195 results on '"A. Loupy"'
Search Results
2. A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk
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Stephen A. Williams, Rachel Ostroff, Michael A. Hinterberg, Josef Coresh, Christie M. Ballantyne, Kunihiro Matsushita, Christian E. Mueller, Joan Walter, Christian Jonasson, Rury R. Holman, Svati H. Shah, Naveed Sattar, Roy Taylor, Michael E. Lean, Shintaro Kato, Hiroaki Shimokawa, Yasuhiko Sakata, Kotaro Nochioka, Chirag R. Parikh, Steven G. Coca, Torbjørn Omland, Jessica Chadwick, David Astling, Yolanda Hagar, Natasha Kureshi, Kelsey Loupy, Clare Paterson, Jeremy Primus, Missy Simpson, Nelson P. Trujillo, and Peter Ganz
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General Medicine ,General Economics, Econometrics and Finance - Abstract
A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about 5000 proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death. The 27 proteins encompassed 10 biologic systems, and 12 were associated with relevant causal genetic traits. We independently validated results in 11,609 participants. Compared to a clinical model, the ratio of observed events in quintile 5 to quintile 1 was 6.7 for proteins versus 2.9 for the clinical model, AUCs (95% CI) were 0.73 (0.72 to 0.74) versus 0.64 (0.62 to 0.65), c -statistics were 0.71 (0.69 to 0.72) versus 0.62 (0.60 to 0.63), and the net reclassification index was +0.43. Adding the clinical model to the proteins only improved discrimination metrics by 0.01 to 0.02. Event rates in four predefined protein risk categories were 5.6, 11.2, 20.0, and 43.4% within 4 years; median time to event was 1.71 years. Protein predictions were directionally concordant with changed outcomes. Adverse risks were predicted for aging, approaching an event, anthracycline chemotherapy, diabetes, smoking, rheumatoid arthritis, cancer history, cardiovascular disease, high systolic blood pressure, and lipids. Reduced risks were predicted for weight loss and exenatide. The 27-protein model has potential as a “universal” surrogate end point for cardiovascular risk.
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- 2022
3. Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study
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Marc Raynaud, Solaf Al-Awadhi, Ivana Juric, Gillian Divard, Yannis Lombardi, Nikolina Basic-Jukic, Olivier Aubert, Laurence Dubourg, Ingrid Masson, Christophe Mariat, Dominique Prié, Vincent Pernin, Moglie Le Quintrec, Timothy S Larson, Mark D Stegall, Boris Bikbov, Piero Ruggenenti, Laurent Mesnard, Hassan N Ibrahim, Marie Bodilsen Nielsen, Arthur J Matas, Brian J Nankivell, Stan Benjamens, Robert A Pol, Stephan J L Bakker, Xavier Jouven, Christophe Legendre, Nassim Kamar, Byron H Smith, Hani M Wadei, Antoine Durrbach, Flavio Vincenti, Giuseppe Remuzzi, Carmen Lefaucheur, Andrew J Bentall, and Alexandre Loupy
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Adult ,Creatinine ,Humans ,Renal Insufficiency ,Chronic/diagnosis ,General Medicine ,Kidney ,Kidney Transplantation ,Glomerular Filtration Rate - Abstract
Objective To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. Design Development and validation study Setting 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). Participants 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. Main outcome measure The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. Results The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient’s creatinine level, age, and sex ( https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/ ). Conclusion A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. Trial registration ClinicalTrials.gov NCT05229939 .
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- 2023
4. Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering
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Aleksandar Senev, Maud Rabeyrin, Valérie Dubois, Dirk Kuypers, Olivier Thaunat, Jasper Callemeyn, Evelyne Lerut, Amaryllis H. Van Craenenbroeck, Elisabet Van Loon, Gillian Divard, T. Vaulet, Katrien De Vusser, Maarten Naesens, Ben Sprangers, Olivier Aubert, Maarten De Vos, Bart De Moor, Alexandre Loupy, and Marie-Paule Emonds
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business.industry ,Rand index ,General Medicine ,Computational biology ,030230 surgery ,medicine.disease ,Phenotype ,Data-driven ,Euclidean distance ,03 medical and health sciences ,0302 clinical medicine ,Categorization ,Nephrology ,Medicine ,Observational study ,030212 general & internal medicine ,business ,Cluster analysis ,Kidney transplantation - Abstract
Background Over the past decades, an international group of experts iteratively developed a consensus classification of kidney transplant rejection phenotypes, known as the Banff classification. Data-driven clustering of kidney transplant histologic data could simplify the complex and discretionary rules of the Banff classification, while improving the association with graft failure. Methods The data consisted of a training set of 3510 kidney-transplant biopsies from an observational cohort of 936 recipients. Independent validation of the results was performed on an external set of 3835 biopsies from 1989 patients. On the basis of acute histologic lesion scores and the presence of donor-specific HLA antibodies, stable clustering was achieved on the basis of a consensus of 400 different clustering partitions. Additional information on kidney-transplant failure was introduced with a weighted Euclidean distance. Results Based on the proportion of ambiguous clustering, six clinically meaningful cluster phenotypes were identified. There was significant overlap with the existing Banff classification (adjusted rand index, 0.48). However, the data-driven approach eliminated intermediate and mixed phenotypes and created acute rejection clusters that are each significantly associated with graft failure. Finally, a novel visualization tool presents disease phenotypes and severity in a continuous manner, as a complement to the discrete clusters. Conclusions A semisupervised clustering approach for the identification of clinically meaningful novel phenotypes of kidney transplant rejection has been developed and validated. The approach has the potential to offer a more quantitative evaluation of rejection subtypes and severity, especially in situations in which the current histologic categorization is ambiguous.
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- 2021
5. Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant Biopsies
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Thibaut Vaulet, Gillian Divard, Olivier Thaunat, Priyanka Koshy, Evelyne Lerut, Aleksandar Senev, Olivier Aubert, Elisabet Van Loon, Jasper Callemeyn, Marie-Paule Emonds, Amaryllis Van Craenenbroeck, Katrien De Vusser, Ben Sprangers, Maud Rabeyrin, Valérie Dubois, Dirk Kuypers, Maarten De Vos, Alexandre Loupy, Bart De Moor, and Maarten Naesens
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Graft Rejection ,phenotyping ,consensus clustering ,Biopsy ,Graft Survival ,kidney transplantation ,General Medicine ,Complement System Proteins ,chronic allograft rejection ,Kidney ,Allografts ,Kidney Transplantation ,machine learning ,Phenotype ,Nephrology ,Banff classification ,Humans ,biopsy ,Kidney Diseases - Abstract
BACKGROUND: No validated system currently exists to realistically characterize the chronic pathology of kidney transplants that represents the dynamic disease process and spectrum of disease severity. We sought to develop and validate a tool to describe chronicity and severity of renal allograft disease and integrate it with the evaluation of disease activity. METHODS: The training cohort included 3549 kidney transplant biopsies from an observational cohort of 937 recipients. We reweighted the chronic histologic lesions according to their time-dependent association with graft failure, and performed consensus k-means clustering analysis. Total chronicity was calculated as the sum of the weighted chronic lesion scores, scaled to the unit interval. RESULTS: We identified four chronic clusters associated with graft outcome, based on the proportion of ambiguous clustering. The two clusters with the worst survival outcome were determined by interstitial fibrosis and tubular atrophy (IFTA) and by transplant glomerulopathy. The chronic clusters partially overlapped with the existing Banff IFTA classification (adjusted Rand index, 0.35) and were distributed independently of the acute lesions. Total chronicity strongly associated with graft failure (hazard ratio [HR], 8.33; 95% confidence interval [CI], 5.94 to 10.88; P
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- 2022
6. Application of the iBox prognostication system as a surrogate endpoint in the TRANSFORM randomised controlled trial: proof-of-concept study
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Yoshihiko Watarai, Peter Bernhardt, Olivier Aubert, Titte Srinivas, Claudia Sommerer, Federico Oppenheimer, Mitchell L. Henry, Alexandre Loupy, Flavio Vincenti, Julio Pascual, H. Tedesco, Franco Citterio, Steve Chadban, Gillian Divard, and Christophe Legendre
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medicine.medical_specialty ,statistics & research methods ,Calcineurin Inhibitors ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Everolimus ,transplant medicine ,clinical trials ,Renal Medicine ,business.industry ,Surrogate endpoint ,General Medicine ,renal transplantation ,Mycophenolic Acid ,Kidney Transplantation ,Transplantation ,Calcineurin ,Clinical trial ,Regimen ,Medicine ,Fast track ,business ,Biomarkers ,medicine.drug - Abstract
ObjectivesDevelopment of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We applied a validated integrative risk-prognostication system integrative Box (iBox) as a surrogate endpoint to the TRANSFORM Study, a large randomised controlled trial, to project individual patient long-term kidney allograft survival from 1 year to 11 years after randomisation.DesignPost-hoc analysis of a randomised open-label controlled trial.SettingMulticentre study including 186 centres in 42 countries worldwide.Participants2037 de novo kidney transplant recipients.InterventionParticipants were randomised (1:1) to receive everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolic acid with standard-exposure CNI (MPA+sCNI).Primary outcome measureThe iBox scores were computed for each participant at 1 year after randomisation using functional, immunological and histological parameters. Individual long-term death-censored allograft survival over 4, 6 and 11 years after randomisation was projected with the iBox risk-prognostication system.ResultsOverall, 940 patients receiving EVR+rCNI and 932 receiving MPA+sCNI completed the 1-year visit. iBox scores generated at 1 year yielded graft survival prediction rates of 90.9% vs 92.1%, 87.9% vs 89.5%, and 80.0% vs 82.4% in the EVR+rCNI versus MPA+sCNI arms at 4, 6, and 11 years post-randomisation, respectively (all differences below the 10% non-inferiority margin defined by study protocol). Inclusion of immunological and histological Banff diagnoses parameters in iBox scores resulted in comparable and non-inferior predicted graft survival for both treatments.ConclusionsThis proof-of-concept study provides the first application of a validated prognostication system as a surrogate endpoint in the field of transplantation. The iBox system, by projecting kidney allograft survival up to 11 years post-randomisation, confirms the non-inferiority of EVR+rCNI versus MPA+sCNI regimen. Given the current process engaged for surrogate endpoints qualification, this study illustrates the potential to fast track development of pharmaceutical agents.Trial registration numberTRANSFORM trial: NCT01950819.iBox prognostication system: NCT03474003.
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- 2021
7. Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival
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Marc Raynaud, Patricia Campbell, Jean-Paul Duong Van Huyen, Yassine Bouatou, Olivier Aubert, Banu Sis, Denis Glotz, Carmen Lefaucheur, Sarah Higgins, Christophe Legendre, Luis G. Hidalgo, Marion Rabant, Nikhil Shah, Alexandre Loupy, Daniel Yoo, Michel Delahousse, Michael Mengel, Denis Viglietti, Xavier Jouven, Graduate School, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, and AII - Inflammatory diseases
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,Biopsy ,030232 urology & nephrology ,Disease ,030230 surgery ,Kidney ,Risk Assessment ,Severity of Illness Index ,Young Adult ,03 medical and health sciences ,Glomerulonephritis ,0302 clinical medicine ,Clinical Research ,Internal medicine ,Humans ,Medicine ,Stage (cooking) ,Kidney transplantation ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Graft Survival ,Transplant glomerulopathy ,Complement System Proteins ,General Medicine ,Middle Aged ,Allografts ,medicine.disease ,Kidney Transplantation ,Survival Rate ,Clinical trial ,Phenotype ,Nephrology ,Cohort ,Kidney Failure, Chronic ,Female ,business ,Software ,Unsupervised Machine Learning - Abstract
Background Transplant glomerulopathy, a common glomerular lesion observed after kidney transplant that is associated with poor prognosis, is not a specific entity but rather the end stage of overlapping disease pathways. Its heterogeneity has not been precisely characterized to date. Methods Our study included consecutive kidney transplant recipients from three centers in France and one in Canada who presented with a diagnosis of transplant glomerulopathy (Banff cg score ≥1 by light microscopy), on the basis of biopsies performed from January of 2004 through December of 2014. We used an unsupervised archetype analysis of comprehensive pathology findings and clinical, immunologic, and outcome data to identify distinct groups of patients. Results Among the 8207 post-transplant allograft biopsies performed during the inclusion period, we identified 552 biopsy samples (from 385 patients) with transplant glomerulopathy (incidence of 6.7%). The median time from transplant to transplant glomerulopathy diagnosis was 33.18 months. Kidney allograft survival rates at 3, 5, 7, and 10 years after diagnosis were 69.4%, 57.1%, 43.3%, and 25.5%, respectively. An unsupervised learning method integrating clinical, functional, immunologic, and histologic parameters revealed five transplant glomerulopathy archetypes characterized by distinct functional, immunologic, and histologic features and associated causes and distinct allograft survival profiles. These archetypes showed significant differences in allograft outcomes, with allograft survival rates 5 years after diagnosis ranging from 88% to 22%. Based on those results, we built an online application, which can be used in clinical practice on the basis of real patients. Conclusions A probabilistic data-driven archetype analysis approach applied in a large, well defined multicenter cohort refines the diagnostic and prognostic features associated with cases of transplant glomerulopathy. Reducing heterogeneity among such cases can improve disease characterization, enable patient-specific risk stratification, and open new avenues for archetype-based treatment strategies and clinical trials optimization.
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- 2019
8. Authors' Reply
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Peter. P. Reese, Olivier Aubert, and Alexandre Loupy
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Nephrology ,General Medicine ,Letters to the Editor - Published
- 2021
9. Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes
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Dirk Kuypers, Stanley C. Jordan, Yassine Bouatou, Antoine Bouquegneau, Christophe Legendre, Xavier Jouven, Carmen Lefaucheur, Jean-Philippe Empana, Ashley Vo, Maarten Naesens, Peter P. Reese, Gillian Divard, Olivier Aubert, Alexandre Loupy, Edmund Huang, Vishnu S. Potluri, Denis Glotz, and Marc Raynaud
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education.field_of_study ,medicine.medical_specialty ,Kidney ,Proportional hazards model ,business.industry ,Population ,030232 urology & nephrology ,Histology ,General Medicine ,030230 surgery ,medicine.disease ,Surgery ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Kidney histology ,medicine.anatomical_structure ,Nephrology ,Cohort ,medicine ,Clinical Epidemiology ,education ,business ,Kidney transplantation - Abstract
Background Many kidneys donated for transplant in the United States are discarded because of abnormal histology. Whether histology adds incremental value beyond usual donor attributes in assessing allograft quality is unknown. Methods This population-based study included patients who received a deceased donor kidney that had been biopsied before implantation according to a prespecified protocol in France and Belgium, where preimplantation biopsy findings are generally not used for decision making in the allocation process. We also studied kidneys that had been acquired from deceased United States donors for transplantation that were biopsied during allocation and discarded because of low organ quality. Using donor and recipient characteristics, we fit multivariable Cox models for death-censored graft failure and examined whether predictive accuracy (C index) improved after adding donor histology. We matched the discarded United States kidneys to similar kidneys transplanted in Europe and calculated predicted allograft survival. Results In the development cohort of 1629 kidney recipients at two French centers, adding donor histology to the model did not significantly improve prediction of long-term allograft failure. Analyses using an external validation cohort from two Belgian centers confirmed the lack of improved accuracy from adding histology. About 45% of 1103 United States kidneys discarded because of histologic findings could be accurately matched to very similar kidneys that had been transplanted in France; these discarded kidneys would be expected to have allograft survival of 93.1% at 1 year, 80.7% at 5 years, and 68.9% at 10 years. Conclusions In this multicenter study, donor kidney histology assessment during allocation did not provide substantial incremental value in ascertaining organ quality. Many kidneys discarded on the basis of biopsy findings would likely benefit United States patients who are wait listed.
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- 2020
10. Alzheimer's Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats
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Laura K. Fonken, Steven F. Maier, Heather M. D'Angelo, Matthew G. Frank, Ahmed I. Elsayed, Christopher A. Lowry, Cristian A. Zambrano, Kelsey M. Loupy, and Thomas Lee
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0301 basic medicine ,Proteomics ,Tuberculosis ,medicine.medical_treatment ,Inflammation ,Hippocampus ,Mycobacterium tuberculosis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Alzheimer Disease ,medicine ,Animals ,RNA, Messenger ,Mycobacteriaceae ,biology ,business.industry ,General Neuroscience ,Vaccination ,Proteins ,Lipid metabolism ,Cerebrospinal Fluid Proteins ,General Medicine ,Immunotherapy ,Blood Proteins ,biology.organism_classification ,medicine.disease ,Lipid Metabolism ,Rats ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,Immunology ,Interleukin-4 ,Geriatrics and Gerontology ,medicine.symptom ,Mycobacterium vaccae ,business ,030217 neurology & neurosurgery ,Mycobacterium - Abstract
Background: Alzheimer’s disease (AD) is an inflammatory neurodegenerative disease that may be associated with prior bacterial infections. Microbial “old friends” can suppress exaggerated inflammation in response to disease-causing infections or increase clearance of pathogens such as Mycobacterium tuberculosis, which causes tuberculosis (TB). One such “old friend” is Mycobacterium vaccae NCTC 11659, a soil-derived bacterium that has been proposed either as a vaccine for prevention of TB, or as immunotherapy for the treatment of TB when used alongside first line anti-TB drug treatment. Objective: The goal of this study was to use a hypothesis generating approach to explore the effects of M. vaccae on physiological changes in the plasma and cerebrospinal fluid (CSF). Methods: Liquid chromatography-tandem mass spectrometry-based proteomics were performed in plasma and CSF of adult male rats after immunization with a heat-killed preparation of M. vaccae NCTC 11659 or borate-buffered saline vehicle. Gene enrichment analysis and analysis of protein-protein interactions were performed to integrate physiological network changes in plasma and CSF. We used RT-qPCR to assess immune and metabolic gene expression changes in the hippocampus. Results: In both plasma and CSF, immunization with M. vaccae increased proteins associated with immune activation and downregulated proteins corresponding to lipid (including phospholipid and cholesterol) metabolism. Immunization with M. vaccae also increased hippocampal expression of interleukin-4 (IL-4) mRNA, implicating anti-inflammatory effects in the central nervous system. Conclusion: M. vaccae alters host immune activity and lipid metabolism. These data are consistent with the hypothesis that microbe-host interactions may protect against possible infection-induced, inflammation-related cognitive impairments.
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- 2020
11. Organ procurement and transplantation during the COVID-19 pandemic
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Olivier Bastien, Olivier Aubert, Alexandre Loupy, Florian Bayer, Christian Jacquelinet, Peter P. Reese, Paris Translational Research Center for Organ Transplantation [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Kidney Transplantation [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Agence de la biomédecine [Saint-Denis la Plaine], 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), Bodescot, Myriam, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Pennsylvania, and 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)
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2019-20 coronavirus outbreak ,Tissue and Organ Procurement ,[SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,030232 urology & nephrology ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,030230 surgery ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Pandemic ,Humans ,Medicine ,Pandemics ,ComputingMilieux_MISCELLANEOUS ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,General Medicine ,medicine.disease ,biology.organism_classification ,Virology ,Transplantation ,Pneumonia ,Organ procurement ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Coronavirus Infections ,business - Abstract
International audience
- Published
- 2020
12. Antibody-Mediated Rejection of Solid-Organ Allografts
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Carmen Lefaucheur and Alexandre Loupy
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Graft Rejection ,0301 basic medicine ,medicine.medical_specialty ,030230 surgery ,Kidney ,Lung pathology ,Antibodies ,Organ transplantation ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,medicine ,Humans ,Complement Activation ,Lung ,business.industry ,Myocardium ,Kidney pathology ,Organ Transplantation ,General Medicine ,Allografts ,Transplantation ,surgical procedures, operative ,030104 developmental biology ,Antibody mediated rejection ,Immunology ,Solid organ ,business - Abstract
Antibody-Mediated Rejection of Solid-Organ Allografts This review focuses on current standards for management of antibody-mediated rejection in solid-organ transplant recipients and emphasizes adva...
- Published
- 2018
13. Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated Rejection
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Jean-Luc Taupin, Olivier Aubert, Denis Glotz, Nassim Kamar, Jean-Paul Duong Van Huyen, Christophe Legendre, Michel Delahousse, Denis Viglietti, Xavier Jouven, Oriol Bestard, Alexandre Loupy, and Carmen Lefaucheur
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Graft Rejection ,medicine.medical_specialty ,030232 urology & nephrology ,Urology ,030230 surgery ,Antibodies ,Prognostic score ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Allograft survival ,Medicine ,Kidney transplantation ,Kidney ,business.industry ,Standard treatment ,General Medicine ,medicine.disease ,Kidney Transplantation ,Clinical trial ,medicine.anatomical_structure ,Nephrology ,Cohort ,Rituximab ,business ,medicine.drug - Abstract
No tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (P
- Published
- 2017
14. Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment
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Anna V. Reisaeter, D. Segev, Philip F. Halloran, Oriol Bestard, Patrick Bruneval, Ibrahim Batal, Nassim Kamar, Denis Glotz, Olivier Aubert, Paolo Rigotti, Robert A. Montgomery, Federico Oppenheimer, Babak J. Orandi, Jean-Paul Duong Van Huyen, Adriana Zeevi, Carmen Lefaucheur, Jean Philippe Empana, Lloyd E. Ratner, Serena M. Bagnasco, Alexandre Loupy, Christophe Legendre, Yvon Lebranchu, Luis G. Hidalgo, Xavier Jouven, and Denis Viglietti
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Graft Rejection ,Male ,030232 urology & nephrology ,030230 surgery ,Kidney ,complement ,kidney transplantation ,rejection ,transcriptional profiling ,Monocytes ,0302 clinical medicine ,HLA Antigens ,Chemokine CCL4 ,Cells, Cultured ,Kidney transplantation ,Complement Inactivator Proteins ,Plasma Exchange ,biology ,Immunoglobulins, Intravenous ,General Medicine ,Middle Aged ,Eculizumab ,Allografts ,Killer Cells, Natural ,Phenotype ,medicine.anatomical_structure ,Nephrology ,Female ,Antibody ,Natural killer cell activation ,medicine.drug ,Adult ,CCL4 ,Antibodies, Monoclonal, Humanized ,Antibodies ,Endothelial activation ,03 medical and health sciences ,Clinical Research ,medicine ,Humans ,Immunologic Factors ,Aged ,business.industry ,Macrophages ,Monocyte ,Receptors, IgG ,Membrane Proteins ,Complement System Proteins ,medicine.disease ,Kidney Transplantation ,Chemokine CXCL11 ,Immunology ,biology.protein ,Transcriptome ,business - Abstract
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.
- Published
- 2017
15. Clinical outcomes after ABO-incompatible renal transplantation
- Author
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Antoine Bouquegneau, Robert A. Montgomery, Mark D. Stegall, and Alexandre Loupy
- Subjects
medicine.medical_specialty ,business.industry ,Graft Survival ,MEDLINE ,General Medicine ,medicine.disease ,Kidney Transplantation ,Transplantation ,Text mining ,Blood Group Incompatibility ,Internal medicine ,ABO blood group system ,Medicine ,Graft survival ,business ,Kidney transplantation - Published
- 2019
16. Exploring the cardiac response to injury in heart transplant biopsies
- Author
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Peter S. Macdonald, Jeff Reeve, Jon A. Kobashigawa, J. Goekler, Marisa G. Crespo-Leiro, Michael D. Parkes, Eugene C. DePasquale, Arezu Aliabadi, Alexandre Loupy, Andreas Zuckermann, Mario C. Deng, Martin Cadeiras, Luciano Potena, Philip F. Halloran, Xavier Jouven, and Daniel Kim
- Subjects
Oncology ,Cardiac response ,Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Adolescent ,Biopsy ,Inflammation ,030204 cardiovascular system & hematology ,030230 surgery ,Organ transplantation ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Archetypal analysis ,Internal medicine ,Parenchyma ,medicine ,Humans ,Prospective Studies ,Child ,Aged ,Ejection fraction ,Ventricular function ,business.industry ,Gene Expression Profiling ,Myocardium ,General Medicine ,Middle Aged ,Transplant Recipients ,Transplantation ,Heart Injuries ,Tissue Array Analysis ,Child, Preschool ,Heart Transplantation ,Female ,medicine.symptom ,Clinical Medicine ,business ,Endocardium - Abstract
BACKGROUND. Because injury is universal in organ transplantation, heart transplant endomyocardial biopsies present an opportunity to explore response to injury in heart parenchyma. Histology has limited ability to assess injury, potentially confusing it with rejection, whereas molecular changes have potential to distinguish injury from rejection. Building on previous studies of transcripts associated with T cell–mediated rejection (TCMR) and antibody-mediated rejection (ABMR), we explored transcripts reflecting injury. METHODS. Microarray data from 889 prospectively collected endomyocardial biopsies from 454 transplant recipients at 14 centers were subjected to unsupervised principal component analysis and archetypal analysis to detect variation not explained by rejection. The resulting principal component and archetype scores were then examined for their transcript, transcript set, and pathway associations and compared to the histology diagnoses and left ventricular function. RESULTS. Rejection was reflected by principal components PC1 and PC2, and by archetype scores S2TCMR, and S3ABMR, with S1normal indicating normalness. PC3 and a new archetype score, S4injury, identified unexplained variation correlating with expression of transcripts inducible in injury models, many expressed in macrophages and associated with inflammation in pathway analysis. S4injury scores were high in recent transplants, reflecting donation-implantation injury, and both S4injury and S2TCMR were associated with reduced left ventricular ejection fraction. CONCLUSION. Assessment of injury is necessary for accurate estimates of rejection and for understanding heart transplant phenotypes. Biopsies with molecular injury but no molecular rejection were often misdiagnosed rejection by histology. TRAIL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02670408","term_id":"NCT02670408"}}NCT02670408 FUNDING. Roche Organ Transplant Research Foundation, the University of Alberta Hospital Foundation, and Alberta Health Services.
- Published
- 2018
17. Correction: Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis
- Author
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Christophe Legendre, Ron Shapiro, E. Steve Woodle, Charlotte Loheac, Yassine Bouatou, Jacqueline G. O'Leary, Robert A. Montgomery, Jon A. Kobashigawa, Stephan Schaub, Dolly B. Tyan, Denis Viglietti, Alexandre Loupy, Xavier Jouven, Jean Luc Taupin, Olivier Aubert, Annette M. Jackson, Jean Philippe Empana, Antoine Bouquegneau, Camilo Ulloa, John J. Friedewald, Mohammad Hassan Murad, Denis Glotz, Luis G. Hidalgo, Elaine F. Reed, Caner Süsal, Patricia Jabre, Adriana Zeevi, and Carmen Lefaucheur
- Subjects
business.industry ,General Medicine ,030230 surgery ,Complement (complexity) ,03 medical and health sciences ,0302 clinical medicine ,Meta-analysis ,Immunology ,Medicine ,Hla antibodies ,030212 general & internal medicine ,business ,Solid organ transplantation - Abstract
[This corrects the article DOI: 10.1371/journal.pmed.1002572.].
- Published
- 2018
18. Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term Survival
- Author
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Olivier Aubert, Xavier Lebreton, Yokarla Veras, Emmanuel Zorn, Dany Anglicheau, Christophe Legendre, Sarah B. See, Baoshan Gao, and Alexandre Loupy
- Subjects
0301 basic medicine ,Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Human leukocyte antigen ,Kaplan-Meier Estimate ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Risk Factors ,Internal medicine ,Malondialdehyde ,Biopsy ,medicine ,Humans ,Postoperative Period ,Risk factor ,Retrospective Studies ,medicine.diagnostic_test ,biology ,business.industry ,Proportional hazards model ,Hazard ratio ,Graft Survival ,Retrospective cohort study ,General Medicine ,Middle Aged ,Allografts ,Kidney Transplantation ,Confidence interval ,030104 developmental biology ,Editorial ,Nephrology ,Immunoglobulin G ,Preoperative Period ,biology.protein ,Female ,Antibody ,business - Abstract
Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens.Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde.Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss.Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.
- Published
- 2017
19. Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes
- Author
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Georg A. Böhmig, Philip F. Halloran, Gunilla Einecke, Carmen Lefaucheur, Jeff Reeve, Farsad Eskandary, and Alexandre Loupy
- Subjects
0301 basic medicine ,Nephrology ,medicine.medical_specialty ,Pathology ,medicine.diagnostic_test ,business.industry ,General Medicine ,Disease ,030230 surgery ,Kidney transplant ,Fully developed ,Transplantation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Archetypal analysis ,Internal medicine ,Biopsy ,medicine ,Radiology ,Medical diagnosis ,business ,Research Article - Abstract
Conventional histologic diagnosis of rejection in kidney transplants has limited repeatability due to its inherent requirement for subjective assessment of lesions, in a rule-based system that does not acknowledge diagnostic uncertainty. Molecular phenotyping affords opportunities for increased precision and improved disease classification to address the limitations of conventional histologic diagnostic systems and quantify levels of uncertainty. Microarray data from 1,208 kidney transplant biopsies were collected prospectively from 13 centers. Cross-validated classifier scores predicting the presence of antibody-mediated rejection (ABMR), T cell–mediated rejection (TCMR), and 5 related histologic lesions were generated using supervised machine learning methods. These scores were used as input for archetypal analysis, an unsupervised method similar to cluster analysis, to examine the distribution of molecular phenotypes related to rejection. Six archetypes were generated: no rejection, TCMR, 3 associated with ABMR (early-stage, fully developed, and late-stage), and mixed rejection (TCMR plus early-stage ABMR). Each biopsy was assigned 6 scores, one for each archetype, representing a probabilistic assessment of that biopsy based on its rejection-related molecular properties. Viewed as clusters, the archetypes were similar to existing histologic Banff categories, but there was 32% disagreement, much of it probably reflecting the “noise” in the current histologic assessment system. Graft survival was lowest for fully developed and late-stage ABMR, and it was better predicted by molecular archetype scores than histologic diagnoses. The results provide a system for precision molecular assessment of biopsies and a new standard for recalibrating conventional diagnostic systems.
- Published
- 2017
20. Yellow Fever Outbreak - Kongo Central Province, Democratic Republic of the Congo, August 2016
- Author
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Loupy-Régence N. Nsibu, John O Otshudiema, Benoit I. Kebela, Jacob Dee, Gaston P. Tshapenda, Coralie Giese, Abdou Salam Gueye, Nestor G. Ndakala, Ray R. Arthur, Elande-taty K. Mawanda, Rossanne M. Philen, Christopher S. Murrill, and Jacques M. Kimfuta
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Veterinary medicine ,Health (social science) ,Adolescent ,Epidemiology ,Health, Toxicology and Mutagenesis ,030231 tropical medicine ,Typhoid fever ,Dengue fever ,Disease Outbreaks ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Health Information Management ,Yellow Fever ,medicine ,Humans ,Full Report ,Socioeconomics ,Child ,Aged ,business.industry ,Yellow fever ,Infant, Newborn ,Outbreak ,Infant ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,Immunization ,Child, Preschool ,Democratic Republic of the Congo ,Female ,Yellow fever virus ,Viral hepatitis ,business ,Malaria - Abstract
On April 23, 2016, the Democratic Republic of the Congo's (DRC's) Ministry of Health declared a yellow fever outbreak. As of May 24, 2016, approximately 90% of suspected yellow fever cases (n = 459) and deaths (45) were reported in a single province, Kongo Central Province, that borders Angola, where a large yellow fever outbreak had begun in December 2015. Two yellow fever mass vaccination campaigns were conducted in Kongo Central Province during May 25-June 7, 2016 and August 17-28, 2016. In June 2016, the DRC Ministry of Health requested assistance from CDC to control the outbreak. As of August 18, 2016, a total of 410 suspected yellow fever cases and 42 deaths were reported in Kongo Central Province. Thirty seven of the 393 specimens tested in the laboratory were confirmed as positive for yellow fever virus (local outbreak threshold is one laboratory-confirmed case of yellow fever). Although not well-documented for this outbreak, malaria, viral hepatitis, and typhoid fever are common differential diagnoses among suspected yellow fever cases in this region. Other possible diagnoses include Zika, West Nile, or dengue viruses; however, no laboratory-confirmed cases of these viruses were reported. Thirty five of the 37 cases of yellow fever were imported from Angola. Two-thirds of confirmed cases occurred in persons who crossed the DRC-Angola border at one market city on the DRC side, where ≤40,000 travelers cross the border each week on market day. Strategies to improve coordination between health surveillance and cross-border trade activities at land borders and to enhance laboratory and case-based surveillance and health border screening capacity are needed to prevent and control future yellow fever outbreaks.
- Published
- 2017
21. Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients
- Author
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Olivier Aubert, Denis Glotz, Jean-Paul Duong Van Huyen, Sarah Higgins, Xavier Jouven, Christophe Legendre, Philip F. Halloran, Luis G. Hidalgo, Denis Viglietti, Carmen Lefaucheur, and Alexandre Loupy
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,030232 urology & nephrology ,Urology ,030230 surgery ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Antibody Specificity ,HLA Antigens ,Biopsy ,medicine ,Humans ,Kidney transplantation ,Kidney ,Proteinuria ,medicine.diagnostic_test ,biology ,business.industry ,Hazard ratio ,Transplant glomerulopathy ,General Medicine ,Middle Aged ,medicine.disease ,Allografts ,Kidney Transplantation ,Tissue Donors ,body regions ,medicine.anatomical_structure ,Nephrology ,biology.protein ,Kidney Failure, Chronic ,Histopathology ,Female ,medicine.symptom ,Antibody ,business - Abstract
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had de novo DSA. Compared with patients with preexisting DSA ABMR, patients with de novo DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. De novo DSA ABMR was characterized by increased expression of IFNγ-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the de novo DSA ABMR (63% versus 34% at 8 years after rejection, respectively; P
- Published
- 2017
22. P137 Real life systematic analysis of trans bronchial biopsy in lung transplantation: Preliminary results
- Author
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Alexandre Loupy, Anouk Asselin, Clément Picard, Abdul Monem Hamid, L. Beaumont, Sandra De Miranda, Antoine Roux, E. Cuquemelle, Leila Zemoura, and Elisabeth Longchampt
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,medicine ,Immunology and Allergy ,Bronchial Biopsy ,Lung transplantation ,General Medicine ,Radiology ,business - Published
- 2019
23. P201 In situ multiplex immunofluorescence analysis of the inflammatory burden in kidney allograft rejection: A new tool to characterize the alloimmune response
- Author
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Jean-Paul Duong Van Huyen, Claire Tinel, Marion Rabant, Alexandre Loupy, Megumi Terada, Baptiste Lamarthée, Patrick Bruneval, Dany Anglicheau, Corinne Lesaffre, Julien Calvani, and Lionel Couzi
- Subjects
In situ ,Kidney ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Immunology ,General Medicine ,Immunofluorescence ,medicine.anatomical_structure ,Allograft rejection ,Immunology and Allergy ,Medicine ,Multiplex ,business - Published
- 2019
24. Value of Donor–Specific Anti–HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft Loss
- Author
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Olivier Aubert, Xavier Jouven, Adriana Zeevi, Clément Gosset, Christophe Legendre, Denis Glotz, Carmen Lefaucheur, Jean-Paul Duong Van Huyen, Dewi Vernerey, Denis Viglietti, Carol Bentlejewski, and Alexandre Loupy
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,030232 urology & nephrology ,Urology ,Anti-HLA antibody ,030230 surgery ,Risk Assessment ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,HLA Antigens ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,Kidney ,Clinical events ,business.industry ,Mean fluorescence intensity ,General Medicine ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Confidence interval ,Tissue Donors ,body regions ,medicine.anatomical_structure ,surgical procedures, operative ,Nephrology ,Risk stratification ,Female ,business - Abstract
The diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor-specific anti-HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic monitoring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post-transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post-transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post-transplant screening identified 186 (21.9%) DSA-positive patients. Post-transplant DSA monitoring improved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statistic from 0.67; 95% confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77). Addition of DSA IgG3 positivity or C1q binding capacity increased discrimination performance of the traditional model at transplant and post-transplant. Compared with DSA mean fluorescence intensity, DSA IgG3 positivity and C1q binding capacity adequately reclassified patients at lower or higher risk for allograft loss at transplant (category-free net reclassification index, 1.30; 95% CI, 0.94 to 1.67; P
- Published
- 2016
25. Preexisting Donor-Specific HLA Antibodies Predict Outcome in Kidney Transplantation
- Author
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Corinne Antoine, Dominique Charron, Gary S. Hill, Joao Andrade, Caroline Suberbielle-Boissel, Alexandre Loupy, Denis Glotz, Dominique Nochy, Chantal Gautreau, and Carmen Lefaucheur
- Subjects
Graft Rejection ,Nephrology ,medicine.medical_specialty ,Urinary system ,Human leukocyte antigen ,Gastroenterology ,Antibodies ,HLA Antigens ,Clinical Research ,Internal medicine ,medicine ,Humans ,Kidney transplantation ,business.industry ,Incidence (epidemiology) ,General Medicine ,Prognosis ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,Confidence interval ,body regions ,Transplantation ,Treatment Outcome ,Relative risk ,Immunology ,business - Abstract
The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceased-donor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (P = 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI >6000 had >100-fold higher risk for AMR than patients with MFI
- Published
- 2010
26. ZnO: a versatile agent for benzylic oxidations
- Author
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Rajive Gupta, Satya Paul, Monika Gupta, and André Loupy
- Subjects
Organic Chemistry ,chemistry.chemical_element ,General Medicine ,Zinc ,Photochemistry ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Microwave irradiation ,Organic chemistry ,Alkylbenzenes ,Selectivity ,Naphthalene - Abstract
Zinc oxide catalyzed oxidation of various alkylbenzenes, naphthalene and 1,2,3,4-tetrahydronaphthalene in air using microwave irradiation or conventional heating in the presence of N,N-dimethylformamide is described.
- Published
- 2005
27. A Mild, Efficient, and Green Procedure for Michael Addition of Active Methylene Compounds to Chalcones Under Microwave Irradiation
- Author
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Parvinder Pal Singh, Monika Gupta, Rajive Gupta, André Loupy, and Satya Paul
- Subjects
Potassium carbonate ,Addition reaction ,chemistry.chemical_compound ,Chemistry ,Organic Chemistry ,Microwave irradiation ,Michael reaction ,Organic chemistry ,Substrate (chemistry) ,General Medicine ,Methylene ,humanities - Abstract
A simple, rapid, and highly efficient method has been developed for the Michael addition of active methylene compounds to chalcones using potassium carbonate and water under microwave irradiation. The method is totally exempt of organic solvents, and pure products were obtained in good to excellent yields. This method can be used for the parallel synthesis and further scale‐up to 50 mmol of substrate.
- Published
- 2005
28. Selective and efficient fluorination of chlorodiazines under solvent-free phase transfer catalysis
- Author
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Hanane Snoussi, André Loupy, Sylvain R. A. Marque, A. Turck, and Nelly Plé
- Subjects
Solvent free ,Chemistry ,Organic Chemistry ,Inorganic chemistry ,Halogenation ,General Medicine ,Photochemistry ,Biochemistry ,Catalysis ,Inorganic Chemistry ,Transfer agent ,Phase (matter) ,Microwave irradiation ,Environmental Chemistry ,Physical and Theoretical Chemistry - Abstract
3-Chloro-6-phenylpyridazine, 2,3-dichloroquinoxaline and 1,4-dichlorophthalazine were reacted with KF under solvent-free conditions in the presence of a phase transfer agent, with or without microwave irradiation. The chlorine–fluorine exchanges were obtained with enhanced yields and selectivities when compared with previous methods.
- Published
- 2004
29. Rh(I)-catalyzed solvent-free ortho-alkylation of aromatic imines under microwave irradiation
- Author
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Hind Lahrache, Duck Ho Chang, In‐Jung Kim, Chul‐Ho Jun, André Loupy, and Giang Vo-Thanh
- Subjects
inorganic chemicals ,chemistry.chemical_classification ,Aldimine ,Solvent free ,integumentary system ,organic chemicals ,Organic Chemistry ,Hydroacylation ,General Medicine ,Alkylation ,Photochemistry ,Biochemistry ,Catalysis ,chemistry ,Drug Discovery ,Microwave irradiation ,bacteria ,Organic chemistry ,heterocyclic compounds ,Microwave - Abstract
The synthesis of ortho-alkylated ketones through a chelation-assisted Rh (I) catalyzed ortho-alkylation reaction of aromatic imines under microwave activated solvent-free conditions in monomode reactors was performed. These conditions have been also applied to hydroacylation and ortho-alkylation reactions with aldimines.
- Published
- 2004
30. Microwave-assisted ruthenium-catalyzed olefin metathesis under solvent-free conditions
- Author
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Giang Vo Thanh and André Loupy
- Subjects
Solvent free ,Olefin metathesis ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,General Medicine ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Metathesis ,Combinatorial chemistry ,Biochemistry ,Microwave assisted ,Ruthenium ,Catalysis ,Drug Discovery ,Salt metathesis reaction ,Ring-opening metathesis polymerisation ,Organic chemistry ,Microwave ,Acyclic diene metathesis - Abstract
An efficient method for ring-closing metathesis under solvent-free conditions and by microwave activation was established. Non-thermal microwave specific effects were evident.
- Published
- 2003
31. Solvent-Free Microwave-Assisted Efficient Synthesis of 4,4-Disubstituted 2-Oxazolines
- Author
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André Loupy, Alma Leilani Marrero-Terrero, Alain Petit, Fernando García-Tellado, Ministerio de Ciencia y Tecnología (España), European Commission, Gobierno de Canarias, and Universidad de La Laguna
- Subjects
Solvent free ,Carboxylic acids ,Chemistry ,Nitrogen heterocycles ,Organic Chemistry ,Condensation ,chemistry.chemical_element ,General Medicine ,Zinc ,Environmentally friendly ,Microwave assisted ,Amino alcohols ,Organic chemistry ,Lewis acids and bases ,Physical and Theoretical Chemistry ,Microwaves - Abstract
5 pages, 3 tables., 4,4-Disubstituted 2-oxazolines have been synthesized by a microwave-promoted solvent-free direct condensation of carboxylic acids and disubstituted -amino alcohols in good to excellent yields. Zinc oxide is a very good solid support in cases where a Lewis acid is required. The method described herein is a very good, safe, clean, economical, and environmentally friendly alternative to the classical procedures., Part of this work was sponsored from 1993 to 1999 by the French-Cuban cooperation within the framework of the agreement CNRS: MINVEC (ref. 5702). We sincerely thank these organisations for their help. Part of this work was supported by the Spanish Ministerio de Ciencia y Tecnología (PB9820443-C02202), the Canary Islands Consejería de Educación y Ciencia (COFI2000/03) and the FEDER (1SD9720747-C4201). A. L. M. T. Thanks to The Third World Academy of Sciences for an equipment budget (research grant N°94-209 RG/CHE/LA), to Universidad La Laguna for an Intercampus Grant.
- Published
- 2003
32. Solvent-free synthesis of 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones under microwave irradiation
- Author
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Rolando Pérez, André Loupy, Hortensia Rodríguez, Margarita Suarez, and Alain Petit
- Subjects
Solvent free ,Methyl acetoacetate ,Aryl ,Organic Chemistry ,Condensation ,General Medicine ,Biochemistry ,Benzaldehyde ,Solvent ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Microwave irradiation ,Polymer chemistry ,Organic chemistry ,Microwave effect ,Ammonium acetate - Abstract
4-Aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones have been prepared in one-pot condensation from Meldrum's acid, methyl acetoacetate and the appropriate benzaldehyde in the presence of ammonium acetate using microwave irradiation without solvent. This rapid method produced pure products in high yields (81–91%) due essentially to a specific non-thermal microwave effect (17–28%) by conventional heating under the same conditions.
- Published
- 2003
33. OR12 Complement-binding donor-specific anti-HLA antibodies predict the response to complement-targeting therapy: A multicenter international study
- Author
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Carmen Lefaucheur, Philip F. Halloran, Massimo Mangiola, Denis Glotz, Olivier Aubert, Alexandre Loupy, Christophe Legendre, Adriana Zeevi, and Denis Viglietti
- Subjects
medicine.medical_specialty ,Kidney ,biology ,Microarray ,business.industry ,Incidence (epidemiology) ,Immunology ,General Medicine ,Eculizumab ,Gastroenterology ,Clinical trial ,Transplantation ,medicine.anatomical_structure ,Internal medicine ,medicine ,biology.protein ,Immunology and Allergy ,Hla antibodies ,Antibody ,business ,medicine.drug - Abstract
Aim We investigated whether circulating complement-binding donor-specific anti-HLA antibodies (DSA) influence response to complement-targeting therapy. Methods We included 116 kidney recipients transplanted between 2011 and 2014 in 10 referral centers (US and Europe) from two prospective clinical trials investigating the effect of complement inhibition for rejection prophylaxis in kidney recipients with anti-HLA DSAs at transplantation (NCT01567085 and 01399593). They received either Eculizumab in the first nine weeks post-transplantation (N = 52) or standard of care (SOC) consisting in plasma exchange and intravenous immunoglobulin (N = 64). All patients were screened for C1q-binding DSAs using SAB in sera collected at transplantation and underwent allograft biopsy at day 14 to assess histological characteristics and allograft gene expression (microarray). We also compared the 3-month incidence of biopsy-proven antibody-mediated rejection (AMR) according to therapy. Results Patient baseline characteristics were similar between the 2 treatment groups. 69 (59%) patients had pre-transplant C1q-binding DSA (32 receiving SOC and 37 receiving Eculizumab) and 47 (41%) had non-C1q-binding DSA (32 receiving SOC and 15 receiving Eculizumab). In patients with C1q-binding DSAs, compared with patients receiving SOC, Eculizumab was associated with decreased glomerulitis (P = 0.001), peritubular capillaritis (P Conclusions Circulating complement-activating anti-HLA DSAs identify kidney transplant recipients who respond to complement inhibition.
- Published
- 2017
34. P001 Changes in anti-HLA antibody complement-binding capacity reflect the efficacy of antibody-mediated rejection therapy and predict kidney allograft survival
- Author
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Alexandre Loupy, Massimo Mangiola, Denis Viglietti, Olivier Aubert, Carmen Lefaucheur, and Adriana Zeevi
- Subjects
Kidney ,medicine.medical_specialty ,Proteinuria ,biology ,Globulin ,business.industry ,Immunology ,Anti-HLA antibody ,Histology ,General Medicine ,Gastroenterology ,body regions ,medicine.anatomical_structure ,Immune system ,Internal medicine ,Allograft survival ,medicine ,biology.protein ,Immunology and Allergy ,medicine.symptom ,Antibody ,business - Abstract
Aim We investigated wether the kinetics of donor-specific anti-HLA antibody (DSA) characteristics might predict kidney allograft survival in patients with antibody-mediated rejection (AMR) receiving standard-of-care therapy. Methods We prospectively enrolled 2666 kidney recipients transplanted between 2004 and 2012 and we included in this study all patients diagnosed with active AMR who received standardized therapy including plasma exchanges (×4–5) and intravenous immune globulins (2 g/kg × 3). Patients were systematically assessed at diagnosis and 3 months post-therapy for circulating anti-HLA DSA (specificity, mean fluorescence intensity, C1q-binding capacity) using Luminex SAB, clinical data (eGFR and proteinuria) and histology (allograft biopsy). Results 278 patients with biopsy-proven acute or chronic active AMR received standard-of-care therapy. At rejection, 76 (27%) patients had class I DSA, 127 (46%) class II DSA and 75 (27%) class I and II DSA. Dominant DSA was C1q binding in 85 (31%) patients. The MFImax decreased from 5223 ± 318 to 3611 ± 280 after AMR therapy ( P P = 0.001). Patients showing a reduction of DSA MFImax after therapy ( N = 207) had a better 5-year graft survival than those who had stable or increasing MFImax (N = 71): 80% vs. 62%; P N = 177) and those with pre-therapy positive/post-therapy negative C1q-DSA ( N = 51) showed a better 5-year graft survival (82% and 94%, respectively) than those with C1q-DSA before and after therapy ( N = 34) and those with pre-therapy negative/post-therapy positive C1q-DSA ( N = 16) (36% and 38%, respectively; P Conclusions The kinetics of circulating anti-HLA DSA C1q-binding capacity in kidney recipients with AMR more accurately identify responders to standard-of-care therapy than DSA MFI level, independently of clinical and histological parameters.
- Published
- 2017
35. OR50 Complement-binding donor-specific anti-HLA antibodies induce a specific histo-molecular kidney allograft rejection phenotype
- Author
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Massimo Mangiola, Adriana Zeevi, Denis Viglietti, Christophe Legendre, Alexandre Loupy, Olivier Aubert, Banu Sis, Carmen Lefaucheur, Denis Glotz, and Philip F. Halloran
- Subjects
Kidney ,Adoptive cell transfer ,medicine.medical_specialty ,Pathology ,biology ,Microarray ,Immunology ,General Medicine ,Phenotype ,body regions ,Transplantation ,medicine.anatomical_structure ,Immunochemistry ,medicine ,biology.protein ,Immunology and Allergy ,Histopathology ,Antibody - Abstract
Aim Complement-binding donor-specific anti-HLA antibodies (DSA) have been associated with impaired kidney transplant outcome. We investigated whether they induce a specific kidney allograft rejection phenotype. Methods We prospectively enrolled 931 kidney recipients transplanted between 2011 and 2014, with systematic screening for circulating DSA in the first year post-transplantation. We assessed DSA specificity, mean fluorescence intensity (MFI), C1q-binding capacity and IgG1-4 subclasses using Luminex SAB. All patients underwent allograft biopsy at the time post-transplant DSA detection. The allograft rejection phenotypes were assessed by histopathology, immunochemistry and allograft gene expression (microarray). A model of fully MHC-mismatched male CBA (H-2 k) kidneys transplanted into B6.RAG1−/− (H-2b) immunodeficient mice with adoptive transfer of complement and non-complement-activating DSA was studied. Results We identified 157 (17%) patients with circulating anti-HLA DSA detected in the first year after transplantation, 44 (28%) with complement-binding DSA, and 113 (72%) with non-complement-binding DSA. Patients with complement-binding DSA showed higher MFI levels (9483±747 vs. 2978±278; P P P P P P P Conclusions Circulating complement-binding anti-HLA DSA induce a specific histo-molecular phenotype of kidney allograft rejection.
- Published
- 2017
36. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts
- Author
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Frank Martinez, Dominique Nochy, Christophe Legendre, Alexandre Loupy, Denis Glotz, Marion Rabant, Olivier Aubert, Jérôme Verine, Carmen Lefaucheur, Jean-Philippe Empana, Dewi Vernerey, Claire Tinel, Xavier Jouven, and Jean-Paul Duong Van Huyen
- Subjects
Graft Rejection ,Male ,Time Factors ,T-Lymphocytes ,Kaplan-Meier Estimate ,Gastroenterology ,Severity of Illness Index ,Cohort Studies ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,Subclinical infection ,Proteinuria ,Incidence ,Biopsy, Needle ,General Medicine ,Middle Aged ,Allografts ,Prognosis ,Immunohistochemistry ,Transplant rejection ,Survival Rate ,Phenotype ,Nephrology ,Female ,France ,medicine.symptom ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,Renal function ,Delayed Graft Function ,Risk Assessment ,Antibodies ,Age Distribution ,Clinical Research ,Internal medicine ,medicine ,Humans ,Sex Distribution ,Survival rate ,Proportional Hazards Models ,business.industry ,Transplant glomerulopathy ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Surgery ,Multivariate Analysis ,business - Abstract
Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P
- Published
- 2014
37. Molecular microscope strategy to improve risk stratification in early antibody-mediated kidney allograft rejection
- Author
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Xavier Jouven, Jean-Paul Duong Van Huyen, Jessica Chang, Olivier Aubert, T. Beuscart, Denis Glotz, Sébastien Dubleumortier, Philip F. Halloran, Luis G. Hidalgo, Dewi Vernerey, Christophe Legendre, Carmen Lefaucheur, Alexandre Loupy, and Jérôme Verine
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Pathology ,Urology ,Transplants ,Kidney ,Risk Assessment ,Medicine ,Humans ,Kidney transplantation ,Aged ,Retrospective Studies ,business.industry ,Gene Expression Profiling ,Hazard ratio ,Kidney metabolism ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Confidence interval ,medicine.anatomical_structure ,Nephrology ,Cohort ,Disease Progression ,Female ,business ,Risk assessment - Abstract
Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant. In addition to conventional features, we assessed microarray-based gene expression in transplant biopsy specimens using relevant molecular measurements: the ABMR Molecular Score and endothelial donor-specific antibody-selective transcript set. The main outcomes were kidney transplant loss and progression to chronic transplant injury. We identified 74 patients with ABMR in the principal cohort and 54 patients with ABMR in the validation cohort. Conventional features independently associated with failure were donor age and humoral histologic score (g+ptc+v+cg+C4d). Adjusting for conventional features, ABMR Molecular Score (hazard ratio [HR], 2.22; 95% confidence interval [95% CI], 1.37 to 3.58; P=0.001) and endothelial donor-specific antibody-selective transcripts (HR, 3.02; 95% CI, 1.00 to 9.16; P
- Published
- 2014
38. Complement-binding anti-HLA antibodies and kidney transplantation
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Carmen Lefaucheur, Adriana Zeevi, and Alexandre Loupy
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Male ,biology ,business.industry ,Graft Survival ,General Medicine ,Human leukocyte antigen ,Complement System Proteins ,medicine.disease ,Kidney Transplantation ,Antibodies ,Complement (complexity) ,HLA Antigens ,Immunology ,medicine ,biology.protein ,Humans ,Hla antibodies ,Graft survival ,Female ,Antibody ,business ,Kidney transplantation - Published
- 2014
39. Fat emboli unleashed: an exceptional etiology of encephalitis in sickle cell disease
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M. Wolff, L. Bouadma, J.-P. Laissy, B. Regnier, A. Loupy, S. Pease, D. Bachir, and Isabelle F. Klein
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medicine.medical_specialty ,Pathology ,Hematology ,business.industry ,Cell ,General Medicine ,Disease ,medicine.disease ,medicine.anatomical_structure ,Internal medicine ,medicine ,Etiology ,business ,Encephalitis - Published
- 2008
40. An unusual cause of pacemaker-induced severe tricuspid regurgitation
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B Lung, Dominique Himbert, A Loupy, David Messika-Zeitoun, Alec Vahanian, Agnès Cachier, and Eric Brochet
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Aortic valve ,Pacemaker, Artificial ,medicine.medical_specialty ,macromolecular substances ,Regurgitation (circulation) ,law.invention ,Tricuspid Valve Insufficiency ,Aortic valve replacement ,law ,Internal medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Aged ,Heart Valve Prosthesis Implantation ,Tricuspid valve ,business.industry ,General Medicine ,medicine.disease ,Cardiac surgery ,Surgery ,medicine.anatomical_structure ,Aortic Valve ,Aortic valve surgery ,cardiovascular system ,Cardiology ,Artificial cardiac pacemaker ,Female ,Tricuspid Valve ,Cardiology and Cardiovascular Medicine ,business - Abstract
Pacemaker (PM) induced tricuspid regurgitation (TR) is a common echocardiographic finding. Although mild or moderate TR is frequently observed, severe TR is rare. We report the exceptional observation of a severe TR due to leaflet malcoaptation occurring late after PM implantation and in the following weeks after an aortic valve replacement. Our hypothesis is that the aortic valve surgery has been responsible for conformational changes between cardiac cavities, tricuspid valve and PM leads resulting in a severe TR.
- Published
- 2008
41. Complement-Binding Anti-HLA Antibodies and Kidney-Allograft Survival
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Arnaud Mejean, Jean-Paul Duong Van Huyen, Dany Anglicheau, Carmen Lefaucheur, Jean-Philippe Empana, Dominique Charron, Gary S. Hill, François Desgrandchamps, Adriana Zeevi, Véronique Frémeaux-Bacchi, Alexandre Loupy, Dominique Nochy, Christof Prugger, Christophe Legendre, Dewi Vernerey, Xavier Jouven, Nuala Mooney, Denis Glotz, Caroline Suberbielle, Michel Delahousse, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Translational Research Center for Organ Transplantation & Department of Nephrology and Transplantation, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Hôpital d'Instruction des Armées du Val de Grâce, Service de Santé des Armées, Laboratoire d'histocompatibilité [Paris], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de néphrologie et transplantation rénale [Hôpital Necker Enfants Malades - APHP], Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Transplantation Rénale, Hôpital Foch [Suresnes], Service de Transplantation Rénale et de Soins Intensifs [Hôpital Necker - APHP], Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), McDonald Observatory, University of Texas at Austin [Austin], Epidémiologie cardiovasculaire et mort subite, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Immunologic Factors ,[SDV]Life Sciences [q-bio] ,030232 urology & nephrology ,Kaplan-Meier Estimate ,030230 surgery ,Gastroenterology ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Internal medicine ,Allograft survival ,medicine ,Humans ,Transplantation, Homologous ,Hla antibodies ,ComputingMilieux_MISCELLANEOUS ,Kidney ,biology ,business.industry ,Hazard ratio ,Graft Survival ,General Medicine ,Complement System Proteins ,Middle Aged ,Kidney Transplantation ,Confidence interval ,3. Good health ,Transplantation ,medicine.anatomical_structure ,Immunology ,biology.protein ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Antibody ,business ,Protein Binding - Abstract
Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure.We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed.The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97).Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.
- Published
- 2013
42. ChemInform Abstract: Nonthermal Effects of Microwaves in Organic Synthesis
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Laurence Perreux, Andre Loupy, and Alain Petit
- Subjects
General Medicine - Published
- 2013
43. ChemInform Abstract: HAP-Pd(0): A Highly Efficient Recyclable Heterogeneous Catalyst for the Selective Reduction of Carbon-Carbon Double Bond in α,β-Unsaturated Ketones
- Author
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Tahira Shamim, Satya Paul, André Loupy, Monika Gupta, Omkar Singh Chambyal, and Rajive Gupta
- Subjects
inorganic chemicals ,chemistry.chemical_classification ,Double bond ,fungi ,Reinforced carbon–carbon ,food and beverages ,chemistry.chemical_element ,General Medicine ,Heterogeneous catalysis ,Catalysis ,law.invention ,chemistry ,Chemical engineering ,law ,Selective reduction ,Filtration ,Palladium - Abstract
The employed catalyst, palladium hydroxyapatite, can be recovered by simple filtration and reused for five consecutive runs without significant loss of activity.
- Published
- 2013
44. Diagnostic criteria for kidney transplant rejection: a call to action - Authors' reply
- Author
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Christophe Legendre, Denis Glotz, Carmen Lefaucheur, Xavier Jouven, and Alexandre Loupy
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,business.industry ,General Medicine ,Kidney Transplantation ,Call to action ,HLA Antigens ,Isoantibodies ,Medicine ,Humans ,Female ,business ,Intensive care medicine ,Kidney transplant rejection - Published
- 2013
45. Antibody-mediated vascular rejection of kidney allografts: a population-based study
- Author
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Carmen Lefaucheur, Jean-Philippe Empana, T. Beuscart, Gary S. Hill, Dominique Nochy, Xavier Jouven, Christophe Legendre, Jérôme Verine, Dominique Charron, Jean-Paul Duong-Van-Huyen, Patrick Bruneval, Alexandre Loupy, Caroline Suberbielle, Dany Anglicheau, Dewi Vernerey, Michel Delahousse, and Denis Glotz
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Gastroenterology ,Endarteritis ,HLA Antigens ,Isoantibodies ,Internal medicine ,Biopsy ,medicine ,Humans ,education ,Dialysis ,education.field_of_study ,Kidney ,biology ,medicine.diagnostic_test ,business.industry ,Histology ,General Medicine ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgery ,Transplantation ,medicine.anatomical_structure ,CD4 Antigens ,biology.protein ,Female ,Antibody ,business ,Vasculitis - Abstract
Rejection of allografts has always been the major obstacle to transplantation success. We aimed to improve characterisation of different kidney-allograft rejection phenotypes, identify how each one is associated with anti-HLA antibodies, and investigate their distinct prognoses.Patients who underwent ABO-compatible kidney transplantations in Necker Hospital and Saint-Louis Hospital (Paris, France) between Jan 1, 1998, and Dec 31, 2008, were included in our population-based study. We assessed patients who provided biopsy samples for acute allograft rejection, which was defined as the association of deterioration in function and histopathological lesions. The main outcome was kidney allograft loss-ie, return to dialysis. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology, C4d in allograft biopsies, and donor-specific anti-HLA antibodies.2079 patients were included in the main analyses, of whom 302 (15%) had acute biopsy-proven rejection. We identified four distinct patterns of kidney allograft rejection: T cell-mediated vascular rejection (26 patients [9%]), antibody-mediated vascular rejection (64 [21%]), T cell-mediated rejection without vasculitis (139 [46%]), and antibody-mediated rejection without vasculitis (73 [24%]). Risk of graft loss was 9·07 times (95 CI 3·62-19·7) higher in antibody-mediated vascular rejection than in T cell-mediated rejection without vasculitis (p0·0001), compared with an increase of 2·93 times (1·1-7·9; P=0·0237) in antibody-mediated rejection without vasculitis and no significant rise in T cell-mediated vascular rejection (hazard ratio [HR] 1·5, 95% CI 0·33-7·6; p=0·60).We have identified a type of kidney rejection not presently included in classifications: antibody-mediated vascular rejection. Recognition of this distinct phenotype could lead to the development of new treatment strategies that could salvage many kidney allografts.None.
- Published
- 2012
46. Early Identification of Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and Consideration for Organ Donation
- Author
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Eloi Marijon, Alain Cariou, Wulfran Bougouin, Nicole Karam, Alexandre Loupy, Corinne Antoine, Carmen Lefaucheur, Jean-Philippe Empana, Pierre Carli, Xavier Jouven, Benjamin Dahan, Patricia Jabre, Frédéric Adnet, Thomas D. Rea, Laurent Jacob, Florence Dumas, Daniel Jost, and Frankie Beganton
- Subjects
Male ,medicine.medical_specialty ,Resuscitation ,Tissue and Organ Procurement ,Clinical Decision-Making ,030204 cardiovascular system & hematology ,Out of hospital cardiac arrest ,03 medical and health sciences ,0302 clinical medicine ,Internal Medicine ,medicine ,Humans ,Organ donation ,Intensive care medicine ,Clinical decision ,Survival analysis ,Aged ,Retrospective Studies ,business.industry ,030208 emergency & critical care medicine ,Retrospective cohort study ,General Medicine ,United States ,Medical services ,Transplantation ,Early Diagnosis ,Female ,France ,business ,Out-of-Hospital Cardiac Arrest - Abstract
In patients with out-of-hospital cardiac arrest (OHCA), care requirements can conflict with the need to promptly focus efforts on organ donation in patients who are pronounced dead.To evaluate objective criteria for identifying patients with OHCA with no chance of survival during the first minutes of cardiopulmonary resuscitation to enable prompt orientation toward organ donation.Retrospective assessment using OHCA data from 2 registries and 1 trial.France (Paris Sudden Death Expertise Center [SDEC] prospective cohort [2011 to 2014] and PRESENCE multicenter cluster randomized trial [ClinicalTrials.gov: NCT01009606] [2009 to 2011]) and the United States (King County, Washington, prospective cohort [2006 to 2011]).1771 patients from the Paris SDEC 1-year cohort (2011 to 2012) and 5192 from the validation cohorts.Evaluation of 3 objective criteria (OHCA not witnessed by emergency medical services personnel, nonshockable initial cardiac rhythm, and no return of spontaneous circulation before receipt of a third 1-mg dose of epinephrine), survival rate at hospital discharge among patients meeting these criteria, performance of the criteria, and number of patients eligible for organ donation.In the Paris SDEC 1-year cohort, the survival rate among the 772 patients with OHCA who met the objective criteria was 0% (95% CI, 0.0% to 0.5%), with a specificity of 100% (CI, 97% to 100%) and a positive predictive value of 100% (CI, 99% to 100%). These results were verified in the validation cohorts. Ninety-five (12%) patients in the Paris SDEC 1-year cohort may have been eligible for organ donation.Several patients had unknown outcomes.Three objective criteria enable the early identification of patients with OHCA with essentially no chance of survival and may help in decision making about the organ donation process.French Ministry of Health.
- Published
- 2016
47. PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor
- Author
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Pascal Houillier, Soline Bourgeois, Bharath Wootla, Dominique Eladari, Renaud de la Faille, Robert H. Dodd, Kamel Laghmani, Corinne Collet, Régine Chambrey, Patrick Bruneval, Hélène Faure, Martial Ruat, Erik Ilsø Christensen, Chantal Mandet, Lydie Cheval, Suresh Krishna Ramakrishnan, Alexandre Loupy, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), CNRS ERL 8228 - Laboratoire de physiologie rénale et tubulopathies, 75006, Paris, France. (TIR), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Métabolisme et physiologie rénales (ERL 8228), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
- Subjects
Male ,MESH: Amino Acids ,[SDV]Life Sciences [q-bio] ,030232 urology & nephrology ,Pamidronate ,Parathyroid hormone ,MESH: Rats, Sprague-Dawley ,MESH: Pamidronate ,Rats, Sprague-Dawley ,0302 clinical medicine ,MESH: Animals ,Amino Acids ,Solute Carrier Family 12, Member 1 ,MESH: Sodium-Potassium-Exchanging ATPase ,0303 health sciences ,Kidney ,Bone Density Conservation Agents ,Diphosphonates ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Chemistry ,Reabsorption ,MESH: Naphthalenes ,General Medicine ,Parathyroid chief cell ,MESH: Parathyroid Hormone ,MESH: Parathyroidectomy ,medicine.anatomical_structure ,Parathyroid Hormone ,Creatinine ,MESH: Permeability ,MESH: Calcium ,MESH: Solute Carrier Family 12, Member 1 ,Sodium-Potassium-Exchanging ATPase ,Calcium-sensing receptor ,MESH: Receptors, Calcium-Sensing ,medicine.medical_specialty ,MESH: Rats ,Hypoparathyroidism ,Sodium-Potassium-Chloride Symporters ,MESH: Diphosphonates ,Osteocalcin ,chemistry.chemical_element ,MESH: Creatinine ,Naphthalenes ,Calcium ,Permeability ,MESH: Osteocalcin ,MESH: Bone Density Conservation Agents ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,030304 developmental biology ,Parathyroidectomy ,Calcium metabolism ,MESH: Hypoparathyroidism ,MESH: Sodium-Potassium-Chloride Symporters ,urogenital system ,medicine.disease ,MESH: Male ,Rats ,Endocrinology ,Loop of Henle ,Receptors, Calcium-Sensing ,MESH: Loop of Henle - Abstract
International audience; Tight regulation of calcium levels is required for many critical biological functions. The Ca2+-sensing receptor (CaSR) expressed by parathyroid cells controls blood calcium concentration by regulating parathyroid hormone (PTH) secretion. However, CaSR is also expressed in other organs, such as the kidney, but the importance of extraparathyroid CaSR in calcium metabolism remains unknown. Here, we investigated the role of extraparathyroid CaSR using thyroparathyroidectomized, PTH-supplemented rats. Chronic inhibition of CaSR selectively increased renal tubular calcium absorption and blood calcium concentration independent of PTH secretion change and without altering intestinal calcium absorption. CaSR inhibition increased blood calcium concentration in animals pretreated with a bisphosphonate, indicating that the increase did not result from release of bone calcium. Kidney CaSR was expressed primarily in the thick ascending limb of the loop of Henle (TAL). As measured by in vitro microperfusion of cortical TAL, CaSR inhibitors increased calcium reabsorption and paracellular pathway permeability but did not change NaCl reabsorption. We conclude that CaSR is a direct determinant of blood calcium concentration, independent of PTH, and modulates renal tubular calcium transport in the TAL via the permeability of the paracellular pathway. These findings suggest that CaSR inhibitors may provide a new specific treatment for disorders related to impaired PTH secretion, such as primary hypoparathyroidism.
- Published
- 2012
48. Selective alkylations of 1,4:3,6-dianhydro-d-glucitol (isosorbide)
- Author
-
R. Tamion, D. Abenhaim, Guy Quéguiner, André Loupy, Francis Marsais, and L. Munnier
- Subjects
Allyl bromide ,Isosorbide ,Bicyclic molecule ,organic chemicals ,Organic Chemistry ,food and beverages ,Regioselectivity ,General Medicine ,Alkylation ,Biochemistry ,Medicinal chemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Benzyl chloride ,chemistry ,Acetylation ,Reagent ,medicine ,lipids (amino acids, peptides, and proteins) ,medicine.drug - Abstract
Each of the two hydroxyl groups of isosorbide can be alkylated selectively, either by direct alkylation with benzyl chloride or allyl bromide according to the reaction conditions, or by a three-step procedure involving selective monoacetylation, alkylation with four different reagents, and finally deacetylation. Monobutyl and monomethyl derivatives from isosorbide are also described.
- Published
- 1994
49. Solvent-free benzylation of polyols by phase-transfer catalysis or supported reagent methods
- Author
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J. Cleophax, André Loupy, and Didier Dubreuil
- Subjects
chemistry.chemical_classification ,Chemistry ,Organic Chemistry ,General Medicine ,Tartrate ,Biochemistry ,Analytical Chemistry ,Catalysis ,Solvent ,chemistry.chemical_compound ,Aldose ,Reagent ,Organic chemistry ,Ammonium ,Selectivity ,Aliphatic compound - Abstract
Solvent-free techniques were successfully and efficiently applied under mild conditions to the perbenzylation of methyl α- d -glucopyranoside and methyl 6-bromo(and 6-chloro)-6-deoxy-α- d -glucopyranoside, and to the selective monobenzylation of diethyl (R,R)-tartrate. Selective 2-O- or 3-O-benzylation of methyl 4,6-O-benzylidene-α- d -galactopyranoside, requiring CH2Cl2 as solvent, was observed depending on the nature of the ammonium catalyst.
- Published
- 1994
50. A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy
- Author
-
Gary S. Hill, Jean-Paul Duong Van Huyen, Olivier Kourilsky, Alexandre Karras, Véronique Frémeaux-Bacchi, Khalil El Karoui, Alexandre Loupy, Christian Jacquot, Patrick Bruneval, Luc Moulonguet, Dominique Nochy, and Michel Delahousse
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Thrombotic microangiopathy ,Adolescent ,Tubular atrophy ,urologic and male genital diseases ,Kidney ,Gastroenterology ,Nephropathy ,Young Adult ,Clinical Research ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Prevalence ,Humans ,Clinical significance ,neoplasms ,Aged ,Retrospective Studies ,business.industry ,Thrombotic Microangiopathies ,Histology ,Glomerulonephritis ,Glomerulonephritis, IGA ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,female genital diseases and pregnancy complications ,medicine.anatomical_structure ,Nephrology ,Hypertension ,Tubulointerstitial fibrosis ,Blood Vessels ,Female ,France ,business - Abstract
Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or
- Published
- 2011
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