco, David Klatzmann, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), 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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie - Immunopathologie - Immunothérapie (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), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de néphrologie et de transplantation rénale [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), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, Chemokine, Time Factors, 030232 urology & nephrology, Glomerulonephritis, Membranous, Severity of Illness Index, T-Lymphocytes, Regulatory, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, regulatory T cells, Podocyte, rituximab, 0302 clinical medicine, natural killer cells, biology, Middle Aged, CD56 Antigen, 3. Good health, Killer Cells, Natural, Phenotype, Treatment Outcome, medicine.anatomical_structure, Nephrology, Female, Rituximab, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Antibody, Immunosuppressive Agents, medicine.drug, Adult, Paris, T cell, B-Lymphocyte Subsets, GPI-Linked Proteins, Immunophenotyping, 03 medical and health sciences, Membranous nephropathy, Predictive Value of Tests, memory B cells, medicine, Humans, In patient, Aged, Autoantibodies, Tumor Necrosis Factor-alpha, business.industry, Receptors, IgG, Interleukin-2 Receptor alpha Subunit, membranous nephropathy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, CD4 Lymphocyte Count, 030104 developmental biology, Supportive psychotherapy, TNF-α, Immunology, biology.protein, Interleukin-5, business, Biomarkers
Abstract

International audience; Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56brightCD16-/lo NK subset. There were a significantly decreased percentage of regulatory T cells, together with an increased plasma concentration of TNF-alpha, IL-5 and IL-2RA. We then investigated 16 patients at eight days and three and six months after treatment with rituximab added to supportive therapy compared to nine patients with supportive therapy alone. After rituximab, B-cell recovery was still incomplete at six months, with persistent alterations of B-cell subsets, a significant increase of both T-regulatory (Treg) cells and NK cells, and a significant decrease of both the CD56brightCD16-/lo NK subset and TNF-alpha levels. The patients who clinically responded to rituximab had a significantly lower percentage of Tregs at baseline compared to non-responders and a significantly increased percentage at day eight. Tregs remained unchanged in non-responders and in patients treated with supportive therapy alone. Thus, evaluation of Tregs might be useful for predicting early response to rituximab.

Published
2017

8. Efficacy and tolerance of sustained low-efficiency dialysis with calcium-free citrate-containing dialysate anticoagulation

Author

Clara Vigneron, Cédric Rafat, Adrien Joseph, Eric Rondeau, Christophe Ridel, Matthieu Jamme, Juliet Schurder, Guillaume Lefèvre, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de néphrologie et de transplantation rénale [CHU Tenon], Service de biochimie et hormonologie [CHU Tenon], and AURA Paris - Plaisance

Subjects
Transplantation, Sustained low-efficiency dialysis, business.industry, 030232 urology & nephrology, chemistry.chemical_element, 030208 emergency & critical care medicine, Calcium, Pharmacology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Text mining, chemistry, Nephrology, Medicine, Letters to the Editor, AcademicSubjects/MED00340, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

9. The cannabinoid receptor 1 is involved in renal fibrosis during chronic allograft dysfunction: Proof of concept

Author

Sophie Vandermeersch, Antoine Durrbach, Lola Lecru, Mélanie Ferreira, Christos Chatziantoniou, Bogdan Hermeziu, Katia Posseme, Hélène François, Myriam Dao, Charlotte Mussini, Sophie Ferlicot, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Galapagos SASU [Romainville, France], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, Cannabinoid receptor, [SDV]Life Sciences [q-bio], Mice, 0302 clinical medicine, Receptor, Cannabinoid, CB1, Rimonabant, Fibrosis, Cells, Cultured, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, chronic allograft dysfunction, Middle Aged, renal transplantation, Endocannabinoid system, renal fibrosis, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, Female, lipids (amino acids, peptides, and proteins), Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, Tacrolimus, 03 medical and health sciences, Internal medicine, Renal fibrosis, medicine, Animals, Humans, Retrospective Studies, business.industry, Original Articles, Cell Biology, medicine.disease, Kidney Transplantation, Mice, Inbred C57BL, Transplantation, cannabinoid receptor 1, 030104 developmental biology, Endocrinology, Chronic Disease, Primary Graft Dysfunction, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Chronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss. The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD. We retrospectively quantified CB1 expression and correlated it with renal fibrosis in 26 kidney-transplanted patients who underwent serial routine kidney biopsies. Whereas CB1 expression was low in normal kidney grafts, it was highly expressed during CAD, especially in tubular cells. CB1 expression significantly increased early on after transplantation, from day 0 (D0) to month 3 post-transplant (M3) (22.5% ± 15.4% vs 33.4% ± 13.8%, P < .01), and it remained stable thereafter. CB1 expression correlated with renal fibrosis at M3 (P = .04). In an in vitro model of tacrolimus-mediated fibrogenesis by tubular cells, we found that tacrolimus treatment significantly induced mRNA and protein expression of CB1 concomitantly to col3a1 and col4a3 up regulation. Administration of rimonabant, a CB1 antagonist, blunted collagen synthesis by tubular cells (P < .05). Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology.

Published
2019

10. Rapid Occurrence of Chronic Kidney Disease in Patients Experiencing Reversible Acute Kidney Injury after Cardiac Surgery

Author

Jean-Luc Hanouz, Pierre Galichon, Alexandre Hertig, Sylvie Chevret, Anne Boutten, Jean-Luc Fellahi, Dimitrios Buklas, Aurélien Bataille, David Legouis, Sophie Provenchère, Service d'Anesthésie - Réanimation Chirurgicale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie [CHU Bichat], Service de chirurgie cardiaque [CHU Caen], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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), Normandie Université (NU), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-UPMC, Gestionnaire

Subjects
Male, Postoperative Complications/epidemiology, Nephrology, medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Urology, Renal function, Comorbidity, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030204 cardiovascular system & hematology, France/epidemiology, Risk Assessment, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Time, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, In patient, 030212 general & internal medicine, Renal Insufficiency, Chronic, Cardiac Surgical Procedures, Propensity Score, Renal Insufficiency, Chronic/epidemiology, 10. No inequality, Aged, Retrospective Studies, business.industry, urogenital system, Acute kidney injury, Retrospective cohort study, Acute Kidney Injury, Middle Aged, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Surgery, Cardiac surgery, Anesthesiology and Pain Medicine, Female, France, business, Acute Kidney Injury/epidemiology, Kidney disease
Abstract

Background There is recent evidence to show that patients suffering from acute kidney injury are at increased risk of developing chronic kidney disease despite the fact that surviving tubular epithelial cells have the capacity to fully regenerate renal tubules and restore renal function within days or weeks. The aim of the study was to investigate the impact of acute kidney injury on de novo chronic kidney disease. Methods The authors conducted a retrospective population-based cohort study of patients initially free from chronic kidney disease who were scheduled for elective cardiac surgery with cardiopulmonary bypass and who developed an episode of acute kidney injury from which they recovered. The study was conducted at two French university hospitals between 2005 and 2015. These individuals were matched with patients without acute kidney injury according to a propensity score for developing acute kidney injury. Results Among the 4,791 patients meeting the authors’ inclusion criteria, 1,375 (29%) developed acute kidney injury and 685 fully recovered. Propensity score matching was used to balance the distribution of covariates between acute kidney injury and non- acute kidney injury control patients. Matching was possible for 597 cases. During follow-up, 34 (5.7%) had reached a diagnosis of chronic kidney disease as opposed to 17 (2.8%) in the control population (hazard ratio, 2.3; bootstrapping 95% CI, 1.9 to 2.6). Conclusions The authors’ data consolidate the recent paradigm shift, reporting acute kidney injury as a strong risk factor for the rapid development of chronic kidney disease.

Published
2016

11. Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In Vivo

Author

Sandrine Placier, Chantal Jouanneau, David Legouis, Alexandre Hertig, Guillaume Lefevre, David Buob, Sophie Vandermeersch, Morgane Wetzstein, Naïke Bigé, Yi-Chun Xu-Dubois, Aurélien Bataille, Caroline Martin, Eric Rondeau, Juan L. Iovanna, Pierre Galichon, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de néphrologie et de transplantation rénale [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), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Cyclosporine/toxicity, Biology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nephrotoxicity, 03 medical and health sciences, Mice, Neoplasm Proteins/genetics, Downregulation and upregulation, In vivo, Stress, Physiological, Cyclosporin a, Gene expression, medicine, Animals, Humans, ATF4, Kidney Diseases/chemically induced/genetics, General Medicine, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Neoplasm Proteins, DNA-Binding Proteins, 030104 developmental biology, Basic Research, Nephrology, Apoptosis, Cancer research, Cyclosporine, Kidney Diseases, Cell activation, DNA-Binding Proteins/genetics
Abstract

International audience; Acute tubular damage is a major cause of renal failure, especially at the early phase of kidney transplant when ischemia-reperfusion injury and cyclosporin A toxicity may coexist. The mechanisms of the latter are largely unknown. Using an mRNA microarray on microdissected tubules from a rat model of cyclosporin A toxicity to describe the related epithelial-specific transcriptional signature in vivo, we found that cyclosporin A induces pathways dependent on the transcription factor ATF4 and identified nuclear protein transcriptional regulator 1 (Nupr1), a stress response gene induced by ATF4, as the gene most strongly upregulated. Upon cyclosporin A treatment, Nupr1-deficient mice exhibited worse renal tubular lesions than wild-type mice. In primary cultures treated with cyclosporin A, renal tubular cells isolated from Nupr1-deficient mice exhibited more apoptosis and ATP depletion than cells from wild-type mice. Furthermore, cyclosporin A decreased protein synthesis and abolished proliferation in wild-type tubular cells, but only reduced proliferation in Nupr1-deficient cells. Compared with controls, mouse models of ischemia-reperfusion injury, urinary obstruction, and hypertension exhibited upregulated expression of renal NUPR1, and cyclosporin A induced Nupr1 expression in cultured human tubular epithelial cells. Finally, immunohistochemical analysis revealed strong expression of NUPR1 in the nuclei of renal proximal tubules of injured human kidney allografts, but not in those of stable allografts. Taken together, these results suggest that epithelial expression of NUPR1 has a protective role in response to injury after renal transplant and, presumably, in other forms of acute tubular damage.

Published
2016

12. Early steroid withdrawal and optimization of mycophenolic acid exposure in kidney transplant recipients receiving mycophenolate mofetil

Author

Antoine Thierry, Yannick Le Meur, Michel Delahousse, Yvon Lebranchu, Nacera Ouali, Denis Glotz, Stephanie Rouanet, Laeticia Albano, Michèle Kessler, Nailya Tagieva, Philippe Lang, François Glowacki, François Vrtovsnik, Maïté Jauréguy, Nassim Kamar, Valérie Garrigue, Jean-Philippe Rerolle, Lionel Couzi, Anne-Elisabeth Heng, Christiane Mousson, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Department of Nephrology, University Hospital, Lille, France., Department of Nephrology, University Hospital, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Department of Nephrology, Transplantation and Peritoneal Dialysis, University Hospital, Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Department of Nephrology and Transplantation, Foch Hospital, Department of Nephrology and Transplantation, University Hospital, Nice, Departement of Nephrology and Transplantation, University Hospital, Nice, Budapest University of Technology and Economics [Budapest] (BME), Department of Nephrology, Transplantation and Dialysis, Bordeaux, France, Department of Nephrology, Transplantation and Dialysis, Bordeaux, Department of Nephrology, University Hospital, Amiens, France, Department of Nephrology, University Hospital, Amiens, Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Roche SAS, Neuilly-sur-Seine, France, Laboratoire Roche SAS, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Graft Rejection, Male, Biopsy, 030232 urology & nephrology, 030230 surgery, Kidney, MESH: Cyclosporine, MESH: Dose-Response Relationship, Drug, MESH: Kidney Transplantation, MESH: Biopsy, 0302 clinical medicine, Adrenal Cortex Hormones, Risk Factors, MESH: Risk Factors, Clinical endpoint, Prospective Studies, Prospective cohort study, MESH: Treatment Outcome, MESH: Middle Aged, medicine.diagnostic_test, MESH: Withholding Treatment, Middle Aged, 3. Good health, Treatment Outcome, Tolerability, Cyclosporine, Corticosteroid, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, Urology, MESH: Graft Rejection, Mycophenolic acid, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, medicine, Humans, MESH: Mycophenolic Acid, Transplantation, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Adult, MESH: Kidney, Mycophenolic Acid, Kidney Transplantation, MESH: Male, MESH: Prospective Studies, Discontinuation, Surgery, Regimen, Withholding Treatment, Therapeutic drug monitoring, Feasibility Studies, business, MESH: Feasibility Studies, MESH: Female
Abstract

International audience; Early posttransplant steroid withdrawal may increase the risk of acute rejection and the occurrence of subclinical acute rejection (SCAR). We assessed the feasibility and safety of early steroid withdrawal in low-risk patients receiving cyclosporine A (CsA) and the impact of optimization of mycophenolic acid exposure on steroid withdrawal success. De novo, low-immunological risk kidney recipients received an anti-interleukin-2-receptor-α antibody induction, a short course of 7 days of corticosteroids, and CsA with 2-hr postdose concentration monitoring. They were randomized to adjusted dose (AD) of mycophenolate mofetil (MMF) using therapeutic drug monitoring (TDM) or a fixed-dose (FD) regimen. MMF 3 g was initiated posttransplant and then adjusted starting at week 2 to a 0 to 12 hr area under the concentration time curve of 40 mg · h/L versus 2 g daily, respectively. The primary endpoint was a composite of the proportion of patients experiencing biopsy-proven acute rejection (BPAR) and those with SCAR identified on the 3-month protocol biopsy. Among 247 analyzed patients, only 22 in the AD group and 17 in the FD group experienced BPAR or SCAR (P=0.46). The rate of SCAR was low: 4% (AD) and 2.5% (FD). No between-group difference in the incidence of BPAR was observed. TDM yielded MMF doses ranging from 1 to 4 g/d and significantly reduced interpatient variability at weeks 26 and 52 in the AD group. In low-immunological risk kidney recipients, MMF combined with CsA allows early corticosteroid discontinuation with good tolerability. In this group of patients, TDM of MMF does not improve clinical outcome.

Published
2011

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