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1. High‐flow arteriovenous fistula and hemodynamic consequences at 1 year after kidney transplantation

Author: Alexandra Monnier, Nicolas Keller, Bernard Geny, Samy Talha, Noëlle Cognard, Bruno Moulin, and Sophie Caillard
Subjects: medicine.medical_specialty, Cardiac output, business.industry, Fistula, Hemodynamics, Arteriovenous fistula, medicine.disease, Kidney Transplantation, Cohort Studies, Arteriovenous Shunt, Surgical, Renal Dialysis, Nephrology, Internal medicine, Arteriovenous Fistula, medicine, Cardiology, Humans, Prospective Studies, business, High flow, Pathological, Kidney transplantation, Cohort study
Abstract: INTRODUCTION There are only scarce data regarding the cardiovascular impact of arteriovenous fistula after kidney transplantation depending on fistula flow. METHODS We performed a single-center, prospective, cohort study including 49 patients with a functional fistula at 1 year from kidney transplantation. Patients were convened for a clinical work-up, a biological analysis, a fistula's Doppler ultrasonography and an echocardiography. Main judgment criterion was comparison of echocardiography parameters between patients with relative (fistula flow >1 L/min and a fistula flow/cardiac output ratio >20%), absolute high-flow fistula (fistula flow >2 L/min) and normal-flow fistula. RESULTS High-flow fistula frequency was 69%. Significantly higher left ventricular end-diastolic and systolic diameters were observed in this group compared with the normal-flow fistula group (53 ± 6 vs. 48 ± 7 mm; p = 0.04 and 33 ± 6 vs. 28 ± 8 mm; p = 0.02) and between the absolute and relative high-flow fistula subgroups (56 ± 6 vs. 51 ± 6 mm; p = 0.009 and 35 ± 6 vs. 31 ± 5 mm; p = 0.01). The study showed no other significant differences. CONCLUSIONS This study showed a significantly higher but not pathological left ventricular end-diastolic and systolic diameters values in patients with high-flow fistula compared with patients with normal-flow fistula and between patients with respectively absolute and relative high-flow fistula.
Published: 2021

2. SARS-Cov-2 Seroprevalence in a French Kidney Transplant Center Located Within a 'High-risk' Zone

Author: Gabriela Gautier Vargas, Vanessa Jegou, Karima Kedjam, Jonas Martzloff, Bruno Moulin, Ilies Benotmane, Céline Meidinger, Audrey Desmarquets, Laura Braun, Lucille Steinmetz, Sophie Caillard, Sandra Ludwiller, Francoise Heibel, Noëlle Cognard, Murielle Morvan, Xavier Bassand, Dominique Schmitt, Danielle Roy, Amandine Bigot, Peggy Perrin, Anne Rihon, Jérôme Olagne, David Marx, and Samira Fafi Kremer
Subjects: Transplantation, medicine.medical_specialty, SARS-CoV-2, Transmission (medicine), business.industry, COVID-19, Outbreak, Seroepidemiologic Studies, Antibodies, Viral, medicine.disease, Kidney Transplantation, Asymptomatic, Covid, Serology, Internal medicine, Cohort, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, medicine, Humans, Seroprevalence, France, medicine.symptom, business, Kidney transplantation
Abstract: Supplemental Digital Content is available in the text., Background. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in kidney transplant recipients (KTRs) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France’s highest risk zone (Grand Est) for coronavirus disease 2019 (Covid-19) during the initial disease outbreak. Methods. To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTRs. Results. SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTRs had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTRs and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission. Conclusions. Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTRs living in one of the France’s highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. Rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.
Published: 2021

3. Living kidney donor evaluation for all candidates with normal estimated GFR for age

Author: Dimitri Titeca-Beauport, Nassim Kamar, Didier Ducloux, Benoit Barrou, Lola Jacquemont, Lionel Couzi, Nicolas Bouvier, Valérie Moal, Fatouma Touré, Bruno Moulin, Yann Le Meur, Cyril Garrouste, Denis Glotz, Lionel Rostaing, Antoine Thierry, Marie Courbebaisse, Hélène Lazareth, Isabelle Etienne, Jonathan M. Chemouny, François Gaillard, Christophe Legendre, Claire Pouteil-Noble, Philippe Rieu, Marc Hazzan, Mathias Büchler, Philippe Grimbert, Laetitia Albano, Michel Delahousse, Maryvonne Hourmant, Pierre Delanaye, Nacera Ouali, Luc Frimat, Christiane Mousson, Moglie Le Quintrec, Alexandre Hertig, Christophe Mariat, Retiveau, Nolwenn, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Clermont-Ferrand, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital de Bohars - CHRU Brest (CHU - BREST ), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Tenon [AP-HP], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, CHU Pontchaillou [Rennes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Liège, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Hôpital Nord (Saint Etienne), CHU Toulouse [Toulouse]-PRES Université de Toulouse, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Population, Urology, Renal function, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Kidney, Nephrectomy, MESH: Kidney Transplantation, 03 medical and health sciences, Age, Living kidney donors, 0302 clinical medicine, Age groups, Living Donors, medicine, Humans, education, MESH: Living Donors, Transplantation, education.field_of_study, MESH: Humans, MESH: Middle Aged, business.industry, Kidney donation, Estimated GFR, MESH: Kidney, Middle Aged, Post-donation GFR, Kidney Transplantation, MESH: Nephrectomy, MESH: Glomerular Filtration Rate, medicine.anatomical_structure, MESH: Kidney Failure, Chronic, Donation, Screening, Kidney Failure, Chronic, 030211 gastroenterology & hepatology, DONOR EVALUATION, business, Glomerular Filtration Rate
Abstract: International audience; Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is 55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.
Published: 2021

4. 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

5. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis

Author: Kastritis E., Palladini G., Minnema M. C., Wechalekar A. D., Jaccard A., Lee H. C., Sanchorawala V., Gibbs S., Mollee P., Venner C. P., Lu J., Schonland S., Gatt M. E., Suzuki K., Kim K., Cibeira M. T., Beksac M., Libby E., Valent J., Hungria V., Wong S. W., Rosenzweig M., Bumma N., Huart A., Dimopoulos M. A., Bhutani D., Waxman A. J., Goodman S. A., Zonder J. A., Lam S., Song K., Hansen T., Manier S., Roeloffzen W., Jamroziak K., Kwok F., Shimazaki C., Kim J. -S., Crusoe E., Ahmadi T., Tran N., Qin X., Vasey S. Y., Tromp B., Schecter J. M., Weiss B. M., Zhuang S. H., Vermeulen J., Merlini G., Comenzo R. L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Kastritis E., Palladini G., Minnema M.C., Wechalekar A.D., Jaccard A., Lee H.C., Sanchorawala V., Gibbs S., Mollee P., Venner C.P., Lu J., Schonland S., Gatt M.E., Suzuki K., Kim K., Cibeira M.T., Beksac M., Libby E., Valent J., Hungria V., Wong S.W., Rosenzweig M., Bumma N., Huart A., Dimopoulos M.A., Bhutani D., Waxman A.J., Goodman S.A., Zonder J.A., Lam S., Song K., Hansen T., Manier S., Roeloffzen W., Jamroziak K., Kwok F., Shimazaki C., Kim J.-S., Crusoe E., Ahmadi T., Tran N., Qin X., Vasey S.Y., Tromp B., Schecter J.M., Weiss B.M., Zhuang S.H., Vermeulen J., Merlini G., and Comenzo R.L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger
Subjects: Male, Treatment outcome, Immunoglobulin Light-chain Amyloidosis/drug therapy, CD38, Dexamethasone, Cyclophosphamide/administration & dosage, Bortezomib, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, CRITERIA, Immunoglobulin Light-chain Amyloidosis, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, Amyloidosis, Antibodies, Monoclonal, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Antibody, Human, Adult, Dexamethasone/administration & dosage, ANTIBODY DARATUMUMAB, Immunoglobulin light chain, DIAGNOSIS, Antibodies, Monoclonal/administration & dosage, Disease-Free Survival, 03 medical and health sciences, Humans, Cyclophosphamide, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Antineoplastic Combined Chemotherapy Protocols/adverse effects, AL AMYLOIDOSIS, Daratumumab, Amyloid fibril, medicine.disease, Molecular biology, Immunoglobulin Light-chain Amyloidosi, biology.protein, Bortezomib/administration & dosage, business, 030215 immunology
Abstract: Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).
Published: 2021

6. La SFNDT dans la crise de l’épidémie COVID-19

Author: Luc Frimat, Bruno Moulin, François Vrtovsnik, and Maryvonne Hourmant
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease, Virology, Transplantation, Nephrology, Pandemic, medicine, business, Dialysis, Kidney transplantation
Published: 2021

7. Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine

Author: Ilies Benotmane, Gabriela Gautier-Vargas, Samira Fafi-Kremer, Noëlle Cognard, Jérôme Olagne, Laura Braun-Parvez, Jonas Martzloff, Peggy Perrin, Francoise Heibel, Bruno Moulin, and Sophie Caillard
Subjects: Immunity, Cellular, Vaccines, Messenger RNA, business.industry, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease, Kidney Transplantation, Kidney transplant, Vaccination, Immunization, Nephrology, Immunity, Antibody Formation, Immunology, medicine, RNA, Messenger, Renal replacement therapy, business, Letter to the Editor, Kidney transplantation
Published: 2021

8. Aspirin-Free Prasugrel Monotherapy Following Coronary Artery Stenting in Patients With Stable CAD

Author: Breno de Alencar Araripe Falcão, Expedito E. Ribeiro, Bruno Moulin, Gustavo R. Morais, Rutao Wang, Masafumi Ono, Hironori Hara, Pedro A. Lemos, Fernanda Barbosa de Almeida Sampaio, Rodrigo Modolo, Norihiro Kogame, João Eduardo Prudêncio Tinoco, Hideyuki Kawashima, Yoshinobu Onuma, Fernando de Martino, George C. Meireles, Rafael Cavalcante, Carlos M. Campos, Patrícia O. Guimarães, Rogério S. Leite, and Patrick W. Serruys
Subjects: medicine.medical_specialty, Aspirin, Prasugrel, business.industry, medicine.medical_treatment, Percutaneous coronary intervention, 030204 cardiovascular system & hematology, medicine.disease, Cardiac surgery, Surgery, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Conventional PCI, medicine, In patient, cardiovascular diseases, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Artery, medicine.drug
Abstract: Objectives The aim of this study was to evaluate the hypothesis that prasugrel monotherapy following successful everolimus-eluting stent implantation is feasible and safe in patients with stable coronary artery disease (CAD). Background Recent studies have suggested that short dual-antiplatelet therapy strategies may provide an adequate balance between ischemic and bleeding risks. However, the complete omission of aspirin immediately after percutaneous coronary intervention (PCI) has not been tested so far. Methods The study was a multicenter, single-arm, open-label trial with a stopping rule based on the occurrence of definite stent thrombosis (if >3, trial enrollment would be terminated). Patients undergoing successful everolimus-eluting stent implantation for stable CAD with SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores Results From February 22, 2018, to May 7, 2019, 201 patients were enrolled. All patients underwent PCI for stable CAD. Overall, 98.5% of patients were adherent to prasugrel at 3-month follow-up. The primary ischemic and bleeding endpoints occurred in 1 patient (0.5%). No stent thrombosis events occurred. Conclusions Aspirin-free prasugrel monotherapy following successful everolimus-eluting stent implantation demonstrated feasibility and safety without any stent thrombosis in selected low-risk patients with stable CAD. These findings may help underpin larger randomized controlled studies to evaluate the aspirin-free strategy compared with traditional dual-antiplatelet therapy following PCI. (Acetyl Salicylic Elimination Trial: The ASET Pilot Study [ASET]; NCT03469856)
Published: 2020

9. 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

10. IMPact of the COVID-19 epidemic on the moRTAlity of kidney transplant recipients and candidates in a French Nationwide registry sTudy (IMPORTANT)

Author: Olivier Thaunat, Camille Legeai, Dany Anglicheau, Lionel Couzi, Gilles Blancho, Marc Hazzan, Myriam Pastural, Emilie Savoye, Florian Bayer, Emmanuel Morelon, Yann Le Meur, Olivier Bastien, Sophie Caillard, Charlene Levi, Fanny Buron, Alice Koenig, Thomas Barba, Bruno Moulin, Samira Fafi-Kremer, Anglicheau Dany, Alexandre Hertig, Jérôme Tourret, Benoit Barrou, Pierre Merville, Anna Kaminski, Valérie Moal, Tristan Legris, Pierre-François Westeel, Maïté Jaureguy, Luc Frimat, Didier Ducloux, Jamal Bamoulid, Dominique Bertrand, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Yannick Le Meur, Christophe Masset, Nassim Kamar, Hélène Francois, Eric Rondeau, Nicolas Bouvier, Christiane Mousson, Matthias Buchler, Philippe Gatault, Jean-François Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Philippe Grimbert, Marie Matignon, Antoine Durrbach, Clarisse Greze, Renaud Snanoudj, Charlotte Colosio, Betoul Schvartz, Paolo Malvezzi, Christophe Mariat, Antoine Thierry, Moglie Le Quintrec, Antoine Sicard, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cellules B normales et pathogéniques - Normal and pathogenic B cell responses (NOPAB), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Agence de la biomédecine [Saint-Denis la Plaine], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, French nationwide Registry of Solid Organ Transplant Recipients with COVID-19: Olivier Thaunat, Emmanuel Morelon, Charlene Levi, Fanny Buron, Alice Koenig, Thomas Barba, Sophie Caillard, Bruno Moulin, Samira Fafi-Kremer, Marc Hazzan, Anglicheau Dany, Alexandre Hertig, Jérôme Tourret, Benoit Barrou, Lionel Couzi, Pierre Merville, Anna Kaminski, Valérie Moal, Tristan Legris, Pierre-François Westeel, Maïté Jaureguy, Luc Frimat, Didier Ducloux, Jamal Bamoulid, Dominique Bertrand, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Yannick Le Meur, Gilles Blancho, Christophe Masset, Nassim Kamar, Hélène Francois, Eric Rondeau, Nicolas Bouvier, Christiane Mousson, Matthias Buchler, Philippe Gatault, Jean-François Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Philippe Grimbert, Marie Matignon, Antoine Durrbach, Clarisse Greze, Renaud Snanoudj, Charlotte Colosio, Betoul Schvartz, Paolo Malvezzi, Christophe Mariat, Antoine Thierry, Moglie Le Quintrec, Antoine Sicard, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, CCSD, Accord Elsevier, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Pediatrics, MESH: Registries, Registry study, 030232 urology & nephrology, Kidney transplant, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Kidney Transplantation, Postoperative Complications, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Postoperative Complications, Pandemic, MESH: COVID-19, Registries, Wasting, Kidney transplantation, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Middle Aged, renal transplantation, 3. Good health, MESH: Waiting Lists, Nephrology, Female, France, medicine.symptom, Adult, medicine.medical_specialty, Waiting Lists, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Intensive care, medicine, Humans, ESRD, Epidemics, MESH: Epidemics, Aged, Retrospective Studies, MESH: Humans, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, mortality, MESH: Male, MESH: France, 030104 developmental biology, business, MESH: Female
Abstract: International audience; End stage kidney disease increase the risk of COVID-19 related death but how the kidney replacement strategy should be adapted during the pandemic is unknown. Chronic hemodialysis makes social distancing difficult to achieve. Alternatively, kidney transplantation could increase the severity of COVID-19 due to therapeutic immunosuppression and contribute to saturation of intensive care units. For these reasons, kidney transplantation was suspended in France during the first epidemic wave. Here, we retrospectively evaluated this strategy by comparing the overall and COVID-19 related mortality in kidney transplant recipients and candidates over the last three years. Cross-interrogation of two national registries for the period 1 March and 1 June 2020, identified 275 deaths among the 42812 kidney transplant recipients and 144 deaths among the 16210 candidates. This represents an excess of deaths for both populations, as compared with the same period the two previous years (mean of two previous years: 253 in recipients and 112 in candidates). This difference was integrally explained by COVID-19, which accounted for 44% (122) and 42% (60) of the deaths in recipients and candidates, respectively. Taking into account the size of the two populations and the geographical heterogeneity of virus circulation, we found that the excess of risk of death due to COVID-19 was similar for recipients and candidates in high viral risk area but four-fold higher for candidates in the low viral risk area. Thus, in case of a second epidemic wave, kidney transplantation should be suspended in high viral risk areas but maintained outside those areas, both to reduce the excess of deaths of candidates and avoid wasting precious resources.
Published: 2020

11. Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study

Author: François Danion, Céline Duval, François Séverac, Philippe Bachellier, Ermanno Candolfi, Vincent Castelain, Raphaël Clere-Jehl, Julie Denis, Laurence Dillenseger, Eric Epailly, Justine Gantzer, Blandine Guffroy, Yves Hansmann, Jean-Etienne Herbrecht, Valérie Letscher-Bru, Pierre Leyendecker, Pauline Le Van Quyen, Pierre-Olivier Ludes, Guillaume Morel, Bruno Moulin, Catherine Paillard, Benjamin Renaud-Picard, Anne-Claude Roche, Marcela Sabou, Francis Schneider, Morgane Solis, Emilie Talagrand-Reboul, Francis Veillon, Marie-Pierre Ledoux, Célestine Simand, Raoul Herbrecht, Pietro Francesco Addeo, Dominique Astruc, Mathieu Baldacini, Karin Bilger, Marie-Pierrette Chenard, Olivier Collange, Tristan Degot, Nadia Dhif, Elise Dicop, Samira Fafi-Kremer, Luc-Matthieu Fornecker, Charline Fuseau, Max Guillot, Mary-Line Harlay, Ralf Janssen-Langenstein, Benoît Jaulhac, Charlotte Kaeuffer, Romain Kessler, Christine Kummerlen, Annegret Laplace, Anne Launoy, Bruno Lioure, Hamid Merdji, Paul-Michel Mertes, Shanti Natarajan-Ame, Gabriel Nisand, Michele Porzio, Julien Pottecher, Maleka Schenck-Dhif, Cécile Sonntag, Elise Toussaint, Anne Zilliox, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Cancérologie de Strasbourg Europe (ICANS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nanomédecine Régénérative (NanoRegMed), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: 0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Coinfections, Computed tomography, Aspergillosis, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Invasive fungal infections, Internal medicine, medicine, Humans, Leukaemia, 030212 general & internal medicine, Mortality, Child, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Retrospective Studies, Aspergillus species, Aged, 80 and over, medicine.diagnostic_test, business.industry, Coinfection, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, medicine.disease, 3. Good health, Transplantation, Infectious Diseases, Fungal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, Child, Preschool, Hematologic Neoplasms, business
Abstract: Objectives To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. Patients and methods We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. Results Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8–43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2–4.4)), other haematological malignancies (OR 2.1 (1.2–3.8)), other underlying diseases (OR 4.3 (1.4–13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2–3.0)), fever (OR 2.4 (1.5–4.1)), tracheal intubation (OR 2.6 (1.5–4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1–6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3–3.7) and OR 2.2 (1.2–4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1–1.9), p Conclusions Coinfections are frequent in IA patients and are associated with higher mortality.
Published: 2021

12. Clinical utility of biochemical markers for the prediction of COVID-19-related mortality in kidney transplant recipients

Author: Sophie Caillard, Nathalie Chavarot, Hélène Francois, Marie Matignon, Renaud Snanoudj, Jérôme Tourret, Clarisse Greze, Olivier Thaunat, Luc Frimat, Pierre François Westeel, Philippe Gatault, Christophe Masset, Gilles Blancho, Tristan Legris, Valérie Moal, Nassim Kamar, Mariam Jdidou, Charlotte Colosio, Christiane Mousson, Valentin Goutadier, Antoine Sicard, Dominique Bertrand, Jamal Bamoulid, Paolo Malvezzi, Lionel Couzi, Jonathan M. Chemouny, Agnès Duveau, Christophe Mariat, Jean-Philippe Rerolle, Antoine Thierry, Nicolas Bouvier, Dany Anglicheau, Yannick Le Meur, Marc Hazzan, Bruno Moulin, Samira Fafi-Kremer, Alexandre Hertig, Benoit Barrou, Emmanuel Morelon, Pierre Merville, Pierre-François Westeel, Maïté Jaureguy, Didier Ducloux, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Eric Rondeau, Matthias Buchler, Jean-François Augusto, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Philippe Grimbert, Antoine Durrbach, Betoul Schvartz, Moglie Le Quintrec, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Foch [Suresnes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Université de Tours, Centre hospitalier universitaire de Nantes (CHU Nantes), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Bicêtre, Université de Reims Champagne-Ardenne (URCA), Université de Bourgogne (UB), Université de Montpellier (UM), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Grenoble Alpes (UGA), CHU Bordeaux [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Université d'Angers (UA), Université Jean Monnet [Saint-Étienne] (UJM), Université de Limoges (UNILIM), Université de Poitiers, Université de Caen Normandie (UNICAEN), 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), CHU Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Tours (UT), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Jean Monnet - Saint-Étienne (UJM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), and Jonchère, Laurent
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], 030232 urology & nephrology, kidney transplantation, Inflammation, 030204 cardiovascular system & hematology, Kidney transplant, Procalcitonin, 03 medical and health sciences, 0302 clinical medicine, Medicine, Kidney transplantation, Biochemical markers, ComputingMilieux_MISCELLANEOUS, biology, business.industry, troponin, biomarkers, COVID-19, medicine.disease, Troponin, Research Letters, 3. Good health, [SDV] Life Sciences [q-bio], Nephrology, inflammation, D-dimer, Immunology, biology.protein, medicine.symptom, business, procalcitonin
Abstract: International audience
Published: 2021

13. Strong antibody response after a first dose of a SARS-CoV-2 mRNA-based vaccine in kidney transplant recipients with a previous history of COVID-19

Author: Aurélie Velay, Noëlle Cognard, Gabriela Gautier-Vargas, Pierre Gantner, Peggy Perrin, Floriane Gallais, Ilies Benotmane, Sophie Caillard, Francoise Heibel, Samira Fafi-Kremer, Jonas Martzloff, Laura Braun-Parvez, Jérôme Olagne, Bruno Moulin, univOAK, Archive ouverte, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), and Fédération de Médecine Translationnelle de Strasbourg (FMTS)
Subjects: 2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Kidney transplant, Letter to the Editors, Immunology and Allergy, Medicine, Humans, Pharmacology (medical), RNA, Messenger, Letter to the Editor, Transplantation, Messenger RNA, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, SARS-CoV-2, COVID-19, Kidney Transplantation, Transplant Recipients, Past history, Antibody response, Immunization, Immunology, Antibody Formation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: A recent study demonstrated that a single dose of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-based vaccine is sufficient to mount a robust immunological response in immunocompetent subjects with a previous history of coronavirus disease 2019 (COVID-19).1,2 While research has suggested that immunocompromised kidney transplant recipients (KTRs) who received mRNA-based vaccines show low immunization rates,3-5 the question as to whether this also applies to KTRs with a past history of COVID-19 remains unanswered. The aim of this study was to describe the results of immunization after one dose of the mRNA-1273 SARS-CoV-2 vaccine in KTRs who were already seropositive at baseline because of previous exposure to SARS-CoV-2.
Published: 2021

14. French nationwide survey of undocumented end-stage renal disease migrant patient access to scheduled haemodialysis and kidney transplantation

Author: Michel Tsimaratos, Jonas Martzloff, Maryvonne Hourmant, Marc Hazzan, Yosu Luque, Thomas Robert, Raphael Godefroy, Eric Rondeau, Laurent Mesnard, Clément Delthombe, Cédric Rafat, Alice Doreille, and Bruno Moulin
Subjects: Transients and Migrants, Transplantation, medicine.medical_specialty, business.industry, medicine.medical_treatment, 030232 urology & nephrology, MEDLINE, medicine.disease, Nationwide survey, Kidney Transplantation, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Renal Dialysis, Surveys and Questionnaires, Emergency medicine, medicine, Humans, Kidney Failure, Chronic, 030212 general & internal medicine, Hemodialysis, business, Kidney transplantation
Published: 2021

15. Pregnancy in a Kidney Transplant Woman Under Treatment With Eculizumab for Atypical Hemolytic Uremic Syndrome: Is It Safe?

Author: Jérôme Olagne, Bruno Moulin, Marion Fourtage, Mélanie Joly, Peggy Perrin, G. Fritz, Sophie Caillard, Gabriela Gautier Vargas, Anna Duval, and Noëlle Cognard
Subjects: Pregnancy, Pediatrics, medicine.medical_specialty, Nephrology, business.industry, Atypical hemolytic uremic syndrome, medicine, Eculizumab, medicine.disease, business, Kidney transplant, Nephrology Round, medicine.drug
Published: 2019

16. Temporal trends in living kidney donation in France between 2007 and 2017

Author: Nicolas Bouvier, Valérie Moal, Antoine Durrbach, Michel Delahousse, Julien Allard, Alexandre Hertig, Cyril Garrouste, Lionel Couzi, Lionel Rostaing, Claire Pouteil-Noble, Laetitia Albano, Christophe Legendre, Marc Hazzan, Mathias Büchler, Cécile Vigneau, Bruno Moulin, Lola Jacquemont, Luc Frimat, Christophe Mariat, Marie Alice Macher, Christiane Mousson, François Gaillard, Moglie Le Quintrec, Isabelle Etienne, Veena Roberts, Dimitri Titeca-Beauport, Nassim Kamar, Antoine Thierry, Didier Ducloux, Philippe Rieu, Philippe Grimbert, Maryvonne Hourmant, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie, Hôpital Pasteur [Nice] (CHU), Laboratoire de Physiologie, Faculté de médecine Rangueil, Sciences Pour l'Oenologie (SPO), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de transplantation rénale, Hôpital Foch [Suresnes], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), U542, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Néphrologie et Transplantation, CHU Strasbourg, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Reims (CHU Reims), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie 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), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Montpellier 1 (UM1)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, 030232 urology & nephrology, Renal function, 030230 surgery, Body Mass Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, temporal trends, Risk Factors, Internal medicine, medicine, Living Donors, Humans, Registries, 2. Zero hunger, Transplantation, Kidney, business.industry, Incidence, Kidney donation, Middle Aged, medicine.disease, Obesity, Kidney Transplantation, living kidney donors, Young age, Increased risk, medicine.anatomical_structure, Nephrology, Donation, Tissue and Organ Harvesting, Kidney Failure, Chronic, Female, France, business, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Glomerular Filtration Rate
Abstract: Background Long-term studies have demonstrated a slight increased risk for end-stage renal disease (ESRD) for living kidney donors (LKD). In France, living kidney donation doubled within the past 10 years. We investigated the change in characteristics of LKD between 2007 and 2017 and the adequacy of follow-up. Methods Data were obtained from the national registry for LKD. We compared characteristics of LKD between two study periods: 2007–11 and 2012–17, and stratified donors by age and relation to recipient. We aggregated four characteristics associated with higher ESRD risk [young age, first-degree relation to recipient, obesity, low glomerular filtration rate (GFR) for age] in a single risk indicator ranging from 0 to 4. Results We included 3483 donors. The proportion of unrelated donors >56 years of age increased significantly. The proportion of related donors Conclusions An increase in living kidney donation in France does not seem to be associated with the selection of donors at higher risk of ESRD and the proportion of donors with adequate annual follow-up significantly increased.
Published: 2021

17. Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients

Author: Ilies Benotmane, Samira Fafi-Kremer, Laura Braun-Parvez, Bruno Moulin, Peggy Perrin, Jérôme Olagne, Francoise Heibel, Gabriela Gautier-Vargas, Noëlle Cognard, Jonas Martzloff, and Sophie Caillard
Subjects: 0301 basic medicine, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, Population, 030232 urology & nephrology, Kidney transplant, Serology, 03 medical and health sciences, 0302 clinical medicine, medicine, Renal replacement therapy, Seroconversion, education, Kidney transplantation, Messenger RNA, education.field_of_study, business.industry, Immunosuppression, medicine.disease, Virology, Vaccination, 030104 developmental biology, Antibody response, Nephrology, business
Abstract: Data concerning the anti-SARS-CoV-2 antibody response after mRNA COVID-19 vaccine in kidney transplant recipients (KTRs) are currently lacking. Here, we sought to examine this issue by analyzing the serological response observed in 241 KTRs after a first vaccine injection. Our results indicate that KTRs have a weak anti-SARS-CoV-2 antibody response, ultimately resulting in a low seroconversion rate (26/241, 10.8%). This phenomenon likely stems from a high immunosuppression burden in this clinical population.
Published: 2021

18. Is COVID‐19 infection more severe in kidney transplant recipients?

Author: Nathalie Chavarot, Bruno Moulin, Valérie Moal, Olivier Thaunat, Marc Hazzan, Jamal Bamoulid, Antoine Durrbach, Christiane Mousson, Nassim Kamar, Yannick Lemeur, Charlotte Kaeuffer, Clarisse Greze, Philippe Grimbert, Ilies Benotmane, Dominique Bertrand, Antoine Thierry, Tristan Legris, Gilles Blancho, Pierre François Westeel, Mariam Jdidou, Hélène François, Sophie Caillard, Marie Matignon, Yvon Ruch, Morgane Solis, Antoine Sicard, Dany Anglicheau, Philippe Gatault, Valentin Goutaudier, François Danion, Lionel Couzi, Charlotte Colosio, Renaud Snanoudj, Christophe Masset, Agnès Duveau, Jonathan M. Chemouny, Luc Frimat, CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Paris Cité (UPCité), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), CHU Henri Mondor [Créteil], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Tours (UT), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Aix Marseille Université (AMU), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Bourgogne (UB), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Poitiers, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), University of Lille, This study was supported by the Strasbourg University Hospital (COVIS-HUS Study- HUS number 7760), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP Hôpital Tenon [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), 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), University Hospital of Montpellier, Hôpital Bicêtre, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), 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)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), PINIER, CHRISTINE, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Registries, Aucun, MESH: Comorbidity, 030230 surgery, law.invention, chemistry.chemical_compound, 0302 clinical medicine, law, cardiovascular disease, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, clinical research / practice, Immunology and Allergy, Cumulative incidence, Pharmacology (medical), kidney transplantation / nephrology, MESH: Incidence, MESH: Aged, Univariate analysis, MESH: France / epidemiology, MESH: Middle Aged, MESH: Transplant Recipients / statistics & numerical data, Acute kidney injury, Intensive care unit, 3. Good health, MESH: COVID-19 / epidemiology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, glomerular filtration rate (GFR), kidney failure / injury, medicine.medical_specialty, infection and infectious agents - viral, infectious disease, Brief Communication, MESH: Graft Rejection / prevention & control, 03 medical and health sciences, Internal medicine, Diabetes mellitus, MESH: Severity of Illness Index, MESH: COVID-19 / diagnosis, medicine, Humans, MESH: SARS-CoV-2, Mechanical ventilation, Creatinine, Transplantation, MESH: Humans, business.industry, SARS-CoV-2, MESH: Graft Rejection / epidemiology, COVID-19, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, Transplant Recipients, MESH: Male, immunosuppressive regimens, MESH: Immunosuppressive Agents / therapeutic use, MESH: Pandemics, MESH: Propensity Score, chemistry, Reinfection, MESH: Immunosuppression / methods, MESH: Intensive Care Units, business, MESH: Female, MESH: Kidney Transplantation
Abstract: International audience; There are no studies which have compared the risk of severe Covid-19 and related mortality between transplant recipients and non-transplant patients. We enrolled two groups of patients hospitalized for Covid-19, i.e., kidney transplant recipients from the French Registry of Solid Organ Transplant (n=306) and a single-center cohort of non-transplant patients (n=795). An analysis was performed among subgroups matched for age and risk factors for severe Covid-19 or mortality. Severe Covid-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death.Transplant recipients were younger and had more comorbidities compared to non-transplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe Covid-19 did not differ between KTR and non-transplant patients; however, 30-day Covid-19-related mortality was significantly higher in KTR (17.9% versus 11.4%, respectively, p=0.038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe Covid-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR=1.55), and creatinine level >115 µmol/L (HR=2.32) were associated with Covid-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. Kidney transplant recipients had a higher Covid-19-related mortality compared to non-transplant hospitalized patients.
Published: 2021

19. Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis

Author: P.E. Gavand, Y. Dimitrov, Frédéric de Blay, Christian Debry, Dan Lipsker, Gilles Blaison, Yves Hansmann, Jean-Christophe Weber, Olivier Imhoff, Emmanuel Andrès, Benoit Nespola, Hanta Nirina Rakotoarivelo, François Chantrel, Bruno Moulin, Thierry Hannedouche, Yannick Dieudonné, Jacques-Eric Gottenberg, Caroline Lohmann, Olivier Hinschberger, Stéphane Giorgiutti, Anne-Sophie Korganow, Thierry Martin, J. Campagne, Aurélien Guffroy, Laurent Arnaud, François Mathiaux, Alexandre Klein, Marie-Caroline Dalmas, and Vincent Poindron
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Rheumatology, Proteinase 3, Internal medicine, medicine, Prevalence, Immunology and Allergy, Humans, 10. No inequality, Child, 030304 developmental biology, Anti-neutrophil cytoplasmic antibody, Aged, 030203 arthritis & rheumatology, Aged, 80 and over, 0303 health sciences, business.industry, Odds ratio, Environmental Exposure, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Female, France, Vasculitis, Microscopic polyangiitis, Granulomatosis with polyangiitis, business
Abstract: OBJECTIVE Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. METHODS Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. RESULTS Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. CONCLUSION In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.
Published: 2020

20. An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants

Author: Sophie Caillard, Dany Anglicheau, Marie Matignon, Antoine Durrbach, Clarisse Greze, Luc Frimat, Olivier Thaunat, Tristan Legris, Valerie Moal, Pierre Francois Westeel, Nassim Kamar, Philippe Gatault, Renaud Snanoudj, Antoine Sicard, Dominique Bertrand, Charlotte Colosio, Lionel Couzi, Jonathan M. Chemouny, Christophe Masset, Gilles Blancho, Jamal Bamoulid, Agnes Duveau, Nicolas Bouvier, Nathalie Chavarot, Philippe Grimbert, Bruno Moulin, Yannick Le Meur, Marc Hazzan, Samira Fafi-Kremer, Alexandre Hertig, Jérôme Tourret, Benoit Barrou, Emmanuel Morelon, Pierre Merville, Valérie Moal, Pierre-François Westeel, Maïté Jaureguy, Didier Ducloux, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Hélène Francois, Eric Rondeau, Christiane Mousson, Matthias Buchler, Jean-François Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Betoul Schvartz, Paolo Malvezzi, Christophe Mariat, Antoine Thierry, Moglie Le Quintrec, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, CHU Amiens-Picardie, Nouvel Hôpital Civil de Strasbourg, 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), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'investigation clinique [Nancy] (CIC), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, Hôpital Pasteur [Nice] (CHU), CHU Bordeaux [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université d'Angers (UA), Université de Caen Normandie (UNICAEN), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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 Toulouse (UT), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Immunosuppression Therapy, law.invention, chemistry.chemical_compound, 0302 clinical medicine, MESH: Aged, 80 and over, law, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, education.field_of_study, MESH: France / epidemiology, immunosuppression, Mortality rate, Immunosuppression, MESH: Kidney Transplantation / mortality, Intensive care unit, 3. Good health, Nephrology, MESH: Young Adult, Covid-19, medicine.medical_specialty, MESH: COVID-19 / complications, MESH: Postoperative Complications / virology, Population, kidney transplantation, Article, 03 medical and health sciences, Tocilizumab, Internal medicine, Diabetes mellitus, education, MESH: Pandemics / statistics & numerical data, business.industry, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Deprescriptions, mortality, 030104 developmental biology, chemistry, prognosis, business, MESH: Female
Abstract: Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging., Graphical abstract
Published: 2020

21. Hemodynamic Management During Kidney Transplantation: A French Survey

Author: Anne Lejay, Olivier Collange, Walid Oulehri, Bruno Moulin, Sophie Caillard, P.M. Mertes, Jérome Biehler, and Charles Tacquard
Subjects: Male, medicine.medical_specialty, Fluid administration, Central Venous Pressure, Frequency of use, Hemodynamics, 030230 surgery, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Hypovolemia, Surveys and Questionnaires, medicine, Humans, Kidney transplantation, Transplantation, Cvp monitoring, Internet, business.industry, Central venous pressure, medicine.disease, Kidney Transplantation, Emergency medicine, Fluid Therapy, 030211 gastroenterology & hepatology, Surgery, France, medicine.symptom, business, Algorithms
Abstract: Background Hypovolemia or excess fluid load during kidney transplantation may have detrimental effects on the recipient and graft. The aim of our survey was to examine hemodynamic monitoring during kidney transplantation (KT) in French KT centers. Basic Procedures The online survey covered the organization of anesthesia, the type of hemodynamic monitoring available in each center, the frequency of use of each hemodynamic parameter, and the hemodynamic algorithm used to manage fluid administration. Main Findings Twenty-four centers answered the survey (70% of all the 34 French KT centers) and reported performing 2029 KTs in 2016. Anesthesia for KT was performed either by a general team (n = 12, 48%) or less often, by a specific team during open hours (n = 7, 28%), a specific 24-hour/24-hour team (n = 5, 20%), or an emergency team (n = 1, 4%). The centers reported that up to 8 different hemodynamic monitoring techniques were available for KT. Central venous pressure (CVP) is the most frequently used hemodynamic parameter (1278 KT, 63%). Among the 17 centers using CVP monitoring, 9 had no specific algorithm and the other 8 centers used a different algorithm to manage fluids with CVP. The total fluids administered during KT varied from 1000 mL to 3500 mL. Conclusions CVP was still the main hemodynamic parameter used in France during KT in 2016. Our results suggest that a large randomized controlled trial should be performed to specifically address the question of hemodynamic management during KT.
Published: 2020

22. Cytokine release syndrome‐associated encephalopathy in patients with COVID‐19

Author: Gabriela Gautier-Vargas, Seyyid Baloglu, Sophie Caillard, Bruno Moulin, Nicolas Keller, Dimitri Bedo, Nicolas Collongues, Thomas Lavaux, Ilies Benotmane, Xavier Bassand, Stéphane Kremer, Samira Fafi-Kremer, and Peggy Perrin
Subjects: Male, encephalitis, neurological disorders, Brain Edema, Gastroenterology, corticosteroids, 0302 clinical medicine, Cerebrospinal fluid, Adrenal Cortex Hormones, intravenous immunoglobulin, cytokine, Longitudinal Studies, 030212 general & internal medicine, Brain Diseases, medicine.diagnostic_test, Brain, Middle Aged, Magnetic Resonance Imaging, Cytokine release syndrome, Treatment Outcome, Neurology, Blood-Brain Barrier, Original Article, Female, medicine.symptom, kidney, medicine.medical_specialty, Encephalopathy, Clinical Neurology, Immunoglobulins, intravenous immunoglobulins, 03 medical and health sciences, COVID‐19, Internal medicine, medicine, Humans, Aged, Ischemic Stroke, Coma, Cerebellar ataxia, business.industry, COVID-19, Dysautonomia, cytokine release syndrome, Magnetic resonance imaging, Original Articles, medicine.disease, Uremia, neurological manifestations, Neurology (clinical), Nervous System Diseases, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND AND PURPOSE: Neurological manifestations in coronavirus disease (COVID)-2019 may adversely affect clinical outcomes. Severe COVID-19 and uremia are risk factors for neurological complications. However, the lack of insight into their pathogenesis, particularly with respect to the role of the cytokine release syndrome (CRS), is currently hampering effective therapeutic interventions. The aims of this study were to describe the neurological manifestations of patients with COVID-19 and to gain pathophysiological insights with respect to CRS. METHODS: In this longitudinal study, we performed extensive clinical, laboratory and imaging phenotyping in five patients admitted to our renal unit. RESULTS: Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Notably, neurological disturbances were accompanied by laboratory evidence of CRS. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was undetectable in the cerebrospinal fluid (CSF). Hyperalbuminorrachia and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain magnetic resonance imaging findings comprised evidence of acute leukoencephalitis (n = 3, one of whom had a hemorrhagic form), cytotoxic edema mimicking ischaemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted, resulting in rapid recovery from neurological disturbances in two cases. SARS-CoV2 was undetectable in 88 of the 90 patients with COVID-19 who underwent Reverse Transcription-PCR testing of CSF. CONCLUSIONS: Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory and imaging similarities with those of chimeric antigen receptor T-cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.
Published: 2020
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23. Biomarkers of Cytokine Release Syndrome Predict Disease Severity and Mortality From COVID-19 in Kidney Transplant Recipients

Author: Francoise Heibel, Ilies Benotmane, Samira Fafi Kremer, Thomas Lavaux, Gabriela Gautier Vargas, Clement Baldacini, Mylene Sagnard, Heloise Delagreverie, Jérôme Olagne, David Marx, Bruno Moulin, Sophie Caillard, Mickaël Ohana, Nicolas Keller, Margaux Della Chiesa, Noëlle Cognard, Xavier Bassand, Laura Braun, Dimitri Bedo, Dogan-Firat Bozman, and Peggy Perrin
Subjects: Male, medicine.medical_specialty, Population, 030230 surgery, Severity of Illness Index, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, medicine, Coagulopathy, Humans, education, Kidney transplantation, Aged, education.field_of_study, Transplantation, biology, business.industry, Interleukin-6, SARS-CoV-2, Mortality rate, C-reactive protein, Troponin I, COVID-19, Middle Aged, medicine.disease, Kidney Transplantation, Hospitalization, Cytokine release syndrome, C-Reactive Protein, biology.protein, 030211 gastroenterology & hepatology, Female, business, Cytokine Release Syndrome, Biomarkers, Cohort study
Abstract: BACKGROUND Data on coronavirus disease 2019 (COVID-19) in immunocompromised kidney transplant recipients (KTR) remain scanty. Although markers of inflammation, cardiac injury, and coagulopathy have been previously associated with mortality in the general population of patients with COVID-19, their prognostic impact amongst KTR with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has not been specifically investigated. METHODS We conducted a cohort study of 49 KTR who presented with COVID-19. Clinical and laboratory risk factors for severe disease and mortality were prospectively collected and analyzed with respect to outcomes. The study participants were divided into 3 groups: (1) mild disease manageable in an outpatient setting (n = 8), (2) nonsevere disease requiring hospitalization (n = 21), and (3) severe disease (n = 20). RESULTS Gastrointestinal manifestations were common at diagnosis. The 30-day mortality rate in hospitalized patients was 19.5%. Early elevations of C-reactive protein (>100 mg/L) and interleukin-6 (>65 ng/L) followed by increases in high-sensitivity troponin I (>30 ng/L) and D-dimer (>960 ng/mL) were significantly associated with severe disease and mortality. Viral load did not have prognostic significance in our sample, suggesting that outcomes were chiefly driven by a cytokine release syndrome (CRS). CONCLUSIONS Regular monitoring of CRS biomarkers in KTR with COVID-19 is paramount to improve clinical outcomes.
Published: 2020
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24. Atypical hemolytic and uremic syndrome due to C3 mutation in pancreatic islet transplantation: a case report

Author: Marie-Pierrette Chenard, Philippe Baltzinger, Laura Braun-Parvez, M. Greget, Sophie Caillard, Jérôme Olagne, Bruno Moulin, Véronique Frémeaux-Bacchi, Thibault Bahougne, Marion Munch, Laurence Kessler, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Nouvel Hôpital Civil de Strasbourg, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre 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), Nanomédecine Régénérative (NanoRegMed), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Nephrology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Mutation, Missense, 030232 urology & nephrology, 030230 surgery, lcsh:RC870-923, Gastroenterology, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Case report, medicine, Humans, Pancreatic islet function, Kidney transplantation, Atypical Hemolytic Uremic Syndrome, geography, geography.geographical_feature_category, business.industry, Acute kidney injury, Complement C3, Acute Kidney Injury, Eculizumab, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Islet, Kidney Transplantation, 3. Good health, Transplantation, Diabetes Mellitus, Type 1, Atypical hemolytic and uremic syndrome, Kidney Failure, Chronic, Islets of Langerhans transplantation, Pancreatic islet transplantation, business, medicine.drug
Abstract: Background We here report on the first observation of a C3 mutation that is related to atypical hemolytic and uremic syndrome (aHUS), which occurred in a pancreatic islet transplant patient. Immunosuppressive treatments, such as calcineurin inhibitors, have been linked to undesirable effects like nephrotoxicity. Case presentation A 40-year-old man with brittle diabetes, who was included in the TRIMECO trial, became insulin-independent 2 months after pancreatic islet transplantation. About 15 months after islet transplantation, the patient exhibited acute kidney injury due to aHUS. Despite plasma exchange and eculizumab treatment, the patient developed end-stage renal disease. A genetic workup identified a missense variant (p.R592Q) in the C3 gene. In vitro, this C3 variant had defective Factor I proteolytic activity with membrane proteins as cofactor proteins, which was thus classified as pathogenic. About 1 year after the aHUS episode, kidney transplantation was carried out under the protection of the specific anti-C5 monoclonal antibody eculizumab. The patient had normal kidney function, with preserved pancreatic islet function 4 years later. Conclusions Pancreatic islet transplantation could have triggered this aHUS episode, but this link needs to be clarified. Although prophylactic eculizumab maintains kidney allograft function, its efficacy still needs to be studied in larger populations.
Published: 2020

25. Impact of polyclonal antithymocyte globulins on kidney transplant outcomes in real-life: a propensity score analysis

Author: Jamal Bamoulid, Bruno Moulin, Christiane Mousson, Cécile Courivaud, Didier Ducloux, Antoine Durrbach, Luc Frimat, Philippe Rieu, Jean-Michel Rebibou, Anne-Elisabeth Heng, Emilie Gaiffe, Thomas Crepin, and Philippe Saas
Subjects: Oncology, medicine.medical_specialty, biology, business.industry, Kidney transplant, Text mining, Polyclonal antibodies, Internal medicine, Propensity score matching, biology.protein, Medicine, In real life, Antithymocyte globulins, business
Abstract: Background: Randomized studies reported a marginal superiority of polyclonal antithymocyte globulins (ATG, Thymoglobulin®, Sanofi, Gentilly, France, or Fresenius®, Bad Homburg, Germany) to prevent acute rejection compared to monoclonal anti-CD25 antibodies (IL2Ra). Nevertheless, the representativeness and the generalizability of these studies are questionable. Methods: We studied the impact of ATG use in real-life conditions in a multicenter study. Propensity score analysis was performed to address potential confounding by indication. Results: 817 patients were included. Logistic regression revealed that age, male gender, a pre-transplant history of cancer, presence of anti-HLA antibodies, previous kidney transplantation, and transplant center were associated with ATG use. The area under the curve of the propensity score was 0.84 + 0.02. ATG use was not associated with a lower rate of acute rejection (18.2% in ATG-treated patients vs 15.8% in non-ATG-treated patients, p =0.356). Adjustment for propensity score slightly modified the relationship between ATG and acute rejection towards a more neutral effect ( p =0.913). Score match analysis recapitulated the previous result. ATG use was associated with the occurrence of opportunistic infection ( p =0.034). There was no difference in graft loss or death between the two groups. Conclusions: In real-life conditions, ATG does not substantially reduce the risk of acute rejection after kidney transplantation. A better discrimination of patients who may benefit from ATG is required.
Published: 2020

26. In‐depth virological assessment of kidney transplant recipients with COVID‐19

Author: Aurélie Velay, Clement Baldacini, Noëlle Cognard, Ilies Benotmane, Louise Gontard, Margaux Della-Chiesa, Samira Fafi-Kremer, Dogan Firat Bozman, Floriane Gallais, Marie Josée Wendling, Heloise Delagreverie, Dimitri Bedo, Sophie Caillard, Gabriela Gautier-Vargas, Bruno Moulin, Francoise Heibel, Laura Braun-Parvez, Morgane Solis, Mylene Sagnard, Jérôme Olagne, David Marx, Xavier Bassand, Baptiste Panaget, and Peggy Perrin
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Enzyme-Linked Immunosorbent Assay, Comorbidity, 030230 surgery, Brief Communication, Antibodies, Viral, Gastroenterology, Kidney transplant, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Nasopharynx, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Viral shedding, Pandemics, Aged, Transplantation, biology, business.industry, SARS-CoV-2, COVID-19, Middle Aged, Viral Load, Kidney Transplantation, Survival Rate, medicine.anatomical_structure, biology.protein, Female, France, Antibody, business, Viral load, Respiratory tract
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via reverse transcription-polymerase chain reaction and SARS-CoV-2 serology via enzyme-linked immunosorbent assay and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study, we examined hospitalized kidney transplant recipients with nonsevere (n = 21) and severe (n = 19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (P = .010) and mortality (P = .010). All patients harbored antibodies during the second week after symptom onset that persisted for 2 months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.
Published: 2020

27. Rapid resolution of cytokine release syndrome and favorable clinical course of severe COVID-19 in a kidney transplant recipient treated with tocilizumab

Author: Ilies Benotmane, Gabriela Gautier-Vargas, Sophie Caillard, Peggy Perrin, Clement Baldacini, Bruno Moulin, and Nicolas Keller
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical course, medicine.disease, Gastroenterology, Kidney transplant recipient, chemistry.chemical_compound, Cytokine release syndrome, Tocilizumab, chemistry, Nephrology, Internal medicine, medicine, business, Kidney transplantation
Published: 2020
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28. Kidney transplantation improves the clinical outcomes of Acute Intermittent Porphyria

Author: Bruno Moulin, Valérie Chatelet, Laurent Gouya, Sophie Caillard, Nassim Kamar, Renaud Snanoudj, Luc Frimat, Jonathan Maurice Chemouny, Charlène Levi, Nicolas Pallet, Neila Talbi, Alexandre Karras, Hervé Puy, Clément Vachey, Caroline Schmitt, Thibaud Lefebvre, Hélène Lazareth, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Strasbourg, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Foch [Suresnes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Porphobilinogen, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Heme, 030105 genetics & heredity, Kidney, Biochemistry, End stage renal disease, End-stage renal disease, 03 medical and health sciences, Young Adult, Acute Intermittent Porphyria, 0302 clinical medicine, Endocrinology, Chronic kidney disease, Internal medicine, Genetics, medicine, Humans, Porphyria cutanea tarda, Molecular Biology, Kidney transplantation, Dialysis, Acute intermittent porphyria, Porphyrin precursors, business.industry, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Transplantation, Porphyria, Treatment Outcome, Porphyria, Acute Intermittent, Kidney Failure, Chronic, Female, Aminolevulinic acid, business, 030217 neurology & neurosurgery, Kidney disease
Abstract: International audience; Background - Acute Intermittent Porphyria (AIP) is a rare inherited autosomal dominant disorder of heme biosynthesis. Porphyria-associated kidney disease occurs in more than 50% of the patients with AIP, and end stage renal disease (ESRD) can be a devastating complication for AIP patients. The outcomes of AIP patients after kidney transplantation are poorly known. Methods - We examined the outcomes of 11 individuals with AIP, identified as kidney transplant recipients in the French Porphyria Center Registry. Results - AIP had been diagnosed on average 19 years before the diagnosis of ESRD except for one patient in whom the diagnosis of AIP had been made 5 years after the initiation of dialysis. Median follow-up after transplantation was 9 years. A patient died 2 months after transplantation from a cardiac arrest and a patient who received a donation after cardiac death experienced a primary non-function. No rejection episode and no noticeable adverse event occurred after transplantation. Serum creatinine was on average 117 μmol/l, and proteinuria
Published: 2020

29. TO006NON-INVASIVE DIAGNOSIS OF BK VIRUS-ASSOCIATED NEPHROPATHY USING URINARY PROTEOMICS IN KIDNEY ALLOGRAFT PATIENTS

Author: William Mullen, Jérôme Olagne, David Marx, Wilfried Gwinner, Dany Anglicheau, Sophie Caillard, Bruno Moulin, Pierre Marquet, Jochen Metzger, Maarten Naesens, Martin Pejchinovski, and Harald Mischak
Subjects: Transplantation, medicine.medical_specialty, Kidney, medicine.diagnostic_test, business.industry, Urinary system, Urology, Glomerulonephritis, medicine.disease_cause, medicine.disease, BK virus, Nephropathy, medicine.anatomical_structure, Specimen collection, Nephrology, Biopsy, Medicine, business
Abstract: Background and Aims BK virus-associated nephropathy (BKvN) is an important complication occurring after kidney transplantation. Its treatment mainly relies on lowering immune suppression. BKvN’s histological aspect can mimic T cell-mediated rejection (TCMR) and other inflammatory conditions featuring tubulitis and interstitial infiltrate. At present, the screening strategy consists of measuring urinary and blood viral loads of BKv. Upon rising BK viremia, BKvN diagnosis is established by a graft biopsy. Biopsies are invasive and are not suitable for repeated screening. Therefore, the aim of this case-control study was to establish a urinary proteome-based test for BKvN diagnosis. Method Urine was obtained from 700 allograft recipients prior to either protocol or „for cause“ biopsies during the first year of post-transplantation surveillance. Aside from normal biopsy findings (N=294), the histological diagnoses included BKvN (N=50), IFTA II-III (N=145), glomerulonephritis (N=17) and T cell-mediated, antibody-mediated, mixed or borderline rejection episodes (N=194). From all patients, relevant clinical and demographic data including Banff classification scores, HLA mismatches and the presence of donor-specific antibodies was collected at the date of sample collection and in further clinical follow-up. BKvN cases were defined as having SV40-positive immunostaining on allograft biopsy. BKvN patients were considered as cases and all other recipients were considered as controls. Patient’s urinary peptide profiles were generated using capillary electrophoresis coupled to mass spectrometry consisting of 9430 different peptides in the mass range of 0.8 to 20 kDa. Results The CE-MS peptide profiles of randomly selected 30 BKvN cases and 307 kidney allograft controls (one sample per patient) were statistically analyzed to identify the most discriminative peptide markers for BKvN. In total, there were 117 peptides detected to have significantly different urinary excretion rates between both patient groups after false discovery rate adjustment for multiple testing. Thirty-two of these peptides were selected by cross-validated variable selection to establish a Support Vector Machine-based multi-marker model. Applying the 32-peptide marker model to an independent validation cohort consisting of 20 BKvN cases and 343 controls resulted in an area under the receiver operating characteristic curve of 0.86 and a 95% confidence interval from 0.82 to 0.89 with the p-value below 0.0001 and sensitivities and specificities for BKvN diagnosis of 85 and 76 %, respectively. Most notably, distribution of the classification values (figure 1) in the different patient groups of the validation set indicated specificities of the peptide marker model for TCMR/borderline of 85% (17 of 20 true negative classifications) and for viruria/viremia of 73% (8 of 11 true negative classifications) Conclusion In conclusion, the established urinary peptide marker model might serve as a non-invasive diagnostic test for BKvN and its differentiation from TCMR and states of isolated viruria or viremia.
Published: 2020

30. First case of COVID‐19 in a kidney transplant recipient treated with belatacept

Author: David Marx, Ilies Benotmane, Samira Fafi-Kremer, Peggy Perrin, Sophie Caillard, Gabriela Gautier, and Bruno Moulin
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), immunosuppressant, infectious disease, kidney transplantation/nephrology, immunosuppression/immune modulation, clinical research/practice, Belatacept, Internal medicine, Pandemic, medicine, infection and infectious agents—viral, Immunology and Allergy, Pharmacology (medical), Letters to the Editor, Letter to the Editor, Kidney transplantation, Transplantation, business.industry, medicine.disease, Kidney transplant recipient, Tomography x ray computed, Infectious disease (medical specialty), business, medicine.drug
Published: 2020
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31. Development and validation of an optimized integrative model using urinary chemokines for noninvasive diagnosis of acute allograft rejection

Author: Renaud Snanoudj, Marie Essig, Maarten Naesens, Agathe Vermorel, Arnaud Devresse, Dany Anglicheau, Jérôme Olagne, David Marx, Sophie Caillard, Fabiola Terzi, Virginia Sauvaget, Pierre Marquet, Claire Tinel, Marion Rabant, Wilfried Gwinner, Marc Olivier Timsit, Bruno Moulin, Lucile Amrouche, Véronique Avettand-Fenoel, Christophe Legendre, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
Subjects: Graft Rejection, medicine.medical_specialty, Urinary system, Urology, Renal function, 030230 surgery, medicine.disease_cause, Chemokine CXCL9, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Transplantation, Creatinine, Polyomavirus Infections, business.industry, Area under the curve, medicine.disease, Allografts, Kidney Transplantation, Confidence interval, BK virus, Chemokine CXCL10, Tumor Virus Infections, chemistry, BK Virus, business, Viral load
Abstract: The urinary chemokines CXCL9 and CXCL10 are promising noninvasive diagnostic markers of acute rejection (AR) in kidney recipients, but their levels might be confounded by urinary tract infection (UTI) and BK virus (BKV) reactivation. Multiparametric model development and validation addressed these confounding factors in a training set of 391 samples, optimizing the diagnostic performance of urinary chemokines. CXCL9/creatinine increased in UTI and BKV viremia with or without nephropathy (BKVN) (no UTI/leukocyturia/UTI: -0.10/1.61/2.09, P = .0001 and no BKV/viremia/BKVN: -0.10/1.90/2.29, P
Published: 2020

32. Does a Useful Test Exist to Properly Evaluate the Pathogenicity of Donor-specific Antibodies? Lessons From a Comprehensive Analysis in a Well-studied Single-center Kidney Transplant Cohort

Author: Mélanie Joly, Nadine Froelich, Peggy Perrin, Philippe Guntz, Jérôme Olagne, Gabriela Gautier Vargas, Christian Gachet, Noëlle Cognard, Bruno Moulin, Sophie Caillard, and A. Parissiadis
Subjects: Graft Rejection, Male, Time Factors, Biopsy, 030230 surgery, Single Center, Gastroenterology, 0302 clinical medicine, HLA Antigens, Isoantibodies, Child, Kidney, medicine.diagnostic_test, biology, Complement Fixation Tests, Graft Survival, Middle Aged, medicine.anatomical_structure, Treatment Outcome, Complement C3d, Child, Preschool, Cohort, 030211 gastroenterology & hepatology, Female, Antibody, Adult, medicine.medical_specialty, Adolescent, Renal function, 03 medical and health sciences, Young Adult, Monitoring, Immunologic, Predictive Value of Tests, Internal medicine, medicine, Humans, Clinical significance, Aged, Retrospective Studies, Transplantation, business.industry, Donor specific antibodies, Complement C1q, Reproducibility of Results, Kidney Transplantation, body regions, biology.protein, business, Biomarkers
Abstract: Background Donor-specific antibodies (DSA) play a major role in antibody-mediated rejection (AMR) and graft dysfunction. However, the clinical relevance of complement-binding anti-HLA antibodies remains unclear. Methods Here, we analyzed DSA detected in the serum (sDSA) using single antigen bead, C1q, and C3d assays combined with the study of intragraft DSA (gDSA) in 86 patients who had DSA and underwent a kidney biopsy for cause (n = 58) or without evidence of kidney dysfunction (n = 28). DSA characteristics were collected and related to the presence of AMR, graft histological features, and allograft survival. Results Forty-five patients (52%) had C1q DSA, and 42 (51%) had C3d DSA. Allograft biopsies revealed AMR in 63 cases (73%), regardless of kidney function. gDSA were identified in 74% of biopsies. We observed a strong correlation among single antigen bead mean fluorescence intensity and complement assays positivity, presence of gDSA, and AMR occurrence. Conclusions Complement-binding DSA per se were not significantly associated with allograft survival in the entire study sample. Finally, gDSA predicted subsequent graft loss in patients who showed a stable renal function at the day of biopsy. Our data suggest that DSA mean fluorescence intensity and presence of gDSA might provide prognostic information during posttransplant monitoring.
Published: 2020

33. A comparative review of use of sulphate and phosphate salts for colonoscopy preparations and their potential for nephrotoxicity

Author: Bruno Moulin and Thierry Ponchon
Subjects: medicine.medical_specialty, chemistry.chemical_element, Review, Nephron, Calcium, Gastroenterology, Nephrotoxicity, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Pharmacology (medical), Phosphate nephropathy, lcsh:RC799-869, Kidney, Creatinine, business.industry, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Toxicity, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, business
Abstract: Background and study aims Colonoscopy is a widely used diagnostic procedure which requires prior cleansing of the bowel. Many different bowel cleansing preparations have been developed, all of which have specific advantages and disadvantages. This review compares two low-volume high-osmolarity bowel cleansing preparations, oral phosphate salts and oral sulphate salts, with a particular focus on risk of nephrotoxicity.Patients and methods An electronic search of the Medline database was performed using the search terms “(phosphates OR sulfates) AND cathartics [MeSH Term] AND kidney” restricted to humans with a cut-off date of December 31, 2016.Results Introduction of oral phosphate salts offered the advantage of low intake volume and low risk of bowel irritation compared to previous options. However, phosphate salts have been associated with renal toxicity (acute phosphate nephropathy [APN]), thought to arise due to perturbations of calcium and phosphate homeostasis as a consequence of increases in serum phosphate. This results in high concentrations of calcium phosphate in the distal tubule and collecting ducts of the kidney, where it may precipitate. Although APN is rare, it may lead to permanent kidney damage. For this reason, phosphate salts are contraindicated in vulnerable patient groups. As an alternative to phosphate salts, oral sulphate salts have recently been introduced. Because sulphate absorption from the intestinal tract is saturable, serum sulphate concentrations increase only minimally after ingestion. Furthermore, excretion of sulphate in the kidney is not accompanied by calcium excretion and urine calcium levels are unchanged. For these theoretical reasons, use of sulphate salts as bowel cleansing solutions is not expected to lead to calcium precipitation in the nephron.Conclusions Oral phosphate salts are no longer recommended for routine use as bowel cleansing preparations as they carry significant risk of kidney damage and a safer alternative is available in the form of oral sulphate solutions. To date, use of sulphate salts has not been associated with elevations in serum creatinine or other markers of renal impairment, nor with clinical manifestations of kidney injury. Nonetheless, experience with sulphate salts in everyday practice is limited and physicians should be vigilant in detecting potential safety issues.
Published: 2018

34. The age-calibrated measured glomerular filtration rate improves living kidney donation selection process

Author: Matthias Büchler, Sophie Caillard, Emmanuelle Vidal-Petiot, Nassim Kamar, Bénédicte Janbon, Pierre Delanaye, Marie-Noëlle Peraldi, François Gaillard, Bruno Moulin, Cyril Garrouste, Arnaud Del Bello, Paolo Malvezzi, Lionel Couzi, Martin Flamant, Sophie Girerd, Christophe Legendre, Michèle Kessler, Olga Roquet, Laurence Dubourg, Pierre Merville, Marie Courbebaisse, Nicolas Maillard, Christophe Mariat, Lionel Rostaing, and Philippe Gatault
Subjects: Adult, Male, medicine.medical_specialty, 030232 urology & nephrology, Urology, Renal function, 030204 cardiovascular system & hematology, Kidney, Donor Selection, 03 medical and health sciences, 0302 clinical medicine, Living Donors, medicine, Humans, Aged, Retrospective Studies, business.industry, Age Factors, Kidney donation, Middle Aged, Kidney Transplantation, Nephrology, Female, France, business, Glomerular Filtration Rate
Abstract: Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m2. While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m2). Three groups of donors were defined according to baseline mGFR: below 80, 80-89.9 and 90 mL/min/1.73 m2 or more. Thirty-two percent of donors were selected despite an mGFR below 90 mL/min/1.73 m2. Donors with the lowest mGFR were significantly older (60 ± 9 vs. 47 ± 11 years) and this applied to both male and female donors. The lifetime-standardized renal reserve, defined as the pre-donation mGFR value divided by the expected number of remaining years of life, was similar irrespective of baseline mGFR groups. Similar results were obtained when eGFR was used instead of mGFR. Finally, in a subgroup of 132 donors with repeated mGFR five years after donation, the magnitude of mGFR decrease was similar in all groups (-34.3%, -33.9%, and -34.9% respectively). Thus, the decision to accept individuals with mGFR lower than 90 mL/min/1.73 m2 for kidney donation is highly dependent on the age of the candidate. Hence, threshold values lower than 90 mL/min/1.73 m2 are reasonable for older donors. Age-calibrated mGFR may improve efficiency of the selection process.
Published: 2018

35. Recurrence of Renal Cell Cancer After Renal Transplantation in a Multicenter French Cohort

Author: Bruno Hurault de Ligny, Johnny Sayegh, Noëlle Cognard, Franck Le Roy, Cyril Garrouste, Philippe Gatault, Yann Le Meur, Antoine Thierry, Sophie Caillard, Marie Essig, Bruno Moulin, Sophie Girerd, Dany Anglicheau, Joseph Rivalan, Charlotte Colosio, and Gabriel Choukroun
Subjects: Male, medicine.medical_specialty, Time Factors, Clinical Decision-Making, 030232 urology & nephrology, urologic and male genital diseases, Risk Assessment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Renal cell carcinoma, Internal medicine, medicine, Carcinoma, Humans, Carcinoma, Renal Cell, Kidney transplantation, Aged, Retrospective Studies, Transplantation, Kidney, business.industry, Incidence, Patient Selection, Mortality rate, Cancer, Retrospective cohort study, Middle Aged, medicine.disease, Kidney Transplantation, Kidney Neoplasms, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, France, Neoplasm Recurrence, Local, business
Abstract: BACKGROUND Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation. METHODS We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed. RESULTS Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period. CONCLUSIONS Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.
Published: 2018

36. Neutralizing Antibody–Mediated Response and Risk of BK Virus–Associated Nephropathy

Author: Wallys Kack-Kack, Aurélie Velay, Samira Fafi-Kremer, Siamak Bahram, Françoise Stoll-Keller, Eric Soulier, Sophie Caillard, Mélanie Joly, Bruno Moulin, Mariam Meddeb, Pilar Domingo-Calap, Morgane Solis, Heidi Barth, and Raphaël Porcher
Subjects: 0301 basic medicine, business.industry, viruses, medicine.medical_treatment, virus diseases, Immunosuppression, Viremia, General Medicine, 030230 surgery, medicine.disease_cause, medicine.disease, Lower risk, BK virus, Nephropathy, 03 medical and health sciences, Titer, 030104 developmental biology, 0302 clinical medicine, Clinical Research, Nephrology, Immunology, medicine, business, Viral load, Kidney transplantation
Abstract: BK virus–associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype–specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; P=0.002). Each log10 increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients’ neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P=0.04). A NAb titer against the donor’s strain
Published: 2017

37. Kidney transplantation in patients with systemic sclerosis: a nationwide multicentre study

Author: Christophe Mariat, Charlotte Brunelle, Antoine Durrbach, Nassim Kamar, Didier Ducloux, Sophie Girerd, Jean-Philippe Rerolle, Valérie Chatelet, Vincent Audard, Marc Hazzan, Dominique Guerrot, Laetitia Albano, Bruno Moulin, Charlotte Colosio, Julien Ott, Anne-Elisabeth Heng, Christelle Barbet, Julien Dehay, Dominique Bertrand, Jacques Dantal, Rebecca Sberro, Pierre Merville, Valérie Garrigue, Service de Néphrologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service de néphrologie, Hôpital Pasteur [Nice] (CHU), and Guerrot, Dominique
Subjects: Adult, Graft Rejection, Male, Nephrology, medicine.medical_specialty, systemic sclerosis, Scleroderma Renal Crisis, kidney transplantation, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Risk factor, Contraindication, Kidney transplantation, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Transplantation, Kidney, Scleroderma, Systemic, business.industry, graft and patient survival, Graft Survival, Middle Aged, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Surgery, surgical procedures, operative, medicine.anatomical_structure, Kidney Failure, Chronic, Female, France, business, Kidney disease
Abstract: Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period.. Initial kidney disease was scleroderma renal crisis in 76.4%. Extra-renal involvement of SS was generally stable, excepted cardiac and gastro intestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3, and 5 years post transplant respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3 years, and 92.8% after 5 years. Recurrence of scleroderma renal crisis was diagnosed in 3 cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extra-renal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation. This article is protected by copyright. All rights reserved.
Published: 2017

38. Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Author: Marie Frimat, Georges Deschênes, Christophe Legendre, Alexandre Hertig, Dominique Bertrand, Jérôme Olagne, Bruno Moulin, Tim Ulinski, Véronique Frémeaux-Bacchi, Stéphane Burtey, Lubka T. Roumenina, Michel Delahousse, Sophie Chauvet, Moglie Le Quintrec, Maria Chiara Marinozzi, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Etudes sur les Réformes, l'Humanisme et l'Age Classique (CERHAC), Institut d'Histoire de la Pensée Classique (IHPC), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP, Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de transplantation rénale, Hôpital Foch [Suresnes], Service de Néphrologie et Transplantation, CHU Strasbourg, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [APHP], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie Pédiatrique [Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Adult, Male, 0301 basic medicine, Adolescent, Glomerulonephritis, Membranoproliferative, [SDV]Life Sciences [q-bio], Complement receptor 1, Complement factor B, Young Adult, 03 medical and health sciences, Clinical Research, Glomerulopathy, Humans, Medicine, complement, Child, ComputingMilieux_MISCELLANEOUS, Autoantibodies, Retrospective Studies, biology, business.industry, Autoantibody, General Medicine, Middle Aged, medicine.disease, C3-convertase, In vitro, 3. Good health, chronic glomerulonephritis, 030104 developmental biology, Nephrology, Immunoglobulin G, Complement C3b, Immunology, Alternative complement pathway, Female, biology.gene, business, Nephrotic syndrome, Complement Factor B, clinical immunology
Abstract: International audience; In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.
Published: 2017

39. Letter to the Editor concerning 'Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy'

Author: Bruno Moulin, Ilies Benotmane, Morgane Solis, Samira Fafi-Kremer, and Sophie Caillard
Subjects: Transplantation, Letter to the editor, Infectious disease (medical specialty), business.industry, medicine, Immunology and Allergy, Pharmacology (medical), Viremia, medicine.disease, business, Virology, Nephropathy
Published: 2019

40. Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD

Author: Ziad A. Massy, Jean Ferrières, Eric Bruckert, Céline Lange, Sophie Liabeuf, Maja Velkovski-Rouyer, Bénédicte Stengel, Carole Ayav, Christian Combe, Denis Fouque, Luc Frimat, Yves-Edouard Herpe, Maurice Laville, Ziad Massy, Karine Legrand, Marie Metzger, Elodie Speyer, Bruno Moulin, Gaétan Lebrun, Éric Magnant, Gabriel Choukroun, Jean Philippe Bourdenx, Marie Essig, Raymond Azar, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Séverine Martin, Eric Thervet, Xavier Belenfant, Pablo Urena, Carlos Vela, Dominique Chauveau, Viktor Panescu, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, 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)-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 Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de la biomédecine [Saint-Denis la Plaine], CHU Amiens-Picardie, Université Paris-Sud - Paris 11 (UP11), 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 d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Nephrology, medicine.medical_specialty, Statin, medicine.drug_class, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, lipids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ezetimibe, Clinical Research, cardiovascular disease, Diabetes mellitus, Internal medicine, medicine, Prospective cohort study, Kidney transplantation, low-density lipoprotein cholesterol, lipid-regulating agents, business.industry, Cholesterol, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, chronic kidney diseases, 3. Good health, chemistry, business, medicine.drug, Kidney disease
Abstract: Introduction: We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients. Methods: CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013−2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients’ interviews and medical records. Patients were followed up at 1 year. Results: Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (
Published: 2019

41. Intravenous Immunoglobulin Administration Significantly Increases BKPyV Genotype-Specific Neutralizing Antibody Titers in Kidney Transplant Recipients

Author: Bruno Moulin, Aurélie Velay, Sophie Caillard, Ilies Benotmane, Eric Soulier, Samira Fafi-Kremer, Pierre Gantner, and Morgane Solis
Subjects: Adult, Male, Adolescent, Genotype, 030230 surgery, medicine.disease_cause, Antiviral Agents, Nephropathy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Pharmacology (medical), Neutralizing antibody, Kidney transplantation, Aged, 030304 developmental biology, Pharmacology, Polyomavirus Infections, 0303 health sciences, biology, business.industry, Immunologic Deficiency Syndromes, Immunoglobulins, Intravenous, Middle Aged, medicine.disease, Antibodies, Neutralizing, Kidney Transplantation, BK virus, Titer, Infectious Diseases, BK Virus, Immunology, biology.protein, Female, Antibody, business
Abstract: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the major causes of kidney graft dysfunction, and there are no BKPyV-specific antiviral therapies available. BKPyV neutralizing antibodies (NAbs) play key roles in protecting against BKPyV replication and represent a potential therapeutic or preventive strategy. In this study, we evaluated NAb titers in intravenous immunoglobulin (i.v. Ig) preparations and in kidney transplant recipients (KTR) before and after i.v. Ig administration. NAb titers directed against major BKPyV genotypes were measured using a BKPyV pseudovirion system. Thirty-three KTR receiving high (1 g/kg of body weight/day; n = 17) or low (0.4 g/kg/day; n = 16) i.v. Ig doses were included. Median NAb titers in i.v. Ig preparations ranged from 5.9 log(10) 50% inhibitory concentration (IC(50)) for genotype I to 4.1 log(10) IC(50) for genotype IV. A mean of 90% of patients (range, 88% to 100%) displaying low or negative BKPyV NAb titers against genotype I reached 4 log(10) IC(50) after the first i.v. Ig administration. This value was reached by a mean of 44% (range, 13% to 83%) and 19% (range, 0% to 38%) of patients against genotype II and genotype IV, respectively. The benefit of i.v. Ig administration persisted until the following course of treatment (day 22 ± 7 days) for genotypes I and II, and no cumulative effect was observed through the three doses. Our findings demonstrate that i.v. Ig administration results in a significant increase in BKPyV NAb titers in KTR. These in vitro and in vivo pharmacokinetic data provide the rationale for a proof-of-concept study investigating the efficacy of i.v. Ig for the prevention of BKPyV infection in KTR.
Published: 2019

42. Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency

Author: Patrícia de Fátima dos Santos Teixeira, Mario Vaisman, Denise P. Carvalho, Larissa Nascimento Gertrudes, Patricia Borges Dos Santos, Flavia Lucia Conceição, and Bruno Moulin de Andrade
Subjects: 0301 basic medicine, Thyroid nodules, medicine.medical_specialty, Goiter, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Population, Levothyroxine, 030209 endocrinology & metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Gastroenterology, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Insulin resistance, insulin resistance, Internal medicine, Medicine, Euthyroid, benign thyroid nodule, education, Original Research, education.field_of_study, lcsh:RC648-665, TSH, business.industry, Thyroid, thyroid volume, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Homeostatic model assessment, metformin, business, thyroid nodules volume, medicine.drug
Abstract: Objectives: To evaluate the impact of metformin (MTF) use on TSH levels, thyroid volume and volume of benign thyroid nodules (TNs). Additionally, to study if iodine status influences the outcomes. Methods: A total of 23 euthyroid patients (42 TNs) with benign thyroid nodules, diagnosed by fine needle aspiration biopsy, were randomly assigned to MTF or placebo (P) use for 6 months. Serum TSH, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary iodine concentrations (UIC) were assessed. Ultrasound was used to evaluate TNs and thyroid volumes (TV) and their variations throughout the study. Diabetic patients, those undergoing levothyroxine replacement, and/or using thyroid- or insulin level-influencing drugs were excluded. Results: The sample consisted predominantly of patients without IR. Both intervention groups were similar regarding several confounding variables and showed a comparable median UIC. Serum TSH decreased significantly after MTF (−0.21 vs. 0.09 mUI/L in the P group; p = 0.015). At 6 months, no significant variations were found between groups with respect to TN volumes, TV, HOMA-IR, or body mass index (BMI). However, a tendency toward enlargement of TV with placebo (16.0%; p = 0.09) and a protective effect of MTF on growing TN (OR: 0.25; CI 0.05–1.20) was detected after excluding patients with IR (a lower UIC subgroup). The reduction on TSH levels with MTF maintained in the population without iodine insufficiency (−0.24 vs. +0.07 in the P group; p = 0.046) and was accentuated in those with excessive or more than adequate UIC (−0.69; p = 0.043). A protective effect of MTF on growing TN was suggested (OR: 0.11; IC: 0.02–0.84) in those with higher UIC. Conclusions: This study demonstrated that MTF caused a reduction in TSH levels in benign nodular goiter. This effect was more accentuated in patients with higher levels of UIC and was accompanied by a suggested protective effect on TN enlargement.
Published: 2019
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43. Impact of estimation versus direct measurement of predonation glomerular filtration rate on the eligibility of potential living kidney donors

Author: Cyril Garrouste, Paolo Malvezzi, Nassim Kamar, Nicolas Maillard, Arnaud Del Bello, Christophe Mariat, Christophe Legendre, Lionel Rostaing, Maryvonne Hourmant, Hans Pottel, Bruno Moulin, Lionel Couzi, Lola Jacquemont, Bénédicte Janbon, Laurence Dubourg, Pierre Delanaye, Pierre Merville, Marie Courbebaisse, François Gaillard, Sandrine Lemoine, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), 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), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), CHU Bordeaux [Bordeaux], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Nouvel Hôpital Civil de Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Jean Monnet [Saint-Étienne] (UJM), Université de Lyon (COMUE), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), CHU Clermont-Ferrand, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université de Liège, Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie - Clinique de la Dyspnée, Paris, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Service de néphrologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Grenoble Alpes (UGA), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie et Immunologie Clinique [CHU de Nantes], Département de Néphrologie et Transplantation d'organes, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Néphrologie-transplantation-dialyse [Bordeaux], Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Néphrologie, Centre Hospitalier Universitaire (CHU), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Saint-Etienne, and Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Absolute threshold, Urology, Renal function, Estimating equations, Kidney, urologic and male genital diseases, Donor Selection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Living Donors, medicine, Humans, measured GFR, Retrospective Studies, Creatinine, business.industry, Age Factors, Kidney donation, Middle Aged, Kidney Transplantation, female genital diseases and pregnancy complications, living kidney donors, 030104 developmental biology, medicine.anatomical_structure, chemistry, Nephrology, Practice Guidelines as Topic, estimated GFR, Kidney Failure, Chronic, Female, business, Glomerular Filtration Rate
Abstract: While direct measurements of glomerular filtration rate (GFR) provide the most accurate evaluation of pre-donation kidney function, guidelines do not systematically require the use of a reference method. We evaluated whether and to what extent relying upon creatinine-based estimating equations (eGFR) rather than direct measurement of GFR (mGFR) alters the selection of potential living donors. We compared the impact of 4 equations (the MDRD study equation, the CKD-EPI equation, the revised Lund-Malmö equation, and the full age spectrum [FAS] equation) on the evaluation of 2733 potential donors with GFR measured by reference methods. We also considered the impact of using either absolute or age-adapted GFR thresholds. The CKD-EPI and FAS equations had the best performances (P10 of 50.6% and 47.8%; P30 of 94.4% and 93.1%, respectively) and led to the lowest proportion of improperly evaluated candidates. Misclassification was more frequent when GFR adequacy was defined as an absolute threshold of 90 ml/min/1.73m2 as compared to an age-adapted definition (26% and 5%, respectively). Interpretation of eGFR according to an absolute threshold of 90 ml/min/1.73m2 identified 1804 candidates eligible to donate, compared to 2648 when mGFR was interpreted with age-adapted thresholds. We conclude that creatinine-based estimates cannot substitute for direct GFR measurement to evaluate candidates for kidney donation. When reference methods for direct GFR measurement are not available, our data suggest that a strategy based on age-adapted eGFR values estimated with either the CKD-EPI or FAS equation should be preferred. ispartof: KIDNEY INTERNATIONAL vol:95 issue:4 pages:896-904 ispartof: location:United States status: published
Published: 2019

44. Assessment of Renal Dysfunction Improves the Simplified Pulmonary Embolism Severity Index (sPESI) for Risk Stratification in Patients with Acute Pulmonary Embolism

Author: Bruno Moulin, Han S. Lim, Antonin Trimaille, Annie Trinh, Mélanie Girardey, C. Muller, Laurence Jesel, Patrick Ohlmann, Olivier Morel, and Benjamin Marchandot
Subjects: medicine.medical_specialty, cardio-renal syndrome, venous thromboembolism, Contrast-induced nephropathy, Hemodynamics, Renal function, lcsh:Medicine, 030204 cardiovascular system & hematology, urologic and male genital diseases, Article, 03 medical and health sciences, 0302 clinical medicine, Cardio-Renal Syndrome, Internal medicine, Medicine, 030212 general & internal medicine, business.industry, lcsh:R, General Medicine, medicine.disease, Pulmonary embolism, contrast-induced nephropathy, Cohort, Cardiology, business, Risk assessment, chronic kidney disease, Kidney disease
Abstract: Background: Whereas the major strength of the simplified pulmonary embolism severity index (sPESI) lies in ruling out an adverse outcome in patients with sPESI of 0, the accuracy of sPESI &ge, 1 in risk assessment remains questionable. In acute pulmonary embolism (APE), the estimated glomerular filtration rate (eGFR) can be viewed as an integrate marker reflecting not only previous chronic kidney disease (CKD) damage but also comorbid conditions and hemodynamic disturbances associated with APE. We sought to determine whether renal dysfunction assessment by eGFR improves the sPESI score risk stratification in patients with APE. Methods: 678 consecutive patients with APE were prospectively enrolled. Renal dysfunction (RD) at diagnosis of APE was defined by eGFR &lt, 60 mL/min/1.73 m2 and acute kidney injury (AKI) by elevation of creatinine level &gt, 25% during in-hospital stay. Results: RD was observed in 26.9% of the cohort. AKI occurred in 18.8%. A stepwise increase in 30-day mortality, cardiovascular mortality and overall mortality was evident with declining renal function. Multivariate analysis identified RD and CRP (C-reactive protein) level but not sPESI score as independent predictors of 30-day mortality. AKI, 30-day mortality, overall mortality, and cardiovascular mortality were at their highest level in patients with eGFR &lt, 60 mL/min/1.73 m2 and sPESI &ge, 1. Conclusion: in patients with APE, the addition of RD to the sPESI score identifies a specific subset of patients at very high mortality.
Published: 2019

45. EPURE Transplant (Eplerenone in Patients Undergoing Renal Transplant) study: study protocol for a randomized controlled trial

Author: Philippe Rieu, Yannick Le Meur, Frederic Jaisser, Luc Frimat, Christophe Mariat, Sophie Girerd, Ludovic Merckle, Nicolas Girerd, Xavier Lepage, Didier Ducloux, Christiane Mousson, Nassim Dali-Youcef, Bruno Moulin, Patrick Rossignol, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Université de Lorraine (UL), Service de Néphrologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Brest (UBO), CHU Saint-Etienne, Université Jean Monnet - Saint-Étienne (UJM), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Université de Strasbourg (UNISTRA), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique [Nancy] (CIC), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), This work was supported by INI-CRCT. The EPURE Transplant study was supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique Inter Régional 2014). The authors are supported by a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program (reference: ANR-15-RHU-0004), and GEENAGE Impact Lorraine Université d’Excellence- reference ANR-15-IDEX-04-LUE)., IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), DALI-YOUCEF, Nassim, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, Service de néphrologie-hémodialyse-transplantation [CHRU Nancy], Service d'urologie, andrologie et transplantation rénale, Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHRU - Service de néphrologie, dialyse et transplantation rénale, Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie et Transplantation, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), 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)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, and 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)
Subjects: medicine.medical_specialty, Hyperkalemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030232 urology & nephrology, Urology, Medicine (miscellaneous), Renal function, 030204 cardiovascular system & hematology, Expanded Criteria Donor, law.invention, Kidney transplantation, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), education, Dialysis, ComputingMilieux_MISCELLANEOUS, Mineralocorticoid Receptor Antagonists, Randomized Controlled Trials as Topic, education.field_of_study, lcsh:R5-920, business.industry, Mineralocorticoid receptor antagonist, Expanded criteria donor, medicine.disease, Tissue Donors, 3. Good health, Eplerenone, [SDV] Life Sciences [q-bio], Data Interpretation, Statistical, Reperfusion Injury, Hemodialysis, medicine.symptom, business, lcsh:Medicine (General), Ischemia/reperfusion lesions, Glomerular Filtration Rate
Abstract: Background Despite advances in immunosuppressive therapy, kidney graft survival has failed to improve during the last decades. Ischemia/reperfusion injury (IRI) is one of the main pathophysiological mechanisms underlying delayed graft function, which is associated with poor long-term graft survival. Due to organ shortage, the proportion of grafts from expanded criteria donors (ECDs) is ever growing. These grafts may particularly benefit from IRI prevention. In preclinical models, mineralocorticoid receptor antagonists (MRAs) have been shown to efficiently prevent IRI. This study aims to assess the effect of MRA administration in the early phase of kidney transplantation (KT) among recipients of ECD grafts on mid-term graft function. Methods/design This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients on hemodialysis and undergoing a single or a dual KT from an ECD will be eligible for inclusion. We plan to randomize 132 patients. Included patients will be randomized (1:1) to receive either eplerenone 25 mg every 12 h during 4 days (the first dose being administered just prior to KT) or placebo. The primary outcome is graft function at 3 months, assessed by glomerular filtration rate (GFR, in mL/min/1.73m2) measured using iohexol clearance. Secondary outcomes include (1) proportion of patients with either dialysis dependency or a GFR
Published: 2018

46. Intraoperative Pleth Variability Index Is Linked to Delayed Graft Function After Kidney Transplantation

Author: L. Jazaerli, Mickaël Schaeffer, Bruno Moulin, P.M. Mertes, C. Biermann, Nabil Chakfe, François Severac, Sophie Caillard, Olivier Collange, A. Lejay, and A. Steib
Subjects: Adult, Male, Central Venous Pressure, Delayed Graft Function, Hemodynamics, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030202 anesthesiology, Monitoring, Intraoperative, Hypovolemia, medicine.artery, medicine, Humans, Prospective Studies, Renal artery, Prospective cohort study, Kidney transplantation, Monitoring, Physiologic, Transplantation, business.industry, Central venous pressure, Reproducibility of Results, Postoperative complication, Middle Aged, medicine.disease, Kidney Transplantation, Plethysmography, Anesthesia, Female, Surgery, medicine.symptom, business
Abstract: Background Delayed graft function (DGF) is an early postoperative complication of kidney transplantation (KT) predisposing to acute rejection and lower graft survival. Intraoperative arterial hypotension and hypovolemia are associated with DGF. Central venous pressure (CVP) is used to estimate volemia but its reliability has been criticized. Pleth variability index (PVI) is a hemodynamic parameter predicting fluid responsiveness. The aim of this study was to examine the relationship between intraoperative PVI and CVP values and the occurrence of DGF. Methods This was a prospective, noninterventional, observational, single-center study. All consecutive patients with KT from deceased donors were included. Recipients received standard, CVP, and PVI monitoring. Intraoperative hemodynamic parameters were recorded from recipients at 5 time points during KT. Results Forty patients were enrolled. There was a poor correlation between PVI and CVP values ( r 2 = 0.003; P = .44). Immediate graft function and DGF patients had similar hemodynamic values during KT, with the exception of PVI values, which were significantly higher in the DGF group. In particular, a PVI >9% before unclamping of the renal artery was the only predictive parameter of DGF in our multivariate analysis ( P = .02). Conclusions This study suggests that PVI values >9% during KT are associated with the occurrence of DGF.
Published: 2016

47. Pretransplant thymic function predicts acute rejection in antithymocyte globulin–treated renal transplant recipients

Author: Luc Frimat, Emilie Gaiffe, Didier Ducloux, Bruno Moulin, Caroline Roubiou, Anne-Elisabeth Heng, Jean-Michel Rebibou, Jamal Bamoulid, Antoine Durrbach, Caroline Laheurte, Thomas Crepin, Clémence Carron, Christiane Mousson, Cécile Courivaud, Philippe Rieu, and Philippe Saas
Subjects: CD4-Positive T-Lymphocytes, Graft Rejection, Male, 0301 basic medicine, Time Factors, 030230 surgery, Gastroenterology, 0302 clinical medicine, Risk Factors, Prospective Studies, education.field_of_study, Hazard ratio, Middle Aged, Platelet Endothelial Cell Adhesion Molecule-1, Phenotype, Treatment Outcome, medicine.anatomical_structure, Nephrology, Acute Disease, Monoclonal, Female, France, Immunosuppressive Agents, Adult, medicine.medical_specialty, T cell, Population, Receptors, Antigen, T-Cell, Recent Thymic Emigrant, Thymus Gland, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, education, Aged, Antilymphocyte Serum, Retrospective Studies, business.industry, Reproducibility of Results, Retrospective cohort study, Kidney Transplantation, Confidence interval, Transplantation, 030104 developmental biology, Immunology, Leukocyte Common Antigens, business
Abstract: Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA + CD31 + CD4 + T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4 + T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01–1.08) for each increased percent in RTE/CD4 + T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm 3 (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody–treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09–5.74) and RTE/mm 3 (>200/mm 3 , hazard ratio, 3.71; 95% confidence interval, 1.59–8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients.
Published: 2016

48. End-Stage Renal Disease-Associated Gut Bacterial Translocation: Evolution and Impact on Chronic Inflammation and Acute Rejection After Renal Transplantation

Author: Clémence Carron, Jean-Paul Pais de Barros, Emilie Gaiffe, Valérie Deckert, Hanane Adda-Rezig, Caroline Roubiou, Caroline Laheurte, David Masson, Dominique Simula-Faivre, Pascale Louvat, Bruno Moulin, Luc Frimat, Philippe Rieu, Christiane Mousson, Antoine Durrbach, Anne-Elisabeth Heng, Philippe Saas, Didier Ducloux, Laurent Lagrost, and Jamal Bamoulid
Subjects: 0301 basic medicine, Graft Rejection, Lipopolysaccharides, Male, chronic inflammation, Lipopolysaccharide, Lipopolysaccharide Receptors, acute rejection, chemistry.chemical_compound, 0302 clinical medicine, Phospholipid transfer protein, Immunology and Allergy, Medicine, Prospective Studies, Intestinal Mucosa, Kidney transplantation, Original Research, Aged, 80 and over, Middle Aged, Intestinal epithelium, 3. Good health, Cytokines, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, Myristic Acids, lcsh:Immunologic diseases. Allergy, Adult, medicine.medical_specialty, Lipoproteins, Immunology, kidney transplantation, Inflammation, End stage renal disease, 03 medical and health sciences, Young Adult, Internal medicine, Humans, Aged, gut bacterial translocation, business.industry, Cholesterol, cholesterol, medicine.disease, Endotoxemia, Gastrointestinal Microbiome, Transplantation, 030104 developmental biology, Endocrinology, chemistry, Bacterial Translocation, Kidney Failure, Chronic, lcsh:RC581-607, business, 030215 immunology
Abstract: Chronic inflammation in end-stage renal disease (ESRD) is partly attributed to gut bacterial translocation (GBT) due to loss of intestinal epithelium integrity. Increased levels of circulating lipopolysaccharide (LPS) –a surrogate marker of GBT– contribute to maintain a chronic inflammatory state. However, circulating LPS can be neutralized by lipoproteins and transported to the liver for elimination. While ESRD-associated GBT has been widely described, less is known about its changes and impact on clinical outcome after kidney transplantation (KT). One hundred and forty-six renal transplant recipients with serum samples obtained immediately before and 1 year after transplantation (1-Year post KT) were included. Intestinal epithelium integrity (iFABP), total LPS (by measuring 3-hydroxymyristate), LPS activity (biologically active LPS measured by the LAL assay), inflammatory biomarkers (sCD14 and cytokines), lipoproteins and LPS-binding proteins (LBP and phospholipid transfer protein [PLTP] activity) were simultaneously measured. At 1-Year post KT, iFABP decreased but remained higher than in normal volunteers. Total LPS concentration remained stable while LPS activity decreased. Inflammation biomarkers decreased 1-Year post KT. We concomitantly observed an increase in lipoproteins. Higher sCD14 levels before transplantation was associated with lower incidence of acute rejection. Although GBT remained stable after KT, the contemporary increase in lipoproteins could bind circulating LPS and contribute concomitantly to neutralization of LPS activity, as well as improvement in ESRD-associated chronic inflammation. Chronic exposure to LPS in ESRD could promote endotoxin tolerance and explain why patients with higher pre-transplant sCD14 are less prompt to develop acute rejection after transplantation.
Published: 2018

49. Pharmacokinetic Therapeutic Drug Monitoring of Advagraf in More Than 500 Adult Renal Transplant Patients, Using an Expert System Online

Author: Bruno Moulin, Marie Essig, Isabelle Etienne, Caroline Monchaud, Elisabeth Cassuto, Pierre Marquet, Anne Bedu, Nassim Kamar, Jean-Philippe Rerolle, Franck Saint-Marcoux, and Jean-Baptiste Woillard
Subjects: Adult, Male, medicine.medical_specialty, MEDLINE, Expert Systems, computer.software_genre, 030226 pharmacology & pharmacy, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Pharmacology (medical), Intensive care medicine, Retrospective Studies, Pharmacology, Internet, medicine.diagnostic_test, business.industry, Area under the curve, Retrospective cohort study, Kidney Transplantation, Expert system, Transplantation, Renal transplant, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Area Under Curve, Female, Drug Monitoring, business, computer, Immunosuppressive Agents
Abstract: Immunosuppressant Bayesian dose adjustment (ISBA) is an online expert system, routinely used by approximately 140 transplantation centers in the world for the dose adjustment of immunosuppressive drugs in transplant patients. This system determines the area under the curve (AUC) of the drug by pharmacokinetic modeling and Bayesian estimation. The purpose of this study was to analyze tacrolimus exposure after administration of its modified-release formulation (Advagraf) in kidney allograft recipients, to optimize its therapeutic drug monitoring.This is a retrospective study of exposure indices measured locally [trough tacrolimus concentration (C0), C0/dose] or estimated through ISBA (AUC, AUC/dose, AUC/C0), of their evolution over posttransplantation time, and of the correlations between them.A total of 922 requests posted by 28 different centers for routine Advagraf adjustment in 530 different patients treated with Advagraf were studied. The exposure to, and dose requirement of, tacrolimus significantly increased across the first posttransplant months before reaching steady state. The AUC:C0 ratio (on which C0 monitoring is implicitly based) was stable across the different posttransplant periods, although with high interindividual variability. C0-AUC correlation was stronger in the late than in the early posttransplant period (r = 0.75 versus 0.63; P = 0.0075). Using the regression equations obtained, AUC ranges corresponding to different applicable C0 target ranges were calculated to guide dose adjustment. When one of the doses recommended was administered, the following AUC was significantly more often in the predicted target ranges (P0.0001).This study improves our knowledge of Advagraf pharmacokinetic variability and relations between exposure indices and the scientific background of the expert service provided through the ISBA Web site.
Published: 2018

50. Quel avenir pour la transplantation rénale face aux défis du plan greffe 2021 ?

Author: Bruno Moulin and Maryvonne Hourmant
Subjects: Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine, MEDLINE, medicine.disease, business, Intensive care medicine, Kidney transplantation, Public health policy, Health policy
Published: 2019

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