Author: "Yannick, Le Meur" / Language: english - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Yannick, Le Meur"' showing total 46 results

Start Over Author "Yannick, Le Meur" Language english

46 results on '"Yannick, Le Meur"'

1. Biopsy-Proven T-Cell Mediated Rejection After Belatacept Rescue Conversion: A Multicenter Retrospective Study

Author: Dominique Bertrand, Nathalie Chavarot, Jérôme Olagne, Clarisse Greze, Philippe Gatault, Clément Danthu, Charlotte Colosio, Maïté Jaureguy, Agnès Duveau, Nicolas Bouvier, Yannick Le Meur, Léonard Golbin, Eric Thervet, Antoine Thierry, Arnaud François, Charlotte Laurent, Mathilde Lemoine, Dany Anglicheau, and Dominique Guerrot
Subjects: transplantation, kidney, belatacept, rejection, CNI toxicity, Specialties of internal medicine, RC581-951
Abstract: After kidney transplantation, conversion to belatacept is a promising alternative in patients with poor graft function or intolerance to calcineurin inhibitors. The risk of acute rejection has not been well described under these conditions. Here we present a retrospective multicenter study investigating the occurrence of acute rejection after conversion in 901 patients (2011–2021). The incidence of cellular and humoral rejection was 5.2% and 0.9%, respectively. T-cell mediated rejection (TCMR) occurred after a median of 2.6 months after conversion. Out of 47 patients with TCMR, death-censored graft survival was 70.1%, 55.1% and 50.8% at 1 year, 3 years and 5 years post-rejection, respectively. Eight patients died after rejection, mainly from infectious diseases. We compared these 47 patients with a cohort of kidney transplant recipients who were converted to belatacept between 2011 and 2017 and did not develop rejection (n = 238). In multivariate analysis, shorter time between KT and conversion, and the absence of anti-thymocyte globulin induction after KT were associated with the occurrence of TCMR after belatacept conversion. The occurrence of rejection after conversion to belatacept appeared to be less frequent than with de novo use. Nevertheless, the risk of graft loss could be significant in patients with already low renal function.
Published: 2024
Full Text: View/download PDF

2. Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study

Author: Magali Giral, Philippe Grimbert, Baptiste Morin, Nicolas Bouvier, Matthias Buchler, Jacques Dantal, Valérie Garrigue, Dominique Bertrand, Nassim Kamar, Paolo Malvezzi, Karine Moreau, Yoni Athea, and Yannick Le Meur
Subjects: extended-release tacrolimus, LCPT, immunosuppression, kidney transplantation, tremor, C0/D ratio, Specialties of internal medicine, RC581-951
Abstract: Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients. The primary endpoint was change in The Essential Tremor Rating Assessment Scale (TETRAS) score; secondary endpoints included 12-item Short Form Survey (SF-12) scores, tacrolimus trough concentrations, neurologic symptoms, and safety assessments. Subgroup analyses were conducted to assess change in TETRAS score and tacrolimus trough concentration/dose (C0/D) ratio by prior tacrolimus formulation and tacrolimus metabolizer status. Among 221 patients, the mean decrease of TETRAS score after switch to LCPT was statistically significant (p < 0.0001 vs. baseline). There was no statistically significant difference in change in TETRAS score after switch to LCPT between patients who had received IR-TAC and those who had received PR-TAC before switch, or between fast and slow metabolizers of tacrolimus. The overall increase of C0/D ratio post-switch to LCPT was statistically significant (p < 0.0001) and from baseline to either M1 or M3 (both p < 0.0001) in the mITT population and in all subgroups. In the fast metabolizers group, the C0/D ratio crossed over the threshold of 1.05 ng/mL/mg after the switch to LCPT. Other neurologic symptoms tended to improve, and the SF-12 mental component summary score improved significantly. No new safety concerns were evident. In this observational study, all patients had a significant improvement of tremor, QoL and C0/D ratio post-switch to LCPT irrespective of the previous tacrolimus formulation administered (IR-TAC or PR-TAC) and irrespective from their metabolism status (fast or slow metabolizers).
Published: 2024
Full Text: View/download PDF

3. Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19

Author: Lidvine Boland, Arnaud Devresse, Caroline Monchaud, Sébastien Briol, Stéphanie Belaiche, Baptiste Giguet, Lionel Couzi, Olivier Thaunat, Laure Esposito, Magdalena Meszaros, Ana Roussoulieres, Vincent Haufroid, Yannick Le Meur, and Florian Lemaitre
Subjects: drug-drug interactions, drug monitoring, nirmatrelvir/ritonavir, pharmacokinetic modelling, tacrolimus, Specialties of internal medicine, RC581-951
Abstract: Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.
Published: 2024
Full Text: View/download PDF

4. Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial

Author: Yannick Le Meur, Emmanuel Nowak, Benoit Barrou, Antoine Thierry, Lionel Badet, Matthias Buchler, Jean-Philippe Rerolle, Leonard Golbin, Agnès Duveau, Jacques Dantal, Pierre Merville, Nassim Kamar, Leïla Demini, and Franck Zal
Subjects: HEMO2life®, Clinical trial, Delayed Graft Function (DGF), Transplantation, Ischemia–Reperfusion Injury (IRI), Kidney IRI, Medicine (General), R5-920
Abstract: Abstract Background Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts. Methods OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation. Discussion The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation. Trial registration ClinicalTrials.gov, ID: NCT04181710 . registered on November 29, 2019.
Published: 2023
Full Text: View/download PDF

5. An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International

Author: Roman-Ulrich Müller, A. Lianne Messchendorp, Henrik Birn, Giovambattista Capasso, Emilie Cornec-Le Gall, Olivier Devuyst, Albertien van Eerde, Patrick Guirchoun, Tess Harris, Ewout J. Hoorn, Nine V.A.M. Knoers, Uwe Korst, Djalila Mekahli, Yannick Le Meur, Tom Nijenhuis, Albert C.M. Ong, John A. Sayer, Franz Schaefer, Aude Servais, Vladimir Tesar, Roser Torra, and Stephen B. Walsh and Ron T. Gansevoort
Subjects: Diseases of the genitourinary system. Urology, RC870-923
Abstract: No abstract
Published: 2022
Full Text: View/download PDF

6. Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME)

Author: Thomas Kerforne, Christiane Mousson, Karim Asehnoune, Fanny Feuillet, Olivier Huet, Bertrand Rozec, Aude Garin, Alexandre Hertig, Jeremy Bourenne, Nassim Kamar, Emmanuel Morelon, Denis Glotz, Morgane Péré, Thierry Boulain, Jean Reignier, René Robert, Dominique Bertrand, Pierre-Yves Egreteau, Thierry Benard, Raphaëlle Larmet, Luc Frimat, Sophie Girerd, Mathias Büchler, Anne Renault, Patrice Tirot, Cécile Vigneau, Eric Delpierre, David Schnell, Olivier Lesieur, Lionel Rostaing, Mathieu Lesouhaitier, Laurent Martin-Lefevre, Antoine Durrbach, Noëlle Brulé, Emmanuel Canet, Maryvonne Hourmant, Agnes Duveau, Laurent Dube, Marc Pierrot, Stanislas Humbert, Jean-Marc Boyer, François Labadie, Antoine Thierry, Jean-François Vincent, Angelique Goepp, Pierre Bouju, Charlotte Quentin, Yannick Le Meur, Jean-Christophe Venhard, Olivier Michel, Marie-Hélène Voellmy, Fabien Herve, Anne Courte, Lucile Amrouche, Marc Hazzan, Valerie Moal, Moglie Le Quintrec-Donnette, Philippe Grimbert, Anne Elisabeth Heng, Pierre Merville, Christian Hiesse, Brice Fermier, Charlotte Guyot-Colosio, Nicolas Bouvier, Jean-Philippe Rerolle, Sarah Drouin, Sophie Caillard, Laetitia Albano, Pierre-Francois Westeel, Florent Montini, Dider Dorez, Eric Alamartine, Carole Ouisse, and Veronique Sebille
Subjects: Medicine
Abstract: Introduction Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysis HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and dissemination The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration number NCT03098706.
Published: 2022
Full Text: View/download PDF

7. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex

Author: Tae Won Yi, Brendan Smyth, Gian Luca Di Tanna, Clare Arnott, Kathryn Cardoza, Amy Kang, Carol Pollock, Rajiv Agarwal, George Bakris, David M. Charytan, Dick de Zeeuw, Hiddo J.L. Heerspink, Bruce Neal, David C. Wheeler, Christopher P. Cannon, Hong Zhang, Bernard Zinman, Vlado Perkovic, Adeera Levin, Kenneth W. Mahaffey, Meg Jardine, Barry M. Brenner, Tom Greene, Meg J. Jardine, Gary Meininger, Nicole Li, Inna Kolesnyk, Diego Aizenberg, Roberto Pecoits-Filho, David Cherney, Gregorio Obrador, Glenn Chertow, Tara Chang, Carmel Hawley, Linong Ji, Takashi Wada, Vivekanand Jha, Soo Kun Lim, Mary Anne Lim-Abrahan, Florence Santos, Dong-Wan Chae, Shang-Jyh Hwang, Evgueniy Vazelov, Ivan Rychlík, Samy Hadjadj, Vera Krane, László Rosivall, Luca De Nicola, Alexander Dreval, Michał Nowicki, Adalbert Schiller, Larry Distiller, Jose L. Górriz, Mykola Kolesnyk, null David, C. Wheeler, Rodolfo Andres Ahuad Guerrero, Juan Pablo Albisu, Andres Alvarisqueta, Ines Bartolacci, Mario Alberto Berli, Anselmo Bordonava, Pedro Calella, Maria Cecilia Cantero, Luis Rodolfo Cartasegna, Esteban Cercos, Gabriela Cecilia Coloma, Hugo Colombo, Victor Commendatore, Jesus Cuadrado, Carlos Alberto Cuneo, Ana Maria Cusumano, Walter Guillermo Douthat, Ricardo Dario Dran, Eduardo Farias, Maria Florencia Fernandez, Hernan Finkelstein, Guillermo Fragale, Jose Osvaldo Fretes, Nestor Horacio Garcia, Anibal Gastaldi, Elizabeth Gelersztein, Jorge Archibaldo Glenny, Joaquin Pablo Gonzalez, Patricia del Carmen Gonzalez Colaso, Claudia Goycoa, Gustavo Cristian Greloni, Adrian Guinsburg, Sonia Hermida, Luis Isaias Juncos, Maria Isabel Klyver, Florencia Kraft, Fernando Krynski, Paulina Virginia Lanchiotti, Ricardo Alfonso Leon de la Fuente, Nora Marchetta, Pablo Mele, Silvia Nicolai, Pablo Antonio Novoa, Silvia Ines Orio, Fabian Otreras, Alejandra Oviedo, Pablo Raffaele, Jorge Hector Resk, Lucas Rista, Nelson Rodriguez Papini, Jorgelina Sala, Juan Carlos Santos, Lilia Beatriz Schiavi, Horacio Sessa, Tomas Smith Casabella, Maria Rosa Ulla, Maria Valdez, Augusto Vallejos, Adriana Villarino, Virginia Esther Visco, Alfredo Wassermann, Cesar Javier Zaidman, Ngai Wah Cheung, Carolyn Droste, Ian Fraser, David Johnson, Peak Mann Mah, Kathy Nicholls, David Packham, Joseph Proietto, Anthony Roberts, Simon Roger, Venessa Tsang, Roberto Abrão Raduan, Fernando Augusto Alves da Costa, Celso Amodeo, Luiz Alberto Andreotti Turatti, Rachel Bregman, Fernanda Cristina Camelo Sanches, Luis Henrique Canani, Antônio Roberto Chacra, João Lindolfo Cunha Borges, Sérgio Alberto Cunha Vêncio, Roberto Jorge da Silva Franco, Domingos d’Avila, Evandro de Souza Portes, Pedro de Souza, Luciane Mônica Deboni, Fadlo Fraige Filho, Bruno Geloneze Neto, Marcus Gomes, Suely Keiko Kohara, Elizete Keitel, Jose Francisco Kerr Saraiva, Hugo Roberto Kurtz Lisboa, Fabiana Loss de Carvalho Contieri, Rosângela Milagres, Renan Montenegro Junior, Claudia Moreira de Brito, Miguel Nasser Hissa, Ângela Regina Nazario Sabbag, Irene Noronha, Daniel Panarotto, Roberto Pecoits Filho, Márcio Antônio Pereira, Wladmir Saporito, Antonio Scafuto Scotton, Tiago Schuch, Roberto Simões de Almeida, Cássio Slompo Ramos, João Soares Felício, Fernando Thomé, Jean Carlo Tibes Hachmann, Sérgio Yamada, Cesar Yoiti Hayashida, Tarissa Beatrice Zanata Petry, Maria Teresa Zanella, Viktoria Andreeva, Angelina Angelova, Stefan Dimitrov, Veselka Genadieva, Gabriela Genova-Hristova, Kiril Hristozov, Zdravko Kamenov, Atanas Koundurdjiev, Lachezar Lozanov, Viktor Margaritov, Boyan Nonchev, Rangel Rangelov, Alexander Shinkov, Margarita Temelkova, Ekaterina Velichkova, Andrian Yakov, Naresh Aggarwal, Ronnie Aronson, Harpreet Bajaj, Guy Chouinard, James Conway, Serge Cournoyer, Gerald DaRoza, Sacha De Serres, François Dubé, Ronald Goldenberg, Anil Gupta, Milan Gupta, Sam Henein, Hasnain Khandwala, Lawrence Leiter, François Madore, Alan McMahon, Norman Muirhead, Vincent Pichette, Remi Rabasa-Lhoret, Andrew Steele, Navdeep Tangri, Ali Torshizi, Vincent Woo, Nadia Zalunardo, María Alicia Fernández Montenegro, Juan Gonzalo Godoy Jorquera, Marcelo Medina Fariña, Victor Saavedra Gajardo, Margarita Vejar, Nan Chen, Qinkai Chen, Shenglian Gan, Yaozhong Kong, Detian Li, Wenge Li, Xuemei Li, Hongli Lin, Jian Liu, Weiping Lu, Hong Mao, Yan Ren, Weihong Song, Jiao Sun, Lin Sun, Ping Tu, Guixia Wang, Jinkui Yang, Aiping Yin, Xueqing Yu, Minghui Zhao, Hongguang Zheng, Jose Luis Accini Mendoza, Edgar Arcos, Jorge Avendano, Jorge Ernesto Andres Diaz Ruiz, Luis Hernando Garcia Ortiz, Alexander Gonzalez, Eric Hernandez Triana, Juan Diego Higuera, Natalia Malaver, Dora Inés Molina de Salazar, Ricardo Rosero, Monica Alexandra Terront Lozano, Luis Valderrama Cometa, Alex Valenzuela, Ruben Dario Vargas Alonso, Ivan Villegas, Hernan Yupanqui, Dagmar Bartaskova, Petr Barton, Jana Belobradkova, Lenka Dohnalova, Tomas Drasnar, Richard Ferkl, Katarina Halciakova, Vera Klokocnikova, Richard Kovar, Jiri Lastuvka, Martin Lukac, Satu Pesickova, Karel Peterka, Jiri Pumprla, Ivan Rychlik, Frantisek Saudek, Vladimir Tesar, Martin Valis, Pavel Weiner, Stanislav Zemek, Eric Alamartine, Sophie Borot, Bertrand Cariou, Bertrand Dussol, Jean-Pierre Fauvel, Pierre Gourdy, Alexandre Klein, Yannick Le Meur, Alfred Penfornis, Ronan Roussel, Pierre-Jean Saulnier, Eric Thervet, Philippe Zaoui, Volker Burst, Markus Faghih, Grit Faulmann, Hermann Haller, Reinhold Jerwan-Keim, Stephan Maxeiner, Björn Paschen, Georg Plassmann, Ludger Rose, Ronaldo Arturo Gonzalez Orellana, Franklin Paul Haase, Juan Pablo Moreira Diaz, Luis Alberto Ramirez Roca, Jose Antonio Sánchez Arenales, José Vicente Sanchez Polo, Erick Turcios Juarez, Gyongyi Csecsei, Botond Csiky, Peter Danos, Laszlo Deak, Mihaly Dudas, Eleonora Harcsa, Katalin Keltai, Sandor Keresztesi, Krisztian Kiss, Laszlo Konyves, Lajos Major, Margit Mileder, Marta Molnar, Janos Mucsi, Tamas Oroszlan, Ivan Ory, Gyorgy Paragh, Eva Peterfai, Gizella Petro, Katalin Revesz, Robert Takacs, Sandor Vangel, Szilard Vasas, Marianna Zsom, Oomman Abraham, Raju Sree Bhushan, Dewan Deepak, Fernando M. Edwin, Natarajan Gopalakrishnan, Noble Gracious, Alva Hansraj, Dinesh Jain, C.B. Keshavamurthy, Dinesh Khullar, Sahay Manisha, Jayameena Peringat, Narayan Prasad, Rao K. Satyanarayana, Reddy Sreedhar, Melemadathil Sreelatha, Bhimavarapu Sudhakar, Ramesh Chandra Vyasam, Riccardo Bonadonna, Pietro Castellino, Antonio Ceriello, Luca Chiovato, Salvatore De Cosmo, Giuseppe Derosa, Alberto Di Carlo, Graziano Di Cianni, Giovanni Frascà, Giorgio Fuiano, Giovanni Gambaro, Giacomo Garibotto, Carlo Giorda, Fabio Malberti, Marcora Mandreoli, Edoardo Mannucci, Emanuela Orsi, Piermarco Piatti, Domenico Santoro, Ferdinando Carlo Sasso, Gaetano Serviddio, Andrea Stella, Roberto Trevisan, Anna Maria Veronelli, Luca Zanoli, Hitoshi Akiyama, Hiromi Aoki, Akimichi Asano, Tadashi Iitsuka, Shizuo Kajiyama, Susumu Kashine, Toshio Kawada, Takamoto Kodera, Hiroshi Kono, Kazunori Koyama, Yasuro Kumeda, Shozo Miyauchi, Kazuyuki Mizuyama, Tetsuji Niiya, Hiroko Oishi, Satoshi Ota, Terue Sakakibara, Masahiko Takai, Osamu Tomonaga, Mitsuru Tsujimoto, Masakiyo Wakasugi, Yasushi Wakida, Takayuki Watanabe, Masayo Yamada, Kazuhiro Yanagida, Toshihiko Yanase, Wataru Yumita, Egle Gaupsiene, Dalia Kozloviene, Antanas Navickas, Egle Urbanaviciene, Rohana Abdul Ghani, Khalid Abdul Kadir, Norsiah Ali, Mohd Daud Che Yusof, Chye Lee Gan, Mastura Ismail, Wei Yen Kong, Swee Win Lam, Li Yuan Lee, Chek Loong Loh, Anita Bhajan Manocha, Kee Sing Ng, Nik Nur Fatnoon Nik Ahmad, Vanassa Ratnasingam, Saiful Shahrizal Bin Shudim, Paranthaman Vengadasalam, Luis David Abraira Munoz, Melchor Alpizar Salazar, Juan Baas Cruz, Mario Burgos Soto, Jose Chevaile Ramos, Alfredo Chew Wong, Jose Ricardo Correa Rotter, Tonatiu Diaz Escalante, Favio Edmundo Enriquez Sosa, Fernando Flores Lozano, Luis Fernando Flota Cervera, Paul Frenk Baron, Cecilia Garcia Ballesteros, Jose David Gomez Rangel, Luis Enrique Herrera Jimenez, Sergio Saul Irizar Santana, Fernando Jimenez Flores, Hugo Laviada Molina, Rosa Isela Luna Ceballos, Belia Martin del Campo Blanco, Guadalupe Morales Franco, Oscar Tarsicio Moreno Loza, Cynthia Mustieles Rocha, Gregorio Obrador Vera, Ricardo Orozco Castellanos, Juan Peralta Calcaneo, Miguel Angel Reyes Rosano, Hiromi Rodriguez Pattzi, Juan Rosas Guzman, Isabel Erika Rucker Joerg, Sandra Berenice Saavedra Sanchez, Jose Hector Sanchez Mijangos, Pablo Serrano Sanson, Juan Alfredo Tamayo y Orozco, Eloisa Tellez Chavez, Alejandro Valdes Cepeda, Luis Venegas Carrillo, Juan Villagordoa Mesa, Rolando Zamarripa Escobedo, John Baker, Paul Noonan, Russell Scott, Robert Walker, Edward Watson, Michael Williams, Simon Young, Zaynab Abejuela, Jeimeen Agra, Grace Aquitania, Clodoaido Caringal, Rhea Severina Comia, Lalaine Delos Santos, Olivert Gomez, Cecilia Jimeno, Gerry Tan, Marsha Tolentino, Christy Yao, Yvette Ethel Yap, Ma. Dovie Lallaine Ygpuara, Renata Bijata-Bronisz, Lucyna Hotlos, Andrzej Januszewicz, Barbara Kaczmarek, Anna Kaminska, Lech Lazuka, Andrzej Madej, Stanislaw Mazur, Dorota Mlodawska-Choluj, Michal Nowicki, Grazyna Orlowska-Kowalik, Grazyna Popenda, Barbara Rewerska, Dariusz Sowinski, Liliana Monica Angelescu, Veronica Anghel, Rodica-Ioana Avram, Mihaela-Magdalena Busegeanu, Adriana Cif, Dana Cosma, Carmen Crisan, Luiza Despina Demian, Ioana Emilia Ferariu, Ildiko Halmagyi, Nicolae Hancu, Mircea Munteanu, Doru Negru, Adriana Gabriela Onaca, Ligia Petrica, Amorin Remus Popa, Aurelian-Emil Ranetti, Cristian Serafinceanu, Cristina Toarba, Alina Agafyina, Olga Barbarash, Olga Barysheva, Daniil Chizhov, Vladimir Dobronravov, Irina Glinkina, Elena Grineva, Vladimir Khirmanov, Elena Kolmakova, Tatiana Koroleva, Liudmila Kvitkova, Viacheslav Marasaev, Ashot Mkrtumyan, Tatiana Morugova, Galina Nagibovich, Oleg Nagibovich, Sergei Nedogoda, Irina Osipova, Tatiana Raskina, Yulia Samoylova, Olga Sazonova, Minara Shamkhalova, Elena Shutemova, Yuriy Shwartz, Oleg Uriasyev, Sergey Vorobyev, Anna Zateyshchikova, Dmitry Zateyshshikov, Tatyana Zykova, Slobodan Antic, Miodrag Djordjevic, Aleksandra Kendereski, Katarina Lalic, Nebojsa Lalic, Vesna Popovic-Radinovic, Jana Babikova, Olga Benusova, Ingrid Buganova, Jan Culak, Andrej Dzupina, Jana Dzuponova, Peter Fulop, Adriana Ilavska, Emil Martinka, Zuzana Ochodnicka, Daniel Pella, Iveta Smatanova, Fayzal Ahmed, Aysha Badat, Johannes Breedt, Lawrence Distiller, Vimladhevi Govender, Ravendran Govender, Mukesh Joshi, Jaco Jurgens, Gulam Latiff, Landman Lombard, Mohamed Mookadam, Nomangesi Ngcakani, Hendrik Nortje, Helena Oosthuizen, Larisha Pillay-Ramaya, Hans Prozesky, Jeevren Reddy, Paul Rheeder, Mary Seeber, Young Min Cho, In-Kyung Jeong, Sin Gon Kim, Yeong Hoon Kim, Hyuk-Sang Kwon, Min Jeong Kwon, Byung-Wan Lee, JungEun Lee, Moon-Kyu Lee, Moon-Suk Nam, Kook-Hwan Oh, Cheol- Young Park, Sun-Hee Park, Kun Ho Yoon, Pere Alvarez Garcia, Luis Asmarats Mercadal, Clara Barrios, Fernando Cereto Castro, Secundino Cigarran Guldris, Marta Dominguez Lopez, Jesus Egido de los Rios, Gema Fernandez Fresnedo, Antonio Galan Serrano, Isabel Garcia, Francisco Javier Gonzalez Martinez, Jose Esteban Jodar Gimeno, Manuel Lopez Mendoza, Tamara Malek Marin, Cristobal Morales Portillo, Maria Antonia Munar Vila, Manuel Muñoz Torres, Javier Nieto Iglesias, Jonay Pantoja Perez, Merce Perez Vera, Jose M. Portoles Perez, María Angustias Quesada Simón, Rafael Simo Canonge, Alfonso Soto Gonzalez, Manel Terns Riera, Francisco Jose Tinahones Madueno, Mercedes Velo Plaza, Chwen-Tzuei Chang, Lee-Ming Chuang, Te-Lin Hsia, Chang-Hsun Hsieh, Chih-Ching Lin, Yung- Chuan Lu, Wayne H-H Sheu, Olga Barna, Svitlana D. Bilyk, Volodymyr Botsyurko, Iryna Dudar, Ivan Fushtey, Olga Godlevska, Oleksandr Golovchenko, Olga Gyrina, Anatoliy Kazmirchuk, Iuliia Komisarenko, Oleksii Korzh, Nonna Kravchun, Oleg Legun, Borys Mankovskyy, Liliya Martynyuk, Yuriy Mostovoy, Nataliia Pashkovska, Larysa Pererva, Tetyana Pertseva, Oleksandr Samoylov, Ivan Smirnov, Yevgeniya Svyshchenko, Halyna Tomashkevych, Ivan Topchii, Nadiya Tryshchuk, Vira Tseluyko, Vadym Vizir, Maryna Vlasenko, Tetiana Zlova, Liliia Zub, Salah Abusnana, Mohamed Railey, Kamal Abouglila, Paul Ainsworth, Zishan Ali, Vijayaraman Arutchelvam, Maria Barnard, Srikanth Bellary, Emyr Davies, Mark Davies, Simon Davies, Alison Dawson, Mohsen El Kossi, Patrick English, Donald Fraser, Luigi Gnudi, Anthony Gunstone, Timothy Hall, Wasim Hanif, Alan Jackson, Andrew Johnson, Franklin Joseph, Singhan Krishnan, Mick Kumwenda, Iain MacDougall, Paul Nixon, Joseph O'Hare, Sam Philip, Shenaz Ramtoola, Manish Saxena, Davesh Sennik, Godwin Simon, Baldev Singh, Jeffrey Stephens, Anna Strzelecka, Rehan Symonds, Wayne Turner, Mona Wahba, John Wakeling, David Wheeler, Peter Winocour, Joseph Abdallah, Raied Abdullah, Matthew Abramowitz, Idalia Acosta, Joseph Aiello, Laura Akright, Ayim Akyea-Djamson, Rajendran Alappan, Radica Alicic, Amer Al-Karadsheh, Dale Crawford Allison, Carlos Arauz-Pacheco, Shahabul Arfeen, Ahmed Arif, Moogali Arvind, Naveen Atray, Ahmed Awad, Peggy Barnhill, Elizabeth Barranco, Carlos Barrera, Matthew Beacom, Venkata Behara, Diogo Belo, Rhonda Bentley-Lewis, Ramon Berenguer, Lidia Bermudez, Marializa Bernardo, Mihaela Biscoveanu, Cynthia Bowman-Stroud, Donald Brandon, Osvaldo Brusco, Robert Busch, Yamil Canaan, Alicia Chilito, Tom Christensen, Cynthia Christiano, Elena Christofides, Caroucel Chuateco, Kenneth Cohen, Robert Cohen, Debbie Cohen-Stein, Charles Cook, Daniel Coyne, Nizar Daboul, Riad Darwish, Adarsh Daswani, Kenneth Deck, Cyrus Desouza, Devasmita Dev, Monika Dhillon, Sohan Dua, Frank Eder, Ana Maria Elosegui, Mohamed El-Shahawy, John Ervin, Alberto Esquenazi, John Evans, Steven Fishbane, Juan Frias, Eugenia Galindo-Ramos, Claude Galphin, Adline Ghazi, Enrique Gonzalez, David Gorson, Anupama Gowda, Barbara Greco, Stephen Grubb, Rakesh Gulati, Jamal Hammoud, Stuart Handelsman, Israel Hartman, Kenneth Hershon, Daniel Hiser, George Hon, Radu Jacob, Maria Jaime, Aamir Jamal, Charles Kaupke, Gerald Keightley, Elizabeth Kern, Rakhi Khanna, Zeid Khitan, Sun Kim, Nelson Kopyt, Csaba Kovesdy, Gopal Krishna, Jeffrey (Jay) Kropp, Amrendra Kumar, Jayant Kumar, Neil Kumar, Jorge Kusnir, Wendy Lane, Mary Lawrence, Lawrence Lehrner, John Lentz, Dennis Levinson, Derek Lewis, Kenneth Liss, Andreas Maddux, Hiralal Maheshwari, Sreedhar Mandayam, Isam Marar, Bhasker Mehta, John Middleton, Jorge Mordujovich, Ramon Moreda, Moustafa Moustafa, Samuel Mujica Trenche, Mohanram Narayanan, Javier Narvarte, Tareq Nassar, George Newman, Brian Nichol, Philip Nicol, Josier Nisnisan, A. Kaldun Nossuli, Chamberlain Obialo, Sarah Olelewe, Michael Oliver, Andrew O'Shaughnessy, John Padron, Rohit Pankhaniya, Reginald Parker, Devesh Patel, Gnyandev Patel, Nina Patel, Humberto Pavon, Armando Perez, Carlos Perez, Alan Perlman, Karlton Pettis, Walter Pharr, Andrea Phillips, Raman Purighalla, Luis Quesada-Suarez, Rajiv Ranjan, Sanjeev Rastogi, Jakkidi Reddy, Marc Rendell, Lisa Rich, Michael Robinson, Hector Rodriguez, Sylvia Rosas, Fadi Saba, Rallabhandi Sankaram, Ravi Sarin, Robert Schreiman, David Scott, Mohamed Sekkarie, John Sensenbrenner, Muhammad Shakeel, Michael Shanik, Sylvia Shaw, Stephen Smith, Richard Solomon, Amy Sprague, Leslie Spry, Pusadee Suchinda, Senan Sultan, Prasanth Surampudi, Sherry Sussman, Anjanette Tan, Antonio Terrelonge, Michael Thompson, Fernando Trespalacios, Bruce Trippe, Pilar Trueba, Marcel Twahirwa, John Updegrove, Peter Van Buren, Mark Vannorsdall, Freemu Varghese, Pedro Velasquez-Mieyer, Sailaja Ventrapragada, Goga Vukotic, Khurram Wadud, Mark Warren, Henry Watson, Ronald Watts, Daniel Weiner, James Welker, Jean Welsh, Shelley Williams, and Michelle Zaniewski-Singh
Subjects: age, diabetes, Nephrology, kidney outcomes, sex, Diabetic kidney disease, canagliflozin, cardiovascular outcomes, chronic kidney disease, sodium/glucose cotransporter 2 inhibitors
Abstract: Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.
Published: 2023
Full Text: View/download PDF

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

Author: Sophie Girerd, Luc Frimat, Didier Ducloux, Yannick Le Meur, Christophe Mariat, Bruno Moulin, Christiane Mousson, Philippe Rieu, Nassim Dali-Youcef, Ludovic Merckle, Xavier Lepage, Patrick Rossignol, Nicolas Girerd, and Frédéric Jaisser
Subjects: Mineralocorticoid receptor antagonist, Ischemia/reperfusion lesions, Kidney transplantation, Expanded criteria donor, Randomized controlled trial, Medicine (General), R5-920
Abstract: 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
Full Text: View/download PDF

9. Novel long-range regulatory mechanisms controlling PKD2 gene expression

Author: Stéphanie Moisan, Stéphanie Levon, Emilie Cornec-Le Gall, Yannick Le Meur, Marie-Pierre Audrézet, Josée Dostie, and Claude Férec
Subjects: ADPKD, PKD2, Chromatin organization, Enhancer, Gene expression, Transcription regulation, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract: Abstract Background Cis-regulatory elements control gene expression over large distances through the formation of chromatin loops, which allow contact between enhancers and gene promoters. Alterations in cis-acting regulatory systems could be linked to human genetic diseases. Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Results By using chromosome conformation capture carbon copy (5C) technology in primary human renal cyst epithelial cells, we identify novel contacts of the PKD2 promoter with chromatin regions, which display characteristics of regulatory elements. In parallel, by using functional analysis with a reporter assay, we demonstrate that three DNAse I hypersensitive sites regions are involved in the regulation of PKD2 gene expression. Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF.
Published: 2018
Full Text: View/download PDF

10. Selection of Pneumocystis jirovecii Inosine 5′-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid

Author: Claire V. Hoffmann, Gilles Nevez, Marie-Christine Moal, Dorothée Quinio, Nathan Le Nan, Nicolas Papon, Jean-Philippe Bouchara, Yannick Le Meur, and Solène Le Gal
Subjects: Pneumocystis jirovecii, IMPDH, transplantation, selection, mycophenolic acid, Biology (General), QH301-705.5
Abstract: Mycophenolic acid (MPA) targets the inosine 5′-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is widely used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who, incidentally, are at risk for Pneumocystis pneumonia (PCP). We hypothesized that MPA exerts selective pressure on P. jirovecii microorganisms considering its in vitro antifungal activity on other fungi. Thus, we analysed impdh gene in P. jirovecii isolates from SOT recipients. P. jirovecii specimens from 26 patients diagnosed with PCP from 2010 to 2020 were retrospectively examined: 10 SOT recipients treated with MPA and 16 non-SOT patients without prior exposure to MPA. The P. jirovecii impdh gene was amplified and sequenced. Nucleotide sequences were aligned with the reference sequences retrieved from available P. jirovecii whole genomes. The deduced IMPDH protein sequences were aligned with available IMPDH proteins from Pneumocystis spp. and other fungal species known to be in vitro sensitive or resistant to MPA. A total of nine SNPs was identified. One SNP (G1020A) that results in an Ala261Thr substitution was identified in all SOT recipients and in none of the non-SOT patients. Considering that IMPDHs of other fungi, resistant to MPA, harbour Thr (or Ser) at the analogous position, the Ala261Thr mutation observed in MPA-treated patients was considered to represent the signature of P. jirovecii exposure to MPA. These results suggest that MPA may be involved in the selection of specific P. jirovecii strains that circulate in the SOT recipient population.
Published: 2021
Full Text: View/download PDF

11. Flank pain has a significant adverse impact on quality of life in ADPKD

Author: Jean Winterbottom, Roslyn J Simms, Anna Caroli, Emilie Cornec-Le Gall, Nathalie Demoulin, Monica Furlano, Esther Meijer, Olivier Devuyst, Ron T Gansevoort, Yannick Le-Meur, Norberto Perico, Roser Torra, Albert C M Ong, Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), and UCL - SSS/IREC/NEFR - Pôle de Néphrologie
Subjects: Transplantation, OUTCOMES, 10 COUNTRIES, VALIDATION, POLYCYSTIC KIDNEY-DISEASE, TRIALS, Nephrology, quality-of-life, pain, total kidney volume, TRANSLATION, kidney function, SF-36 HEALTH SURVEY, VERSION, ADPKD
Abstract: Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder and a major cause of kidney failure worldwide. However, its impact on quality-of-life has not been systematically explored. Methods The CYSTic-QoL study was an observational study designed to study quality-of-life in adult European ADPKD patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. A total of 465 patients were recruited from six expert European centres with baseline data recorded, including health-related quality-of-life (HRQoL), incorporating a Kidney Disease QoL short form questionnaire (KDQoL-SF, version 1.3), magnetic resonance imaging (MRI) for total kidney volume (TKV) measurements and DNA for genotyping. The cohort was stratified by baseline eGFR, TKV or genotype and correlated with HRQoL scores. Bivariate and multivariate analyses were applied to examine the relationship between HRQoL and variables of interest. KDQoL-SF scores were calculated using an online tool provided by the RAND organization. For 36-item short form values, mean centre scores were normalized to their native populations. Results The mean age of participants was 43 years and 55% were female, with a mean eGFR of 77 mL/min/1.73 m2 and height-adjusted TKV (ht-TKV) of 849 mL/min; 66% had PKD1 pathogenic variants. ADPKD patients uniformly reported decreased general health and less energy, with the majority also experiencing poorer physical, mental or emotional health and limitations in social functioning. A total of 32.5% of participants experienced flank pain, which was significantly and negatively correlated with the majority of KDQoL-SF subscales by multivariate analysis. Higher ht-TKV and lower eGFR were negatively associated with decreased energy and poorer physical health, respectively, although not with flank pain. Conclusion ADPKD patients suffer from significantly decreased QoL in multiple domains, exacerbated particularly by chronic pain.
Published: 2022
Full Text: View/download PDF

12. Absence of Mortality Differences Between the First and Second COVID-19 Waves in Kidney Transplant Recipients

Author: Bastien Berger, Marc Hazzan, Nassim Kamar, Hélène Francois, Marie Matignon, Clarisse Greze, Philippe Gatault, Luc Frimat, Pierre F. Westeel, Valentin Goutaudier, Renaud Snanoudj, Charlotte Colosio, Antoine Sicard, Dominique Bertrand, Christiane Mousson, Jamal Bamoulid, Antoine Thierry, Dany Anglicheau, Lionel Couzi, Jonathan M. Chemouny, Agnes Duveau, Valerie Moal, Yannick Le Meur, Gilles Blancho, Jérôme Tourret, Paolo Malvezzi, Christophe Mariat, Jean-Philippe Rerolle, Nicolas Bouvier, Sophie Caillard, Olivier Thaunat, Hospices Civils de Lyon (HCL), 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), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-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), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), 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 ), 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), Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), OT is supported by the Etablissement Français du Sang and the Fondation pour la Recherche Médicale (PME20180639518)., 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 de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: Transplantation, Nephrology, [SDV]Life Sciences [q-bio], SARS-CoV2
Abstract: International audience; Introduction - SARS-CoV-2 pandemic evolved in 2 consecutive waves during 2020. Improvements in the management of COVID-19 led to a reduction in mortality rates among hospitalized patients during the second wave. Whether this progress benefited kidney transplant recipients (KTRs), a population particularly vulnerable to severe COVID-19, remained unclear. Methods - In France, 957 KTRs were hospitalized for COVID-19 in 2020 and their data were prospectively collected into the French Solid Organ Transplant (SOT) COVID registry. The presentation, management, and outcomes of the 359 KTRs diagnosed during the first wave were compared to those of the 598 of the second wave. Results - Baseline comorbidities were similar between KTRs of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs. 58.4%, < 0.001) or calcineurin inhibitor (32.1% vs. 16.6%, < 0.001) was less frequent during the second wave. Hydroxychloroquine and azithromycin that were commonly used during the first wave (21.7% and 30.9%, respectively) but were almost abandoned during the second wave. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, < 0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, = 0.48) and COVID-19 hospitalization period was not associated with death due to COVID-19 in multivariate analysis (Hazard ratio 0.89, 95% confidence interval 0.67-1.17, = 0.4). Conclusion - We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality among KTRs. Our data indirectly support the importance of vaccination and neutralizing monoclonal anti-SARS-CoV-2 antibodies to protect KTRS from severe COVID-19.
Published: 2022
Full Text: View/download PDF

13. Diagnosis and Risk Factors for Intracranial Aneurysms in Autosomal Polycystic Kidney Disease: A cross-sectional study from the Genkyst Cohort

Author: Siriane, Lefèvre, Marie-Pierre, Audrézet, Jean-Michel, Halimi, Hélène, Longuet, Frank, Bridoux, Laure, Ecotière, Jean-François, Augusto, Agnès, Duveau, Eric, Renaudineau, Cécile, Vigneau, Thierry, Frouget, Christophe, Charasse, Lorraine, Gueguen, Régine, Perrichot, Grégoire, Couvrat, Guillaume, Seret, Yannick, Le Meur, Emilie, Cornec-Le Gall, S, Martin, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CH de Saint-Malo [Broussais], 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre hospitalier Saint-Brieuc, Centre Hospitalier Intercommunal de Cornouaille (CHIC), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Association ECHO [Expansion des Centres d’Hémodialyse de l’Ouest], 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), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Chard-Hutchinson, Xavier
Subjects: Male, subarachnoid hemorrhage, PKD2, PKD1, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Humans, risk factors, genetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, autosomal dominant polycystic kidney disease (ADPKD), Polycystic Kidney Diseases, Transplantation, intracranial aneurysms, Intracranial Aneurysm, Estrogens, Polycystic Kidney, Autosomal Dominant, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, female genital diseases and pregnancy complications, Cross-Sectional Studies, Nephrology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Background Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyse the risk factors associated with the occurrence of IAs in ADPKD patients. Methods A cross-sectional study was performed in 26 nephrology centres from the western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes. Results Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9%, 6.2% and 8.1% at 50, 60 and 70 years, respectively. While this risk appeared to be similar in male and female individuals 2-fold higher in PKD1 compared with PKD2, with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension Conclusions This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of oestrogen.
Published: 2022
Full Text: View/download PDF

14. HEMO 2 life® improves renal function independent of cold ischemia time in kidney recipients: A comparison with a large multicenter prospective cohort study

Author: Yannick Le Meur, Eric Delpy, Felix Renard, Thierry Hauet, Lionel Badet, Jean Philippe Rerolle, Antoine Thierry, Matthias Büchler, Franck Zal, Benoit Barrou, 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-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), HEMARINA SA, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie et Transplantation [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Department of Nephrology, CHU de Poitiers, Poitiers, France, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Département D'urologie, Néphrologie et Transplantation, Sorbonne Université, Assistance Publique - Hôpitaux de Paris AP-HP, Hôpitaux Universitaires PitiéSalpêtrière - Charles Foix, Paris, France
Subjects: Biomaterials, delayed graft function, oxygen carrier, Biomedical Engineering, Medicine (miscellaneous), [SDV.IMM]Life Sciences [q-bio]/Immunology, Bioengineering, General Medicine, organ preservation, renal transplantation
Abstract: International audience; M101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO2 life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO2 life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO2 life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys.
Published: 2021
Full Text: View/download PDF

15. 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
Full Text: View/download PDF

16. Selection of Pneumocystis jirovecii Inosine 5′-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid

Author: Nicolas Papon, Gilles Nevez, Dorothée Quinio, Marie-Christine Moal, Claire V Hoffmann, Jean-Philippe Bouchara, Yannick Le Meur, Nathan Le Nan, Solène Le Gal, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
Subjects: Microbiology (medical), QH301-705.5, [SDV]Life Sciences [q-bio], Population, selection, Plant Science, Pneumocystis pneumonia, Mycophenolic acid, Article, Pneumocystis jirovecii, Microbiology, IMPDH, 03 medical and health sciences, parasitic diseases, medicine, Inosine-5′-monophosphate dehydrogenase, Biology (General), education, Inosine, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, education.field_of_study, biology, 030306 microbiology, medicine.disease, biology.organism_classification, 3. Good health, Transplantation, biology.protein, mycophenolic acid, medicine.drug, transplantation
Abstract: Mycophenolic acid (MPA) targets the inosine 5′-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is widely used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who, incidentally, are at risk for Pneumocystis pneumonia (PCP). We hypothesized that MPA exerts selective pressure on P. jirovecii microorganisms considering its in vitro antifungal activity on other fungi. Thus, we analysed impdh gene in P. jirovecii isolates from SOT recipients. P. jirovecii specimens from 26 patients diagnosed with PCP from 2010 to 2020 were retrospectively examined: 10 SOT recipients treated with MPA and 16 non-SOT patients without prior exposure to MPA. The P. jirovecii impdh gene was amplified and sequenced. Nucleotide sequences were aligned with the reference sequences retrieved from available P. jirovecii whole genomes. The deduced IMPDH protein sequences were aligned with available IMPDH proteins from Pneumocystis spp. and other fungal species known to be in vitro sensitive or resistant to MPA. A total of nine SNPs was identified. One SNP (G1020A) that results in an Ala261Thr substitution was identified in all SOT recipients and in none of the non-SOT patients. Considering that IMPDHs of other fungi, resistant to MPA, harbour Thr (or Ser) at the analogous position, the Ala261Thr mutation observed in MPA-treated patients was considered to represent the signature of P. jirovecii exposure to MPA. These results suggest that MPA may be involved in the selection of specific P. jirovecii strains that circulate in the SOT recipient population.
Published: 2021
Full Text: View/download PDF

17. 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
Full Text: View/download PDF

18. 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
Full Text: View/download PDF

19. Mesangial Cell-Specific Antibodies Are Central to the Pathogenesis of Lupus Nephritis

Author: Guillaume Seret, Yannick Le Meur, Yves Renaudineau, and Pierre Youinou
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Not only is nephritis a common complaint in systemic lupus erythematosus, but it is also the most life-threatening complication of the disease. Anti-double-stranded DNA antibodies (Abs), which are found in up to 80% of these patients, might be nephritogenic per se. That is, they may cross-react with mesangial cell (MC) surface proteins, such as alpha-actinin and annexin A2, they may cross-react with mesangial matrix protein such as laminine and fibronectin, or they may recognize chromatin material previously deposited in the glomeruli. The consequence of the binding of anti-MC Abs may be their internalization, which results in activation and proliferation of these MCs. In turn, these activated MCs are suspected of promoting immune complex formation by sequestering and thereby protecting chromatin from degradation. The present paper will explain the mechanisms through which such autoAbs may initiate nephritis.
Published: 2012
Full Text: View/download PDF

20. Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial

Author: Ruilope, Luis M, Agarwal, Rajiv, Anker, Stefan D, Bakris, George L, Filippatos, Gerasimos, Nowack, Christina, Kolkhof, Peter, Joseph, Amer, Mentenich, Nicole, Pitt, Bertram, Diego, Besada, Alfredo, Wassermann, Julio, Bittar, Alicia, Elbert, Augusto, Vallejos, Gloria, Viñes, Hugo, Sanabria, Federico Pérez Manghi, Alberto, Liberman, Inés, Bartolacci, Diego, Aizenberg, Mariano, Chahin, Laura, Maffei, Elizabeth, Gelersztein, Bernhard, Ludvik, Hans-Robert, Schönherr, Heinz, Drexel, Wolfgang, Preiß, Ursula, Hanusch, Peter, Neudorfer, Friedrich, Prischl, Bernhard, Paulweber, Christoph, Ebenbichler, Rudolf, Prager, Harald, Sourij, Gerit-Holger, Schernthaner, Martin, Clodi, Evelyn, Fliesser-Görzer, Elif, Ekinci, Richard, Macisaac, David, Packham, Hugo, Stephenson, Michael, Suranyi, Gary, Wittert, Katie-Jane, Wynne, Alexia, Pape, Duncan, Topliss, Peter, Colman, Craig, Nelson, James, Vandeleur, David, Colquhoun, Simon, Roger, Peak Mann Mah, Walter, Abhayaratna, Luc VAN Gaal, Pieter, Gillard, Jean-Michel, Hougardy, Marijn, Speeckaert, Koen, Stas, Wendy, Engelen, Francis, Duyck, André, Scheen, Hilde, Vanbelleghem, Peter, Doubel, Svetla, Vasileva, Rosen, Rashkov, Boyan, Nonchev, Theodora, Temelkova-Kurktschieva, Mariana, Yoncheva-Mihaylova, Rangel, Rangelov, Neli, Klyuchkova, Pavel, Stanchev, Zhivko, Tagarev, Radostina, Boshnyashka, Petya, Manova, Zhulieta, Prakova, Mariya, Lucheva, Valentina, Gushterova, Ghassan, Farah, Dimitar, Georgiev, Mariyana, Pichmanova, Dotska, Minkova, Bilyana, Stoyanovska-Elencheva, Maria Eugenia Canziani, Miguel, Hissa, Irene, Noronha, Joao Eduardo Salles, Daniela, Antunes, Freddy, Eliaschewitz, Carlos Eduardo Figueiredo, Rogerio de Paula, Luis, Canani, Maurilo Leite Jr, Bruno, Paolino, Rosangela, Rea, Sergio, Vencio, Claudia, Brito, Raphael, Paschoalin, Roberto Pecoits Filho, Eduardo, Vasconcellos, Nathalia, Paschoalin, Adriana, Forti, Roberto, Botelho, Miguel, Riella, Dalton, Precoma, Maria, Cerqueira, Lilia, Maia, Evandro, Portes, Marcio, Pereira, Joanne, Liutkus, Dennis, O Keefe, Richard, Tytus, Brian, Carlson, James, Conway, Michael, Walsh, Igor, Wilderman, Andrew, Steele, Sheldon, Tobe, Louise, Vitou, Karthik, Tennankore, Valdemar, Martinho, Philip, Mcfarlane, Daniel, Shu, Serge, Cournoyer, Richard, Dumas, Giuseppe, Mazza, Guy, Tellier, George, Tsoukas, Stanley, Weisnagel, Jean-Francois, Yale, Sameh, Fikry, Randolph, Hart, Pavel, Hamet, Francois, Madore, Paul, Barre, Daniel, Schwartz, Allan, Kelly, Ivor, Teitelbaum, Sean, Peterson, Sam, Henein, Richard, Goluch, Gregoire, Wuerzner, Markus, Laimer, Stefan, Bilz, Marc, Donath, Gottfried, Rudofsky, Christopher, Strey, Antoinette, Pechère-Bertschi, Paola, Varleta, Fernando, González, Marcelo, Medina, Carmen, Romero, Victor, Saavedra, Juan Carlos Prieto, Eliana, Reyes, Juan Carlos Palma, Jorge, Cobos, Zhihong, Liu, Dalong, Zhu, Nan, Chen, Fang, Liu, Wang, Li, Qing, Su, Bingyin, Shi, Aiping, Yin, Hao, Wang, Yan, Li, Jianying, Niu, Chaoqing, Wu, Xinjun, Wang, Ying, Zhang, Peng, Ai, Jianhua, Ma, Yuxiu, Li, Hongguang, Zheng, Minxiang, Lei, Zhaohui, Mo, Nanwei, Tong, Jinluo, Cheng, Youping, Dong, Xudong, Xu, Qinkai, Chen, Tianjun, Guan, Gang, Long, Changying, Xing, Ling, Li, Yinghong, Liu, Hao, Zhang, Ling, Zhong, Zhonghe, Li, Longyi, Zeng, Jiali, Wei, Hanqing, Cai, Tianfeng, Wu, Weiping, Lu, Ning, Xu, Yibing, Lu, Dejun, Chen, Ruifang, Bu, Jiansong, Shen, Junwu, Dong, Zhiquan, Zhao, Fei, Xiong, Fangfang, Jiang, Jinkui, Yang, Jian, Kuang, Guoyuan, Lu, Lihua, Wang, Yanlin, Zhang, Shuifu, Tang, Weiying, Guo, Jian, Liu, Sheng, Jiang, Fang, Yi, Yuming, Du, Zhuxing, Sun, Yuantao, Liu, Liyong, Zhong, Dongmei, Li, Hongmei, Li, Chuanming, Hao, Feixia, Shen, Jianqin, Wang, Jingmei, Li, Dora, Molina, Carlos, Cure, Jaime, Ibarra, Gustavo, Aroca, Hernán, Yupanqui, Eric, Hernández, Mónica, López, Gregorio, Sánchez, Germán, Barreto, Edgar, Arcos, Miguel, Urina, William, Kattah, Carlos, Durán, Clara, Arango, Julian, Coronel, Guillermo, Blanco, Mónica, Terront, Gustavo, Guzmán, Luis, García, Carlos, Jaramillo, Manuel, Liévano, Diego, Benitez, Tatiana, Cárdenas, Iván, Villegas, Sandra, Barrera, Nicolás, Jaramillo, Rodrigo, Botero, Nelly Beltrán López, Freddy, Trujillo, Martin, Prazny, Jitka Hasalova Zapletalova, Libor, Okenka, Dino, Alferi, Tomas, Edelsberger, Pavel, Tomanek, Jiri, Brezina, Olga, Hola, Jana, Houdova, Petr, Bucek, David, Karasek, Sarka, Kopecka, Richard, Kovar, Michal, Brada, Lucie, Hornova, Eva, Krcova, Hana, Lubanda, Vlasta, Kutejova, Jiri, Kuchar, Helena, Hrmova, Jiri, Pumprla, Magdalena, Mokrejsova, Drahomira, Gulakova, Ivo, Matyasek, Thilo, Krüger, Hermann, Haller, Thorsten, Koch, Ludger, Rose, Diethelm, Tschöpe, Lutz, Stemler, Volker, Schettler, Andreas, Pfützner, Karl, Derwahl, Thomas, Horacek, Helena, Sigal, Heidrun, Täschner, Ingolf, Schiefke, Andreas, Hagenow, Andreas, Birkenfeld, Christoph, Axthelm, Christoph, Wanner, Klaus, Busch, Heike, Schlichthaar, Christoph, Hasslacher, Stefan, Degenhardt, Markus van der Giet, Georg, Strack, Norbert, Schöll, Bernhard, R Winkelmann, Lars, Rump, Ruth, Nischik, Bernd, Schröppel, Thomas, Giebel, Achim, Ulmer, Andrea, Rinke, Christel, Contzen, Wolfgang, Jungmair, Nicole, Toursarkissian, Christof, Kloos, Joachim, Müller, Thomas, Schürholz, Hermann, Braun, Frank, Pistrosch, Per, Poulsen, Claus, Juhl, Joan, Nielsen, Jesper, Bech, Ole, Rasmussen, Peter, Rossing, Jens, Faber, Thure, Krarup, Morten, Lindhardt, Ulrik Pedersen-Bjergaard Pedersen-Bjergaard, Karoline, Schousboe, Jørgen, Hangaard, Sten, Madsbad, Gunnar, Gislason, Grzegorz Jaroslaw Pacyk, Olga González Albarrán, Carlos Sánchez Juan, José Julián Segura de la Morena, Secundino Cigarrán Guldris, Francisco Martínez Deben, José María Pascual Izuel, Julio Pascual Santos, Francesca, Calero, Alfonso, Soto, Manuel Polaina Rusillo, Josep, Redón, Josep, Galcerán, Juan, Mediavilla, Mª Dolores Martínez Esteban, Alfredo, Michán, Fernando de Álvaro, Javier Escalada San Martín, Josep Cruzado Garrit, Cristina, Castro, Fernando Cereto Castro, Rafael Santamaría Olmo, Esteban, Poch, Judith, Martins, Julio Hernández Jaras, Meritxell, Ibernón, Daniel, Seron, Hanane, Bouarich, Maribel, Troya, Jorma, Strand, Ilkka, Kantola, Sakari, Nieminen, Arvo, Koistinen, Kristiina, Kananen, Sakari, Sulosaari, Mikko, Honkasalo, Pirkko, Korsoff, Tuomo, Nieminen, Karita, Sadeharju, Kari, Humaloja, Jorma, Lahtela, Philippe, Zaoui, Jean-Pierre, Fauvel, Ronan, Roussel, Didier, Gouet, Pierre, Serusclat, Sylvaine, Clavel, Bruno, Guerci, Bruno, Verges, Olivier, Moranne, Arnaud, Monier, Alexandre, Klein, François, Chantrel, Yannick LE Meur, Rafik, Mesbah, Bertrand, Cariou, Dominique, Guerrot, Karim, Gallouj, Kieran, Mccafferty, Arutchelvam, Vijayaraman, Yuk-Ki, Wong, Dhanya, Kalathil, Sam, Rice, Sui Phi Kon, Hassan, Kahal, Cuong, Dang, Fahmy, Hanna, Christina, Kyriakidou, Imrozia, Arif, Anne, Kilvert, Pauline, Swift, Ioannis, Stefanidis, Ploumis, Passadakis, Aikaterini, Papagianni, Erifili, Hatziagelaki, Dorothea, Papadopoulou, Ioannis, Boletis, Ioanna, Makriniotou, Theodora, Kounadi, Ioannis, Ioannidis, Paul, Lee, Ching Wan Ronald Ma, Vincent, Yeung, Tai Pang Ip, Ebrahim, Noori, Julianna, Kiss, Eleonora, Harcsa, Albert, Szocs, Szilard, Vasas, Krisztina, Wudi, Robert, Kirschner, Dora, Bajcsi, Beata, Lamboy, Botond, Literati-Nagy, Gabor, Nyirati, Gizella, Petro, Karoly, Schneider, Katalin, Keltai, Akos, Kalina, Peter, Danos, Szilvia, Kazup, Zsolt, Zilahi, Judit, Simon, Laszlo, Kovacs, Marianna, Zsom, Margit, Mileder, Laszlo, Nagy, Yoram, Yagil, Julio, Wainstein, Ofri, Mosenzon, Rosane Abramof Ness, Sydney Ben Chetrit, Faiad, Adawi, Idit, Liberty, Ehud, Grossman, Mazen, Elias, Zaher, Armaly, Evgeny, Farber, Assy, Nimer, Amir, Bashkin, Gil, Chernin, Shai, Efrati, Doron, Schwartz, Noa Berar Yanay, Mariela, Glandt, Robert, Zukermann, Majdi, Halabi, Shaul, Atar, Mahmud, Darawsha, Norberto, Perico, Gaetano La Manna, Giovanni Giorgio Battaglia, Domenico, Santoro, Piermarco, Piatti, Bonora, Enzo, Davide Carlo Maggi, Paolo, Calabrò, Roberto, Cimino, Roberto, Trevisan, Paolo, Fiorina, Antonio, Pisani, Antonello, Pani, Gennaro, Santorelli, Carlo Antonio Bossi, Giancarlo, Tonolo, Enrico, Fiaccadori, Anna Maria Veronelli, Michele, Emdin, Paola, Ponzani, Maria Cristina Gregorini, Franco Luigi Cavalot, Carlo Bruno Giorda, Taro, Shibasaki, Akihiro, Hamasaki, Takashi, Nomiyama, Sunao, Matsubayashi, Junji, Shinoda, Kazunari, Matsumoto, Hideo, Kanehara, Yoshihide, Hirohata, Masayo, Yamada, Jun, Nakazawa, Yoshimitsu, Yamasaki, Mikihiro, Nakayama, Ryuichi, Furuya, Osamu, Ebisui, Satsuki, Kawasaki, Daishiro, Yamada, Masayuki, Noritake, Tamayo, Ishiko, Nobuhiro, Sasaki, Daisuke, Suzuki, Asami, Tanaka, Miyuki, Kubota, Hideo, Araki, Hiroshi, Ohashi, Takeshi, Osonoi, Kazuo, Yamagata, Naruhiro, Fujita, Daisuke, Kanda, Seiichi, Tanaka, Junko, Koide, Masao, Ishii, Takayuki, Ogiwara, Masaaki, Suzuki, Taiji, Sekigami, Takayuki, Higashi, Yuko, Yambe, Yoshiro, Kusano, Hidetoshi, Kikuchi, Hiroaki, Miyaoka, Kiyoe, Kato, Masayuki, Kashima, Fumiko, Yamakawa, Shuji, Horinouchi, Hirofumi, Imoto, Hiroshi, Sobajima, Hidetoshi, Kanai, Naoki, Matsuoka, Hirotaka, Shibata, Akemi, Inagaki, Toshiyuki, Sugiura, Toru, Sugiyama, Hidekatsu, Yanai, Yoshiyuki, Hamamoto, Masahiro, Hatazaki, Terumasa, Hayashi, Kunihisa, Kobayashi, Satoshi, Murao, Makoto, Ujihara, Kazuya, Sugitatsu, Katsunori, Kawamitsu, Ken, Yamakawa, Izumi, Tsunematsu, Fumi, Kikuchi, Hideaki, Jinnouchi, Tetsuyuki, Yasuda, Hajime, Maeda, Yasuto, Matsuo, Hideki, Okamoto, Takeshi, Katsuki, Ken, Yajima, Takeshi, Morita, Masayuki, Inagaki, Wooje, Lee, Jungoo, Kang, Cheol Young Park, Hyesoon, Kim, Singon, Kim, Youcheol, Hwang, Injoo, Kim, Jaehyeon, Kim, Young Min Cho, Byungwan, Lee, Choonhee, Chung, Soo, Lim, Jae Myung Yu, Dovile, Kriauciuniene, Antanas, Navickas, Audrone, Velaviciene, Egle, Urbanaviciene, Gediminas, Urbonas, Jurate, Lasiene, Lina, Radzeviciene, Ron, Gansevoort, Adriaan, Kooy, G Lieverse, A, L Penne, E, Ruud J, M van Leendert, M van Buren, H Boonstra, A, C Bakker, R, Marielle, Krekels, B Brouwer, C, T Luik, P, J N, M Barendregt, Bert-Jan van den Born, Trine, Finnes, Thomas, Karlsson, Hilde, Selsås, Emil, Asprusten, Robert, Hagemeier, Erik, Eriksen, Knut, Risberg, Hans, Høivik, Leidulv, Solnør, Frode, Thorup, Jan, Rocke, Rick, Cutfield, Peter, Dunn, Jeremy, Krebs, Russell, Scott, Kingsley, Nirmalaraj, Nine, Smuts, John, Baker, Veronica, Crawford, Albert, Bautista, Roberto, Mirasol, Elizabeth, Catindig, Glenda, Pamugas, Louie, Tirador, Maribel, Tanque, Janusz, Gumprecht, Piotr, Napora, Edward, Franek, Andrzej, Stankiewicz, Katarzyna, Landa, Agnieszka, Tiuryn-Petrulewicz, Kazimierz, Ciechanowski, Bogna, Wierusz-Wysocka, Barbara, Rewerska, Grazyna, Cieslik, Michal, Hoffmann, Michal, Nowicki, Jolanta, Krzykowska, Stanislaw, Mazur, Katarzyna, Wasilewska, Anna, Ocicka-Kozakiewicz, Ewa, Skokowska, Renata, Wnetrzak-Michalska, Jan, Ruxer, Patrycja, Butrymowicz, Katarzyna, Madziarska, Ilona, Kurnatowska, Teresa, Rusicka, Adam, Madrzejewski, Tomasz, Stompor, Jose, Guia, Amalia, Pereira, Pedro, Melo, Cristina, Roque, Francisco, Rosario, Fernando Teixeira, E Costa, Fernando, Nolasco, Edgar, Almeida, Pedro, Matos, Cesar, Esteves, Rui, Carvalho, Ilidio, Brandao, Susana, Heitor, Ana Vila Lobos, Rosa, Ballesteros, Gil, Silva, Carlos, Barreto, Ana, Silva, Natalya, Vorokhobina, Alexander, Sherenkov, Ivan, Gordeev, Olga, Semenova, Sergey, Levashov, Vyacheslav, Marasaev, Ruslan, Sardinov, Vadim, Klimontov, Vitaliy, Baranov, Nadezhda, Verlan, Albert, Galyavich, Arkadiy, Demko, Zhanna, Kobalava, Elena, Zakharova, Lyudmila, Kvitkova, Oleg, Solovev, Elena, Smolyarchuk, Larisa, Zhukova, Elena, Zhdanova, Andrey, Babkin, Galina, Nechaeva, Olga, Barbarash, Elena, Rechkova, Roman, Libis, Elena, Kosmacheva, Tatyana, Rodionova, Irina, Ipatko, Alexander, Dreval, Nina, Petunina, Elena, Chernyavskaya, Alsu, Zalevskaya, Yuriy, Khalimov, Tatyana, Zykova, Anton, Edin, Ashot, Mkrtumyan, Shamil, Palyutin, Vyacheslav, Mareev, Leonid, Strongin, Olga, Ukhanova, Mikhail, Antsiferov, Davyd, Yakhontov, Leonid, Pimenov, Natalya, Koziolova, Konstantin, Nikolaev, Imad, Merai, Olga, Zanozina, Leyla, Gaysina, Mikhail, Arkhipov, Natalia, Malykh, Oksana, Rymar, Vladimir, Martynenko, Sofya, Malyutina, Polina, Ermakova, Marina, Kalashnikova, Bengt-Olov, Tengmark, Carl-Johan, Lindholm, Dan, Curiac, Ken, Eliasson, Erik, Rein-Hedin, Gregor, Guron, Inga, Soveri, Annette, Bruchfeld, Jonas, Spaak, Malin, Frank, Magnus, Löndahl, Hans, Larnefeldt, Margareta, Hellgren, Olof, Hellberg, Yong Mong Bee, Chee Fang Sum, Ru San Tan, Piyamitr, Sritara, Chaicharn, Deerochanawong, Chatlert, Pongchaiyakul, Natapong, Kosachunhanan, Bancha, Satirapoj, Ahmet, Temizhan, Ibrahim, Gul, Ramazan, Sari, Aytekin, Oguz, Mustafa, Tigen, Huseyin, Yilmaz, Ozer, Badak, Oner, Ozdogan, Talat, Tavli, Necmi, Eren, Murat, Cayli, Sedat, Ustundag, Yavuz, Yenicerioglu, Ismail, Kocyigit, Abdulbaki, Kumbasar, Idris, Sahin, Lee-Ming, Chuang, Ju-Ying, Jiang, Chien-Te, Lee, Der-Cherng, Tarng, Shih-Te, Tu, Mai-Szu, Wu, Ming-Ju, Wu, Chiz-Tzung, Chang, Cheng-Chieh, Hung, Liubov, Sokolova, Borys, Mankovsky, Dmytro, Kogut, Viktoriia, Chernikova, Kateryna, Malyar, Nonna, Kravchun, Volodymyr, Botsyurko, Vitaliy, Maslyanko, Liliya, Martynyuk, Oleksandr, Serhiyenko, Vasyl, Stryzhak, Halyna, Myshanych, Oleksandra, Donets, Iryna, Bondarets, Maryna, Vlasenko, Nataliia, Pertseva, Mariia, Grachova, Ivan, Smirnov, Larysa, Pererva, Ivan, Fushtey, Julia, Komisarenko, Anna, Isayeva, Carl, Meisner, Bobby, Khan, Louis, Maletz, Bradley, Dixon, Ahmed, Arif, Timothy, Jackson, Mirela, Ponduchi, Mahfouz El Shahawy, Salil, Nadkarni, Daniel, Urbach, Jorge, Paoli-Bruno, Henry, Lora, Umar, Farooq, Steven, Zeig, Lance, Rudolph, Nabil, Andrawis, William, Kaye, Jill, Meyer, Khalid, Bashir, Glenn, Heigerick, James, Smelser, Javier Ricardo Colomar, David, Scott, Brian, First, Stuart, Handelsman, Jose, Bautista, Rajesh, Patel, Stephen, Minton, Juan, Frias, Luis, Ramos-Gonez, John, Bertsch, Ali, Iranmanesh, Vivian, Fonseca, Michael, Yuryev, Larry, Popeil, Jose, Cardona, Sanjeev, Saxena, Santosh, Sharma, Edgar, Gonzalez, Richard, Solomon, Muhammad, Khan, Ahmed, Awad, David, Fitz-Patrick, Douglas, Linfert, David, Grant, Susan, Brian, Leon, Fogelfeld, Rafael, Canadas, Pablo, Pergola, Joseph, Soufer, Rakesh, Patel, Shujauddin, Valika, Jonathan, Winston, Allison, D, Maria, Caramori, Stanley, Koch, Anjay, Rastogi, Jonathan, Bornfreund, Michael, Rocco, Maxine, Hamilton, Luis, Garcia-Mayol, Peter, Weissman, Suzanne, Oparil, Gary, Ruoff, Kyaw, Soe, Gary, Korff, Robert, Busch, Alexander, Lurie, Israel, Hartman, Garfield, Samuels, Derek, Lejeune, Visal, Numrungroad, Stephen, Brietzke, Zeid, Kayali, Harold, Szerlip, Steven, Barag, Gilberto, Seco, Damaris, Vega, Osvaldo, Brusco, Camil, Kreit, Humberto, Cruz, Bharat, Mocherla, Sharma, Prabhakar, George, Fadda, Martin, Valdes, Eugene, Soroka, Ramin, Berenji, Sreedhara, Alla, Shweta, Bansal, Odugbesan, A, Karlton, Pettis, Masoud, Azizad, Idalia, Acosta, Atoya, Adams, William, Sanchez, Rosa, Suarez, Efrain, Reisin, Carlos, Herrera, Keung, Lee, Csaba, Kovesdy, Adam, Whaley-Connell, Aldo, Peixoto, Ronald, Mayfield, Mahendra, Jain, Earl, Martin, Paul, Norwood, Jonathan, Wise, Hugo, Romeu, Stephen, Halpern, Mustafa, Mandviwala, Thomas, Turk, Anna, Burgner, David, Bleich, Ankur, Doshi, Jose, Carpio, Jorge, Posada, Alexander, Magno, Samer, Nakhle, Gary, Goldstein, Caroline, Mbogua, Dierdre, Mcmullen, Dilawar, Ajani, Wayne, Kotzker, Nelson, Kopyt, Richard, Treger, Yusuf, Ruhullah, Sharon, Adler, Harjeet, Brar, Marc, Rendell, Dennis, Ross, Srinivasan, Beddhu, German, Hernandez, Sylvia, Rosas, M Sue Kirkman, Mohammed, El-Shahawy, Jeffrey, Rothman, Ahmad, Barakzoy, Aparna, Tamirisa, Sabrina, Benjamin, Michael, Bahrami, Prabir, Roy-Chaudhury, Ramprasad, Dandillaya, Gretel, Trullenque, Jose, Birriel, John, Flack, Karen, Johnson, Brenda, Lemus, Guillermo, Umpierrez, Geetha, Maddukuri, Kenneth, Jamerson, Christopher, Case, Patrick, Fluck, Saeed, Kronfli, Violet, Habwe, Bala, Subramanian, Tariq, Shafi, Rupesh, Raina, Roland, Fernando, Sourabh, Kharait, Carlos, Hernandez-Cassis, Raymond, Fink, Jamal, Hammoud, Amer, Al-Karadsheh, Manuel, Montero, Philip, Nicol, Jesus, Navarro, Michael, Shanik, Zia, Din, Francisco, Gonzalez-Abreu, Sam, Lerman, Claude, Galphin, John, Evans, Ashwini, Gore, Radica, Alicic, Mandeep, Sahani, Roberto, Pisoni, Tuan-Huy, Tran, Jeffrey, Ryu, Harvey, Serota, Nilda, Neyra, Richard, O Donovan, Sreedhar, Mandayam, Moustafa, Moustafa, Mark, Smith, Arvind, Krishna, Arjun, Sinha, Anuj, Bhargava, Kodangudi, Ramanathan, Soni, Dhanireddy, Stephen, Thomson, Romanita, Nica, Emaad, Abdel-Rahman, Mark, Barney, Mariana, Markell, Nauman, Shahid, David, Oliver, Tran, Khanh, Pham Nguyen Son, Lam VAN Hoang, Boi Ngoc Nguyen, Nguyen Minh Nui, Lan Phuong Tran, Fayzal, Ahmed, Dorothea, Urbach, Dirkie Jansen van Rensburg, Gracjan, Podgorski, Aslam, Amod, Sindeep, Bhana, Shaifali, Joshi, Essack, Mitha, Deepak, Lakha, Louis van Zyl, Trokis, J, Naresh, Ranjith, Mary, Seeber, Mohamed, Sarvan, Mohammed, Tayob, Brian, Rayner, Larry, Distiller, Heidi, Siebert, Mukesh, Joshi, Paul, Rheeder, Magdalena Madero Rovalo, Gustavo Solache Ortiz, Gustavo Méndez Machado, Rafael Valdez Ortiz, Juan Villagordoa Mesa, Saúl Irizar Santana, Sandro Avila Pardo, Jorge Escobedo de la Peña, Guillermo González Gálvez, Leobardo Sauque Reyna, Miriam Bastidas Adrian, Guillermo Fanghänel Salmón, Ramiro Gutiérrez Ochoa, Luis Nevarez Ruiz, Gabriel Ramos López, Alfredo Chew Wong, Arturo Saldaña Mendoza, Pedro García Hernández, José González González, Melchor Alpizar Salazar, José Lazcano Soto, Amaury, Roman-Miranda, Gregorio, Cortes-Maisonet, Liana, Turcu, Adriana, Dumitrescu, Gabriela, Radulian, Hortensia, Barbonta, Cristina, Mistodie, Georgeta, Vacaru, Alexandrina, Popescu, Adrian, Vlad, Silvia, Paveliu, Nicoleta, Mindrescu, Adrian, Albota, Ella, Pintilei, Lavinia, Pop, Gabriela, Negrisanu, Doina, Catrinoiu, Cornelia, Bala, Amorin, Popa, Iosif, Szilagyi, Ciprian, Constantin, Elena, Caceaune, Adriana, Onaca, Li Yuan Lee, Nor Azizah Aziz, Wan Mohd Izani Wan Mohamed, Wan Hasnul Halimi Bin Wan Hasan, Jeyakantha, Ratnasingam, Nik Nur Fatnoon Nik Ahmad, Rizmy Najme Khir, Norhaliza Mohd Ali, Masni, Mohamad, Chek Loong Loh, Joe, Eustace, John, Holian, Donal, Reddan, Yvonne, O Meara, Mensud, Hatunic, Zuzana, Ochodnicka, Dalibor, Sosovec, Andrej, Dzupina, Ingrid, Buganova, Jana, Babikova, Denisa, Spodniakova, Ruilope, L, Agarwal, R, Anker, S, Bakris, G, Filippatos, G, Nowack, C, Kolkhof, P, Joseph, A, Mentenich, N, Pitt, B, Trevisan, R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic
Subjects: Male, Endocrinology, Diabetes and Metabolism, Enfermedad cardiovascular, 030232 urology & nephrology, BAY 94-8862, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabete, Kidney, Aparato circulatorio, Azúcar, chemistry.chemical_compound, Mineralocorticoid Receptor Antagonists/therapeutic use, 0302 clinical medicine, Medicine and Health Sciences, Diabetic Nephropathies, Myocardial infarction, Renal Insufficiency, Chronic, Aldosterone, Outcome, Mineralocorticoid Receptor Antagonists, RISK, COMPLICATIONS, Diabetes, Middle Aged, SPIRONOLACTONE, CHRONIC HEART-FAILURE, Treatment Outcome, Mineralocorticoid, Nephrology, Cardiovascular Diseases, Research Design, Disease Progression, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Type 2, Glomerular Filtration Rate, medicine.medical_specialty, Finerenone, Naphthyridines/therapeutic use, Renal function, Outcomes, 03 medical and health sciences, Clinical, Double-Blind Method, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Humans, Naphthyridines, Renal Insufficiency, Chronic, ANTAGONIST, Sistema cardiovascular, Aged, Patient-Oriented, Translational Research: Research Article, Diabetic Nephropathies/complications, Renal Insufficiency, Chronic/drug therapy, RECEPTOR, Aldosterone, Clinical, Diabetes, Kidney, Mineralocorticoid, Outcomes, business.industry, Cardiovascular Diseases/epidemiology, Diabetes Mellitus, Type 2/complications, MILD, WORSENING RENAL-FUNCTION, EFFICACY, medicine.disease, chemistry, Diabetes Mellitus, Type 2, Spironolactone, Albuminuria, business, Kidney disease, Follow-Up Studies
Abstract: Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
Published: 2019
Full Text: View/download PDF

21. Pharmacokinetics of Prolonged-Release Once-Daily Formulations of Tacrolimus in De Novo Kidney Transplant Recipients: A Randomized, Parallel-Group, Open-Label, Multicenter Study

Author: Mirco Govoni, Paolo Malvezzi, Valérie Garrigue, Arnaud Del Bello, Yannick Le Meur, Giorgia Ciurlia, Silvia Geraci, Elisabeth Cassuto, Lionel Rostaing, Nassim Kamar, Gianluigi Poli, Gabriele Nicolini, Marie Essig, Christophe Mariat, Giovanni Piotti, Michel, Geneviève, 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), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de néphrologie et transplantation rénale [Nice], Hôpital Pasteur [Nice] (CHU), Kidney and Pancreas Transplantation, Global Clinical Development, CHU Saint-Etienne, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Nephrologie-Transplantation Rénale et Hémodialyse [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Departements of nephrology and organ transplantation [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Néphrologie et Transplantation d'organes, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Département de Diabétologie, Urologie, Néphrologie et Endocrinologie (CHU-Grenoble), CHU Grenoble, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Néphrologie, and Hôpital Lapeyronnie
Subjects: Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Urology, Cmax, Biological Availability, 030230 surgery, 030226 pharmacology & pharmacy, Kidney transplant, Drug Administration Schedule, Tacrolimus, PR Tac, 03 medical and health sciences, 0302 clinical medicine, Therapeutic index, Pharmacokinetics, Prolonged release, medicine, Humans, Pharmacology (medical), Molecular Targeted Therapy, Prospective Studies, De novo kidney transplantation, ComputingMilieux_MISCELLANEOUS, Original Research, business.industry, Envarsus, Advagraf, General Medicine, Middle Aged, Kidney Transplantation, 3. Good health, Bioavailability, LCPT, Treatment Outcome, Multicenter study, Research Design, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Immunosuppressive Agents
Abstract: Introduction Different prolonged-release formulations of tacrolimus are available. To date, the pharmacokinetic (PK) profile of LCP-tacrolimus (LCPT; Envarsus®) has not been compared with PR-Tac (Advagraf®) in de novo kidney transplant recipients. These profiles will guide clinical recommendations for the initiation and dose titration strategies of once-daily tacrolimus formulations. Methods This randomized, parallel-group, open-label, multicenter PK study randomized 75 de novo, adult, white kidney transplant recipients to LCPT 0.17 mg/kg/day (n = 37) or PR-Tac 0.20 mg/kg/day (n = 38) for 4 weeks. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations. Results PK analysis (days 1, 3, 7 and 14) included 68 patients (LCPT, n = 33; PR-Tac, n = 35). Similar proportions of patients were within the pre-defined therapeutic tacrolimus trough blood concentration range, with
Published: 2019
Full Text: View/download PDF

22. Vitamin K antagonist has a higher impact than heparin in preventing circuit clotting in chronic haemodialysis patients

Author: Pierre-Yves Charles, Yannick Le Meur, Tugdual Tanquerel, Hubert Galinat, Michel, Geneviève, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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), Laboratoire d'hématologie (Labo Hémato - BREST), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: vitamin K antagonist, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, medicine.medical_treatment, 030232 urology & nephrology, heparin, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine, Chronic hemodialysis, Dosing, coagulation, AcademicSubjects/MED00340, Dialysis, ComputingMilieux_MISCELLANEOUS, Transplantation, chronic haemodialysis, business.industry, Original Articles, Heparin, Vitamin K antagonist, University hospital, 3. Good health, Coagulation, Nephrology, Anesthesia, [SDV.IMM]Life Sciences [q-bio]/Immunology, Hemodialysis, business, medicine.drug
Abstract: Background In dialysis sessions, some data suggest that decreasing or even avoiding additional anticoagulation by heparin is possible among patients already treated with oral anticoagulation. However, the required dose of heparin may actually depend on the pre-dialysis international normalized ratio (INR), which varies from one session to another. The aim of our study was to determine the respective role of INR and heparin dosing in the risk of circuit clotting during chronic haemodialysis. Methods From early 2012 to July 2016, we analysed the totality of dialysis sessions performed at Brest University Hospital among haemodialysis patients treated by vitamin K antagonists (VKA). We established a prediction of circuit clotting on the basis of a simplified score obtained by combining INR and heparin dosing. Results In total, 7184 dialysis sessions among chronic haemodialysis patients under VKA were identified, including 233 with clotting events. The mean INR without clotting events was 2.5 versus 1.8 with clotting events (P 3.0; P Conclusion. Our study established a predictive model of thrombosis risk of dialysis circuits in patients treated by VKA for a given heparin dose and a given INR. This model shows a marginal contribution of heparin to protect against the risk of thrombosis compared with VKA. Moreover, heparin would not appear to be necessary for patients with an INR >2.2.
Published: 2019
Full Text: View/download PDF

23. 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
Full Text: View/download PDF

24. Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8

Author: Béatrice Josselin-Foll, Laurent Meijer, Katy Billot, Yannick Le Meur, Benoit Villiers, Alain Fautrel, Oxana Ibraghimov-Beskrovnaya, Darren P. Wallace, Pamela V. Tran, Alessandra Boletta, Nikolay O. Bukanov, Charlène Coquil, Nassima Oumata, Claire Delehouzé, Ralph Witzgall, Sophie Saunier, Thomas Weimbs, Melanie Grosch, Evelyne Fischer, Marie Trudel, Marco Pontoglio, Michal Mrug, Nathalie Desban, ManRos Therapeutics, Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Nephrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Division of Genetics and Cell Biology Dibit San Raffaele Scientific Institute, University of California [Santa Barbara] (UCSB), University of California, University of Regensburg - Institute for Molecular and Cellular Anatomy, Institute for Molecular and Cellular Anatomy, Universität Regensburg (UR), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Détoxication et réparation tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of Alabama at Birmingham [ Birmingham] (UAB), University of Kansas [Kansas City], Institut De Recherches Cliniques De Montreal - IRCM [Canada], Sanofi Genzyme, University of California [Santa Barbara] (UC Santa Barbara), University of California (UC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Physiology, Casein Kinase 1 epsilon, Pyridines, [SDV]Life Sciences [q-bio], Mice, Transgenic, Kidney, Catalysis, Chromatography, Affinity, 03 medical and health sciences, 0302 clinical medicine, Cyclin-dependent kinase, Polycystic kidney disease, medicine, Roscovitine, Animals, Humans, Beneficial effects, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, Polycystic Kidney Diseases, biology, Kinase, Chemistry, Casein Kinase Ialpha, R-roscovitine, medicine.disease, 3. Good health, Disease Models, Animal, 030104 developmental biology, Purines, 030220 oncology & carcinogenesis, biology.protein, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Casein kinase 1, Research Article, Protein Binding, Signal Transduction
Abstract: Following the discovery of (R)-roscovitine’s beneficial effects in three polycystic kidney disease (PKD) mouse models, cyclin-dependent kinases (CDKs) inhibitors have been investigated as potential treatments. We have used various affinity chromatography approaches to identify the molecular targets of roscovitine and its more potent analog (S)-CR8 in human and murine polycystic kidneys. These methods revealed casein kinases 1 (CK1) as additional targets of the two drugs. CK1ε expression at the mRNA and protein levels is enhanced in polycystic kidneys of 11 different PKD mouse models as well as in human polycystic kidneys. A shift in the pattern of CK1α isoforms is observed in all PKD mouse models. Furthermore, the catalytic activities of both CK1ε and CK1α are increased in mouse polycystic kidneys. Inhibition of CK1ε and CK1α may thus contribute to the long-lasting attenuating effects of roscovitine and (S)-CR8 on cyst development. CDKs and CK1s may constitute a dual therapeutic target to develop kinase inhibitory PKD drug candidates.
Published: 2018
Full Text: View/download PDF

25. Can we further enrich autosomal dominant polycystic kidney disease clinical trials for rapidly progressive patients? Application of the PROPKD score in the TEMPO trial

Author: Peter C. Harris, John Ouyang, Yannick Le Meur, Arlene B. Chapman, Christina M. Heyer, Sarah R. Senum, Ron T. Gansevoort, Ronald D. Perrone, Frank S. Czerwiec, Maria V. Irazabal, Jaime D. Blais, Vicente E. Torres, Olivier Devuyst, Emilie Cornec-Le Gall, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Mayo Clinic [Rochester], Otsuka PDC, Rockville, MD, USA, Otsuka PDC, Institute of Nephrology, University of Zurich, Switzerland, Department of Nephrology, University Medical Center, University of Groningen, Tufts University School of Medicine [Boston], Section of Nephrology University of Chicago, University of Chicago, Division of Nephrology and Hypertension, Mayo Clinic, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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), University of Zurich, Cornec-Le Gall, Emilie, Cardiovascular Centre (CVC), and Groningen Kidney Center (GKC)
Subjects: Nephrology, Male, Pathology, 2747 Transplantation, PKD2, PKD1, 030232 urology & nephrology, Tolvaptan, 030204 cardiovascular system & hematology, Kidney, Severity of Illness Index, 10052 Institute of Physiology, 0302 clinical medicine, DESIGN, Risk Factors, genetics, Prospective Studies, Prospective cohort study, TOLVAPTAN, ComputingMilieux_MISCELLANEOUS, Gene Rearrangement, Clinical Trials as Topic, 2727 Nephrology, autosomal dominant polycystic kidney disease, MOLECULAR DIAGNOSTICS, Age Factors, Middle Aged, Polycystic Kidney, Autosomal Dominant, Research Design, Predictive value of tests, Hypertension, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antidiuretic Hormone Receptor Antagonists, medicine.drug, Glomerular Filtration Rate, Adult, medicine.medical_specialty, TRPP Cation Channels, Adolescent, Autosomal dominant polycystic kidney disease, Urology, Renal function, 610 Medicine & health, Risk Assessment, TEMPO 3/4, 03 medical and health sciences, Young Adult, Clinical Research, Predictive Value of Tests, Internal medicine, medicine, Journal Article, Humans, ADPKD, Transplantation, IDENTIFICATION, business.industry, MUTATIONS, Gene rearrangement, medicine.disease, GENE, VOLUME, 570 Life sciences, biology, ORIGINAL ARTICLES, business
Abstract: Background: The PROPKD score has been proposed to stratify the risk of progression to end-stage renal disease in autosomal dominant polycystic kidney disease (ADPKD) subjects. We aimed to assess its prognostic value in a genotyped subgroup of subjects from the Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (TEMPO3/4) trial.Methods: In the post hoc analysis, PKD1 and PKD2 were screened in 770 subjects and the PROPKD score was calculated in mutation-positive subjects (male: 1 point; hypertension Results: The PROPKD score was calculated in 749 subjects (LR = 132, IR = 344 and HR = 273); age was inversely related to risk (LR = 43.6 years, IR = 39.5 years, HR = 36.2 years; P Conclusion: This study confirms the prognostic value of the PROPKD score and suggests that it could reduce costs and enhance endpoint sensitivity by enriching future study populations for rapidly progressing ADPKD subjects.
Published: 2017
Full Text: View/download PDF

26. PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis

Author: Laure Ecotiere, Philippe Saliou, Aude Kersalé, Cécile Vigneau, Lise Mandart, Peter C. Harris, Maryvonne Hourmant, Pascale Siohan, Catherine Hanrotel-Saliou, Eric Michez, Marie Pierre Audrézet, Guillaume Seret, C. Stanescu, Hélène Longuet, Jean-François Augusto, Philippe Gatault, Eric Renaudineau, Christophe Charasse, Frank Bridoux, Claude Férec, Yannick Le Meur, Sophie Gié, Thierry Frouget, Jian-Min Chen, Sandrine Maestri, Emilie Cornec-Le Gall, Jacques Dantal, Pascale Depraetre, Michiel Massad, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de néphrologie et d'hémodialyse, Centre hospitalier de Saint Malo-Aide aux Urémiques de Bretagne (AUB), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CH de Saint-Brieuc, Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Cancer du rein : bases moléculaires de la tumorogenèse, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS), Orange Labs [Cesson-Sévigné], Orange Labs, Service de Néphrologie, Service de Néphrologie CHU TOURS, Service de néphrologie et immunologie clinique [CHRU Tours], Université de Tours (UT)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Service de Néphrologie CH Vannes, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), AUB Nephrology Brest, AUB Nephrology, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Lab-STICC_UBO_CACS_MOCS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry and Molecular Biology, Mayo Clinic, Division of Nephrology and Hypertension, Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), National Plan for Clinical Research, Groupement Inter-Régional de Recherche Clinique et d’Innovation, Société Française de Néphrologie, Institut National de la Santé et de la Recherche Médicale, EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), CHU de Saint-Brieuc, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-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 Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Néphrologie, Immunologie clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Pediatrics, Pathology, mutation detection, PKD2, 030232 urology & nephrology, Disease, urologic and male genital diseases, 0302 clinical medicine, genetics, kidney function, Aged, 80 and over, education.field_of_study, case series, Autosomal dominant polycystic kidney disease (ADPKD), sequencing, Middle Aged, Polycystic Kidney, Autosomal Dominant, female genital diseases and pregnancy complications, 3. Good health, Nephrology, Mutation (genetic algorithm), Cohort, genetic prevalence, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, disease severity, Presentation (obstetrics), Adult, medicine.medical_specialty, TRPP Cation Channels, Adolescent, Population, Autosomal dominant polycystic kidney disease, renal survival, Renal function, Young Adult, 03 medical and health sciences, disease progression, medicine, Humans, Mutation detection, Renal Insufficiency, Chronic, education, Aged, business.industry, urogenital system, medicine.disease, Cross-Sectional Studies, 030104 developmental biology, end-stage renal disease (ESRD), Mutation, mutation spectrum, prognosis, business
Abstract: International audience; Background - PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. Study design - Case series, January 2010 to March 2016. Settings & participants - Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. Outcomes - Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. Results - The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. Limitations - Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. Conclusions - Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.
Published: 2017
Full Text: View/download PDF

27. Tolvaptan in later-stage autosomal dominant polycystic kidney disease

Author: Patricia Van der Niepen, Vladimir Tesar, Yannick Le Meur, Jonathan Barratt, Vicente Torres, Michal Nowicki, Paolo Manunta, Daniel Gale, Jesper Nørgaard Bech, Oleg Nagibovich, Frederic Rahbari-Oskoui, Bert Bammens, Miguel Hueso, Olivier Devuyst, Torres, Vicente E., Chapman, Arlene B., Devuyst, Olivier, Gansevoort, Ron T., Perrone, Ronald D., Koch, Gary, Ouyang, John, Mcquade, Robert D., Blais, Jaime D., Czerwiec, Frank S., Sergeyeva, Olga, on behalf of the REPRISE Trial, Investigator, Manunta, P, Clinical sciences, Clinical Pharmacology and Clinical Pharmacy, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), University of Zurich, and Torres, Vicente E
Subjects: 0301 basic medicine, Male, Vasopressin, Clinical Trial, Phase III, 030232 urology & nephrology, Tolvaptan, VASOPRESSIN, PROGRESSION, 2700 General Medicine, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, 10052 Institute of Physiology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, biology, Research Support, Non-U.S. Gov't, Medicine (all), Alanine Transaminase, General Medicine, Middle Aged, Polycystic Kidney, Autosomal Dominant, female genital diseases and pregnancy complications, Multicenter Study, Randomized Controlled Trial, young adult, SECRETION, Female, Glomerular filtration rate, Antidiuretic Hormone Receptor Antagonists, CLINICAL-TRIALS, medicine.drug, Glomerular Filtration Rate, Human, Adult, medicine.medical_specialty, CYST GROWTH, Adolescent, Autosomal dominant polycystic kidney disease, Urology, Renal function, Benzazepine, 610 Medicine & health, Kidney Volume, Placebo, 03 medical and health sciences, Young Adult, Double-Blind Method, Internal medicine, Journal Article, medicine, Humans, ADPKD, Aged, urogenital system, business.industry, Bilirubin, Benzazepines, medicine.disease, Antidiuretic Hormone Receptor Antagonist, MODEL, RENAL-DISEASE, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 030104 developmental biology, Endocrinology, Alanine transaminase, VOLUME, biology.protein, 570 Life sciences, Kidney Failure, Chronic, business
Abstract: Item does not contain fulltext BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, >/=60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m(2) of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m(2) were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTS: The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m(2) (95% confidence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute per 1.73 m(2) (95% CI, -4.08 to -3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m(2); 95% CI, 0.86 to 1.68; P3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONS: Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .).
Published: 2017
Full Text: View/download PDF

28. Mutations in GANAB, Encoding the Glucosidase IIα Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease

Author: Cécile Vigneau, Binu Porath, Elizabeth K. Dillinger, Saurabh Baheti, Marie C. Hogan, José Ignacio Herrero, Sarah R. Mauritz, Katharina Hopp, Emilie Cornec-Le Gall, Peter C. Harris, Vladimir G. Gainullin, Christina M. Heyer, Vicente E. Torres, Velibor Tasic, Marie Pierre Audrézet, Marie E. Edwards, Terry Watnick, Charles D. Madsen, Arlene B. Chapman, Yannick Le Meur, Frédéric Lavainne, Carly J. Banks, Claude Férec, Jesus M. Banales, Bharathi V. Reddy, Division of Nephrology and Hypertension, Mayo Clinic, Service de néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry and Molecular Biology, University of Southampton, Mayo Clinic [Rochester], University of Chicago, Clínica Universidad de Navarra [Pamplona], Department of Liver and Gastrointestinal Diseases (Biodonista Health Research Institute), Department of Liver and Gastrointestinal Diseases, Department of Pediatric Nephrology, University Children’s Hospital, Division of Nephrology, University of Maryland [Baltimore], Section of Nephrology University of Chicago, CHU Pontchaillou [Rennes], Service de Néphrologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, This study received support from NIDDK grant DK058816, the Mayo PKD Translational Center (DK090728), an American Heart Association postdoctoral fellowship (B.P.), the Mayo Clinic Nephrology Training Grant (T32DK007013 to V.G.G.), an American Society of Nephrology (ASN) Foundation Kidney Research Fellowship (E.C.-L.G.) and Ben J. Lipps Research Fellowship (K.H.), the Mayo Graduate School (E.K.D.), the Zell Family Foundation, and Robert M. and Billie Kelley Pirnie. The CRISP and HALT-PKD studies were supported by NIDDK cooperative agreements (DK056943, DK056956, DK056957, DK056961, DK062410, DK062408, DK062402, DK082230, DK062411, and DK062401), National Center for Research Resources General Clinical Research Centers, and National Center for Advancing Translational Sciences Clinical and Translational Science Awards. The Genkyst cohort was supported by National Plans for Clinical Research, Groupement Interrégional de Recherche Clinique et d’Innovation (GIRCI Grand Ouest), and the French Society of Nephrology., CHRU - Service de néphrologie, dialyse et transplantation rénale, Hospital Donostia. CIBERehd, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Universidade de Aveiro, National Physical Laboratory [Teddington] (NPL), Cancer du rein : bases moléculaires de la tumorogenèse, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]-Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Michel, Geneviève, EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: 0301 basic medicine, Male, Candidate gene, 030232 urology & nephrology, Fluorescent Antibody Technique, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Polycystic kidney disease, Genetics(clinical), Child, Genetics (clinical), Cells, Cultured, Microscopy, Confocal, Cysts, Polycystic liver disease, Liver Diseases, Middle Aged, Polycystic Kidney, Autosomal Dominant, female genital diseases and pregnancy complications, 3. Good health, Pedigree, Female, Adult, medicine.medical_specialty, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Article, 03 medical and health sciences, SEC63, Internal medicine, medicine, Genetics, Humans, Immunoprecipitation, Amino Acid Sequence, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, PKD1, Sequence Homology, Amino Acid, PRKCSH, Genetic heterogeneity, alpha-Glucosidases, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Transplantation, 030104 developmental biology, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, CRISPR-Cas Systems
Abstract: International audience; Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (∼85% and ∼15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ∼50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit α (GIIα). Because PRKCSH encodes GIIβ, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIα for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIα. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation.
Published: 2016
Full Text: View/download PDF

29. Can ultrasound kidney length qualify as an early predictor of progression to renal insufficiency in autosomal dominant polycystic kidney disease?

Author: Yannick Le Meur, Emilie Cornec-Le Gall, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), and Université de Brest (UBO)-IFR148
Subjects: medicine.medical_specialty, Population, 030232 urology & nephrology, Autosomal dominant polycystic kidney disease, Urology, Renal function, Kidney Volume, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Stage (cooking), education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Kidney, business.industry, medicine.disease, Endocrinology, medicine.anatomical_structure, Nephrology, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Kidney disease
Abstract: To the Editor: We read with great interest the article of Bhutani et al.,1 which highlights the prognostic value of ultrasound (US) kidney length (KL) in the CRISP cohort2 of autosomal dominant polycystic kidney disease (ADPKD) patients, which included a selected population of young patients (age 15–46 years) with estimated glomerular filtration rate (eGFR) values over 70 ml/min per 1.73 m2. The authors demonstrated that US KL over 16.5 cm predicts the onset of chronic kidney disease stage 3 within 8 years, and suggest that it could represent an alternative to height-adjusted total kidney volume (HtTKV)3 to assess ADPKD prognosis and enable therapeutic decision making. Although we understand that the US KL threshold proposed by the authors allows anticipating a few years—or months—the eGFR decline in young patients who have a preserved kidney function, the applicability of this prognostic biomarker in the general ADPKD population remains uncertain. Using personal data from the Genkyst cohort,4 we observed that before exceeding this US KL threshold, a significant number of the patients had already eGFR values below 70 ml/min per 1.73 m2 (Figure 1). Furthermore, patients with an eGFR over 70 ml/min per 1.73 m2 and a US KL over 16.5 cm represent a minority of the patients of our cohort. Therefore, we are unsure whether US KL can qualify as an early prognostic biomarker.
Published: 2015
Full Text: View/download PDF

30. Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis

Author: Felipe Cañas, Pierre Youinou, Antoine Valeri, Laurence Pougnet-Di Costanzo, Chaim Putterman, Alain Saraux, Juan-Manuel Anaya, Sandrine Jousse-Joulin, Yannick Le Meur, Yves Renaudineau, Adriana Rojas-Villarraga, Catherine Hanrotel-Saliou, Guillaume Seret, LabEX IGO Immunothérapie Grand Ouest, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Service d'Urologie (BREST - Urologie), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rheumatology, Albert Einstein College of Medicine [New York], Laboratoire d'Immunologie et Immunothérapie, Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Escuela Universitaria de Informatica, Universidad Politécnica de Madrid (UPM), and Michel, Geneviève
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Lupus nephritis, Enzyme-Linked Immunosorbent Assay, Immunoglobulin G, Young Adult, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Actinin, Cells, Cultured, Aged, Autoantibodies, Autoimmune disease, Lupus erythematosus, biology, medicine.diagnostic_test, business.industry, Cell Membrane, Autoantibody, Middle Aged, Flow Cytometry, medicine.disease, Lupus Nephritis, 3. Good health, HEK293 Cells, Rheumatoid arthritis, Mesangial Cells, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Renal biopsy, Antibody, business
Abstract: International audience; Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.
Published: 2015

31. Building a network of ADPKD reference centres across Europe: The EuroCYST initiative

Author: Tevfik Ecder, Andreas L. Serra, Yannick Le Meur, Dominique Chaveau, Ron T. Gansevoort, Olivier Devuyst, Rudolf P. Wüthrich, Kai-Uwe Eckardt, Giuseppe Remuzzi, Anna Köttgen, Richard Sandford, Klemens Budde, Albert C.M. Ong, Katja Petzold, Vladimir Tesar, Laura Rotar, Roser Torra, Yves Pirson, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), University of Zurich, and Serra, Andreas L
Subjects: Pediatrics, Pathology, 2747 Transplantation, Health Status, medicine.medical_treatment, 030232 urology & nephrology, PROGRESSION, SIROLIMUS, 030204 cardiovascular system & hematology, urologic and male genital diseases, 10052 Institute of Physiology, POLYCYSTIC KIDNEY-DISEASE, 0302 clinical medicine, EVEROLIMUS, DESIGN, Medizinische Fakultät, Surveys and Questionnaires, Epidemiology, Polycystic kidney disease, risk factors, Longitudinal Studies, Referral and Consultation, 2727 Nephrology, Standard of Care, cohort, Health Services, Polycystic Kidney, Autosomal Dominant, Prognosis, DEPRESSION, Magnetic Resonance Imaging, 3. Good health, Europe, EuroCYST, Research Design, Nephrology, 10076 Center for Integrative Human Physiology, Cohort, biomarker, Glomerular Filtration Rate, Cohort study, medicine.medical_specialty, CYST GROWTH, Autosomal dominant polycystic kidney disease, 610 Medicine & health, DIAGNOSIS, Young Adult, 03 medical and health sciences, medicine, Humans, ddc:610, Renal replacement therapy, ADPKD, Transplantation, business.industry, medicine.disease, VOLUME, 570 Life sciences, biology, business, Biomarkers, Kidney disease
Abstract: Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic inherited kidney disease, affecting an estimated 600 000 individuals in Europe. The disease is characterized by age-dependent development of a multiple cysts in the kidneys, ultimately leading to end-stage renal failure and the need of renal replacement therapy in the majority of patients, typically by the fifth or sixth decade of life. The variable disease course, even within the same family, remains largely unexplained. Similarly, assessing disease severity and prognosis in an individual with ADPKD remains difficult. Epidemiological studies are limited due to the fragmentation of ADPKD research in Europe.Methods. The EuroCYST initiative aims: (i) to harmonize and develop common standards for ADPKD research by starting a collaborative effort to build a network of ADPKD reference centres across Europe and (ii) to establish a multicentric observational cohort of ADPKD patients. This cohort will be used to study factors influencing the rate of disease progression, disease modifiers, disease stage-specific morbidity and mortality, health economic issues and to identify predictive disease progression markers. Overall, 1100 patients will be enrolled in 14 study sites across Europe. Patients will be prospectively followed for at least 3 years. Eligible patients will not have participated in a pharmaceutical clinical trial 1 year before enrolment, have clinically proven ADPKD, an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m(2) and above, and be able to provide written informed consent. The baseline visit will include a physical examination and collection of blood, urine and DNA for biomarker and genetic studies. In addition, all participants will be asked to complete questionnaires detailing self-reported health status, quality of life, socioeconomic status, health-care use and reproductive planning. All subjects will undergo annual follow-up. A magnetic resonance imaging (MRI) scan will be carried out at baseline, and patients are encouraged to undergo a second MRI at 3-year follow-up for qualitative and quantitative kidney and liver assessments.Conclusions. The ADPKD reference centre network across Europe and the observational cohort study will enable European ADPKD researchers to gain insights into the natural history, heterogeneity and associated complications of the disease as well as how it affects the lives of patients across Europe.
Published: 2014

32. Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency

Author: Yannick Le Meur, Emilie Cornec-Le Gall, Yahsou Delmas, Véronique Frémeaux-Bacchi, Laurent Doucet, Loïc De Parscau, Jean-François Benoist, Hélène Ogier, Service de Nephrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Réseau Maladies Métaboliques, Hôpitaux Universitaires du Grand Ouest, Service de Pédiatrie et Génétique Médicale, CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Comité d'Evaluation du Traitement pour les maladies de Niemann-Pick (CETNP), Société Française des Erreurs Innées du Métabolisme (SFEIM), Centre Référence des Maladies Héréditaires du Métabolisme [Paris-Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Service de neurologie, maladies métaboliques, Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), LabEX IGO Immunothérapie Grand Ouest, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Néphrologie, and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST )
Subjects: Male, Biopsy, MESH: Hydroxocobalamin, Drug Resistance, Leucovorin, Kidney, Kidney Function Tests, Gastroenterology, Hypertension, Malignant, chemistry.chemical_compound, MESH: Biopsy, Methionine, Recurrence, Hydroxocobalamin, MESH: Renal Dialysis, Homocysteine, MESH: Treatment Outcome, Lipotropic Agents, MESH: Immunologic Factors, Eculizumab, 3. Good health, Treatment Outcome, Hemolytic uremic syndrome (HUS), Nephrology, MESH: Kidney Function Tests, Vitamin B Complex, MESH: Betaine, MESH: Drug Resistance, [SDV.IMM]Life Sciences [q-bio]/Immunology, Homocystinuria, Oxidoreductases, MESH: Homocystinuria, medicine.drug, Adult, medicine.medical_specialty, Thrombotic microangiopathy, MESH: Mutation, MESH: Methylmalonic Acid, MESH: Carrier Proteins, Complement factor I, Antibodies, Monoclonal, Humanized, MESH: Lipotropic Agents, Cobalamin, Diagnosis, Differential, Renal Dialysis, MESH: Diagnosis, Differential, Internal medicine, Atypical hemolytic uremic syndrome, medicine, Humans, Immunologic Factors, MESH: Amino Acid Metabolism, Inborn Errors, MESH: Homocysteine, MESH: Hypertension, Malignant, Amino Acid Metabolism, Inborn Errors, MESH: Humans, MESH: Vitamin B Complex, business.industry, Vitamin B 12 Deficiency, MESH: Adult, MESH: Kidney, medicine.disease, MMACHC, MESH: Male, MESH: Recurrence, Betaine, Endocrinology, Methylmalonic aciduria, chemistry, MESH: Antibodies, Monoclonal, Humanized, MESH: Methionine, Mutation, Carrier Proteins, business, MESH: Leucovorin, Methylmalonic Acid
Abstract: International audience; A 20-year-old man was hospitalized for malignant hypertension, mechanical hemolysis, and kidney failure. Kidney biopsy confirmed glomerular and arteriolar thrombotic microangiopathy. Etiologic analyses, which included ADAMTS13 activity, stool culture, complement factor proteins (C3, C4, factor H, factor I, and MCP [membrane cofactor protein]), anti-factor H antibodies, HIV (human immunodeficiency virus) serology, and antinuclear and antiphospholipid antibodies, returned normal results. Malignant hypertension was diagnosed. Ten months later, we observed a relapse of acute kidney injury and mechanical hemolysis. Considering a diagnosis of complement dysregulation-related atypical hemolytic uremic syndrome (HUS), we began treatment with eculizumab. Despite the efficient complement blockade, the patient's kidney function continued to decline. We performed additional analyses and found that the patient's homocysteine levels were dramatically increased, with no vitamin B12 (cobalamin) or folate deficiencies. We observed very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. We stopped the eculizumab infusions and initiated specific treatment, which resulted in complete cessation of hemolysis. MMACHC (methylmalonic aciduria and homocystinuria type C protein) sequencing revealed compound heterozygosity for 2 causative mutations. To our knowledge, this is the first report of adult-onset cobalamin C-related HUS. Considering the wide availability and low cost of the homocysteine assay, we suggest that it be included in the diagnostic algorithm for adult patients who present with HUS.
Published: 2014
Full Text: View/download PDF

33. Abnormal distribution of B-cell populations associated with impaired regulatory functions in the chronic antibody mediated rejection

Author: I. Ségalen, Alexandre Nouël, Sophie Hillion, Anne Grall-Jezequel, Yannick Le Meur, Jacques-Olivier Pers, LabEX IGO Immunothérapie Grand Ouest, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Néphrologie, and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST )
Subjects: 0303 health sciences, Immunology, Biology, Abnormal distribution, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Antibody mediated rejection, medicine, Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, B cell, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology
Abstract: International audience
Published: 2013
Full Text: View/download PDF

34. Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8.

Author: Billot, Katy, Coquil, Charlène, Villiers, Benoit, Josselin-Foll, Béatrice, Desban, Nathalie, Delehouzé, Claire, Oumata, Nassima, Yannick Le Meur, Boletta, Alessandra, Weimbs, Thomas, Grosch, Melanie, Witzgall, Ralph, Saunier, Sophie, Fischer, Evelyne, Pontoglio, Marco, Fautrel, Alain, Mrug, Michal, Wallace, Darren, Tran, Pamela V., and Trudel, Marie
Abstract: Following the discovery of (R)-roscovitine’s beneficial effects in three polycystic kidney disease (PKD) mouse models, cyclin-dependent kinases (CDKs) inhibitors have been investigated as potential treatments. We have used various affinity chromatography approaches to identify the molecular targets of roscovitine and its more potent analog (S)- CR8 in human and murine polycystic kidneys. These methods revealed casein kinases 1 (CK1) as additional targets of the two drugs. CK1ε expression at the mRNA and protein levels is enhanced in polycystic kidneys of 11 different PKD mouse models as well as in human polycystic kidneys. A shift in the pattern of CK1 isoforms is observed in all PKD mouse models. Furthermore, the catalytic activities of both CK1ε and CK1 are increased in mouse polycystic kidneys. Inhibition of CK1ε and CK1 may thus contribute to the long-lasting attenuating effects of roscovitine and (S)-CR8 on cyst development. CDKs and CK1s may constitute a dual therapeutic target to develop kinase inhibitory PKD drug candidates [ABSTRACT FROM AUTHOR]
Published: 2018
Full Text: View/download PDF

35. Mesangial Cell-Specific Antibodies Are Central to the Pathogenesis of Lupus Nephritis

Author: Yannick Le Meur, Yves Renaudineau, Guillaume Seret, Pierre Youinou, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire d'Immunologie et Immunothérapie, and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Subjects: lcsh:Immunologic diseases. Allergy, MESH: Annexin A2, media_common.quotation_subject, Immunology, Lupus nephritis, Review Article, Biology, Immune complex formation, 03 medical and health sciences, 0302 clinical medicine, MESH: Mesangial Cells, MESH: Actinin, medicine, MESH: Autoantibodies, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, MESH: Lupus Erythematosus, Systemic, Actinin, Internalization, Annexin A2, Autoantibodies, 030304 developmental biology, media_common, 030203 arthritis & rheumatology, 0303 health sciences, MESH: Humans, Lupus erythematosus, Mesangial cell, General Medicine, medicine.disease, MESH: Lupus Nephritis, Lupus Nephritis, 3. Good health, Chromatin, Mesangial Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC581-607, Nephritis
Abstract: International audience; Not only is nephritis a common complaint in systemic lupus erythematosus, but it is also the most life-threatening complication of the disease. Anti-double-stranded DNA antibodies (Abs), which are found in up to 80% of these patients, might be nephritogenic per se. That is, they may cross-react with mesangial cell (MC) surface proteins, such as alpha-actinin and annexin A2, they may cross-react with mesangial matrix protein such as laminine and fibronectin, or they may recognize chromatin material previously deposited in the glomeruli. The consequence of the binding of anti-MC Abs may be their internalization, which results in activation and proliferation of these MCs. In turn, these activated MCs are suspected of promoting immune complex formation by sequestering and thereby protecting chromatin from degradation. The present paper will explain the mechanisms through which such autoAbs may initiate nephritis.
Published: 2012
Full Text: View/download PDF

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

Author: Antoine Thierry, Yannick Le Meur, Michel Delahousse, Yvon Lebranchu, Nacera Ouali, Denis Glotz, Stephanie Rouanet, Laeticia Albano, Michèle Kessler, Nailya Tagieva, Philippe Lang, François Glowacki, François Vrtovsnik, Maïté Jauréguy, Nassim Kamar, Valérie Garrigue, Jean-Philippe Rerolle, Lionel Couzi, Anne-Elisabeth Heng, Christiane Mousson, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Department of Nephrology, University Hospital, Lille, France., Department of Nephrology, University Hospital, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Department of Nephrology, Transplantation and Peritoneal Dialysis, University Hospital, Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Department of Nephrology and Transplantation, Foch Hospital, Department of Nephrology and Transplantation, University Hospital, Nice, Departement of Nephrology and Transplantation, University Hospital, Nice, Budapest University of Technology and Economics [Budapest] (BME), Department of Nephrology, Transplantation and Dialysis, Bordeaux, France, Department of Nephrology, Transplantation and Dialysis, Bordeaux, Department of Nephrology, University Hospital, Amiens, France, Department of Nephrology, University Hospital, Amiens, Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Roche SAS, Neuilly-sur-Seine, France, Laboratoire Roche SAS, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, Male, Biopsy, 030232 urology & nephrology, 030230 surgery, Kidney, MESH: Cyclosporine, MESH: Dose-Response Relationship, Drug, MESH: Kidney Transplantation, MESH: Biopsy, 0302 clinical medicine, Adrenal Cortex Hormones, Risk Factors, MESH: Risk Factors, Clinical endpoint, Prospective Studies, Prospective cohort study, MESH: Treatment Outcome, MESH: Middle Aged, medicine.diagnostic_test, MESH: Withholding Treatment, Middle Aged, 3. Good health, Treatment Outcome, Tolerability, Cyclosporine, Corticosteroid, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, Urology, MESH: Graft Rejection, Mycophenolic acid, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, medicine, Humans, MESH: Mycophenolic Acid, Transplantation, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Adult, MESH: Kidney, Mycophenolic Acid, Kidney Transplantation, MESH: Male, MESH: Prospective Studies, Discontinuation, Surgery, Regimen, Withholding Treatment, Therapeutic drug monitoring, Feasibility Studies, business, MESH: Feasibility Studies, MESH: Female
Abstract: International audience; Early posttransplant steroid withdrawal may increase the risk of acute rejection and the occurrence of subclinical acute rejection (SCAR). We assessed the feasibility and safety of early steroid withdrawal in low-risk patients receiving cyclosporine A (CsA) and the impact of optimization of mycophenolic acid exposure on steroid withdrawal success. De novo, low-immunological risk kidney recipients received an anti-interleukin-2-receptor-α antibody induction, a short course of 7 days of corticosteroids, and CsA with 2-hr postdose concentration monitoring. They were randomized to adjusted dose (AD) of mycophenolate mofetil (MMF) using therapeutic drug monitoring (TDM) or a fixed-dose (FD) regimen. MMF 3 g was initiated posttransplant and then adjusted starting at week 2 to a 0 to 12 hr area under the concentration time curve of 40 mg · h/L versus 2 g daily, respectively. The primary endpoint was a composite of the proportion of patients experiencing biopsy-proven acute rejection (BPAR) and those with SCAR identified on the 3-month protocol biopsy. Among 247 analyzed patients, only 22 in the AD group and 17 in the FD group experienced BPAR or SCAR (P=0.46). The rate of SCAR was low: 4% (AD) and 2.5% (FD). No between-group difference in the incidence of BPAR was observed. TDM yielded MMF doses ranging from 1 to 4 g/d and significantly reduced interpatient variability at weeks 26 and 52 in the AD group. In low-immunological risk kidney recipients, MMF combined with CsA allows early corticosteroid discontinuation with good tolerability. In this group of patients, TDM of MMF does not improve clinical outcome.
Published: 2011
Full Text: View/download PDF

37. Glomerular antibodies in lupus nephritis

Author: Catherine Hanrotel-Saliou, Yannick Le Meur, Yves Renaudineau, Pierre Youinou, I. Ségalen, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire d'Immunologie et Immunothérapie, and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Subjects: Kidney Glomerulus, Lupus nephritis, Autoantigens, Antigen-Antibody Reactions, Pathogenesis, MESH: Cross Reactions, Mice, 0302 clinical medicine, Glomerular Basement Membrane, Immunology and Allergy, MESH: Antigen-Antibody Reactions, MESH: Autoantibodies, MESH: Animals, skin and connective tissue diseases, 0303 health sciences, Kidney, Proteinuria, biology, Glomerular basement membrane, General Medicine, Lupus Nephritis, MESH: Lupus Nephritis, 3. Good health, medicine.anatomical_structure, MESH: Autoantigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Antibody, MESH: Glomerular Basement Membrane, MESH: Immune Complex Diseases, Cross Reactions, 03 medical and health sciences, MESH: Proteinuria, MESH: Cell Proliferation, medicine, MESH: Antibody-Dependent Cell Cytotoxicity, Animals, Humans, Immune Complex Diseases, MESH: Mice, Autoantibodies, Cell Proliferation, 030304 developmental biology, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Antibody-Dependent Cell Cytotoxicity, Autoantibody, MESH: Kidney Glomerulus, medicine.disease, Immunology, biology.protein, business, Immune complex disease
Abstract: International audience; Lupus nephritis (LN) remains the most common severe manifestation of systemic lupus erythematosus (SLE) characterized by the presence of autoantibodies (Abs) that are believed to play a central role in the pathogenesis of LN. Among more than 100 Abs reported in SLE, only a few display a direct glomerular binding capacity. Such antiglomerular Abs are detected at the onset of the disease before antinuclear Abs detection and proteinuria, this detection is associated with the related autoantigen overexpression. Antiglomerular Abs are able to interfere with cell metabolism, to penetrate living cells, and to induce glomerular cell proliferation. In addition, antiglomerular Abs could be nephritogenic causing proteinuria, particularly when they cross-react with anti-dsDNA Abs. Antiglomerular Abs encompass anti-α-actinin, anti-laminin-1, antifibronectin, antimyosin, and anticollagen Abs. The pathogenic activity of anti-α-actinin Abs has been demonstrated in non-autoimmune mice after immunization with α-actinin, but not with dsDNA, leading to a SLE-like disease with proteinuria and glomerular immune complex deposition. Similarly, extracorporeal immunoabsorption to remove anti-laminin-1 Abs reduces kidney-Abs deposition and proteinuria in mice and humans proving their pathogenic effect. Altogether this suggests that antiglomerular Abs participate, at least at the beginning, in the glomerular immune complex deposition and in the kidney damage.
Published: 2011
Full Text: View/download PDF

38. Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil

Author: Nicolas Picard, Olivier Gensburger, Annick Rousseau, Jean-Baptiste Woillard, Teun van Gelder, Yannick Le Meur, Ron H.N. van Schaik, Pierre Marquet, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Chemistry, Erasmus University Medical Centre, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Université de Limoges (UNILIM), Departments of Internal Medicine, Erasmus Medical Centre, Marquet, Pierre, Clinical Chemistry, and Pharmacy
Subjects: Inosine monophosphate, Male, Single, Single-nucleotide polymorphism, Pharmacology, Biology, Mycophenolate, 030226 pharmacology & pharmacy, Polymorphism, Single Nucleotide, Mycophenolic acid, Article, 03 medical and health sciences, 0302 clinical medicine, IMP Dehydrogenase, IMP dehydrogenase, Polymorphism (computer science), Genetics, medicine, Humans, General Pharmacology, Toxicology and Pharmaceutics, Inosine, Molecular Biology, Genetics (clinical), Genetic Association Studies, 030304 developmental biology, Demography, 0303 health sciences, Inosine Monophosphate Dehydrogenase, Therapeutic Drug Monitoring, Middle Aged, Mycophenolic Acid, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Nucleotide Polymorphism, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Logistic Models, Treatment Outcome, Molecular Medicine, Regression Analysis, Female, Pharmacogenetics, medicine.drug
Abstract: Background Type I and II inosine monophosphate dehydrogenases (IMPDH) are the targets of mycophenolic acid (MPA), a widely used immunosuppressant. The aims of this study were: to check the presence of controversial polymorphisms in the IMPDH II gene; to look for new ones; and to investigate potential associations between the most frequent SNPs in both IMPDH genes and clinical outcome in renal transplant recipients. Methods The DNA and clinical data of 456 patients from two clinical trials were collected. We sequenced the IMPDH II gene in 80 patients and we genotyped the 456 patients' DNA for the IMPDH II rs4974081, rs11706052, 787C > T and the IMPDH I rs2278293 and rs2278294 SNPs, all of which were earlier reported to be potentially involved in MPA treatment related outcome. We investigated the associations of biopsy proven acute rejection (BPAR), leucopenia, cytomegalovirus infections and other infections with these IMPDH polymorphisms, as well as with demographic, biological and treatment data using multivariate analysis. Results Many IMPDH II variant alleles referenced in Genbank were not detected and no new polymorphisms were identified. In the whole group of 456 patients, the IMPDH I rs2278294 SNP was associated with a lower risk of BPAR and a higher risk of leucopenia over the first year post-transplantation. No other IMPDH I or IMPDH II polymorphism was significantly associated with any clinical outcome. Interestingly, calcineurin inhibitor and MPA exposures below the therapeutic range increased the risk of BPAR. Cytomegalovirus infection was the factor most closely linked with leucopenia, whereas tacrolimus was associated with fewer infections than cyclosporine. Conclusion IMPDH II genotyping may not improve MPA treatment outcome over the first year post-transplantation, in contrast to MPA and calcineurine inhibitor therapeutic drug monitoring and IMPDH I genotyping. Pharmacogenetics and Genomics 20: 537-543 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Published: 2010
Full Text: View/download PDF

39. Risk of diarrhoea in a long-term cohort of renal transplant patients given mycophenolate mofetil: the significant role of the UGT1A8 2 variant allele

Author: Jean-Baptiste Woillard, Annick Rousseau, Marie Essig, Nicolas Picard, Yannick Le Meur, Pierre Marquet, Mireille Drouet, Eliza Munteanu, Jean-Philippe Rerolle, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], Service d'Immunologie et immunogénétique [CHU Limoges], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), and Kidney transplantation, mycophenolate mofetil, pharmacogenetics, diarrhea, uridine diphosphate-glucuronosyltransferase, UGT1A8*2
Subjects: MESH: Drug Interactions, diarrhea, Pharmacology, Mycophenolate, 030226 pharmacology & pharmacy, Gastroenterology, MESH: Cyclosporine, MESH: Glucuronosyltransferase, MESH: Kidney Transplantation, Kidney transplantation, MESH: Proportional Hazards Models, MESH: Genotype, 0302 clinical medicine, Pharmacology (medical), MESH: Cohort Studies, pharmacogenetics, 0303 health sciences, MESH: Risk, uridine diphosphate-glucuronosyltransferase, MESH: Polymorphism, Single Nucleotide, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, MESH: Diarrhea, MESH: Survival Analysis, MESH: Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, Biology, Mycophenolic acid, MESH: Multivariate Analysis, 03 medical and health sciences, Internal medicine, medicine, MESH: Tacrolimus, Adverse effect, Survival analysis, 030304 developmental biology, MESH: Mycophenolic Acid, UGT1A8*2, MESH: Drug Combinations, MESH: Humans, mycophenolate mofetil, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Tacrolimus, MESH: Male, Sirolimus, MESH: Sirolimus, MESH: Female, Pharmacogenetics
Abstract: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Mycophenolate mofetil (MMF), the most widely used drug in allograft transplantation, is subject to hepatic and intestinal glucuronidation and entero-hepatic cycling. • Diarrhoea is its most frequent adverse event leading to non-compliance, treatment interruption and ultimately to an increased rate of acute rejection. • Cyclosporin reduces the biliary excretion of mycophenolate metabolites, presumably by inhibiting the efflux transporter MRP2. • When combined with MMF, cyclosporin reduces the incidence of diarrhoea, suggesting the role played by biliary excretion of mycophenolate glucuronides in this adverse event. WHAT THIS STUDY ADDS • In a long-term cohort of renal transplant patients on MMF, the two factors significantly associated with a reduced incidence of diarrhoea were the co-medication with cyclosporin (as opposed to tacrolimus or sirolimus) and the *2 variant allele of the intestinal UGT1A8. • Polymorphisms in the other UDP-glucuronosyl-transferases and MRP2 were not significant. AIM In renal transplant patients given mycophenolate mofetil (MMF), we investigated the relationship between the digestive adverse events and polymorphisms in the UGT genes involved in mycophenolic acid (MPA) intestinal metabolism and biliary excretion of its phase II metabolites. METHODS Clinical data and DNA from 256 patients transplanted between 1996 and 2006 and given MMF with cyclosporin (CsA, n = 185), tacrolimus (TAC, n = 49) or sirolimus (SIR, n = 22), were retrospectively analysed. The relationships between diarrhoea and polymorphisms in UGT1A8 (*2; 518C>G, *3; 830G>A), UGT1A7 (622C>T), UGT1A9 (−275T>A), UGT2B7 (−840G>A) and ABCC2 (−24C>T, 3972C>T) or the co-administered immunosuppressant were investigated using the Cox proportional hazard model. RESULTS Multivariate analysis showed that patients on TAC or SIR had a 2.8 higher risk of diarrhoea than patients on CsA (HR = 2.809; 95%CI (1.730, 4.545); P
Published: 2010
Full Text: View/download PDF

40. Cost-Effectiveness Analysis of Individualized Mycophenolate Mofetil Dosing in Kidney Transplant Patients in the APOMYGRE Trial

Author: Marie-Laure Laroche, Nicolas Venisse, Mathias Büchler, Claire Villeneuve, Guillaume Hoizey, Pierre Marquet, Yannick Le Meur, Lionel Hary, Evelyne Jacqz-Aigrain, Patricia Compagnon, Annick Rousseau, Sylvie Saivin, Danièle Debruyne, Alain Vergnenègre, Cecile Loichot-Roselmac, Alain Turcant, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Limoges (UNILIM), Equipe de Recherche Médicale Appliquée (ERMA), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Modélisations pharmacocinétiques-pharmacodynamiques pour un meilleur usage des anti-infectieux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Université de Reims Champagne-Ardenne (URCA), Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Service de Pharmacologie Pédiatrique et Pharmacogénétique [Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Francois Rabelais [Tours], Service de Pathologie respiratoire et allergologie [CHU Limoges], CHU Limoges, Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Graft Rejection, Male, Reoperation, medicine.medical_specialty, Basiliximab, Cost effectiveness, Recombinant Fusion Proteins, [SDV]Life Sciences [q-bio], Population, 030230 surgery, 030226 pharmacology & pharmacy, Mycophenolic acid, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Adrenal Cortex Hormones, Internal medicine, medicine, Ambulatory Care, Humans, Treatment Failure, education, health care economics and organizations, Aged, Immunosuppression Therapy, Transplantation, education.field_of_study, business.industry, Histocompatibility Testing, Antibodies, Monoclonal, Cost-effectiveness analysis, Middle Aged, Mycophenolic Acid, Kidney Transplantation, Confidence interval, 3. Good health, Discontinuation, Female, business, Immunosuppressive Agents, Switzerland, medicine.drug
Abstract: LDM TEP COLL; International audience; BACKGROUND:In the prospective, randomized, multicenter APOMYGRE trial conducted in France, concentration-controlled mycophenolate mofetil (MMF) dosing based on mycophenolic acid (MPA) exposure significantly reduced the treatment failure and acute rejection during the first posttransplantation year compared with fixed-dose MMF. This analysis investigated the cost effectiveness of dose individualization.METHOD:The study included 65 patients per group (intent-to-treat population). Treatment failure (primary efficacy endpoint) was defined as death, graft loss, acute rejection, or MMF discontinuation because of adverse effects. Data on hospitalizations, drugs prescribed, physicians' fees, laboratory expenses, ambulatory visits, and transportation were retrieved. Costs were calculated from the French National Health System perspective.RESULTS:The mean (95% confidence interval) total yearly cost per patient was Euro 47,477 (Euro 43,933; Euro 51,020) in the concentration-controlled group and Euro 46,783 ( Euro 44,152; Euro 49,414) in the fixed-dose group (P=0.7). The observed incremental cost-effectiveness ratio was Euro 3757 per treatment failure (Purchasing Power Parities United States/France: $4129). Hospitalization and drug costs accounted for approximately 50% and 25% of total costs, respectively. The cost for MPA area under the concentration-time curve and dose calculation was Euro 452 per patient, less than 1% of the total cost.CONCLUSION:In the APOMYGRE trial, therapeutic MPA monitoring using a limited sampling strategy reduced the risk of treatment failure and acute rejection in renal allograft recipients during the first 12 months posttransplantation, at neutral cost.
Published: 2010
Full Text: View/download PDF

41. TCF7L2 polymorphism associates with new-onset diabetes after transplantation

Author: Mireille Drouet, Yvon Lebranchu, Karl Martin Wissing, Pascale Cochaux, Daniel Abramowicz, Jean-Michel Halimi, Arnaud Lionet, Yannick Le Meur, Jean-Philippe Rerolle, Marc Abramowicz, Lidia Ghisdal, Christophe Baron, Hakim El Housni, Christian Noel, François Glowacki, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de néphrologie et immunologie clinique, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Immunologie et immunogénétique [CHU Limoges], Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), BUSOC, Ministere belge de la politique scientifique, Internal Medicine Specializations, Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Service de néphrologie et immunologie clinique [CHRU Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)
Subjects: Male, Type 2 diabetes, 030230 surgery, Gastroenterology, polymorphism, MESH: Kidney Transplantation, 0302 clinical medicine, Postoperative Complications, MESH: Postoperative Complications, Kidney transplantation, 2. Zero hunger, 0303 health sciences, education.field_of_study, MESH: Middle Aged, diabetes, General Medicine, Middle Aged, 3. Good health, Nephrology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, Population, 03 medical and health sciences, Clinical Research, Internal medicine, Diabetes mellitus, MESH: Polymorphism, Genetic, medicine, Humans, education, new-onset, 030304 developmental biology, Polymorphism, Genetic, MESH: Humans, business.industry, Odds ratio, medicine.disease, Kidney Transplantation, MESH: Male, Transplantation, TCF7L2, Endocrinology, Diabetes Mellitus, Type 2, business, Body mass index, MESH: Female, MESH: TCF Transcription Factors, transplantation
Abstract: International audience; New-onset diabetes after transplantation (NODAT) is a serious and frequent complication in transplant recipients. Whether NODAT shares the same susceptibility genes as type 2 diabetes is unknown. In this multicenter study, we genotyped 1076 white patients without diabetes at transplantation for 11 polymorphisms that associate with type 2 diabetes. We defined NODAT as a fasting plasma glucose > or =126 mg/dl on at least two occasions or de novo hypoglycemic therapy. We compared clinical and genetic factors between patients who developed NODAT within 6 mo of transplantation (n = 118; incidence 11%) and patients without diabetes (n = 958). In multivariate analysis, NODAT significantly associated with the following characteristics: TCF7L2 polymorphism (odds ratio [OR] 1.60 per each T allele; P = 0.002), age (OR 1.03 per year; P < 0.001), body mass index at transplantation (OR 1.09 per unit; P < 0.001), tacrolimus use (OR 2.26; P < 0.001), and the occurrence of a corticoid-treated acute rejection episode (OR 2.78; P < 0.001). In summary, our data show that the TCF7L2 rs7903146 polymorphism, a known risk factor for type 2 diabetes in the general population, also associates with NODAT.
Published: 2009
Full Text: View/download PDF

42. A double absorption-phase model adequately describes mycophenolic acid plasma profiles in de novo renal transplant recipients given oral mycophenolate mofetil.

Author: Prémaud, Aurélie, Debord, Jean, Rousseau, Annick, Yannick Le Meur, Toupance, Olivier, Lebranchu, Yvon, Hoizey, Guillaume, Chantal Le Guellec, Marquet, Pierre, Prémaud, Aurélie, Le Meur, Yannick, and Le Guellec, Chantal
Subjects: ABSORPTION, CHROMATOGRAPHIC analysis, PHARMACOKINETICS, CHEMICAL kinetics, DRUG metabolism, LIQUID chromatography
Abstract: Background: Mycophenolic acid (MPA) shows complex plasma concentration-time profiles, particularly in the immediate (first month) post-transplantation phase for which no relevant pharmacokinetic model has been proposed thus far.Objective: The aim of this study was to develop a model to accurately describe the time profile of plasma MPA concentrations after oral administration of mycophenolate mofetil in adult kidney transplant patients, in any post-transplantation period.Method: Full interdose pharmacokinetic profiles were collected in 45 adult renal transplant patients who were orally administered mycophenolate mofetil and ciclosporin; 25 patients were de novo transplant patients for whom individual pharmacokinetics were assessed at three post-transplantation periods (days 3, 7 and 30) and 20 patients were stable transplant patients (>3 months post-transplantation). MPA was determined in plasma by liquid chromatography-mass spectrometry. Models combining a single- or double-input (described as single or double gamma distributions) with one- or two-compartments were developed using in-house software and fitted to the individual profiles by nonlinear regression.Results: Visual inspection of the pharmacokinetic profiles showed highly variable absorption profiles and secondary peaks of various intensity. The pharmacokinetic models including a double gamma distribution best fitted these various profiles in the immediate post-transplantation period (mean bias and precision of -0.92% and 20.19%; -1.5% and 18.02%, on day 7 and day 30, respectively), while in the stable post-grafting phase (beyond 3 months), the single- and double-absorption models performed similarly (mean bias and precision of -3.37% and 17.64%; -3.12% and 18.44%, on day 7 and day 30, respectively).Conclusion: The proposed pharmacokinetic models adequately describe the concentration-time profiles of MPA in renal transplant patients and could be helpful in the development of tools for MPA monitoring. [ABSTRACT FROM AUTHOR]
Published: 2005

43. Comparison of Liquid Chromatography-Tandem Mass Spectrometry with a Commercial Enzyme-Multiplied Immunoassay for the Determination of Plasma MPA in Renal Transplant Recipients and Consequences for Therapeutic Drug Monitoring.

Author: Aurlie Prmaud, Annick Rousseau, Yannick Le Meur, Grard Lachtre, and Pierre Marquet
Published: 2004

44. Serum levels of macrophage-colony stimulating factor (M-CSF): a marker of kidney allograft rejection.

Author: Yannick Le Meur, Valérie Leprivey-Lorgeot, Sandrine Mons, Mattew José, Jacques Dantal, Brigitte Lemauff, Jean-Claude Aldigier, Claude Leroux-Robert, and Vincent Praloran
Abstract: Background. Macrophage-colony stimulating factor (M-CSF) is the principal factor for survival of monocytes and macrophages that play an important role in allograft rejection. We studied M-CSF serum levels during successful renal transplantation and acute graft rejection.Methods. A total of 114 kidney allograft recipients were assessed for M-CSF levels by enzyme-linked immunosorbent assay (ELISA).Results. M-CSF serum levels were elevated in pre-transplant haemodialysis patients (611±355 IU/ml vs 168±61 in normal controls, P<0.01). Following successful renal transplantation, M-CSF decreased in the first month, stabilizing at 257±222 IU/ml (not significantly different from normal controls) in 52 post-transplant stable patients. There was no correlation between M-CSF level and creatinine clearance. M-CSF levels increased significantly (2–5 times) during biopsy-proven acute rejection episodes in 20 of 25 patients. All rejection episodes were successfully treated and serum M-CSF decreased rapidly to pre-rejection levels in 17/20 patients. In contrast, in five patients with cyclosporin toxicity and four patients with other causes of allograft dysfunction, M-CSF serum levels did not change.Conclusions. M-CSF serum level might be a specific marker of acute rejection. The source of increased production during rejection warrants further investigation, with infiltrating T cells and resident kidney cells being likely candidates. [ABSTRACT FROM AUTHOR]
Published: 2004
Full Text: View/download PDF

45. Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial

Author: Lionel Rostaing, Suphamai Bunnapradist, Josep M. Grinyó, Kazimierz Ciechanowski, Jason E. Denny, Helio Tedesco Silva, Klemens Budde, Sanjay Kulkarni, Donald Hricik, Barbara A. Bresnahan, Rafik A. El-Sabrout, Laurence K. Chan, Gaetano Ciancio, Mohamed A. El-Ghoroury, Michael J. Goldstein, Robert S. Gaston, Reginald Y. Gohh, Mary T. Killackey, Anne King, Richard J. Knight, Arputharaj H. Kore, Debra L. Sudan, Javier Chapochnick Friedmann, Shamkant P. Mulgaonkar, Charles Nolan, Oleh G. Pankewycz, John D. Pirsch, Heidi M. Schaefer, Steven M. Steinberg, Bruce E. Gelb, Karin A. True, Patricia M. West-Thielke, Mary M. Waybill, Joshua H. Wolf, Beverley L. Ketel, Robert C. Harland, Fuad S. Shihab, Elisabeth Cassuto, Yannick Le Meur, Christophe Mariat, Josep Maria Grinyó, Jose Puig, Daniel Seron, Giuseppe Tisone, Bartosz Foroncewicz, Zbigniew Wlodarczyk, Oliver Witzke, Guillermo A. Mondragon, Eduardo Mancilla Urrea, Josefina Alberu Gomez, Rafael Reyes Acevedo, Maria del Carmen Rial, Pablo A. Novoa, Helio T. Silva, Valter D. Garcia, Deise D. Carvalho, Luciana T. Santamaria Saber, Fabiana L. Contieri, Marcos G. Bastos, Roberto C. Manfro, John Kanellis, Josette Eris, Philip O’Connell, Peter Hughes, Graeme Russ, Grant B. Pidgeon, Ian D. Dittmer, Terence Kee, Anantharaman Vathsala, Radomir Naumovic, Igor Mitic, and Randhawa Parmjeet
Subjects: Adult, Male, safety, medicine.medical_specialty, Time Factors, medicine.medical_treatment, efficacy, Renal function, kidney transplantation, formulation, 030230 surgery, Drug Administration Schedule, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, transplant recipient, randomized controlled trial (RCT), law, Diabetes mellitus, Internal medicine, medicine, Humans, biopsy-proven acute rejection, Prospective Studies, Adverse effect, Prospective cohort study, tacrolimus, Kidney transplantation, Aged, extended-release, treatment failure, business.industry, Envarsus, pill burden, Immunosuppression, Middle Aged, medicine.disease, Tacrolimus, Surgery, Nephrology, end-stage renal disease (ESRD), 030211 gastroenterology & hepatology, Female, business, bioavailability, Immunosuppressive Agents
Abstract: Background1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation.Study DesignFinal 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial.Setting & Participants543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study.InterventionLCPT tablets once daily at 0.17mg/kg/d or IR-Tac twice daily at 0.1mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11ng/mL; thereafter, 4-11ng/mL). The intervention was 24 months; the study was double blinded for the entirety.Outcomes & MeasurementsTreatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels.Results24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, −4.14% [95% CI, −11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P
Full Text: View/download PDF

46. CMV infections after two doses of daclizumab versus thymoglobulin in renal transplant patients receiving mycophenolate mofetil, steroids and delayed cyclosporine A.

Author: Ramzi Abou-Ayache, Mathias Büchler, Patrick Lepogamp, Pierre-François Westeel, Yannick Le Meur, Isabelle Etienne, Thierry Lobbedez, Olivier Toupance, Sophie Caillard, Jean-Michel Goujon, Loïc Bergougnoux, and Guy Touchard
Subjects: CYTOMEGALOVIRUS diseases, TRANSPLANTATION of organs, tissues, etc., IMMUNOGLOBULINS, STEROIDS
Abstract: Background. Cytomegalovirus (CMV) infection is a major complication after renal transplantation and is involved in graft rejection. The anti-interleukin-2-receptor antibody daclizumab reduces the incidence of acute rejection without increasing the incidence of CMV infection. Methods. This multicentre, randomized trial compared safety and efficacy, at 1 year, of two doses of daclizumab (54 patients, group D) with thymoglobulin (55 patients, group T) plus delayed cyclosporine (CsA), MMF (mycophenolate mofetil) and steroids in first cadaver kidney transplant patients. Primary criterion was CMV infection/syndrome/disease. D+/R− patients received oral ganciclovir prophylaxis for 90 days. Results. Status for CMV was identical in the both groups. The incidence of CMV infection/syndrome/disease was 39% in group D versus 51% in group T (NS). Time to onset of CMV replication was delayed in group D (P = 0.015) and mean number of pp65-positive cells was lower at 4 and 6 months (P P = 0.028). Patient and graft survivals and incidence of biopsy-proven acute rejection were identical. Conclusions. Limited dosing regimen of daclizumab with MMF, steroids and delayed CsA introduction was safe and effective. The incidence of CMV infection was not significantly different, but without chemoprophylaxis, clinical manifestations and viral replication were reduced with this regimen. [ABSTRACT FROM AUTHOR]
Published: 2008
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

46 results on '"Yannick, Le Meur"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources