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1. The Cost-effectiveness of Valganciclovir Prophylaxis Versus Preemptive Therapy in CMV R+ Kidney Transplant Recipients Over the First Year Posttransplantation

Author: Claire Villeneuve, PhD, Jean-Phillipe Rerolle, MD, Lionel Couzi, MD, PhD, Pierre-Francois Westeel, MD, Isabelle Etienne, MD, Laure Esposito, MD, Nassim Kamar, MD, PhD, Mathias Büchler, MD, PhD, Antoine Thierry, MD, PhD, Pierre Marquet, MD, PhD, and Caroline Monchaud, PharmD, PhD
Subjects: Surgery, RD1-811
Abstract: Background. In kidney transplant recipients with positive serology (R+) for the cytomegalovirus (CMV), 2 strategies are used to prevent infection, whose respective advantages over the other are still debated. This study aimed to evaluate the cost-effectiveness and cost utility of antiviral prophylaxis against CMV versus preemptive therapy, considering CMV infection–free survival over the first year posttransplantation as the main clinical outcome. Methods. Clinical, laboratory, and economic data were collected from 186 kidney transplant patients CMV (R+) included in the cohort study (85 patients who benefited from CMV prophylaxis and 101 from preemptive therapy). Costs were calculated from the hospital perspective and quality-adjusted life years (QALYs) using the EQ5D form. Using nonparametric bootstrapping, the incremental cost-effectiveness ratio (ICER) and cost utility were estimated (euros) for each case of infection avoided and each QALY gained for 1 y, respectively. Results. Prophylaxis significantly decreased the risk of CMV infection over the first year posttransplantation (hazard ratio 0.22, 95% confidence interval = 0.12-0.37, P
Published: 2024
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2. 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
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3. Impact of Calcineurin Inhibitor-Based Immunosuppression Maintenance During the Dialysis Period After Kidney Transplant Failure on the Next Kidney Graft Outcome: A Retrospective Multicenter Study With Propensity Score Analysis

Author: Juliette Noelle, Valentin Mayet, Céline Lambert, Lionel Couzi, Bertrand Chauveau, Antoine Thierry, Laure Ecotière, Dominique Bertrand, Charlotte Laurent, Richard Lemal, Clarisse Grèze, Marine Freist, Anne-Elisabeth Heng, Paul-Olivier Rouzaire, and Cyril Garrouste
Subjects: kidney retransplant, kidney transplant failure, calcineurin inhibitor maintenance, waiting list, immunosuppression, Specialties of internal medicine, RC581-951
Abstract: The impact of immunosuppressive therapy (IS) strategies after kidney transplant failure (KTF) on potential future new grafts is poorly established. We assessed the potential benefit of calcineurin inhibitor (CNI)-based IS maintenance throughout the dialysis period on the outcome of the second kidney transplant (KT). We identified 407 patients who underwent a second KT between January 2008 and December 2018 at four French KT centers. Inverse probability of treatment weighting was used to control for potential confounding. We included 205 patients with similar baseline characteristics at KTF: a total of 53 received at least CNIs on the retransplant day (G-CNI), and 152 did not receive any IS (G-STOP). On the retransplant date, G-STOP patients experienced a longer pretransplant dialysis time, were more often hyperimmunized, and underwent more expanded-criteria donor KTs than G-CNI patients. During the second KT follow-up period, rejection episodes were similar in both groups. The 10-year survival rates without death and dialysis were 98.7% and 59.5% in G-CNI and G-STOP patients, respectively. In the multivariable analysis, CNI-based IS maintenance was associated with better survival (hazard ratio: 0.08; 95% confidence interval: 0.01–0.58, p = 0.01). CNI-based IS maintenance throughout the dialysis period after KTF may improve retransplantation outcomes.
Published: 2023
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4. Early activation and recruitment of invariant natural killer T cells during liver ischemia-reperfusion: the major role of the alarmin interleukin-33

Author: Aurélie Robin, Claire Mackowiak, Romain Bost, Fanny Dujardin, Alice Barbarin, Antoine Thierry, Thierry Hauet, Luc Pellerin, Jean-Marc Gombert, Ephrem Salamé, André Herbelin, and Louise Barbier
Subjects: innate like T cell, iNKT cell, interleukin-33, sterile Inflammation, alarmin, liver transplantation, Immunologic diseases. Allergy, RC581-607
Abstract: Over the past thirty years, the complexity of the αβ-T cell compartment has been enriched by the identification of innate-like T cells (ITCs), which are composed mainly of invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells. Based on animal studies using ischemia-reperfusion (IR) models, a key role has been attributed to iNKT cells in close connection with the alarmin/cytokine interleukin (IL)-33, as early sensors of cell-stress in the initiation of acute sterile inflammation. Here we have investigated whether the new concept of a biological axis of circulating iNKT cells and IL-33 applies to humans, and may be extended to other ITC subsets, namely MAIT and γδ-T cells, in the acute sterile inflammation sequence occurring during liver transplant (LT). From a prospective biological collection of recipients, we reported that LT was accompanied by an early and preferential activation of iNKT cells, as attested by almost 40% of cells having acquired the expression of CD69 at the end of LT (i.e. 1-3 hours after portal reperfusion), as opposed to only 3-4% of conventional T cells. Early activation of iNKT cells was positively correlated with the systemic release of the alarmin IL-33 at graft reperfusion. Moreover, in a mouse model of hepatic IR, iNKT cells were activated in the periphery (spleen), and recruited in the liver in WT mice, as early as the first hour after reperfusion, whereas this phenomenon was virtually missing in IL-33-deficient mice. Although to a lesser degree than iNKT cells, MAIT and γδ-T cells also seemed targeted during LT, as attested by 30% and 10% of them acquiring CD69 expression, respectively. Like iNKT cells, and in clear contrast to γδ-T cells, activation of MAIT cells during LT was closely associated with both release of IL-33 immediately after graft reperfusion and severity of liver dysfunction occurring during the first three post-operative days. All in all, this study identifies iNKT and MAIT cells in connection with IL-33 as new key cellular factors and mechanisms of acute sterile inflammation in humans. Further investigations are required to confirm the implication of MAIT and iNKT cell subsets, and to precisely assess their functions, in the clinical course of sterile inflammation accompanying LT.
Published: 2023
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5. 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
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6. Endogenous Interleukin-33 Acts as an Alarmin in Liver Ischemia-Reperfusion and Is Associated With Injury After Human Liver Transplantation

Author: Louise Barbier, Aurélie Robin, Rémy Sindayigaya, Héloïse Ducousso, Fanny Dujardin, Antoine Thierry, Thierry Hauet, Jean-Philippe Girard, Luc Pellerin, Jean-Marc Gombert, André Herbelin, and Ephrem Salamé
Subjects: interleukin-1 family, interleukin-33, inflammation, alarmin, liver transplantation, delayed graft function, Immunologic diseases. Allergy, RC581-607
Abstract: Ischemia and reperfusion injury is an early inflammatory process during liver transplantation that impacts on graft function and clinical outcomes. Interleukin (IL)-33 is a danger-associated molecular pattern involved in kidney ischemia/reperfusion injury and several liver diseases. The aims were to assess whether IL-33 was released as an alarmin responsible for ischemia/reperfusion injury in a mouse model of warm hepatic ischemia, and whether this hypothesis could also apply in the setting of human liver transplantation. First, a model of warm hepatic ischemia/reperfusion was used in wild-type and IL-33–deficient mice. Severity of ischemia/reperfusion injury was assessed with ALT and histological analysis. Then, serum IL-33 was measured in a pilot cohort of 40 liver transplant patients. Hemodynamic postreperfusion syndrome, graft dysfunction (assessed by model for early allograft scoring >6), renal failure, and tissue lesions on time-zero biopsies were assessed. In the mouse model, IL-33 was constitutively expressed in the nucleus of endothelial cells, immediately released in response to hepatic pedicle clamping without neosynthesis, and participated in the recruitment of neutrophils and tissue injury on site. The kinetics of IL-33 in liver transplant patients strikingly matched the ones in the animal model, as attested by serum levels reaching a peak immediately after reperfusion, which correlated to clinical outcomes including postreperfusion syndrome, posttransplant renal failure, graft dysfunction, and histological lesions of ischemia/reperfusion injury. IL-33 was an independent factor of graft dysfunction with a cutoff of IL-33 at 73 pg/ml after reperfusion (73% sensitivity, area under the curve of 0.76). Taken together, these findings establish the immediate implication of IL-33 acting as an alarmin in liver I/R injury and provide evidence of its close association with cardinal features of early liver injury-associated disorders in LT patients.
Published: 2021
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7. Allotransplantation Is Associated With Exacerbation of CD8 T-Cell Senescence: The Particular Place of the Innate CD8 T-Cell Component

Author: Lauren Daniel, Marion Tassery, Clara Lateur, Antoine Thierry, André Herbelin, Jean-Marc Gombert, and Alice Barbarin
Subjects: innate memory CD8(+) T-cells, NK-like T-cells, allotransplantation, senescence, immune memory, innateness gradient, Immunologic diseases. Allergy, RC581-607
Abstract: Immunosenescence is a physiological process that is associated with changes in the immune system, particularly among CD8 T-cells. Recent studies have hypothesized that senescent CD8 T-cells are produced with chronologic age by chronic stimulation, leading to the acquisition of hallmarks of innate-like T-cells. While conventional CD8 T-cells are quite well characterized, CD8 T-cells sharing features of NK cells and memory CD8 T-cells, are a newly described immune cell population. They can be distinguished from conventional CD8 T-cells by their combined expression of panKIR/NKG2A and Eomesodermin (E), a unique phenotype closely associated with IFN-γ production in response to innate stimulation. Here, we first provided new evidence in favor of the innate character of panKIR/NKG2A(+) E(+) CD8 T-cells in normal subjects, documenting their position at an intermediate level in the innateness gradient in terms of both innate IFN-γ production and diminished mitochondrial mass. We also revealed that CD8 E(+) panKIR/NKG2A(+) T-cells, hereafter referred to as Innate E(+) CD8 T-cells, exhibit increased senescent (CD27(-) CD28(-)) phenotype, compared to their conventional memory counterparts. Surprisingly, this phenomenon was not dependent on age. Given that inflammation related to chronic viral infection is known to induce NK-like marker expression and a senescence phenotype among CD8 T-cells, we hypothesized that innate E(+) CD8 T-cells will be preferentially associated with exacerbated cellular senescence in response to chronic alloantigen exposure or CMV infection. Accordingly, in a pilot cohort of stable kidney allotransplant recipients, we observed an increased frequency of the Innate E(+) CD8 T-cell subset, together with an exacerbated senescent phenotype. Importantly, this phenotype cannot be explained by age alone, in clear contrast to their conventional memory counterparts. The senescent phenotype in CD8 T-cells was further increased in cytomegalovirus (CMV) positive serology transplant recipients, suggesting that transplantation and CMV, rather than aging by itself, may promote an exacerbated senescent phenotype of innate CD8 T-cells. In conclusion, we proposed that kidney transplantation, via the setting of inflammatory stimuli of alloantigen exposure and CMV infection, may exogenously age the CD8 T-cell compartment, especially its innate component. The physiopathological consequences of this change in the immune system remain to be elucidated.
Published: 2021
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8. Hypercholesterolemia-induced increase in plasma oxidized LDL abrogated pro angiogenic response in kidney grafts

Author: Thomas Kerforne, Frédéric Favreau, Tackwa Khalifeh, Souleymane Maiga, Geraldine Allain, Antoine Thierry, Manuel Dierick, Edouard Baulier, Clara Steichen, and Thierry Hauet
Subjects: Oxidized LDL, Kidney transplantation, Vascular remodeling, Medicine
Abstract: Abstract Background Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could affect vascular repair processes and promote post-transplant renal vascular remodeling through the over-expression of the anti-angiogenic thrombospondin-1 interacting with vascular endothelial growth factor-A levels. Methods We tested this hypothesis in vitro, in vivo and in a human cohort using (1) endothelial cells; (2) kidney auto-transplanted pig subjected (n = 5) or not (n = 6) to a diet enriched in cholesterol and (3) a renal transplanted patient cohort (16 patients). Results Cells exposed to oxidized LDL showed reduced proliferation and an increased expression of thrombospondin-1. In pigs, 3 months after transplantation of kidney grafts, we observed a deregulation of the hypoxia inducible factor 1a—vascular endothelial growth factor-A axis induced in cholesterol-enriched diet animals concomitant with an overexpression of thrombospondin-1 and a decrease in cortical microvessel density promoting vascular remodeling. In patients, hypercholesterolemia was associated with decreased vascular endothelial growth factor-A plasma levels during early follow up after renal transplantation and increased chronic graft dysfunction. Conclusions These results support a potential mechanism through which a high fat-diet impedes vascular repair in kidney graft and suggest the value of controlling cholesterolemia in recipient even at the early stage of renal transplantation.
Published: 2019
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9. Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after Kidney Transplantation.

Author: Dominique Bertrand, Rangolie Kaveri, Charlotte Laurent, Philippe Gatault, Maïté Jauréguy, Cyril Garrouste, Johnny Sayegh, Nicolas Bouvier, Sophie Caillard, Luca Lanfranco, Antoine Thierry, Arnaud François, Françoise Hau, Isabelle Etienne, Dominique Guerrot, and Fabienne Farce
Subjects: Medicine, Science
Abstract: De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.
Published: 2021
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10. Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury

Author: Maxime Rossi, Antoine Thierry, Sandrine Delbauve, Nicolas Preyat, Miguel P. Soares, Thierry Roumeguère, Oberdan Leo, Véronique Flamand, Alain Le Moine, and Jean-Michel Hougardy
Subjects: Medicine, Science
Abstract: Abstract Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1M-KO), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1M-KO exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1M-KO mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b+ F4/80lo subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1+ CD11b+ F4/80lo myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1M-KO mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.
Published: 2017
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11. The Impact of Invariant NKT Cells in Sterile Inflammation: The Possible Contribution of the Alarmin/Cytokine IL-33

Author: Maroua Haroun Ferhat, Aurélie Robin, Louise Barbier, Antoine Thierry, Jean-Marc Gombert, Alice Barbarin, and André Herbelin
Subjects: iNKT, sterile inflammatory response, alarmin IL-33, ischemia reperfusion, CD1d-restricted T cells, tissue repair, Immunologic diseases. Allergy, RC581-607
Abstract: Although the contribution of iNKT cells to induction of sterile inflammation is now well-established, the nature of the endogenous compounds released early after cellular stress or damage that drive their activation and recruitment remains poorly understood. More precisely, iNKT cells have not been described as being reactive to endogenous non-protein damage-associated molecular-pattern molecules (DAMPs). A second subset of DAMPs, called alarmins, are tissue-derived nuclear proteins, constitutively expressed at high levels in epithelial barrier tissues and endothelial barriers. These potent immunostimulants, immediately released after tissue damage, include the alarmin IL-33. This factor has aroused interest due to its singular action as an alarmin during infectious, allergic responses and acute tissue injury, and as a cytokine, contributing to the latter resolutive/repair phase of sterile inflammation. IL-33 targets iNKT cells, inducing their recruitment in an inflammatory state, and amplifying their regulatory and effector functions. In the present review, we introduce the new concept of a biological axis of iNKT cells and IL-33, involved in alerting and controlling the immune cells in experimental models of sterile inflammation. This review will focus on acute organ injury models, especially ischemia-reperfusion injury, in the kidneys, liver and lungs, where iNKT cells and IL-33 have been presumed to mediate and/or control the injury mechanisms, and their potential relevance in human pathophysiology.
Published: 2018
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12. An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies.

Author: Aurélie Prémaud, Matthieu Filloux, Philippe Gatault, Antoine Thierry, Matthias Büchler, Eliza Munteanu, Pierre Marquet, Marie Essig, and Annick Rousseau
Subjects: Medicine, Science
Abstract: Most predictive models and scores of graft survival in renal transplantation include factors known before transplant or at the end of the first year. They cannot be updated thereafter, even in patients developing donor-specific anti-HLA antibodies and acute rejection.We developed a conditional and adjustable score for prediction of graft failure (AdGFS) up to 10 years post-transplantation in 664 kidney transplant patients. AdGFS was externally validated and calibrated in 896 kidney transplant patients.The final model included five baseline factors (pretransplant non donor-specific anti-HLA antibodies, donor age, serum creatinine measured at 1 year, longitudinal serum creatinine clusters during the first year, proteinuria measured at 1 year), and two predictors updated over time (de novo donor-specific anti-HLA antibodies and first acute rejection). AdGFS was able to stratify patients into four risk-groups, at different post-transplantation times. It showed good discrimination (time-dependent ROC curve at ten years: 0.83 (CI95% 0.76-0.89).
Published: 2017
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13. The alarmin concept applied to human renal transplantation: evidence for a differential implication of HMGB1 and IL-33.

Author: Antoine Thierry, Sébastien Giraud, Aurélie Robin, Anne Barra, Franck Bridoux, Virginie Ameteau, Thierry Hauet, Jean-Philippe Girard, Guy Touchard, Jean-Marc Gombert, and André Herbelin
Subjects: Medicine, Science
Abstract: The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been identified as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. We analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme-linked immunosorbent assay, in a cohort of 26 deceased renal transplant recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to those before treatment. Moreover, both serum and urinary IL-33 (but not HMGB1) increase was positively correlated with cold ischemia time, from 30 min to 3 days post-transplantation. In vitro, human umbilical vein endothelial cells subjected to hypoxia conditions released both HMGB-1 and IL-33, while only the latter was further increased upon subsequent re-oxygenation. Finally, we postulate that leukocytes from renal recipient patients are targeted by both HMGB1 and IL-33, as suggested by increased transcription of their respective receptors (TLR2/4 and ST2L) shortly after transplantation. Consistent with this view, we found that iNKT cells, an innate-like T cell subset involved in IRI and targeted by IL-33 but not by HMGB1 was activated 1 hour post-transplantation. Altogether, these results are in keeping with a potential role of IL-33 as an innate-immune mediator during kidney IRI in humans.
Published: 2014
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14. Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

Author: Aude Mignot, Frank Bridoux, Antoine Thierry, Shaida Varnous, Myriam Pujo, Annick Delcourt, Jean Marc Gombert, Jean-Michel Goujon, Fréderic Favreau, Guy Touchard, Daniel Herpin, and Arnaud Jaccard
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.
Published: 2008
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15. Les pratiques et les espaces funéraires antiques en Normandie occidentale : premiers résultats

Author: Vanessa Brunet, Laurent Paez-Rezende, Laurence Jeanne, Erwan Nivez, Aurélien Piolot, Guy Leclerc, Vincent Carpentier, Karine Chanson, Annabelle Cocollos, Dominique Corde, Caroline Duclos, Romuald Ferrette, David Flotté, Laurette Fromentin, David Giazzon, Magali Heppe, Benjamin Hérard, Vincent Hincker, Ivan Jahier, Aurore Lacroix, Gaël Lėon, Isabelle Le Goff, Myriam Le Puil-Texier, Marc-Antoine Thierry, Didier Paillard, Grégory Schütz, Aminte Thomann, Cécile Torrubia Besnard, Institut national de recherches archéologiques préventives (Inrap), Centre Michel de Boüard - Centre de recherches archéologiques et historiques anciennes et médiévales (CRAHAM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Archéologie, Terre, Histoire, Sociétés [Dijon] (ARTeHiS), Ministère de la Culture et de la Communication (MCC)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), EVEHA (Etudes et valorisations archeologiques), AccelLAB Inc, Groupe de recherches archéologiques du Contentin (GRAC), Conseil général du Calvados, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Modélisation du climat (CLIM), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Archéologie Préventive, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Funéraire, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Anthropologie biologique, Normandie Région, Anthropologie Funéraire, General Medicine, Archéologie antique, Antiquité Romaine
Abstract: International audience; This article proposes a first synthesis of ancient funerary practices in western Normandy based on a corpus of 29 sites selected from a very dense documentation of uneven quality. Most of them are unpublished, some have been partially published. This corpus illustrates a wide range of funerary practices identified at regional level and covers a vast chronological range from the 1st century BC to the 5th century AC.The cremation of corpses largely dominates the Lower Normandy funerary landscape since the Conquest and throughout the Early Roman Empire. This practice gradually gave way to that of inhumations, which in turn became predominant in the 2nd century. However, numerous sites prove that these two rites coexisted for a long time. Beyond these considerations, the ancient funerary sites of western Normandy reflect a variety of occupations from the isolated tomb to the family mausoleum, via the community necropolis. Only the urban necropolises remain undocumented to this day.; Le dernier bilan de la recherche archéologique portant sur le fait funéraire antique en Normandie a été mené entre 2004 et 2010. Il a mis en évidence un fort potentiel d'étude avec pas moins de 41 indices. En quelques années, ce chiffre a triplé du fait de l'essor de l'archéologie préventive sur le territoire normand. Fin 2015, ce sont pas moins de 158 sites funéraires recensés dont 50 % des découvertes, soit près de 80 sites, sont postérieures à 1984. Parallèlement, peu de publications ont vu le jour ces trois dernières décennies. L'atelier "funéraire" du PCR Arbano s'est donné comme objectif de prendre en compte la totalité des découvertes anciennes (études complémentaires) comme récentes (sites inédits) et de dresser un premier état des connaissances sur le fait funéraire antique en Normandie occidentale.
Published: 2023

16. La production céramique en Normandie occidentale au Haut-Empire : une terra incognita ?

Author: Marc-Antoine Thierry, Anne Bocquet-Liénard, Marie-Paule Bataillé, Stéphanie Dervin, Juliette Dupré, Hugo Gagnant, Karine Jardel, and Xavier Savary
Subjects: General Medicine
Published: 2023

17. Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial

Author: Marie Courbebaisse, Aurelie Bourmaud, Jean-Claude Souberbielle, Rebecca Sberro-Soussan, Valérie Moal, Yannick Le Meur, Nassim Kamar, Laetitia Albano, Antoine Thierry, Jacques Dantal, Clément Danthu, Karine Moreau, Emmanuel Morelon, Anne-Elisabeth Heng, Dominique Bertrand, Nadia Arzouk, Peggy Perrin, Marie-Pascale Morin, Philippe Rieu, Claire Presne, Philippe Grimbert, Didier Ducloux, Matthias Büchler, Moglie Le Quintrec, Nacéra Ouali, Vincent Pernin, Nicolas Bouvier, Antoine Durrbach, Eric Alamartine, Christine Randoux, Virginie Besson, Marc Hazzan, Justine Pages, Sandra Colas, Marie-Liesse Piketty, Gérard Friedlander, Dominique Prié, Corinne Alberti, and Eric Thervet
Subjects: Transplantation, Immunology and Allergy, Pharmacology (medical)
Published: 2023

18. Comparison of High-Flux, Super High-Flux, Medium Cut-Off Hemodialysis and Online Hemodiafiltration on the Removal of Uremic Toxins

Author: Mohamed Belmouaz, Guillaume Goussard, Florent Joly, Audrey Sibille, Cecile Martin, Thomas Betous, Antoine Thierry, Marc Bauwens, and Frank Bridoux
Subjects: Nephrology, Hematology, General Medicine
Abstract: Introduction: Online hemodiafiltration (OL-HDF) and hemodialysis (HD) using high-performance membranes such as adsorptive, medium cut-off (MCO), and super high-flux (SHF) dialyzers have been implemented to enhance the removal of middle molecules (MM). The aim of this study was to compare the efficacy of different dialysis strategies and dialyzers on small solutes and MM reduction ratio (RR) and mass removal. Methods: We performed a prospective study in 8 HD patients. Each patient underwent 9 dialysis sessions: seven sessions on HD using either Theranova 500™, Elisio 21H™, Renak PS-2.0W™, Filtryzer BK-2.1F™, Vie 21X™, TS-2.1UL™ or FDY 210-GW™ dialyzers and two sessions on OL-HDF using Elisio 21H™ or Renak PS-2.0W™ dialyzers. Results: Urea mass removal and RR were similar between all dialysis strategies. The lowest beta2-microglobulin RR was achieved with Filtryzer BK-2.1F™ HD (p < 0.05). Compared to Elisio 21H™ HD, Renak PS-2.0W™ OL-HDF produced higher beta2-microglobulin mass removal (181 ± 46 vs. 317 ± 161 mg, p < 0.05). Theranova 500™ HD, Vie 21X™ HD, FDY 210-GW™ HD, Elisio 21H™ OL-HDF, and Renak PS-2.0W™ OL-HDF induced higher RR for kappa and lambda FLC, as compared to Elisio 21H™ HD and Filtryzer BK-2.1F™ HD (p < 0.05). Renak PS-2.0W™ OL-HDF achieved higher kappa FLC mass removal compared to Elisio 21H™ HD (563 ± 515 vs. 141 ± 47 mg, p < 0.01) and to Renak PS-2.0W™ HD (563 ± 515 vs. 153 ± 25 mg, p < 0.05). Albumin loss varied from 0.02 ± 0.05 to 7.6 ± 3.8 g/session with Elisio 21H™ HD and Renak PS-2.0W™ OL-HDF, respectively. Compared to all other strategies, Renak PS-2.0W™ OL-HDF induced a significantly higher albumin loss (p < 0.05). Conclusion: This study confirms that albumin loss and removal of MM are similar using conventional Elisio 21H™ OL-HDF, MCO-HD, and SHF type V dialyzers. Although Renak PS-2.0W™ OL-HDF provides high performance for MM depuration, this protein-permeable dialyzer should not be used in OL-HDF because of excessive albumin loss.
Published: 2022

19. Paving the Way for Personalized Medicine in First Kidney Transplantation: Interest of a Creatininemia Latent Class Analysis in Early Post-transplantation

Author: Héloïse Ducousso, Maxime Vallée, Thomas Kerforne, Ines Castilla, Fabien Duthe, Pierre-Jean Saulnier, Stéphanie Ragot, and Antoine Thierry
Subjects: Transplantation
Abstract: Plasma creatinine is a marker of interest in renal transplantation but data on its kinetics in the first days following transplantation are scarce. The aim of this study was to identify clinically relevant subgroups of creatinine trajectories following renal transplantation and to test their association with graft outcome. Among 496 patients with a first kidney transplant included in the French ASTRE cohort at the Poitiers University hospital, 435 patients from donation after brain death were considered in a latent class modeling. Four distinct classes of creatinine trajectories were identified: “poor recovery” (6% of patients), “intermediate recovery” (47%), “good recovery” (10%) and “optimal recovery” (37%). Cold ischemia time was significantly lower in the “optimal recovery” class. Delayed graft function was more frequent and the number of hemodialysis sessions was higher in the “poor recovery” class. Incidence of graft loss was significantly lower in “optimal recovery” patients with an adjusted risk of graft loss 2.42 and 4.06 times higher in “intermediate recovery” and “poor recovery” patients, respectively. Our study highlights substantial heterogeneity in creatinine trajectories following renal transplantation that may help to identify patients who are more likely to experience a graft loss.
Published: 2023

20. Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study

Author: Paolo Malvezzi, Dany Anglicheau, Sophie Caillard, Julien Aniort, Betoul Schvartz, Antoine Thierry, Nicolas Bouvier, Christophe Legendre, Vincent Pernin, Clarisse Greze, Coralie Poulain, Nicolas Maillard, Jean Philippe Rerolle, Camille Lanaret, Nassim Kamar, Didier Ducloux, Arnaud Del Bello, Charlotte Uro‐Coste, Cyril Garrouste, Franck Martinez, Julie Oniszczuk, Dominique Bertrand, Lionel Couzi, Anne Elisabeth Heng, Laurent Mesnard, Céline Lambert, Johnny Sayegh, Vincent Audard, Marie-Pascale Morin, and Mathias Büchler
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, 030230 surgery, Gastroenterology, Hypogammaglobulinemia, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Kidney transplantation, Retrospective Studies, Transplantation, Glomerulosclerosis, Focal Segmental, Primary Focal Segmental Glomerulosclerosis, business.industry, medicine.disease, Kidney Transplantation, Calcineurin, Treatment Outcome, Plasmapheresis, Rituximab, Complication, business, Kidney disease, medicine.drug
Abstract: Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia
Published: 2021

21. 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

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

Author: Dimitri Titeca-Beauport, Nassim Kamar, Didier Ducloux, Benoit Barrou, Lola Jacquemont, Lionel Couzi, Nicolas Bouvier, Valérie Moal, Fatouma Touré, Bruno Moulin, Yann Le Meur, Cyril Garrouste, Denis Glotz, Lionel Rostaing, Antoine Thierry, Marie Courbebaisse, Hélène Lazareth, Isabelle Etienne, Jonathan M. Chemouny, François Gaillard, Christophe Legendre, Claire Pouteil-Noble, Philippe Rieu, Marc Hazzan, Mathias Büchler, Philippe Grimbert, Laetitia Albano, Michel Delahousse, Maryvonne Hourmant, Pierre Delanaye, Nacera Ouali, Luc Frimat, Christiane Mousson, Moglie Le Quintrec, Alexandre Hertig, Christophe Mariat, Retiveau, Nolwenn, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Clermont-Ferrand, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital de Bohars - CHRU Brest (CHU - BREST ), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Tenon [AP-HP], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, CHU Pontchaillou [Rennes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Liège, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Hôpital Nord (Saint Etienne), CHU Toulouse [Toulouse]-PRES Université de Toulouse, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Population, Urology, Renal function, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Kidney, Nephrectomy, MESH: Kidney Transplantation, 03 medical and health sciences, Age, Living kidney donors, 0302 clinical medicine, Age groups, Living Donors, medicine, Humans, education, MESH: Living Donors, Transplantation, education.field_of_study, MESH: Humans, MESH: Middle Aged, business.industry, Kidney donation, Estimated GFR, MESH: Kidney, Middle Aged, Post-donation GFR, Kidney Transplantation, MESH: Nephrectomy, MESH: Glomerular Filtration Rate, medicine.anatomical_structure, MESH: Kidney Failure, Chronic, Donation, Screening, Kidney Failure, Chronic, 030211 gastroenterology & hepatology, DONOR EVALUATION, business, Glomerular Filtration Rate
Abstract: International audience; Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is 55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.
Published: 2021

23. Chronic Hepatitis C Virus Infection After Kidney Transplantation With or Without Direct-Acting Antivirals in a Real-Life Setting: A French Multicenter Experience

Author: Nicolas Bouvier, Yannick Le Meur, Cyril Garrouste, Dominique Bertrand, Johnny Sayegh, Eloi Chevallier, Matthias Büchler, Sophie Caillard, Joseph Rivalan, Antoine Thierry, Lionel Rostaing, Philippe Gatault, Charlotte Colosio, Jean-Philippe Rerolle, Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratory of Immunology, CHRU de Tours, Tours, France, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Nephrology, Reims University Hospital, Reims, France, Centre Hospitalier Universitaire de Rennes (CHU Rennes), Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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), Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie [Clermont-Ferrand], CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Adult, Male, Ledipasvir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, 030232 urology & nephrology, Antiviral Agents, Gastroenterology, Group A, Virus, Group B, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Kidney transplantation, Retrospective Studies, Fluorenes, Transplantation, business.industry, Imidazoles, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, chemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Benzimidazoles, Female, 030211 gastroenterology & hepatology, Surgery, Carbamates, France, business, Viral hepatitis, medicine.drug
Abstract: Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.
Published: 2020

24. Clinical Pharmacokinetics and Bayesian Estimators for the Individual Dose Adjustment of a Generic Formulation of Tacrolimus in Adult Kidney Transplant Recipients

Author: Nicolas Picard, Alexandre Destere, Caroline Monchaud, Jean-Baptiste Woillard, Jean Debord, Hakim Mazouz, Isabelle Etienne, Antoine Thierry, Pierre Marquet, Jean-Philippe Rerolle, and Matthias Büchler
Subjects: Adult, Pharmacology, Mean squared error, Bayesian probability, Estimator, Bayes Theorem, 030230 surgery, Kidney Transplantation, Models, Biological, 030226 pharmacology & pharmacy, Kidney transplant, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Area Under Curve, Covariate, Statistics, Humans, Pharmacology (medical), Individual dose, Immunosuppressive Agents, Mathematics
Abstract: Tacrolimus has a narrow therapeutic range and requires dose adjustment, usually based on the trough blood concentration but preferably on the area under the concentration–time curve over 12 h post-dose (AUC0–12h). The single-arm, multicentre, clinical study IMPAKT aimed: (i) to develop, in de novo kidney transplant recipients, pharmacokinetic models and maximum a-posteriori Bayesian estimators for a generic, immediate-release, oral formulation of tacrolimus to estimate tacrolimus AUC0–12h at different post-transplant periods using a limited sampling strategy, and considering the CYP3A5*3 polymorphism as a covariate and (ii) to compare the performance of these Bayesian estimators to those previously developed for the original formulation. Thirty patients were enrolled and 29 provided nine blood samples over 9 h at day 7 and months 1 and 3 post-transplant. Tacrolimus blood profiles measured with liquid chromatography-tandem mass spectrometry were modelled using one-compartment, double gamma absorption, linear elimination models developed in-house. Different limited sampling strategies of three time-points within 4 h post-dose were tested for the maximum a-posteriori Bayesian estimator of tacrolimus AUC0–12h. The models and estimators were validated internally and their performance compared to that of models previously developed for the original formulation. The concentration–time curves, AUC0–12h/dose and trough blood concentration/dose exhibited wide inter-individual variability. The covariate-free pharmacokinetic models developed for the three post-transplant periods closely fitted the individual profiles. Maximum a-posteriori Bayesian estimators based on three different limited sampling strategies and no covariate yielded accurate AUC0–12h estimates, including for the five cytochrome P450 3A5 expressers and for the four patients without corticosteroids. The 0–1 h–3 h strategy finally chosen had very low bias (− 4.0 to − 2.5%) and imprecision (root mean square error 5.5–9.2%). The maximum a-posteriori Bayesian estimators previously developed for the reference product fitted the generic profiles with similar performance. We developed original pharmacokinetic models and accurate maximum a-posteriori Bayesian estimators to estimate patient exposure and adjust the dose of generic tacrolimus, and confirmed that the robust tools previously developed for the original formulation can be applied to this generic.
Published: 2020

25. Opportunistic infections after conversion to belatacept in kidney transplantation

Author: Isabelle Etienne, Rebecca Sberro, Cyril Garrouste, Ludivine Lebourg, Charlotte Colosio, Mathilde Lemoine, Antoine Thierry, Nicolas Bouvier, Dominique Bertrand, Philippe Gatault, Leonard Golbin, Sophie Caillard, Nathalie Chavarot, Maïté Jauréguy, Anne Grall-Jezequel, Johnny Sayegh, Dominique Guerrot, and Jean-Philippe Rerolle
Subjects: Graft Rejection, Male, medicine.medical_specialty, 030232 urology & nephrology, Renal function, Opportunistic Infections, 030230 surgery, Pneumocystis pneumonia, Belatacept, Gastroenterology, Abatacept, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Kidney transplantation, Retrospective Studies, Transplantation, business.industry, Incidence, Incidence (epidemiology), Graft Survival, Middle Aged, medicine.disease, Kidney Transplantation, Lymphoproliferative Disorders, Calcineurin, Nephrology, Cohort, Female, France, business, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.drug
Abstract: Background Belatacept (bela) rescue therapy seems to be a valuable option for calcineurin inhibitor chronic toxicity in kidney transplantation. Nevertheless, the risk of infection associated with bela is not well reported. Methods We report the rate of opportunistic infections (OPI) after a switch to bela in a multicentric cohort of 280 kidney transplant patients. Results Forty-two OPI occurred in 34 patients (12.1%), on average 10.8 ± 11.3 months after the switch. With a cumulative exposure of 5128 months of bela treatment, we found an incidence of 0.008 OPI/month of exposure, and 9.8 OPI/100 person-years. The most common OPI was cytomegalovirus (CMV) disease in 18/42 OPI (42.9%) and pneumocystis pneumonia in 12/42 OPI (28.6%). Two patients presented a progressive multifocal leucoencephalopathy and two patients developed a cerebral Epstein–Barr virus-induced post-transplant lymphoproliferative disease. OPI led to death in 9/34 patients (26.5%) and graft failure in 4/34 patients (11.8%). In multivariate analysis, estimated glomerular filtration rate Conclusions The risk of OPI is significant post-conversion to bela and may require additional monitoring and prophylactic therapy, particularly regarding pneumocystis pneumonia and CMV disease. These data need to be confirmed in a larger case–control study.
Published: 2020

26. 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

27. Comparison of the injection of low-molecular weight heparin in the arterial vs. venous blood line for preventing extracorporeal circuit clotting during hemodialysis

Author: Mohamed Belmouaz, Guillaume Goussard, Florent Joly, Francois Grand, Audrey Sibille, Laure Ecotiere, Estelle Desport, Marc Bauwens, Antoine Thierry, and Frank Bridoux
Subjects: Molecular Weight, Nephrology, Renal Dialysis, Anticoagulants, Humans, Thrombosis, Hematology, Hemodiafiltration, Enoxaparin, Heparin, Low-Molecular-Weight
Abstract: Low-molecular weight heparins (LMWH) are widely used for preventing clotting during hemodialysis (HD). Although injection in the venous blood line is recommended to avoid initial loss of LMWH through the dialyzer, LMWH is still frequently administered in the arterial blood line at the start of dialysis. This study aimed to compare the safety and efficacy of the same enoxaparin dose administered through the venous blood line or arterial blood line. We also evaluated antifactor Xa (aXa) activity according to the injection route and dialysis modalities: high-flux (HF) HD, medium cut-off (MCO) HD, and online hemodiafiltration (OL-HDF). Forty-three patients were studied over 18 consecutive dialysis sessions using a fixed enoxaparin dose (20 or 40 mg), first administered through the arterial blood line bolus and then through the venous blood line for another 18 sessions. Compared to arterial blood line administration, venous blood line bolus resulted in a significant increase in median post-dialysis aXa activity: 0.16 (0.1-0.6) IU/ml versus 0.31 (0.1-1.3) IU/ml, respectively, p = 0.006. After arterial blood line bolus of 40 mg enoxaparin, median post-dialysis aXa activity was significantly lower with OL-HDF compared to HF-HD: 0.14 (0.1-0.35) versus 0.32 (0.15-0.49), p = 0.02. A trend for lower clotting within lines and bubble trap using venous blood line bolus was observed. In conclusion, venous blood line enoxaparin injection is safe in OL-HDF patients. However, in HF-HD and MCO-HD, venous blood line injection of 40 mg enoxaparin may increase overdosing risk. Thus, aXa activity should be monitored in HF-HD and MCO-HD patients at risk of bleeding and/or on vitamin K antagonists and careful surveillance is required when administering a 40 mg enoxaparin dose through the venous blood line route.
Published: 2021

28. 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

29. HEMO

Author: Yannick, Le Meur, Eric, Delpy, Felix, Renard, Thierry, Hauet, Lionel, Badet, Jean Philippe, Rerolle, Antoine, Thierry, Matthias, Büchler, Franck, Zal, and Benoit, Barrou
Subjects: Hemoglobins, Risk Factors, Cold Ischemia, Graft Survival, Delayed Graft Function, Humans, Prospective Studies, Kidney, Kidney Transplantation
Abstract: M101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMOAn additional analysis was conducted including OXYOP patients and patients from the ASTRE database (n = 6584) to verify that the decrease in DGF rates observed in the HEMOKaplan-Meier estimate curves confirmed the existence of a relation between DGF and CIT and Cox analysis showed a benefit in the HEMOThe present study suggested that the better recovery of renal function observed among kidneys preserved with HEMO
Published: 2021

30. 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

31. Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome

Author: David Navarro, Sophie Caillard, Leila Tricot, Marie Frimat, Rebecca Sberro Soussan, Jamal Bamoulid, Antoine Thierry, Christophe Legendre, Nassim Kamar, Pierre-François Westeel, Laetitia Albano, Magali Louis, Christophe Charasse, Chantal Loirat, Emilie Cornec-Le Gall, Dominique Bertrand, Jean-Philippe Rerolle, Lionel Couzi, Philippe Gatault, Cyril Garrouste, Aude Servais, Marie-Noëlle Peraldi, Sophie Chauvet, Joseph Rivalan, Yahsou Delmas, Guillaume Claisse, Jean-Philippe Coindre, Ziad A. Massy, Maryvonne Hourmant, Claire Pouteil-Noble, Michelle Elias, Johnny Sayegh, Charlotte Colosio, Luc Frimat, Nadia Arzouk, Noemie Jourde-Chiche, Eric Rondeau, Moglie Le Quintrec, Florent Petitprez, Raphaël Gaisne, Khalil El Karoui, Fadi Fakhouri, Véronique Frémeaux-Bacchi, Julien Zuber, Valérie Chatelet, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Emmanuel Boussard Foundation Fukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation
Subjects: Male, [SDV]Life Sciences [q-bio], Mutant Chimeric Proteins, 030232 urology & nephrology, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Epidemiology, Secondary Prevention, Medicine, complement, Registries, Kidney transplantation, Atypical Hemolytic Uremic Syndrome, education.field_of_study, Graft Survival, General Medicine, Middle Aged, Eculizumab, 3. Good health, Nephrology, Female, France, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Population, kidney transplantation, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Clinical Research, Internal medicine, Preoperative Care, Atypical hemolytic uremic syndrome, Complement C3b Inactivator Proteins, Humans, INHIBITOR ECULIZUMAB, RECURRENCE, education, Proportional Hazards Models, Retrospective Studies, MUTATIONS, business.industry, Complement System Proteins, medicine.disease, Complement Inactivating Agents, hemolytic uremic syndrome, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.Results The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.
Published: 2019

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

Author: Bénédicte Janbon, Sophie Caillard, Isabelle Jollet, Elisabeth Cassuto, Elodie Bailly, Bruno Hurault de Ligny, Michel Delahousse, Marc Hazzan, Anne Devys, Antoine Thierry, Pierre Merville, Sophie Girerd, Renaud Snanoudj, Dany Anglicheau, Vincent Vuiblet, Nassim Kamar, Kahina Amokrane, Philippe Grimbert, Eric Rondeau, Gabriel Choukroun, Alexandre Hertig, Marie Metzger, Jean-Luc Taupin, Yann Le Meur, Christophe Legendre, Emmanuel Morelon, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie [Amiens], CHU Amiens-Picardie-hôpital Sud, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Etablissement français du sang [Angers], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Foch [Suresnes], Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Graft Rejection, Male, 0301 basic medicine, Isoantigens, Allosensitization, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, kidney transplantation, Human leukocyte antigen, acute rejection, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA-DQ Antigens, immunosuppression minimization, Humans, Transplantation, Homologous, Medicine, Everolimus, education, Kidney transplantation, education.field_of_study, biology, Drug Substitution, business.industry, Histocompatibility Testing, Patient Selection, Graft Survival, Immunosuppression, Middle Aged, epitopes, medicine.disease, HLA mismatching, 3. Good health, 030104 developmental biology, Nephrology, Immunology, Cyclosporine, antibody-mediated rejection, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies
Abstract: International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
Published: 2019

33. No impact of disseminated intravascular coagulation in kidney donors on long-term kidney transplantation outcome: A multicenter propensity-matched study

Author: Julie Oniszczuk, Philippe Gatault, Cyril Garrouste, Julien Aniort, Marion Rabant, Bruno Pereira, Anne Elisabeth Heng, Antoine Thierry, Nora Szlavik, Julien Baudenon, Isabelle Etienne, Johnny Sayegh, Dany Anglicheau, and Céline Lambert
Subjects: Adult, Male, Brain Death, medicine.medical_specialty, Tissue and Organ Procurement, Urology, Delayed Graft Function, Renal function, 030230 surgery, Kidney Function Tests, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Organ donation, Contraindication, Kidney transplantation, Aged, Retrospective Studies, Disseminated intravascular coagulation, Transplantation, Kidney, business.industry, Incidence, Graft Survival, Disseminated Intravascular Coagulation, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Tissue Donors, Calcineurin, medicine.anatomical_structure, Kidney Failure, Chronic, Female, France, business, Follow-Up Studies, Glomerular Filtration Rate, circulatory and respiratory physiology
Abstract: The diagnosis of disseminated intravascular coagulation (DIC) is often considered to be a contraindication to organ donation. The aim of this study was to evaluate the impact of DIC+ donors on kidney recipient (KR) evolution. We identified 169 KRs with DIC+ donation after brain death donors between January 1996 and December 2012 in 6 French transplant centers. Individuals were matched using propensity scores to 338 recipients with DIC- donors according to donor age and sex, whether expanded criteria for the donor existed, graft year, and transplantation center. After kidney transplantation, delayed graft function was observed in 28.1% of DIC+ KRs and in 22.8% of DIC- KRs (NS). Renal allograft survival at 1, 5, and 10 years was 94.5%, 89.3%, and 73.9% and 96.2%, 90.8%, and 81.3% in DIC+ KRs and DIC- KRs, respectively (NS). The median estimated glomerular filtration rate (eGFR) was similar between DIC+ and DIC- KRs at 3 months, 1 year, and 10 years: 45.9 vs 48.1 mL/min, 42.1 vs 43.1 mL/min, and 33.9 vs 38.1 mL/min, respectively. Delayed calcineurin inhibitor introduction or induction had no impact on delayed graft function rate or eGFR evolution at 10 years after transplantation in DIC+ KRs. Donor DIC did not seem to affect initial outcome, long-term graft function, or allograft survival.
Published: 2019

34. Evaluation of the early venous thromboses of renal grafts: a French multicentric retrospective study

Author: Romain Chauvet, Francis Pesteil, Mattias Buchler, Antoine Thierry, Isabelle Etienne, and Marie Essig
Subjects: Surgery, General Medicine, Cardiology and Cardiovascular Medicine
Published: 2022

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

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

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

Author: Nathalie Chavarot, Bruno Moulin, Valérie Moal, Olivier Thaunat, Marc Hazzan, Jamal Bamoulid, Antoine Durrbach, Christiane Mousson, Nassim Kamar, Yannick Lemeur, Charlotte Kaeuffer, Clarisse Greze, Philippe Grimbert, Ilies Benotmane, Dominique Bertrand, Antoine Thierry, Tristan Legris, Gilles Blancho, Pierre François Westeel, Mariam Jdidou, Hélène François, Sophie Caillard, Marie Matignon, Yvon Ruch, Morgane Solis, Antoine Sicard, Dany Anglicheau, Philippe Gatault, Valentin Goutaudier, François Danion, Lionel Couzi, Charlotte Colosio, Renaud Snanoudj, Christophe Masset, Agnès Duveau, Jonathan M. Chemouny, Luc Frimat, CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Tours (UT), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Aix Marseille Université (AMU), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Bourgogne (UB), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Poitiers, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), University of Lille, This study was supported by the Strasbourg University Hospital (COVIS-HUS Study- HUS number 7760), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP Hôpital Tenon [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University Hospital of Montpellier, Hôpital Bicêtre, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), PINIER, CHRISTINE, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Registries, Aucun, MESH: Comorbidity, 030230 surgery, law.invention, chemistry.chemical_compound, 0302 clinical medicine, law, cardiovascular disease, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, clinical research / practice, Immunology and Allergy, Cumulative incidence, Pharmacology (medical), kidney transplantation / nephrology, MESH: Incidence, MESH: Aged, Univariate analysis, MESH: France / epidemiology, MESH: Middle Aged, MESH: Transplant Recipients / statistics & numerical data, Acute kidney injury, Intensive care unit, 3. Good health, MESH: COVID-19 / epidemiology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, glomerular filtration rate (GFR), kidney failure / injury, medicine.medical_specialty, infection and infectious agents - viral, infectious disease, Brief Communication, MESH: Graft Rejection / prevention & control, 03 medical and health sciences, Internal medicine, Diabetes mellitus, MESH: Severity of Illness Index, MESH: COVID-19 / diagnosis, medicine, Humans, MESH: SARS-CoV-2, Mechanical ventilation, Creatinine, Transplantation, MESH: Humans, business.industry, SARS-CoV-2, MESH: Graft Rejection / epidemiology, COVID-19, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, Transplant Recipients, MESH: Male, immunosuppressive regimens, MESH: Immunosuppressive Agents / therapeutic use, MESH: Pandemics, MESH: Propensity Score, chemistry, Reinfection, MESH: Immunosuppression / methods, MESH: Intensive Care Units, business, MESH: Female, MESH: Kidney Transplantation
Abstract: International audience; There are no studies which have compared the risk of severe Covid-19 and related mortality between transplant recipients and non-transplant patients. We enrolled two groups of patients hospitalized for Covid-19, i.e., kidney transplant recipients from the French Registry of Solid Organ Transplant (n=306) and a single-center cohort of non-transplant patients (n=795). An analysis was performed among subgroups matched for age and risk factors for severe Covid-19 or mortality. Severe Covid-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death.Transplant recipients were younger and had more comorbidities compared to non-transplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe Covid-19 did not differ between KTR and non-transplant patients; however, 30-day Covid-19-related mortality was significantly higher in KTR (17.9% versus 11.4%, respectively, p=0.038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe Covid-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR=1.55), and creatinine level >115 µmol/L (HR=2.32) were associated with Covid-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. Kidney transplant recipients had a higher Covid-19-related mortality compared to non-transplant hospitalized patients.
Published: 2021

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

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

38. Characteristics of T- and NK-cell Lymphomas After Renal Transplantation: A French National Multicentric Cohort Study

Author: Valérie Moal, Véronique Leblond, Gilles Salles, Valérie Chatelet, Benoit Barrou, Alizée Maarek, Sophie Caillard, Christiane Mousson, Laurent Genestier, Luc Frimat, Antoine Durrbach, Vincent Pernin, Emmanuel Bachy, Philippe Rieu, Olivier Thaunat, Didier Ducloux, Valérie Dubois, Manon Charrier, Bénédicte Janbon, Thomas Barba, Dany Anglicheau, Antoine Thierry, Jacques Dantal, Gaelle Fossard, Anne-Elisabeth Heng, Mathias Büchler, Pierre-François Westeel, François Provôt, Denis Glotz, Elisabeth Cassuto, Jean-Philippe Rerolle, Philippe Grimbert, Philippe Gaulard, Jonathan M. Chemouny, Nacera Ouali, Christophe Mariat, and Emmanuel Morelon
Subjects: Adult, Male, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, Lymphoproliferative disorders, Disease, Lymphoma, T-Cell, Gastroenterology, Cohort Studies, hemic and lymphatic diseases, Internal medicine, Medicine, Humans, Prospective Studies, Aged, Transplantation, Chemotherapy, business.industry, Hazard ratio, Middle Aged, medicine.disease, Kidney Transplantation, surgical procedures, operative, Cohort, Registry data, Female, business, Cohort study
Abstract: BACKGROUND Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients. METHODS All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients. RESULTS T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001). CONCLUSIONS This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.
Published: 2021

39. Apport du mobilier antique du musée Quesnel-Morinière à l’étude de la cité de Cosedia/Constantia (Coutances)

Author: Jan Veron, Marc-Antoine Thierry, Eva Bisson, Amélie Marie, and Guillaume Blanchet
Abstract: Veron Jan, Thierry Marc-Antoine, Bisson Eva, Marie Amélie, Blanchet Guillaume. Apport du mobilier antique du musée Quesnel-Morinière à l’étude de la cité de Cosedia/Constantia (Coutances). In: Aremorica. Études sur l'ouest de la Gaule romaine, n°10, 2021. pp. 115-141.
Published: 2021

40. 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

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

Author: Cécile Couchoud, Florian Bayer, Carole Ayav, Clémence Béchade, Philippe Brunet, François Chantrel, Luc Frimat, Roula Galland, Maryvonne Hourmant, Emmanuelle Laurain, Thierry Lobbedez, Lucile Mercadal, Olivier Moranne, Abdelhamid Abbassi, Alain Debure, Abdallah Guerraoui, Abdelatif Benmoussa, Abdelaziz Hamani, Abdelaziz Ziane, Abdelhamid Nefti, Abdelkader Hadj, Abderrahim El Amari, Abderrahmane Ghazali, Abo Bakr Abd El Fatah Mohamed, Achour Laradi, Adel Ben Ahmed, Adel Sahar, Adele Pillet, Adeline Lacraz, Adnan Moinat, Afshin Massoumi, Agathe Pardon, Agnes Caillette Beaudoin, Agnes Chapelet Debout, Agnes Mariot, Ahmed Rachi, Aida Afiani, Aime Remy Boula, Al Jalaby, Alain Cremault, Alain Fournier, Alain Jeanson, Alain Lyon, Alain Nony, Alain Robert, Alain Slingeneyer, Alanor Agnes Labatide, Albane Brodin Sartorius, Albert Bensman, Albert Fournier, Alex Ranlin, Alex Vido Sandor, Alexandra Colombo, Alexandra Duhem, Alexandra Stancu, Alexandre Dufay, Alexandre Dumoulin, Alexandre Ebel, Alexandre Klein, Alexandre Martin, Alexandre Mouneimne, Alexandre Seidowsky, Alfio De Martin, Alfredo Zannier, Ali Aizel, Ali Hafi, Ali Zineddine Diddaoui, Alim Heyani, Alina Mocanu, Alina Preda, Aline Hafi, Aline Talaszka, Alyette Duquesne, Amar Amaouche, Amel Ghemmour, Amelie Simon, Amina Skalli, Amine Boukadida, Amr Ekhlas Ragab Eid, Ana Fedorca, Anabelle Baillet, Anais Poyet, Ancuta Bouffandeau Giorgita, Anderson Ratsimbazafy, Andre Pruna, Angel Argiles, Angelo Testa, Ann Karolien Vandooren, Anne Jolivot, Anne Kolko Labadens, Anne Lataste, Anne Maisin, Anne Paris, Anne Sechet, Anne Wuillai, Anne Elisabeth Heng, Anne Gaelle Josse, Anne Helene Querard, Anne Helene Reboux, Anne Laure Adra, Anne Laure Faller, Anne Laure Leclerc, Anne Laure Poitou, Annie Lahoche Manucci, Antoine Jacquet, Antoine Pommereau, Antoine Thierry, Arezki Adem, Arielle Chapelet, Arnaud Del Bello, Arnaud Delezire, Arnaud Garnier, Arnaud Guerard, Arnaud Klisnick, Arnaud Lionet, Arnaud Roccabianca, Arnaud Stolz, Arthur Capdeville, Asma Allal, Assem Alrifai, Assetou Diarrassouba, Assia Djema, Assia Ferhat Carre, Astrid Godron Dubrasquet, Atman Haddj Elmrabet, Audrey Jegado, Aurelia Bertholet Thomas, Aurelie Davourie Salandre, Aurelie Pajot, Aurelien Lorthioir, Aurelien Tiple, Aurore Sury, Ayman Abokasem, Ayman Sarraj, Bachir Henaoui, Baher Chaghouri, Bassem Wehbe, Beatrice Ball, Beatrice Viron, Belkassem Issad, Benedicte Hodemon Corne, Benedicte Janbon, Benjamin Deroure, Benjamin Savenkoff, Benoit Jonon, Benoit Vendrely, Benyakoub Djelaleddine, Bernard Ohry, Bernard Painchart, Bernard Strullu, Bernard Temperville, Bertin Ebikili, Bertrand Hacq, Bertrand Morel, Bilal Aoun, Blanca Muniz, Bouchra Chlih, Brahim Amara, Brice Mayor, Brigitte Gilson, Brigitte Llanas, Brigitte Zins, Bruno Bourgeon, Bruno Coevoet, Bruno Guery, Bruno Legallicier, Bruno Paris, Bruno Ranchin, Bruno Seigneuric, Camelia Ghiciuc Dita, Camelia Prelipcean, Carine Achard Hottelart, Carine Diet, Carlos Frangie, Carlos Vela, Carmina Muresan, Carole Deprele, Caroline Araujo, Caroline Bidault, Caroline Creput, Caroline Delclaux, Caroline Du Halgouet, Caroline Favennec, Caroline Freguin, Caroline Gourraud Vercel, Caroline Mesguen, Caroline Ndomo Obama, Caroline Poitou, Caroline Preissig Dirhold, Caroline Roubiou, Catherine Albert, Catherine Bessin, Catherine De Marion Gaja, Catherine Godart, Catherine Lasseur, Catherine Leocardi, Catherine Lumbroso, Catherine Melander, Catherine Michel, Catherine Quere Maurouard, Catherine Rouannet, Catherine Taddei, Cathy Verove, Cecile Guiraud, Cecile Tafelin, Cecile Turc Baron, Cedric Formet, Cedric Pinier, Celia Lessore De Ste Foy, Celine Granolleras, Chaouki Bennini, Charles Cartou, Charles Chazot, Charlotte Jouzel, Cherif Badid, Christa Roubicek, Christel Viaud, Christelle Verrier, Christian Chuet, Christian Combe, Christian Dabot, Christian Duvic, Christian Emond, Christian Lagarde, Christian Lamotte, Christian Pain, Christiane Mousson, Christie Lorriaux, Christine Beauchamp, Christine Fumeron, Christine Le Gurun, Christine Leroy, Christine Pietrement, Christine Richer, Christophe Bouaka, Christophe Charasse, Christophe Goupy, Christophe Ridel, Cindy Castrale, Cindy Detourne, Clair Francois, Claire Presne, Claire Trivin, Clarissa Von Kotze, Claude Bernard, Claude Bonniol, Claude Desvergnes, Claude Raharivelina, Claudia Nistor, Claudine Gueret, Claudine Lloret, Claudine Saltiel, Clelia Rosati, Clementine Rabate, Corina Stanescu, Corinne Ferrandini, Corinne Guibergia, Corinne Lemoine, Corinne Passeron, Cynthia Kahil, Cyril Garrouste, Cyril Vo Van, Cyrille Jolimoy, Dalila Kesraoui, Damien Jolly, Damien Thibaudin, Dan Teboulle, Daniel Daubresse, Daniel Louvet, Daniel Rasamimanantsoa, Daniel Toledano, Daniela Babici, Daniela David, Daniela Dincu, Danielle Bruno, Delia May, Delphine Haussaire, Delphine Henriet Viprey, Denis Bugnon, Denis Fouque, Denis Morin, Derradji Nour, Diab Mohamed Mahmoud, Diana Istrati Cristescu, Didier Aguilera, Didier Coste, Didier Hamel, Didier Le Chapois, Didier Testou, Dilaver Erbilgin, Djamal Dahmane, Doan Bui Quang, Dominique Bertrand, Dominique Besnier, Dominique Blanchier, Dominique Briffa, Dominique Caux, Dominique Durand, Dominique Fleury, Dominique Guerrot, Dominique Hestin, Dominique Jaubert, Dominique Joly, Dominique Lombart, Dominique Pagniez, Dominique Pierre, Dominique Schohn, Donatien Ikonga, Dorina Visanica, Dorothee Bazin, Edouard Boury, Edouard Maksour, Ekoue Agbonon, Elarbi Harrami, Elena Marcu, Elena Tudorache, Elisabeth Caniot, Elisabeth Semjen, Elisabeth Tomkiewicz, Elise Scheidt, Elke Gaboriau, Elodie Lamouroux, Elsa Guiard, Elsa Martin Passos, Emerson Nsembani, Emilie Fache, Emilie Kalbacher, Emilie Pambrun, Emilie Pincon, Emma Allain Launay, Emmanuel Baron, Emmanuel Dupuis, Emmanuel Villar, Emmanuelle Charlin, Emmanuelle Hecquet, Emmanuelle Kohler, Emmanuelle Rosier, Enrique Figueroa, Eric Azoulay, Eric Canivet, Eric Daugas, Eric Gauthier, Eric Laruelle, Eric Le Guen, Eric Legrand, Eric Moumas, Eric Postec, Eric Prinz, Eric Renaudineau, Estelle Desport, Estelle Ricard Sutra, Etienne Berard, Etienne Ged, Etienne Robin, Eve Vilaine, Evelyne Bargas, Evelyne Mac Namara, François Combarnous, Fatima Yazbeck, Fabien Gerard, Fabien Metivier, Fabien Parazols, Fabien Soulis, Fabrice Garnier, Fadhila Pech Messaoudene, Fadi Haidar, Fanny Boullenger, Fanny Lepeytre, Fanny Leroy, Fares Frejate, Farid Bellahsene, Farid Bellhasene, Farid Saidani, Fatouma Toure, Faycal Kriaa, Fazia Nemmar, Fernando Vetromile, Florence Chalmin, Florence Lucats, Florence Sens, Florence Villemain, Florent Plasse, Fouad Lebhour, Francis Schillinger, Franck Berge, Franck Bourdon, Franck Bridoux, Franck Reynaud, Francois Babinet, Francois Basse, Francois Chantrel, Francois Clair, Francois Coulomb, Francois De Cornelissen, Francois Glowacki, Francois Marchal, Francois Maurice, Francois Nobili, Francois Pourreau, Francois Provot, Francois Roux Amani, Francoise Broux, Francoise Bulte, Francoise Heibel, Francoise Leonetti, Francoise Moussion Schott, Frank Le Roy, Frederic Besson, Frederic Lavainne, Frederic Tollis, Frederique Bocquentin, Frederique Meeus, Frederique Vecina, Friederike Von Ey, Gabriel Balit, Gabriel Choukroun, Gabriel Gruget, Gabriel Huchard, Gabriella Golea, Gabrielle Duneau, Gaelle Lefrancois, Gaelle Pelle, Gaetan Lebrun, Genevieve Dumont, Georges Brillet, Georges Deschenes, Georges Mourad, Georges Stamatakis, Geraldine Cazajous, Geraldine D'ythurbide, Geraldine Robitaille Wiart, Gerard Cardon, Gerard Champion, Gerard Deschodt, Gerard Mangenot, Gerard Motte, Gerard Schortgen, Ghada Boulahia, Ghassan Maakaroun, Ghylene Bourdat Michel, Gilbert Zanetta, Gilles Hufnagel, Gilles Messier, Giorgina Piccoli, Gregoire Couvrat Desvergnes, Guillaume Bobrie, Guillaume Bonnard, Guillaume Clement, Guillaume Jean, Guillaume Queffeulou, Guillaume Seret, Guillaume Vernin, Guy Delavaud, Guy Lambrey, Guy Rostoker, Gwenaelle Poussard, Gwenaelle Roussey Kesler, H. Leon, Habib Aboubekr, Hacene Boulechfar, Hacene Sekhri, Hadia Hebibi, Hadjira Benalia, Hafed Fessi, Hafsabhai Atchia, Haiat Bittar, Hakim Maiza, Hakim Mazouz, Hamid El Ali, Hammouche Bougrida, Hans Van Der Pijl, Hassan Lokmane, Hassane Izzedine, Hassen Adda, Helene De Preneuf, Helene Leray, Helene Philippot, Henri Boulanger, Henri Merault, Henri Renaud, Herve Bonarek, Herve Maheut, Hilaire Nzeyimana, Hocine Mehama, Hocine Zaidi, Hugo Weclawiak, Hugues Flodrops, Huseyin Karaaslan, Ibrahim Haskour, Ihssen Belhadj, Imad Almoubarak, Imad Haddad, Ines Castellano, Ines Ferrandiz, Ioana Daniliuc, Ioana Darie, Ioana Enache, Ionut Prunescu, Irenee Djiconkpode, Irina Shahapuni, Isabelle Bouchoule, Isabelle Devriendt, Isabelle Kazes, Isabelle Kolb, Isabelle Landru, Isabelle Poli, Isabelle Rey, Isabelle Segalen, Isabelle Selcer, Isabelle Vernier, Isabelle Vrillon, Ismahane Guenifi, J. Dominique Gheerbrandt, Jacky Potier, Jacques Becart, Jacques Cledes, Jacques Ducros, Jacques Duvic, Jacques Fourcade, Jacques Gaultier, Jacques Jurine, Jacques Lebleu, Jacques Ollier, Jacques Ibsen Charles, Jamal Yazji, Janette Mansour, Jean Arnautou, Jean Brocard, Jean Carolfi, Jean Montoriol, Jean Baptiste Gouin, Jean Bernard Palcoux, Jean Christophe Bendini, Jean Claude Aldigier, Jean Claude Alphonse, Jean Daniel Delbet, Jean Francois Bonne, Jean Francois Cantin, Jean Francois De Fremont, Jean Francois Dessassis, Jean Francois Subra, Jean Francois Valentin, Jean Francois Verdier, Jean Jacques Dion, Jean Jacques Haultier, Jean Jacques Montseny, Jean Louis Bacri, Jean Louis Bouchet, Jean Luc Mahe, Jean Marc Chalopin, Jean Marc Gabriel, Jean Marc Hurot, Jean Marc Lanau, Jean Marie Batho, Jean Marie Coulibaly, Jean Michel Hardin, Jean Michel Marc, Jean Michel Poux, Jean Michel Rebibou, Jean Michel Tivollier, Jean Noel Ottavioli, Jean Paul Faucon, Jean Paul Imiela, Jean Paul Jaulin, Jean Paul Masselot, Jean Paul Ortiz, Jean Philippe Bourdenx, Jean Philippe Devaux, Jean Philippe Hammelin, Jean Pierre Rivory, Jean Pierre Wauquier, Jean Rene Larue, Jean Rene Mondain, Jean Sebastien Borde, Jean Simon Virot, Jean Yves Bosc, Jedjiga Achiche, Jennifer Parasote, Jeremie Diolez, Jerome Harambat, Jerome Potier, Jerome Sampol, Jihad Mustel, Jean Jacques Lefevre, Jocelyne Maurizi, Joel Gamberoni, Joelle Claudeon, Joelle Terzic, Joffrey Rogol, Johnny Sayegh, Jorge Cardozo, Jose Brasseur, Jose Guiserix, Joseph Barsumau, Julie Albaret, Julie Beaume, Julie Sohier Attias, Julien Dehay, Julien Hogan, Julien Journet, Julien Ott, Juliette Baleynaud, Justine Bacchetta, Justine Faucher, Kamel Yousfi, Karim Dardim, Karine Clabault, Karine Moreau, Kedna Thomas, Khaled Sirajedine, Khalil Chedid, Khalil El Kaeoui, Khalil El Karoui, Khedidja Bouachi, Kheira Hue, Khuzama El Nasser, Kodso Akposso, Kristian Kunz, Krzysztof Bijak, Lilia Kihal, L. Rasoloarijaona, Laid Harbouche, Larbi Bencheikh, Larbie Lamriben, Latifa Hanafi, Laura Braun Parvez, Laure Champion, Laure Croze, Laure Eprinchard, Laure Patrier, Laurence Nicolet, Laurence Vrigneaud, Laurent Duflot, Leandre Mackaya, Leila Chenine, Leon Odry, Lili Taghipour Tamiji, Lilia Antri Bouzar, Liliane Ngango Nga Messi, Lionel Le Mouellic, Lise Mandart, Lise Weis, Lise Marie Pouteau, Lora Georgieva, Lorita Vitanova, Lotfi Chalabi, Luc Delvallez, Luc Fromentin, Luc Marty, Luc Monjot, Luciana Spataru, Lucie Bessenay, Lucie Boissinot, Lucie Wajsbrot, Lucien Rakoff, Ludivine Lebourg, Lydie Perez, Lyliane Lafage, Lynda Azzouz, Madeleine Dumoulin, Messaoud Ouziala, Maan Joseph, Mabrouk Brahimi, Maeva Wong Fat, Magalie Fort, Magued Nakhla, Mahdi Abtahi, Mahen Albadawy, Mahmoud Alouach, Mahmoud Mezghani, Maite Daroux, Maklouf Boukelmoune, Malek Dhib, Malik Touam, Malina Dubau, Mamadou Balde, Man Nguyen Khoa, Manfred Ismer, Manolie Mehdi, Manon Laforet, Marc Bouiller, Marc Eugene, Marc Fila, Marc Hazzan, Marc Kribs, Marc Ladriere, Marc Lebot, Marc Padilla, Marc Souid, Marcel Marraoui, Maren Burbach, Maria Manescu, Maria Eugenia Noguera Gonzalez, Mariana Revenco, Marianne Terrasse, Marie Essi, Marie Alice Macher, Marie Beatrice Nogier, Marie Cecile Cazin, Marie Christine Schweitzer Camoin, Marie Christine Thouret, Marie Claude Hannaert, Marie France Servel, Marie Helene Chabannier, Marie Jeanne Coudert Krier, Marie Noelle Catoliquot, Marie Paule Guillodo, Marie Sophie Gavard, Marie Xaviere Vairon Codaccioni, Marina Rabec, Marine Freist, Marion Gauthier, Marion Lemaire, Marion Mehrenberger, Marion Venot, Marios Pongas, Marlene Beaubrun Diant, Martial Levannier, Martine Bertaux, Mathieu Jablonski, Mathieu Sacquepee, Mathilde Dargelos, Mathilde Lemoine, Mathilde Tamain, Matthieu Monge, Matthieu Reberolle, Maud Cousin, Maud Francois, Maurice Baron, Maxime Hoffmann, Maxime Ingwiller, Maxime Touzot, Mederick Mohajer, Mehadji Maaz, Melanie Hanoy, Melanie Marroc, Melodie Cuny, Menno Van Der Straaten, Mf. Serveaux, Michel Basteri, Michel Fen Chong, Michel Hecht, Michel Massad, Michel Normand, Michel Olmer, Michel Tolani, Michel Tsimaratos, Michele Hemery, Michele Kessler, Miguel Esposito, Milad Shenouda, Mimi Kareche, Mina Khalili, Mirella Diaconita, Mohamad Khair Rifard, Mohamed Aladib, Mohamed Belmouaz, Mohamed Brahim, Mohamed Diouani, Mohamed Fodil Cherif, Mohamed Jamali, Mohamed Maghlaoua, Mohamed Meddeb, Mohamed Ramdane, Mohamed Rifaat, Mohamed Sharifull Islam, Mohamed Adnan Abbade, Mokhtar Amrandi, Mokhtar Chawki, Monica Ciobotaru, Monica Indrieis, Monique Chanas, Monique Hoarau, Monzer Tomeh, Moufida Bellou, Mouloud Bouzernidj, Mounia Ammor, Mounir Guergour, Mountassir Benzakour, Mourad Hachicha, Moussa Coulibaly, Mustafa Smati, Mustapha Al Morabiti, Mustapha Amirou, Myriam Isnard, Myriam Pastural, Myriam Pujo, Nourredine Boumendjel, Nabil Majbri, Nabila Goumri, Nadege Mingat, Nader Bassilios, Nadia Kerkeni, Nadia Sedrati, Nadia Soltani, Nadine Maroun, Nadine Neyrat, Nahn Luang, Najeh El Esper, Naji Ammar, Nasredine Ghali, Nasser Hamdini, Natacha Noel, Natacha Potelune, Nathalie Maisonneuve, Nathalie Pertuiset, Nathalie Raynal, Nathalie Vittoz, Nazim Terki, Nelly Castin, Nestor Nankeu, Nicolas Bouvier, Nicolas Keller, Nicolas Legros, Nicolas Peters, Nicolas Quirin, Nicole Lefrancois, Nicole Monnier, Nicole Rance, Niels Bruckmann, Noel Mertens, Nolwenn Lorcy, Olivia Gilbert, Olivier Coldefy, Olivier Drouineau, Olivier Dunand, Olivier Fritz, Olivier Imhoff, Olivier Kourilsky, Olivier Lavelle, Olivier Papin, Olivier Roques, Ophelie Le Maner, Oussamah Fikri Benbrahim, Pablo Antonio Erina Torres, Pablo Antonio Urena Torres, Paolo Malvezzi, Pascal Bindi, Pascal Cluzel, Pascal Fontanier, Pascal Wheatley, Pascale Depraetre, Pascale Dubosq, Pascale Halin, Pascale Sebahoun, Pascale Siohan, Pascale Testevuide, Patrice Deteix, Patrice Nolen, Patricia Hue, Patricia Lemarchand, Patrick Donnadieu, Patrick Fievet, Patrick Fohrer, Patrick Francais, Patrick Giraud, Patrick Hallonet, Patrick Henri, Patrick Michaut, Patrick Niaudet, Patrick Pauly, Patrick Thomas, Patrik Deleaval, Paul Finielz, Paul Stroumza, Paule Hardy Yverneau, Pauline Caillard, Pedro Palacin, Perrine Aubertin, Philippe Attias, Philippe Chauveau, Philippe Coindre, Philippe Coste, Philippe Dubot, Philippe Fournier, Philippe Hiernaux, Philippe Jousset, Philippe Lan Yue Wah, Philippe Lang, Philippe Le Cacheux, Philippe Martin Dupont, Philippe Michel, Philippe Mirgaine, Philippe Moriniere, Philippe Nicoud, Philippe Rieu, Philippe Rousseau, Philippe Sporer, Philippe Thorel, Philippe Vanhille, Philippe Vigeral, Philippe Zaoui, Pierre Bataille, Pierre Brignon, Pierre Filipozzi, Pierre Housset, Pierre Peyronnet, Pierre Ramperez, Pierre Vautrin, Pierre Alexandre Michel, Pierre Francois Westeel, Pierre Louis Carron, Pierre Yves Durand, Pierrot Parent, Piotr Seniuta, François Kuentz, Rabah Fraoui, Rachel Tetaz, Rachid Amaria, Rachid Bourouma, Rachid Djeffal, Rachida Nebbad, Radia Allal, Radu Dimulescu, Rafaat Boustani, Rafik Mesbah, Raifat Makdassi, Raji Diab, Raluca Puslenghea, Raoul Roura, Rateb Khayat, Raymond Azar, Raymond Frayssinet, Regine Monkam, Rehouni Boulahrouz, Remi Boudet, Renato Demontis, Renaud Gansey, Rene Cuvelier, Renee Schmitt, Reschad Noordally, Reynald Binaut, Rezkallah Latif, Richard Dufresne, Richard Montagnac, Richard Reade, Robert Genin, Robert Novo, Rocsana Fickl, Roger Dufresne, Roger Magnol, Roland Issautier, Romain Mortelette, Ronan Delaval, Ronan Lohro, Roseline M'barga, S. Beau, Clémentine Dupuis, Marie Jacques Vidil, Sabria Hacini, Said Dahmoune, Saliha Lekhal, Salima Ahriz Sakso, Salima Saksi, Salvatore Citarda, Samir Boubenider, Samuel Kassis, Sandra Verhille, Sandrine Genestier, Sandrine Muller, Saoussen Krid, Sarah Richter, Sebastien Delbes, Sebastien Mailliez, Sebastien Veillon, Sébastien Nony, Seddick Benarbia, Severine Beaudreuil, Sidi Ali Benyaghla, Simon Duquennoy, Simona Baluta, Simona Boncila, Sonia Mzoughi, Sonia Ribal, Sophie Acamer, Sophie Chauvet, Sophie Girerd, Sophie Ozenne, Sophie Parahy, Sophie Rubens Duval, Sophie Taque, Soraya Menouer, Soumaya Chargui, Stanislas Bataille, Stephane Barbier, Stephane Billion, Stephane Roueff, Stephane Torner, Stephane Jean Martin, Stephanie Coupel, Sylvie Cloarec, Sylvie Lavaud, Sylvie Leou, T. Chatelet, Tania Onesta, Tassadit Benhabib, Tayeb Bensalem, Theodora Dimulescu, Theophile Sawadogo, Thibault Dolley Hitze, Thierry Baranger, Thierry Boudemaghe, Thierry Hannedouche, Thierry Krummel, Thierry Milcent, Thomas Dervaux, Thomas Guincestre, Thomas Kofman, Thomas Raphael, Thomas Sadreux, Tim Ulinski, Tiphaine Guyon Roger, Tomas Serrato, Tomek Kofman, Tony Wong, Toufik Boubia, Ubald Assogba Gbindoun, Usama Khuzaie, Valerie Caudwell, Valerie Chatelet, Valerie Crougneau, Valerie De Precigout, Valerie Drouillat, Valerie Galantine, Valerie Granveau Hugot, Valerie Leroy, Veronique Boubia, Veronique Falque, Veronique Fournier, Veronique Queron, Veronique Viviani, Victor Gueuttin, Victor Panescu, Victorio Menoyo Calonge, Viet Nguyen, Vincent Allot, Vincent Delattre, Vincent Leduc, Vincent Pradier, Violaine Emal Aglae, Viorica Badulescu, Virginia Molina, Virginie Besson, Virginie Chaigne, Waddah Jaber, Wael Boudi, Wael El Haggan, Wen Qin Guillon, Wided Tabbi Aneni, William Hanf, Wladimir Kohn, Xavier Bellenfant, Xavier Moreau Gaudry, Yahsou Delmas, Yannick Knefati, Yannick Saingra, Yannick Tirolien, Youssef Mann, Yvan Brunak, Yves Dimitrov, Yves Doussy, Yves Tanter, Zaid Benabid, Zaara Soltani, Zacharia Boukerroucha, Zafer Takla, Zana Ramanantsialonina, Zara Dickson, Zead Tubail, Zoe Koochaki Pour, Zohra Boukhalfa, Zohra Jacquot, Agence de la biomédecine [Saint-Denis la Plaine], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Caen Normandie (UNICAEN), Normandie Université (NU), CALYDIAL Vienne, Partenaires INRAE, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Armand Trousseau [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM), Service de diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Diabétologie [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodialysis, Home, Disease, MESH: COVID-19 / therapy, registry, Ambulatory Care Facilities, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Aged, 80 and over, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, 80 and over, Prevalence, covid, dialysis, epidemiology, mortality, Aged, Aged, 80 and over, COVID-19, Case-Control Studies, Critical Care, Female, France, Humans, Incidence, Middle Aged, Patient Acuity, Protective Factors, Registries, Renal Dialysis, SARS-CoV-2, Sex Factors, Hypoalbuminemia, MESH: France / epidemiology, education.field_of_study, Incidence (epidemiology), 3. Good health, MESH: COVID-19 / epidemiology, Nephrology, Hemodialysis, medicine.medical_specialty, Population, Lower risk, Article, 03 medical and health sciences, MESH: Sex Factors, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Renal Dialysis / statistics & numerical data, education, Dialysis, Vascular disease, business.industry, medicine.disease, Former Smoker, MESH: Critical Care / statistics & numerical data, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Home, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Hemodialysis, Home / statistics & numerical data
Abstract: The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract
Published: 2020

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

Author: Noëlle Brulé, Emmanuel Canet, Morgane Péré, Fanny Feuillet, Maryvonne Hourmant, Karim Asehnoune, Bertrand Rozec, Agnes Duveau, Laurent Dube, Marc Pierrot, Stanislas Humbert, Patrice Tirot, Jean-Marc Boyer, Laurent Martin-Lefevre, François Labadie, René Robert, Thierry Benard, Thomas Kerforne, Antoine Thierry, Olivier Lesieur, Jean-François Vincent, Mathieu Lesouhaitier, Raphaelle Larmet, Cecile Vigneau, Angelique Goepp, Pierre Bouju, Charlotte Quentin, Pierre-Yves Egreteau, Olivier Huet, Anne Renault, Yannick Le Meur, Jean-Christophe Venhard, Mathias Buchler, Olivier Michel, Marie-Hélène Voellmy, Fabien Herve, David Schnell, Anne Courte, Denis Glotz, Lucile Amrouche, Marc Hazzan, Nassim Kamar, Valerie Moal, Jeremy Bourenne, Moglie Le Quintrec-Donnette, Emmanuel Morelon, Thierry Boulain, Philippe Grimbert, Anne Elisabeth Heng, Pierre Merville, Aude Garin, Christian Hiesse, Brice Fermier, Christiane Mousson, Charlotte Guyot-Colosio, Nicolas Bouvier, Jean-Philippe Rerolle, Antoine Durrbach, Sarah Drouin, Sophie Caillard, Luc Frimat, Sophie Girerd, Laetitia Albano, Lionel Rostaing, Dominique Bertrand, Alexandre Hertig, Pierre-Francois Westeel, Florent Montini, Eric Delpierre, Dider Dorez, Eric Alamartine, Carole Ouisse, Veronique Sebille, and Jean Reignier
Subjects: Graft Survival, Humans, Multicenter Studies as Topic, Transplants, Hypothermia, General Medicine, Kidney, Kidney Transplantation, Tissue Donors, Randomized Controlled Trials as Topic
Abstract: IntroductionExpanded-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 analysisHYPOREME 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 disseminationThe 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 numberNCT03098706.
Published: 2022

43. Ischémie reperfusion en transplantation rénale

Author: Lea Dufour, Aurélie Robin, Maroua Ferhat, Thierry Hauet, Frédéric Favreau, Antoine Thierry, Jean Michel Goujon, Sofiane Inal, André Herbelin, Jean-Marc Gombert, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, CCSD, Accord Elsevier, and Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Gynecology, medicine.medical_specialty, business.industry, Sterile inflammation, [SDV]Life Sciences [q-bio], Perfusion machine, 030232 urology & nephrology, Cold ischemia, Oxydative stress, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Nephrology, Danger pattern, Medicine, business, Signal danger
Abstract: Resume Le syndrome d’ischemie reperfusion est un phenomene incontournable en transplantation renale. Il associe des processus lesionnels d’origines biochimiques lies au stress oxydant et immunologiques en rapport avec le recrutement et l’activation de cellules de l’immunite innee. Les lesions histologiques associent notamment une necrose tubulaire aigue et un œdeme interstitiel, qui peuvent evoluer vers une fibrose interstitielle. L’importance de ces lesions depend notamment des caracteristiques du donneur (âge, donneur a criteres elargis, etc.) et de la duree d’ischemie froide. A court terme, les consequences deleteres du syndrome d’ischemie reperfusion se traduisent principalement par une reprise differee de la fonction renale. A plus long terme, la duree d’ischemie froide a aussi un impact sur la survie du greffon. Les modeles precliniques, en particulier murins et porcins, ont permis de nombreuses avancees dans la comprehension physiopathologique du phenomene d’ischemie reperfusion. Le porc, par sa proximite anatomique renale avec l’homme, est un modele pertinent pour l’evaluation de molecules administrees chez le donneur ou le receveur, ou encore additives aux solutions de conservation. Enfin, differentes strategies de reanimation du donneur et de perfusion du greffon renal peuvent etre etudiees chez le porc. Chez l’homme, la prevention du syndrome d’ischemie reperfusion fait l’objet de recherches cliniques a travers le conditionnement du donneur, les molecules additives aux solutions de conservation, les modalites de perfusion du greffon renal ou encore les molecules administrees chez le receveur. Dans l’attente d’avancees significatives dans ces differentes voies de recherches, l’objectif d’une duree d’ischemie froide courte reste primordial.
Published: 2020

44. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort

Author: Rebecca Sberro, Antoine Thierry, Johan Noble, Anne Grall-Jezequel, Paolo Malvezzi, Johnny Sayegh, Nicolas Bouvier, Sophie Caillard, Florian Terrec, Maïté Jauréguy, Cyril Garrouste, Leonard Golbin, Eric Thervet, Thomas Jouve, Lionel Rostaing, Jean-Philippe Rerolle, Nathalie Chavarot, Philippe Gatault, Charlotte Colosio, Bénédicte Janbon, Dominique Bertrand, and Isabelle Etienne
Subjects: medicine.medical_specialty, 030232 urology & nephrology, Renal function, kidney transplantation, lcsh:Medicine, 030230 surgery, Pneumocystis pneumonia, Belatacept, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Cumulative incidence, tacrolimus, Kidney transplantation, belatacept, business.industry, Incidence (epidemiology), pneumocystis pneumonia, lcsh:R, General Medicine, opportunistic infections, medicine.disease, Cohort, business, CMV infection, medicine.drug, Cohort study
Abstract: Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13&ndash, 431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/&minus, 13 months. OPIs developed in 42(9.3%) patients after 14 +/&minus, 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%, p &lt, 0.001, and 11.6% vs. 2.4%, p &lt, 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person&ndash, years. Incidence of CMV disease was 2.8/100 person&ndash, years, of pneumocystis pneumonia 1.6/100 person&ndash, years, and of aspergillosis 0.2/100 person&ndash, years. Multivariate analyses showed that estimated glomerular filtration (eGFR) &lt, 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 &minus, 10.3), p &lt, 0.001). The incidence of EBV DNAemia was 17.3 events /100 person&ndash, years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/&minus, 18 mL/min/1.73 m2 to 42.2 +/&minus, 18 mL/min/1.73 m2 (p &lt, 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.
Published: 2020

45. [Ischemia-reperfusion injury after kidney transplantation]

Author: Léa, Dufour, Maroua, Ferhat, Aurélie, Robin, Sofiane, Inal, Frédéric, Favreau, Jean-Michel, Goujon, Thierry, Hauet, Jean-Marc, Gombert, André, Herbelin, and Antoine, Thierry
Subjects: Perfusion, Mice, Swine, Reperfusion Injury, Animals, Humans, Organ Preservation, Kidney, Kidney Transplantation
Abstract: Ischemia-reperfusion injury is an inescapable phenomenon in kidney transplantation. It combines lesional processes of biochemical origin associated with oxydative stress and of immunological origin in connection with the recruitment and activation of innate immunity cells. Histological lesions associate acute tubular necrosis and interstitial œdema, which can progress to interstitial fibrosis. The extent of these lesions depends on donor characteristics (age, expanded criteria donor, etc.) and cold ischemia time. In the short term, ischemia-reperfusion results in delayed recovery of graft function. Cold ischemia time also impacts long-term graft survival. Preclinical models, such as murine and porcine models, have furthered understanding of the pathophysiological mechanisms of ischemia-reperfusion injury. Due to its renal anatomical proximity to humans, the porcine model is relevant to assessment of the molecules administered to a donor or recipient, and also of additives to preservation solutions. Different donor resuscitation and graft perfusion strategies can be studied. In humans, prevention of ischemia-reperfusion injury is a research subject as concerns donor conditioning, additive molecules in preservation solutions, graft reperfusion modalities and choice of the molecules administered to the recipient. Pending significant advances in research, the goal is to achieve the shortest possible cold ischemia time.
Published: 2020

46. P1757RITUXIMAB FOR RECURRENCE OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS AFTER KIDNEY TRANSPLANTATION: RESULTS OF A NATIONWIDE STUDY

Author: Matthias Büchler, Nicolas Maillard, Nicolas Bouvier, Céline Lambert, Dany Anglicheau, Camille Lanaret, Vincent Pernin, Clarisse Greze, Coralie Poulain, Audard Vincent, Antoine Thierry, Paolo Malvezzi, Rérolle Jean-Philippe, Nassim Kamar, Didier Ducloux, Anne Elisabeth Heng, Lionel Couzi, Sophie Ohlmann, Dominique Bertrand, Betoul Schvartz, Leonard Golbin, Cyril Garrouste, and Frank Martinez
Subjects: Transplantation, medicine.medical_specialty, business.industry, Primary Focal Segmental Glomerulosclerosis, medicine.medical_treatment, ADRENAL CORTICOSTEROIDS, Urology, medicine.disease, Hypogammaglobulinemia, Study report, Nephrology, Medicine, Rituximab, Plasmapheresis, business, Survival rate, Kidney transplantation, medicine.drug
Abstract: Background and Aims The indication of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation (KT) remains controversial. The objective of our study was to evaluate the benefit and tolerability of adding RTX to the standard of care (SOC) comprising plasmapheresis (PP), corticosteroids, and high-dose anticalcineurins for the treatment of FSGS recurrence after KT. Method This retrospective, multicenter study reports on 148 patients, transplanted between 31 December 2004 and 31 December 2018, aged 39.9 + 13.4 years, who developed FSGS recurrence at 7 [3–23] days. In all 109 patients received a SOC (Group 1). RTX was introduced in this group after more than 28 days of SOC for failure or for therapeutic intensification (n = 19, Group 1a), or for early discontinuation of PP (n = 12, Group 1b); 39 patients received RTX associated at the outset with SOC (Group 2). Results We observed 46.6% complete remission (CR) and 33.1% partial remission (PR). Ten-year graft survival was 65.6% [51.4–76.6] and 13.4% [3.4–30.0] in responders and non-responders respectively. There was no difference in CR + PR rate between G1 (82.5%) and G2 (71.8%), p = 0.08, confirmed by propensity score +4.3% (95% CI [−9.0%-17.5%], p = 0.53). Following addition of RTX (Group 1a), we observed a CR rate of 26.3% and a PR rate of 31.6%. Patients with and without RTX experienced similar rejection rates (18.6% and 28.2%, p = 0.17) and infection rates (71.4% and 79.5%, p = 0.40). In multivariate analysis, the infections were associted with hypogammaglobulinemia Conclusion Rituximab could be used in cases of SOC failure or in remission patients for early weaning of plasmapheresis, without increasing infectious risk.
Published: 2020

47. Adherence profiles in kidney transplant patients: Causes and consequences

Author: J.P. Rerolle, Claire Villeneuve, Pierre Marquet, Laure Esposito, Lionel Couzi, Antoine Thierry, Pierre-François Westeel, Annick Rousseau, Mathias Büchler, Caroline Monchaud, Nassim Kamar, Marie Essig, Isabelle Etienne, Centre régional de pharmacovigilance, de pharmaco-épidémiologie et d'information sur les médicaments [Limoges], CHU Limoges, Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation (FHU SUPORT), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours-Université de Tours, Faculté de Pharmacie [Limoges], Université de Limoges (UNILIM), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), 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), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Amiens-Picardie, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CCSD, Accord Elsevier, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT)-Université de Tours (UT)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), and Université de Tours (UT)-Université de Tours (UT)
Subjects: medicine.medical_specialty, Longitudinal study, [SDV]Life Sciences [q-bio], Kidney transplant, Medication Adherence, Kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, medicine, Humans, 030212 general & internal medicine, Longitudinal Studies, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, Immunosuppressant, business.industry, 030503 health policy & services, General Medicine, Middle Aged, medicine.disease, Mental health, 3. Good health, Transplantation, [SDV] Life Sciences [q-bio], Adherence, Quality of Life, Transplant patient, 0305 other medical science, business, Immunosuppressive Agents
Abstract: International audience; Objective: Adherence is a dynamic phenomenon and a critical determinant of transplant patients outcome. The objective of this longitudinal study was to explore adherence in kidney transplant patients followed-up for up to three years after transplantation.Methods: Adherence was repeatedly estimated using the Morisky-Green-Levine 4-Item Medication Adherence Scale, in two successive cohorts of 345 (EPIGREN) and 367 (EPHEGREN) kidney transplant recipients. Mixed effect modeling with latent processes and latent classes was used to describe adherence time-profiles.Results: Two latent classes were identified. The adherent class represented 85% of the patients. Patients of the poorer-adherence class displayed a lower adherence at one month (p50 years, fewer depression episodes (5% vs. 13%, p = 0.001) and a better mental health component of quality of life (MCS-SF36 47 ± 11 vs. 41 ± 13, p = 0.015). Survival without acute rejection episodes was longer in the adherent class (p = 0.004).Conclusions: The risk of poor adherence in renal transplant patients can be detected as early as one month post-transplantation, using appropriate and easy tools adapted to routine monitoring.Practice implications: An early focus on vulnerable patients should allow putting into place actions in order to reduce the risk of poor outcome related to poor adherence.
Published: 2020

48. The GETUG SEMITEP Trial: De-Escalating Chemotherapy in Good-Risk Metastatic Seminoma Based on Early FDG-PET/CT

Author: Sophie Abadie-Lacourtoisie, Emmanuelle Bompas, Carole Helissey, Christine Abraham, Christophe Massard, M. Texier, Sylvain Ladoire, Serena Grimaldi, Gwenaelle Gravis, Lionel Geoffrois, Christine Chevreau, Karim Fizazi, Stéphane Culine, Yohann Loriot, Hakim Mahammedi, Antoine Thierry-Vuillemin, Marine Gross-Goupil, Aude Flechon, Brigitte Laguerre, and Philippe Barthélémy
Subjects: medicine.medical_specialty, business.industry, Informed consent, General surgery, Metastatic seminoma, Ethics committee, Medicine, Stage iib, Fdg pet ct, Good prognosis, NOT EVALUABLE, business, Trial registration
Abstract: Background: Negative positron emission tomography/computed tomography (FDG-PET/CT) predicts the absence of viable seminoma cells in residual disease after chemotherapy in men with metastatic seminoma. In this study, we assessed whether men with good-prognosis metastatic seminoma could be treated with 2 cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) based on a negative interim FDG-PET/CT, thereby limiting the burden of treatment and toxicity. Methods: In this non-randomised, multicentre, phase 2 trial (NCT01887340), we enrolled patients with good-prognosis metastatic seminoma (stage IIB, IIC and III with a good prognosis according to the Medical Research Council classification). All patients with baseline-positive FDG-PET/CT received EP for two cycles. After completing the first two cycles, the patients underwent a second FDG-PET/CT scan to assess the response between days 17 and 20. Patients with persistent positive FDG-PET/CT (based on local review) proceeded directly to two additional EP cycles (for a total of 4 cycles); those who achieved FDG-PET/CT negativity received only one cycle of CARBO AUC=7. The primary outcome was the proportion of patients with a negative FDG-PET/CT on interim assessment who received de-escalating chemotherapy. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Findings: Between June 2013 and July 2017, 102 patients were enrolled in the study. Three patients were deemed ineligible or not evaluable; thus, 99 patients received treatment. After the first 2 EP cycles, FDG-PET/CT was available in 98 pts. Overall, 67 patients (68.4%; 95% CI: 58.2-77.4) had a negative FDG-PET/CT and proceeded to a single CARBO cycle. Twenty-seven patients (27.6%; 95% CI: 19.0-37.5) still had a positive FDG-PET/CT after 2 EP cycles; overall, 31 patients received two additional cycles of EP. After a median follow-up of 39.4 months, only 9 patients relapsed (3/31 in the EP group and 6/67 in the CARBO group). The 3-year PFS rate was 90.0% (95% CI: 74.4-96.5) in the EP group and 90.2% (95% CI: 80.2-95.5) in the CARBO group. One patient died from sepsis during the first two cycles. Interpretation: De-escalating treatment based on a negative FDG-PET/CT after 2 cycles of chemotherapy appears to be safe and feasible in most men with good-prognosis metastatic seminoma. Trial Registration: The trial was registered at ClinicalTrials.gov (NCT01887340). Funding Statement: Programme Hospitalier de Recherche Clinique (PHRC) from the Institut National du Cancer (INCA), France. Declaration of Interests: Yohann Loriot: Dr Loriot reports grants from CELSIUS, grants from SANOFI, grants and personal fees from JANSSEN, personal fees from ASTELLAS, grants and personal fees from MSD, personal fees from ASTRA ZENECA, personal fees from BMS, personal fees from SEATTLE GENETICS, personal fees from PFIZER, personal fees from ROCHE, personal fees from IMMUNOMEDICS outside the submitted work; Matthieu Texier: Dr Texier has nothing to disclose; Stephane Culine: Dr Culine has nothing to disclose; Aude Flechon: Dr Flechon has nothing to disclose; Antoine Thierry-Vuillemin: Dr Thierry-Vuillemin reports personal fees from Pfizer, Astra Zeneca, Sanofi, Janssen, Novartis, Ipsen, Roche, Bristol-Myers Squibb, MSD, Astellas; Gwenaelle Gravis: Dr Gravis has nothing to disclose; Lionel Geoffrois: Dr Geoffrois reports personal fees from BMS, personal fees from NOVARTIS, personal fees and other from IPSEN, personal fees from PFIZER, personal fees from A-Z, personal fees from MSD, outside the submitted work; Christine Chevreau: Dr Chevreau has nothing to disclose; Marine Gross-Goupil: Dr Gross-Goupil has nothing to disclose; Philippe Barthelemy: Dr Barthelemy reports advisory board and travels from BMS, advisory board from MSD, advisory board and travels from IPSEN, advisory board from EUSAPHARMA, advisory board from NOVARTIS, advisory board and travels from ROCHE, advisory board and travels from PFIZER, advisory board and travels from JANSSEN, advisory board from ASTELLAS, outside the submitted work; Emmanuelle Bompas: Dr Bompas has nothing to disclose; Hakim Mahammedi : Dr Mahammedi reports personal fees from Bayer, personal fees from BMS , personal fees from Roche , personal fees from MSD , personal fees from Astra Zeneca , personal fees from Sanofi , personal fees and other from Janssen , personal fees and other from Astellas , outside the submitted work; Brigitte Laguerre: Dr Laguerre has nothing to disclose; Sophie Abadie Lacourtoisie : Dr Abadie Lacourtoisie has nothing to disclose; Carole Helissey: Dr Helissey reports personal fees from Sanofi, Janssen, Astellas and Roche; Sylvain Ladoire : Dr Ladoire reports grants from Pfizer, grants from Astellas, grants from Roche , grants from Novartis , grants from BMS, grants from Ipsen, grants from Janssen, grants from Sanofi, outside the submitted work; Christine Abraham: Dr Abraham has nothing to disclose; Christophe Massard: Dr Massard reports Consultant/Advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion; Serena Grimaldi: Dr Grimaldi has nothing to disclose; Karim Fizazi: Dr Fizazi reports Consultant/Advisory fees from Amgen, Astellas, Bayer, Jansen, Takeda, Sanofi, Orion, Essa, Genentech, Astra Zeneca, Clovis. Ethics Approval Statement: Written informed consent was obtained from all the patients. The study was approved by the ethics committee of Ile de France II (N°2013-02-12 MS1) and the French Healthcare Agency (N°130253B-12).
Published: 2020

49. The FcγRIIIA-158 VV genotype increased the risk of post-transplant lymphoproliferative disorder in T-cell-depleted kidney transplant recipients – a retrospective study

Author: Christophe Mariat, Emmanuel Morelon, Nassim Kamar, Valérie Gouilleux-Gruart, Marc Hazzan, Nicolas Bouvier, Cécile Vigneau, Marc Ladrière, Laurie Lajoie, Jean-Michel Halimi, Sophie Caillard, David Martinez, Marie Essig, Stéphanie Moyrand, Matthias Büchler, Philippe Gatault, Gilles Thibault, Pierre Marquet, Antoine Thierry, Pierre-François Westeel, Jana Stojanova, Isabelle Etienne, Pierre Merville, Cellules Dendritiques, Immunomodulation et Greffes [Tours] (UFR de Médecine - EA4245), Université Francois Rabelais [Tours], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), CHU Limoges, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Picardie Jules Verne (UPJV), 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010), 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), and Université de Tours
Subjects: medicine.medical_specialty, Genotype, gene polymorphism, T cell, T-Lymphocytes, post-transplant lymphoproliferative disorder, T lymphocyte-depleting antibodies, 030230 surgery, Post-transplant lymphoproliferative disorder, Organ transplantation, 03 medical and health sciences, 0302 clinical medicine, Fc gamma receptor IIIA, medicine, Animals, Retrospective Studies, Transplantation, biology, business.industry, Receptors, IgG, medicine.disease, Kidney Transplantation, Allotype, Lymphoproliferative Disorders, 3. Good health, medicine.anatomical_structure, surgical procedures, operative, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Polyclonal antibodies, Immunology, biology.protein, 030211 gastroenterology & hepatology, Gene polymorphism, Rabbits, solid-organ transplantation, Antibody, business
Abstract: International audience; Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication in organ transplant recipients. The use of T lymphocyte-depleting antibodies (TLDAb), especially rabbit TLDAb, contributes to PTLD, and the V158F polymorphism of Fc gamma receptor IIIA (FcγRIIIA) also named CD16A could affect the concentration–effect relationship of TLDAb. We therefore investigated the association of this polymorphism with PTLD in kidney transplant recipients. We characterized the V158F polymorphism in two case–control cohorts (discovery, n = 196; validation, n = 222). Then, we evaluated the binding of rabbit IgG to human FcγRIIIA-158V and FcγRIIIA-158F. The V158F polymorphism was not linked to PTLD in the overall cohorts, but risk of PTLD was increased in VV homozygous recipients receiving TLDAb compared with F carriers in both cohorts, especially in recipients receiving TLDAb without muromonab (discovery HR = 2.22 [1.03–4.76], P = 0.043, validation HR = 1.75 [1.01–3.13], P = 0.049). In vitro, we found that the binding of rabbit IgG to human NK-cell FcγRIIIA was increased when cells expressed the 158-V versus the 158-F allotype. While the 158-V allotype of human FcγRIIIA binds rabbit immunoglobulin-G with higher affinity, the risk of PTLD was increased in homozygous VV kidney transplant recipients receiving polyclonal TLDAb.
Published: 2020

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

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

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