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1. Comparison between the EKFC-equation and machine learning models to predict Glomerular Filtration Rate

Author

Felipe Kenji Nakano, Anna Åkesson, Jasper de Boer, Klest Dedja, Robbe D’hondt, Fateme Nateghi Haredasht, Jonas Björk, Marie Courbebaisse, Lionel Couzi, Natalie Ebert, Björn O. Eriksen, R. Neil Dalton, Laurence Derain-Dubourg, Francois Gaillard, Cyril Garrouste, Anders Grubb, Lola Jacquemont, Magnus Hansson, Nassim Kamar, Christophe Legendre, Karin Littmann, Christophe Mariat, Toralf Melsom, Lionel Rostaing, Andrew D. Rule, Elke Schaeffner, Per-Ola Sundin, Arend Bökenkamp, Ulla Berg, Kajsa Åsling-Monemi, Luciano Selistre, Anders Larsson, Ulf Nyman, Antoine Lanot, Hans Pottel, Pierre Delanaye, and Celine Vens

Subjects
Medicine, Science
Abstract

Abstract In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC.

Published
2024
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2. Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study

Author

Julien Aniort, Felix Richard, François Thouy, Louis Le Guen, Carole Philipponnet, Cyril Garrouste, Anne Elisabeth Heng, Claire Dupuis, Mireille Adda, Durif Julie, Lebredonchel Elodie, Laurent Chupin, Damien Bouvier, Bertrand Souweine, and Nicolae Cindea

Subjects
Hemodialysis, Calcium, Citrate, Dialysate, Modeling, Anticoagulation, Medicine, Science
Abstract

Abstract Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.

Published
2024
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3. Impact of Calcineurin Inhibitor-Based Immunosuppression Maintenance During the Dialysis Period After Kidney Transplant Failure on the Next Kidney Graft Outcome: A Retrospective Multicenter Study With Propensity Score Analysis

Author

Juliette Noelle, Valentin Mayet, Céline Lambert, Lionel Couzi, Bertrand Chauveau, Antoine Thierry, Laure Ecotière, Dominique Bertrand, Charlotte Laurent, Richard Lemal, Clarisse Grèze, Marine Freist, Anne-Elisabeth Heng, Paul-Olivier Rouzaire, and Cyril Garrouste

Subjects
kidney retransplant, kidney transplant failure, calcineurin inhibitor maintenance, waiting list, immunosuppression, Specialties of internal medicine, RC581-951
Abstract

The impact of immunosuppressive therapy (IS) strategies after kidney transplant failure (KTF) on potential future new grafts is poorly established. We assessed the potential benefit of calcineurin inhibitor (CNI)-based IS maintenance throughout the dialysis period on the outcome of the second kidney transplant (KT). We identified 407 patients who underwent a second KT between January 2008 and December 2018 at four French KT centers. Inverse probability of treatment weighting was used to control for potential confounding. We included 205 patients with similar baseline characteristics at KTF: a total of 53 received at least CNIs on the retransplant day (G-CNI), and 152 did not receive any IS (G-STOP). On the retransplant date, G-STOP patients experienced a longer pretransplant dialysis time, were more often hyperimmunized, and underwent more expanded-criteria donor KTs than G-CNI patients. During the second KT follow-up period, rejection episodes were similar in both groups. The 10-year survival rates without death and dialysis were 98.7% and 59.5% in G-CNI and G-STOP patients, respectively. In the multivariable analysis, CNI-based IS maintenance was associated with better survival (hazard ratio: 0.08; 95% confidence interval: 0.01–0.58, p = 0.01). CNI-based IS maintenance throughout the dialysis period after KTF may improve retransplantation outcomes.

Published
2023
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4. Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults

Author

Thomas Barbour, Marie Scully, Gema Ariceta, Spero Cataland, Katherine Garlo, Nils Heyne, Yosu Luque, Jan Menne, Yoshitaka Miyakawa, Sung-Soo Yoon, David Kavanagh, Sunil Babu, Nilufer Broeders, Nicole Lietar, Fiona Brown, Philip Campbell, Josep M. Campistol, Paramit Chowdhury, Theo Kasimatis, Lino Cirami, Leonardo Caroti, Guilia Antognoli, Yahsou Delmas, Vladimir Dobronravov, Anja Gaeckler, Cyril Garrouste, Gregory Greenwood, Siân Griffin, Chiu-Ching Huang, I-Ru Chen, Susan Huang, Jin Seok Kim, Gaetano La Manna, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Eric Rondeau, Hermann Haller, Johan Morelle, Eric Goffin, Anja Muhlfeld, Shashi Nagaraj, Gowthami Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, Francois Provot, Ulf Schönermarck, Michael Fischereder, Natalia Ramos Terrada, Barbara Seitz-Polski, Guillaume Favre, Sonia Boyer-Suavet, Maria Vinogradova, Tatiana Kirsanova, and Edwin K.S. Wong

Subjects
atypical hemolytic uremic syndrome, complement, hemolytic uremic syndrome, kidney failure, ravulizumab, thrombotic microangiopathy, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. Methods: The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6–118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. Results: A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. Conclusion: This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment.

Published
2021
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5. Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study

Author

Elodie Miquelestorena-Standley, Charlotte Jaulerry, Marie-Christine Machet, Nolwenn Rabot, Christelle Barbet, Aurélie Hummel, Alexandre Karras, Cyril Garrouste, Thomas Crepin, Didier Ducloux, Maud Cousin, Catherine Albert, Joseph Rivalan, Emilie Cornec-Le Gall, François Pourreau, Clément Deltombe, Dominique Nochy, Nora Szlavik, Sophie Felix, Anne Croué, David Buob, Nathalie Rioux-Leclerc, Laurent Doucet, Jean-Michel Goujon, Karine Renaudin, Emmanuelle Blanchard, Sébastien Eymieux, Marion Rabant, and Jean-Michel Halimi

Subjects
Infection, Kidney, Staphylococcus, IgA, Diabetes, Pathology, RB1-214
Abstract

Abstract Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007–2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Published
2020
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7. Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after Kidney Transplantation.

Author

Dominique Bertrand, Rangolie Kaveri, Charlotte Laurent, Philippe Gatault, Maïté Jauréguy, Cyril Garrouste, Johnny Sayegh, Nicolas Bouvier, Sophie Caillard, Luca Lanfranco, Antoine Thierry, Arnaud François, Françoise Hau, Isabelle Etienne, Dominique Guerrot, and Fabienne Farce

Subjects
Medicine, Science
Abstract

De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.

Published
2021
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8. Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

Author

Julien Aniort, Marine Freist, Aurélien Piraud, Carole Philipponnet, Mohamed Hadj Abdelkader, Cyril Garrouste, Elodie Gentes, Bruno Pereira, and Anne-Elisabeth Heng

Subjects
Medicine, Science
Abstract

Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40[0.26-0.55] μg/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.

Published
2020
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9. Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E [v2; ref status: indexed, http://f1000r.es/2q8]

Author

Xavier Moisset, Nicolas Vitello, Elodie Bicilli, Romain Courtin, Anna Ferrier, Frederic Taithe, Clément Lahaye, Ali Ait Hssain, Cyril Garrouste, and Clavelou Pierre

Subjects
Musculoskeletal Pain & Analgesia, Neuromuscular Diseases, Viral Infections (without HIV), Medicine, Science
Abstract

Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. Case report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding. A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has not yet been determined.

Published
2014
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10. Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E [v1; ref status: indexed, http://f1000r.es/29a]

Author

Xavier Moisset, Nicolas Vitello, Elodie Bicilli, Romain Courtin, Anna Ferrier, Frederic Taithe, Clément Lahaye, Ali Ait Hssain, Cyril Garrouste, and Clavelou Pierre

Subjects
Musculoskeletal Pain & Analgesia, Neuromuscular Diseases, Viral Infections (without HIV), Medicine, Science
Abstract

Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. Case report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding. A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has not yet been determined.

Published
2013
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12. Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study

Author

Paolo Malvezzi, Dany Anglicheau, Sophie Caillard, Julien Aniort, Betoul Schvartz, Antoine Thierry, Nicolas Bouvier, Christophe Legendre, Vincent Pernin, Clarisse Greze, Coralie Poulain, Nicolas Maillard, Jean Philippe Rerolle, Camille Lanaret, Nassim Kamar, Didier Ducloux, Arnaud Del Bello, Charlotte Uro‐Coste, Cyril Garrouste, Franck Martinez, Julie Oniszczuk, Dominique Bertrand, Lionel Couzi, Anne Elisabeth Heng, Laurent Mesnard, Céline Lambert, Johnny Sayegh, Vincent Audard, Marie-Pascale Morin, and Mathias Büchler

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, 030230 surgery, Gastroenterology, Hypogammaglobulinemia, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Kidney transplantation, Retrospective Studies, Transplantation, Glomerulosclerosis, Focal Segmental, Primary Focal Segmental Glomerulosclerosis, business.industry, medicine.disease, Kidney Transplantation, Calcineurin, Treatment Outcome, Plasmapheresis, Rituximab, Complication, business, Kidney disease, medicine.drug
Abstract

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia

Published
2021
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14. Living kidney donor evaluation for all candidates with normal estimated GFR for age

Author

Dimitri Titeca-Beauport, Nassim Kamar, Didier Ducloux, Benoit Barrou, Lola Jacquemont, Lionel Couzi, Nicolas Bouvier, Valérie Moal, Fatouma Touré, Bruno Moulin, Yann Le Meur, Cyril Garrouste, Denis Glotz, Lionel Rostaing, Antoine Thierry, Marie Courbebaisse, Hélène Lazareth, Isabelle Etienne, Jonathan M. Chemouny, François Gaillard, Christophe Legendre, Claire Pouteil-Noble, Philippe Rieu, Marc Hazzan, Mathias Büchler, Philippe Grimbert, Laetitia Albano, Michel Delahousse, Maryvonne Hourmant, Pierre Delanaye, Nacera Ouali, Luc Frimat, Christiane Mousson, Moglie Le Quintrec, Alexandre Hertig, Christophe Mariat, Retiveau, Nolwenn, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Clermont-Ferrand, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital de Bohars - CHRU Brest (CHU - BREST ), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Tenon [AP-HP], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, CHU Pontchaillou [Rennes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Liège, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Hôpital Nord (Saint Etienne), CHU Toulouse [Toulouse]-PRES Université de Toulouse, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Population, Urology, Renal function, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Kidney, Nephrectomy, MESH: Kidney Transplantation, 03 medical and health sciences, Age, Living kidney donors, 0302 clinical medicine, Age groups, Living Donors, medicine, Humans, education, MESH: Living Donors, Transplantation, education.field_of_study, MESH: Humans, MESH: Middle Aged, business.industry, Kidney donation, Estimated GFR, MESH: Kidney, Middle Aged, Post-donation GFR, Kidney Transplantation, MESH: Nephrectomy, MESH: Glomerular Filtration Rate, medicine.anatomical_structure, MESH: Kidney Failure, Chronic, Donation, Screening, Kidney Failure, Chronic, 030211 gastroenterology & hepatology, DONOR EVALUATION, business, Glomerular Filtration Rate
Abstract

International audience; Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is 55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.

Published
2021
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16. Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate

Author

Hans Pottel, Lola Jacquemont, Lionel Rostaing, Stephen T. Turner, Jonas Björk, Christophe Mariat, Andrew D. Rule, Anders Grubb, Kajsa Åsling-Monemi, Ulla B. Berg, Anna Åkesson, Lionel Couzi, Cyril Garrouste, Anders Larsson, Edmund J. Lamb, Per-Ola Sundin, Christophe Legendre, Elke Schaeffner, Luciano Selistre, Magnus Hansson, Toralf Melsom, Karin Littmann, Laurence Dubourg, Nassim Kamar, Arend Bökenkamp, François Gaillard, R Neil Dalton, Bjørn Odvar Eriksen, Pierre Delanaye, Natalie Ebert, Marie Courbebaisse, Ulf Nyman, Pediatric surgery, and Amsterdam Reproduction & Development (AR&D)

Subjects
medicine.medical_specialty, Creatinine, Cross-sectional study, business.industry, 010102 general mathematics, Urology, External validation, Renal function, General Medicine, medicine.disease, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Internal Medicine, medicine, Pooled data, 030212 general & internal medicine, 0101 mathematics, Young adult, Internal validation, business, Kidney disease
Abstract

Background The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. Objective To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. Design Cross-sectional analysis with separate pooled data sets for development and validation. Setting Research and clinical studies (n = 13) with measured GFR available. Patients 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). Measurements Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. Results The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. Limitation No Black patients were included. Conclusion The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. Primary funding source Swedish Research Council (Vetenskapsradet).

Published
2021
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17. Belatacept-based immunosuppressive regimen in HIV-positive kidney transplant recipients

Author

Karim El Sakhawi, Philippe Attias, Anissa Moktefi, Alexandre Ingels, Philippe Remy, Dominique Bertrand, Marie Matignon, C. Champy, Giovanna Melica, Cyril Garrouste, Anne Scemla, David Mokrani, David Kheav, Antoine Morel, Philippe Grimbert, Paolo Malvezzi, and Jean-Daniel Lelièvre

Subjects
medicine.medical_specialty, medicine.medical_treatment, Population, 030232 urology & nephrology, graft survival, kidney transplantation, 030230 surgery, Belatacept, acute rejection, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Adverse effect, education, AcademicSubjects/MED00340, Kidney transplantation, Transplantation, education.field_of_study, immunosuppression, business.industry, graft function, Immunosuppression, Original Articles, medicine.disease, Calcineurin, Nephrology, Cohort, business, medicine.drug
Abstract

Background Kidney allograft survival in human immunodeficiency virus (HIV)-positive patients is lower than that in the general population. Belatacept increases long-term patient and allograft survival rates when compared with calcineurin inhibitors (CNIs). Its use in HIV-positive recipients remains poorly documented. Methods We retrospectively report a French cohort of HIV-positive kidney allograft recipients who were switched from CNI to belatacept, between June 2012 and December 2018. Patient and allograft survival rates, HIV immunovirological and clinical outcomes, acute rejection, opportunistic infections (OIs) and HLA donor-specific antibodies (DSAs) were analysed at 3 and 12 months, and at the end of follow-up (last clinical visit attended after transplantation). Results were compared with HIV-positive recipients group treated with CNI. Results Twelve patients were switched to belatacept 10 (2–25) months after transplantation. One year after belatacept therapy, patient and allograft survival rates scored 92% for both, two (17%) HIV virological rebounds occurred due to antiretroviral therapy non-compliance, and CD4+ and CD8+ T-cell counts remained stable over time. Serious adverse events included two (17%) acute steroid-resistant T-cell-mediated rejections and three (25%) OIs. Kidney allograft function significantly increased over the 12 post-switch months (P = 0.009), and DSAs remained stable at 12 months after treatment. The control group showed similar results in terms of patient and kidney allograft survival rates, DSA characteristics and proteinuria Conclusions Switch from CNI to belatacept can be considered safe and may increase long-term kidney allograft survival in HIV-positive kidney allograft recipients. These results need to be confirmed in a larger cohort.

Published
2020

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

Author

Nicolas Bouvier, Yannick Le Meur, Cyril Garrouste, Dominique Bertrand, Johnny Sayegh, Eloi Chevallier, Matthias Büchler, Sophie Caillard, Joseph Rivalan, Antoine Thierry, Lionel Rostaing, Philippe Gatault, Charlotte Colosio, Jean-Philippe Rerolle, Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratory of Immunology, CHRU de Tours, Tours, France, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Nephrology, Reims University Hospital, Reims, France, Centre Hospitalier Universitaire de Rennes (CHU Rennes), Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie [Clermont-Ferrand], CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble

Subjects
Adult, Male, Ledipasvir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, 030232 urology & nephrology, Antiviral Agents, Gastroenterology, Group A, Virus, Group B, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Kidney transplantation, Retrospective Studies, Fluorenes, Transplantation, business.industry, Imidazoles, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, chemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Benzimidazoles, Female, 030211 gastroenterology & hepatology, Surgery, Carbamates, France, business, Viral hepatitis, medicine.drug
Abstract

Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.

Published
2020
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20. MO385: Performance of Creatinine-Based Equations to Estimate Glomerular Filtration Rate in White and Black Subjects From Europe, Brazil and Africa

Author

Pierre Delanaye, Jonas Bjork, Emmanuelle Vidal-Petiot, Natalie Ebert, Bjørn Odvar Eriksen, Laurence Dubourg, Anders Grubb, Magnus Hansson, Edmund Lamb, Karin Littman, Christophe Mariat, Toralf Melsom, Elke Schaeffner, Per-Ola Sundin, Arend Bokenkamp, Ulla Berg, Kasja Asling-Monemi, Anna Åkesson, Anders Larsson, Etienne Cavalier, Neil Dalton, Marie Courbebaisse, Lionel Couzi, François Gaillard, Cyril Garrouste, Lola Jacquemont, Nassim Kamar, Christophe Legendre, Lionel Rostaing, Thomas Stehlé, Jean-Philippe Haymann, Luciano Selistre, Jorge Strogoff-de-Matos, Justine Bukabau, Ernest Sumaili, Eric Yayo, Dagui Monnet, Ulf Nyman, Hans Pottel, and Martin Flamant

Subjects
Transplantation, Nephrology
Abstract

BACKGROUND AND AIMS Current Glomerular filtration rate (GFR) estimating equations based on serum creatinine are facing increased criticism due to the inclusion of a race correction in black Americans with the CKD-EPI equation (CKD-EPIASR, A = Age, S = Sex, R = Race). A new equation without race (CKD-EPIAS) has been proposed. However, this equation was developed mainly from US cohorts. The performance of this new equation has been poorly compared with current European-developed creatinine-based equations, i.e. the Lund-Malmö Revised (LMR), and the new European Kidney Function Consortium (EKFC) METHOD Data from subjects over 18 years, representing 11 cohorts from Europe (previously described as the EKFC dataset, n = 13 856), and enhanced with data from Brazil (n = 100), France (n = 4429) and Africa [Democratic Republic of Congo (DRC) and Côte d'Ivoire, n = 508] were considered (n = 18 893 for the whole cohort). The EKFC cohort was considered as non-black population. All data from Africa derived from black individuals. From France, 964 subjects were self-reported as black (=Blacks from Paris). Measured GFR as a reference method and IDMS creatinine results were available. Median bias (eGFR—mGFR) with 95% confidence intervals (CI), imprecision (interquartile range: IQR), and P30 accuracy (percentage of eGFR-values within ± 30% of mGFR) with 95% CI were calculated. RESULTS Results are summarized in Table. CONCLUSION The new CKD-EPIAS has been launched in the USA for societal reasons and is now recommended by US guidelines. However, in Europe and Africa, its performance was suboptimal. The EKFC equation, using the usual Q values, or population-specific Q values (when available), displays the best performance over the whole age range for populations in Europe and Africa.

Published
2022
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21. Opportunistic infections after conversion to belatacept in kidney transplantation

Author

Isabelle Etienne, Rebecca Sberro, Cyril Garrouste, Ludivine Lebourg, Charlotte Colosio, Mathilde Lemoine, Antoine Thierry, Nicolas Bouvier, Dominique Bertrand, Philippe Gatault, Leonard Golbin, Sophie Caillard, Nathalie Chavarot, Maïté Jauréguy, Anne Grall-Jezequel, Johnny Sayegh, Dominique Guerrot, and Jean-Philippe Rerolle

Subjects
Graft Rejection, Male, medicine.medical_specialty, 030232 urology & nephrology, Renal function, Opportunistic Infections, 030230 surgery, Pneumocystis pneumonia, Belatacept, Gastroenterology, Abatacept, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Kidney transplantation, Retrospective Studies, Transplantation, business.industry, Incidence, Incidence (epidemiology), Graft Survival, Middle Aged, medicine.disease, Kidney Transplantation, Lymphoproliferative Disorders, Calcineurin, Nephrology, Cohort, Female, France, business, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.drug
Abstract

Background Belatacept (bela) rescue therapy seems to be a valuable option for calcineurin inhibitor chronic toxicity in kidney transplantation. Nevertheless, the risk of infection associated with bela is not well reported. Methods We report the rate of opportunistic infections (OPI) after a switch to bela in a multicentric cohort of 280 kidney transplant patients. Results Forty-two OPI occurred in 34 patients (12.1%), on average 10.8 ± 11.3 months after the switch. With a cumulative exposure of 5128 months of bela treatment, we found an incidence of 0.008 OPI/month of exposure, and 9.8 OPI/100 person-years. The most common OPI was cytomegalovirus (CMV) disease in 18/42 OPI (42.9%) and pneumocystis pneumonia in 12/42 OPI (28.6%). Two patients presented a progressive multifocal leucoencephalopathy and two patients developed a cerebral Epstein–Barr virus-induced post-transplant lymphoproliferative disease. OPI led to death in 9/34 patients (26.5%) and graft failure in 4/34 patients (11.8%). In multivariate analysis, estimated glomerular filtration rate Conclusions The risk of OPI is significant post-conversion to bela and may require additional monitoring and prophylactic therapy, particularly regarding pneumocystis pneumonia and CMV disease. These data need to be confirmed in a larger case–control study.

Published
2020
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22. IMPact of the COVID-19 epidemic on the moRTAlity of kidney transplant recipients and candidates in a French Nationwide registry sTudy (IMPORTANT)

Author

Olivier Thaunat, Camille Legeai, Dany Anglicheau, Lionel Couzi, Gilles Blancho, Marc Hazzan, Myriam Pastural, Emilie Savoye, Florian Bayer, Emmanuel Morelon, Yann Le Meur, Olivier Bastien, Sophie Caillard, Charlene Levi, Fanny Buron, Alice Koenig, Thomas Barba, Bruno Moulin, Samira Fafi-Kremer, Anglicheau Dany, Alexandre Hertig, Jérôme Tourret, Benoit Barrou, Pierre Merville, Anna Kaminski, Valérie Moal, Tristan Legris, Pierre-François Westeel, Maïté Jaureguy, Luc Frimat, Didier Ducloux, Jamal Bamoulid, Dominique Bertrand, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Yannick Le Meur, Christophe Masset, Nassim Kamar, Hélène Francois, Eric Rondeau, Nicolas Bouvier, Christiane Mousson, Matthias Buchler, Philippe Gatault, Jean-François Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Philippe Grimbert, Marie Matignon, Antoine Durrbach, Clarisse Greze, Renaud Snanoudj, Charlotte Colosio, Betoul Schvartz, Paolo Malvezzi, Christophe Mariat, Antoine Thierry, Moglie Le Quintrec, Antoine Sicard, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cellules B normales et pathogéniques - Normal and pathogenic B cell responses (NOPAB), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Agence de la biomédecine [Saint-Denis la Plaine], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, French nationwide Registry of Solid Organ Transplant Recipients with COVID-19: Olivier Thaunat, Emmanuel Morelon, Charlene Levi, Fanny Buron, Alice Koenig, Thomas Barba, Sophie Caillard, Bruno Moulin, Samira Fafi-Kremer, Marc Hazzan, Anglicheau Dany, Alexandre Hertig, Jérôme Tourret, Benoit Barrou, Lionel Couzi, Pierre Merville, Anna Kaminski, Valérie Moal, Tristan Legris, Pierre-François Westeel, Maïté Jaureguy, Luc Frimat, Didier Ducloux, Jamal Bamoulid, Dominique Bertrand, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Yannick Le Meur, Gilles Blancho, Christophe Masset, Nassim Kamar, Hélène Francois, Eric Rondeau, Nicolas Bouvier, Christiane Mousson, Matthias Buchler, Philippe Gatault, Jean-François Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Philippe Grimbert, Marie Matignon, Antoine Durrbach, Clarisse Greze, Renaud Snanoudj, Charlotte Colosio, Betoul Schvartz, Paolo Malvezzi, Christophe Mariat, Antoine Thierry, Moglie Le Quintrec, Antoine Sicard, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, CCSD, Accord Elsevier, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Pediatrics, MESH: Registries, Registry study, 030232 urology & nephrology, Kidney transplant, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Kidney Transplantation, Postoperative Complications, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Postoperative Complications, Pandemic, MESH: COVID-19, Registries, Wasting, Kidney transplantation, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Middle Aged, renal transplantation, 3. Good health, MESH: Waiting Lists, Nephrology, Female, France, medicine.symptom, Adult, medicine.medical_specialty, Waiting Lists, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Intensive care, medicine, Humans, ESRD, Epidemics, MESH: Epidemics, Aged, Retrospective Studies, MESH: Humans, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, mortality, MESH: Male, MESH: France, 030104 developmental biology, business, MESH: Female
Abstract

International audience; End stage kidney disease increase the risk of COVID-19 related death but how the kidney replacement strategy should be adapted during the pandemic is unknown. Chronic hemodialysis makes social distancing difficult to achieve. Alternatively, kidney transplantation could increase the severity of COVID-19 due to therapeutic immunosuppression and contribute to saturation of intensive care units. For these reasons, kidney transplantation was suspended in France during the first epidemic wave. Here, we retrospectively evaluated this strategy by comparing the overall and COVID-19 related mortality in kidney transplant recipients and candidates over the last three years. Cross-interrogation of two national registries for the period 1 March and 1 June 2020, identified 275 deaths among the 42812 kidney transplant recipients and 144 deaths among the 16210 candidates. This represents an excess of deaths for both populations, as compared with the same period the two previous years (mean of two previous years: 253 in recipients and 112 in candidates). This difference was integrally explained by COVID-19, which accounted for 44% (122) and 42% (60) of the deaths in recipients and candidates, respectively. Taking into account the size of the two populations and the geographical heterogeneity of virus circulation, we found that the excess of risk of death due to COVID-19 was similar for recipients and candidates in high viral risk area but four-fold higher for candidates in the low viral risk area. Thus, in case of a second epidemic wave, kidney transplantation should be suspended in high viral risk areas but maintained outside those areas, both to reduce the excess of deaths of candidates and avoid wasting precious resources.

Published
2020
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23. Impact of obesity in kidney transplantation: a prospective cohort study from French registries between 2008 and 2014

Author

Laurent Guy, Guillaume Clerfond, Clémentine Millet, Anne-Elisabeth Heng, Yves Boirie, Clarisse Greze, Cyril Garrouste, Bruno Pereira, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand

Subjects
medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Obesity, Prospective Studies, Registries, Risk factor, Prospective cohort study, Survival rate, Kidney transplantation, Dialysis, Transplantation, business.industry, Graft Survival, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, Nephrology, Kidney Failure, Chronic, medicine.symptom, Complication, business
Abstract

Background The access of obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis. The aim of this study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes. Methods We carried out a prospective cohort study using two French registries, the Renal Epidemiology and Information Network and CRISTAL, on 7270 kidney transplant patients between 2008 and 2014 in France. We compared obese patients with non-obese patients and obese patients who lost more than 10% of weight before the transplant (obese WL and obese nWL). Results The mean BMI in our obese patients was 32 kg/m2. Graft survival was lower in obese patients than in non-obese patients {hazard ratio (HR) = 1.40, [95% confidence interval (95% CI) 1.09; 1.78], P = 0.007}, whereas patient survival was similar [HR = 0.94, (95% CI 0.73; 1.23), P = 0.66]. Graft survival was significantly lower in obese WL than in obese nWL [HR = 2.17, (1.02; 4.63), P = 0.045], whereas patient survival was similar in the two groups [HR = 0.79, (0.35; 1.77), P = 0.56]. Conclusion Grade 1 obesity does not seem to be a risk factor for excess mortality after kidney transplantation and should not be an obstacle to having access to a graft. Weight loss before a kidney transplant in these patients should not be essential for registration on waiting list.

Published
2021
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24. Case Report: Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E [version 2; referees: 4 approved]

Author

Xavier Moisset, Nicolas Vitello, Elodie Bicilli, Romain Courtin, Anna Ferrier, Frederic Taithe, Clément Lahaye, Ali Ait Hssain, Cyril Garrouste, and Clavelou Pierre

Subjects
Case Report, Articles, Musculoskeletal Pain & Analgesia, Neuromuscular Diseases, Viral Infections (without HIV), Amyotrophic neuralgia, Hepatitis E, dysphagia
Abstract

Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. Case report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding. A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has not yet been determined.

Published
2014
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25. Clinical utility of biochemical markers for the prediction of COVID-19-related mortality in kidney transplant recipients

Author

Sophie Caillard, Nathalie Chavarot, Hélène Francois, Marie Matignon, Renaud Snanoudj, Jérôme Tourret, Clarisse Greze, Olivier Thaunat, Luc Frimat, Pierre François Westeel, Philippe Gatault, Christophe Masset, Gilles Blancho, Tristan Legris, Valérie Moal, Nassim Kamar, Mariam Jdidou, Charlotte Colosio, Christiane Mousson, Valentin Goutadier, Antoine Sicard, Dominique Bertrand, Jamal Bamoulid, Paolo Malvezzi, Lionel Couzi, Jonathan M. Chemouny, Agnès Duveau, Christophe Mariat, Jean-Philippe Rerolle, Antoine Thierry, Nicolas Bouvier, Dany Anglicheau, Yannick Le Meur, Marc Hazzan, Bruno Moulin, Samira Fafi-Kremer, Alexandre Hertig, Benoit Barrou, Emmanuel Morelon, Pierre Merville, Pierre-François Westeel, Maïté Jaureguy, Didier Ducloux, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Eric Rondeau, Matthias Buchler, Jean-François Augusto, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Philippe Grimbert, Antoine Durrbach, Betoul Schvartz, Moglie Le Quintrec, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Foch [Suresnes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Université de Tours, Centre hospitalier universitaire de Nantes (CHU Nantes), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Bicêtre, Université de Reims Champagne-Ardenne (URCA), Université de Bourgogne (UB), Université de Montpellier (UM), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Grenoble Alpes (UGA), CHU Bordeaux [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Université d'Angers (UA), Université Jean Monnet [Saint-Étienne] (UJM), Université de Limoges (UNILIM), Université de Poitiers, Université de Caen Normandie (UNICAEN), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Tours (UT), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Jean Monnet - Saint-Étienne (UJM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), and Jonchère, Laurent

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], 030232 urology & nephrology, kidney transplantation, Inflammation, 030204 cardiovascular system & hematology, Kidney transplant, Procalcitonin, 03 medical and health sciences, 0302 clinical medicine, Medicine, Kidney transplantation, Biochemical markers, ComputingMilieux_MISCELLANEOUS, biology, business.industry, troponin, biomarkers, COVID-19, medicine.disease, Troponin, Research Letters, 3. Good health, [SDV] Life Sciences [q-bio], Nephrology, inflammation, D-dimer, Immunology, biology.protein, medicine.symptom, business, procalcitonin
Abstract

International audience

Published
2021
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26. Complement Activation and Thrombotic Microangiopathy Associated With Monoclonal Gammopathy: A National French Case Series

Author

Manon Martins, Frank Bridoux, Jean Michel Goujon, Marie Sophie Meuleman, David Ribes, Eric Rondeau, Mary-Jane Guerry, Yahsou Delmas, Bénédicte Levy, Didier Ducloux, Christine Kandel-Aznar, Awena Le Fur, Cyril Garrouste, François Provot, Jean-Baptiste Gibier, Eric Thervet, Patrick Bruneval, Marion Rabant, Alexandre Karras, Marie Agnès Dragon Durey, Veronique Fremeaux-Bacchi, and Sophie Chauvet

Subjects
Adult, Nephrology, Thrombotic Microangiopathies, Paraproteinemias, Humans, Complement System Proteins, Antibodies, Monoclonal, Humanized, Complement Activation, Atypical Hemolytic Uremic Syndrome, Retrospective Studies
Abstract

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy (TMA) with kidney involvement, is a rare condition in patients with monoclonal gammopathy. In the absence of known causes of TMA, the role of complement activation in endothelial injury in patients with monoclonal gammopathy remains unknown and was the focus of this investigation.Case series.We studied the 24 patients in the French national registry of HUS between 2000 and 2020 who had monoclonal gammopathy without other causes of secondary TMA. We provide the clinical histories and complement studies of these patients.Monoclonal gammopathy-associated TMA with kidney involvement is estimated to be 10 times less frequent than adult atypical HUS (aHUS) in the French national registry. It is characterized by severe clinical features, with 17 of 24 patients requiring dialysis at disease onset, and with median renal survival of only 20 months. TMA-mediated extrarenal manifestations, particularly cutaneous and neurological involvement, were common and associated with poor overall prognosis. Complement studies identified low C3, normal C4, and high soluble C5b-9 levels in 33%, 100%, and 77% of tested patients, respectively, indicating a contribution of the alternative and terminal complement pathways in the pathophysiology of the disease. Genetic abnormalities in complement genes known to be associated with aHUS were found in only 3 of 17 (17%) who were tested.Retrospective study without comparison group; limited number of patients, limited available blood samples.Within the spectrum of TMA, TMA associated with monoclonal gammopathy represents a distinct subset. Our findings suggest that HUS associated with monoclonal immunoglobulin is a complement-mediated disease akin to aHUS.

Published
2021

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

Author

David Navarro, Sophie Caillard, Leila Tricot, Marie Frimat, Rebecca Sberro Soussan, Jamal Bamoulid, Antoine Thierry, Christophe Legendre, Nassim Kamar, Pierre-François Westeel, Laetitia Albano, Magali Louis, Christophe Charasse, Chantal Loirat, Emilie Cornec-Le Gall, Dominique Bertrand, Jean-Philippe Rerolle, Lionel Couzi, Philippe Gatault, Cyril Garrouste, Aude Servais, Marie-Noëlle Peraldi, Sophie Chauvet, Joseph Rivalan, Yahsou Delmas, Guillaume Claisse, Jean-Philippe Coindre, Ziad A. Massy, Maryvonne Hourmant, Claire Pouteil-Noble, Michelle Elias, Johnny Sayegh, Charlotte Colosio, Luc Frimat, Nadia Arzouk, Noemie Jourde-Chiche, Eric Rondeau, Moglie Le Quintrec, Florent Petitprez, Raphaël Gaisne, Khalil El Karoui, Fadi Fakhouri, Véronique Frémeaux-Bacchi, Julien Zuber, Valérie Chatelet, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Emmanuel Boussard Foundation Fukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation

Subjects
Male, [SDV]Life Sciences [q-bio], Mutant Chimeric Proteins, 030232 urology & nephrology, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Epidemiology, Secondary Prevention, Medicine, complement, Registries, Kidney transplantation, Atypical Hemolytic Uremic Syndrome, education.field_of_study, Graft Survival, General Medicine, Middle Aged, Eculizumab, 3. Good health, Nephrology, Female, France, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Population, kidney transplantation, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Clinical Research, Internal medicine, Preoperative Care, Atypical hemolytic uremic syndrome, Complement C3b Inactivator Proteins, Humans, INHIBITOR ECULIZUMAB, RECURRENCE, education, Proportional Hazards Models, Retrospective Studies, MUTATIONS, business.industry, Complement System Proteins, medicine.disease, Complement Inactivating Agents, hemolytic uremic syndrome, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.Results The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

Published
2019
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28. No impact of disseminated intravascular coagulation in kidney donors on long-term kidney transplantation outcome: A multicenter propensity-matched study

Author

Julie Oniszczuk, Philippe Gatault, Cyril Garrouste, Julien Aniort, Marion Rabant, Bruno Pereira, Anne Elisabeth Heng, Antoine Thierry, Nora Szlavik, Julien Baudenon, Isabelle Etienne, Johnny Sayegh, Dany Anglicheau, and Céline Lambert

Subjects
Adult, Male, Brain Death, medicine.medical_specialty, Tissue and Organ Procurement, Urology, Delayed Graft Function, Renal function, 030230 surgery, Kidney Function Tests, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Organ donation, Contraindication, Kidney transplantation, Aged, Retrospective Studies, Disseminated intravascular coagulation, Transplantation, Kidney, business.industry, Incidence, Graft Survival, Disseminated Intravascular Coagulation, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Tissue Donors, Calcineurin, medicine.anatomical_structure, Kidney Failure, Chronic, Female, France, business, Follow-Up Studies, Glomerular Filtration Rate, circulatory and respiratory physiology
Abstract

The diagnosis of disseminated intravascular coagulation (DIC) is often considered to be a contraindication to organ donation. The aim of this study was to evaluate the impact of DIC+ donors on kidney recipient (KR) evolution. We identified 169 KRs with DIC+ donation after brain death donors between January 1996 and December 2012 in 6 French transplant centers. Individuals were matched using propensity scores to 338 recipients with DIC- donors according to donor age and sex, whether expanded criteria for the donor existed, graft year, and transplantation center. After kidney transplantation, delayed graft function was observed in 28.1% of DIC+ KRs and in 22.8% of DIC- KRs (NS). Renal allograft survival at 1, 5, and 10 years was 94.5%, 89.3%, and 73.9% and 96.2%, 90.8%, and 81.3% in DIC+ KRs and DIC- KRs, respectively (NS). The median estimated glomerular filtration rate (eGFR) was similar between DIC+ and DIC- KRs at 3 months, 1 year, and 10 years: 45.9 vs 48.1 mL/min, 42.1 vs 43.1 mL/min, and 33.9 vs 38.1 mL/min, respectively. Delayed calcineurin inhibitor introduction or induction had no impact on delayed graft function rate or eGFR evolution at 10 years after transplantation in DIC+ KRs. Donor DIC did not seem to affect initial outcome, long-term graft function, or allograft survival.

Published
2019
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30. [Evaluation of serum iron as a predictor of a hemoglobin response to injectable iron treatment in chronic hemodialysis patients]

Author

Clarisse, Grèze, Cyril, Garrouste, Bruno, Pereira, Mohammed, Hadj-Abdelkader, Anne-Élisabeth, Heng, and Julien, Aniort

Subjects
Hemoglobins, Anemia, Iron-Deficiency, Renal Dialysis, Iron, Ferritins, Hematinics, Transferrin, Humans, Kidney Failure, Chronic, Retrospective Studies
Abstract

The detection and correction of iron deficiency are essential for the treatment of anemia in chronic hemodialysis patients. The aim of our study was to assess the ability of serum iron to predict hemoglobin response to intravenous iron supplementation in hemodialysis patients.It is a retrospective study in 91 hemodialysis patients during 2016 at Clermont-Ferrand University Hospital for whom intravenous iron supplementation had been started. A responder patient was defined as an increase in hemoglobin greater than or equal to 1 g/dL/month and/or a decrease in the dose of erythropoiesis stimulating agent after two months of iron supplementation.In responding patients, serum iron was significantly lower (6.7 ± 2.7 μmol/L) compared to non-responding patients (8.9±2.9 μmol/L; P0.001). The positive response to iron supplementation was significantly associated with low serum iron (odds ratio = 0.58 [0.42-0.81]; P=0.002) in a logistic regression model taking into account ferritin, transferrin saturation coefficient, dose variation monthly iron and erythropoiesis stimulating agent and the duration of dialysis. The area under the receiver operating characteristic curve of serum iron, ferritin and transferrin saturation coefficient to predict the response to iron supplementation were 0.72, 0.51 and 0.64, respectively (serum iron versus ferritin [P=0.006] and serum iron versus transferrin saturation coefficient [P=0.04]). The sensitivity for serum iron below 7.5 μmol/L was better than that for ferritin below 86 ng/mL (P0.001) and the specificity for serum iron below 7.5 μmol/L was better than that for TSC less than 19% (P=0.02).Serum iron below 7.5 μmol/L can predict the success of the response to iron supplementation in chronic hemodialysis patients.

Published
2021

31. FC 055PERCENTILES OF NORMAL MEASURED GLOMERULAR FILTRATION RATE BASED ON DATA FROM LIVING KIDNEY DONORS

Author

Maryvonne Hourmant, Jessica Van Der Weijden, Karolien Goffin, Elke Schaeffner, Torbjörn Åkerfeldt, Christophe Legendre, Marco van Londen, Nassim Kamar, Laurence Dubourg, Hans Pottel, Cyril Garrouste, Geir Mjøen, Natalie Ebert, François Gaillard, Pierre Delanaye, Christophe Mariat, Laurent Weekers, Ingela Fehrman-Ekholm, Lionel Rostaing, Martin H. de Borst, Lionel Couzi, Antoine Bouquegneau, and Marie Courbebaisse

Subjects
Transplantation, medicine.medical_specialty, Kidney, medicine.anatomical_structure, Nephrology, business.industry, Urology, medicine, Renal function, business
Abstract

Background and Aims Studies of healthy individuals or candidates for living kidney donation, in various geographical areas and ethnic groups, describe a decline of glomerular filtration rate (GFR) with age. Most data on GFR are obtained from subjects in the general population or from candidates for kidney donation who are younger than 65 years. It is currently unknown whether the definition of normal GFR in subjects older than 65 years is similar to the definition in those younger than 65 years. Because the age of candidates for living kidney donation is increasing worldwide, lack of GFR references for older donors complicates the selection process. Moreover, older individuals are most likely to have a mildly decreased GFR that may be misinterpreted as chronic kidney disease. In this study, we calculated percentiles of measured GFR (mGFR) from a large cohort of effective kidney donors (EKD) younger than 65 years, and extrapolated them to subjects older than 65 years. Additionnaly, we collected mGFR data from different centers within Europe from EKD and/or healthy people (HP) from the general population older than 65 years. We tested if the distribution of mGFR of these older subjects fitted with the extrapolated percentiles. Method In this retrospective, observational, multi-center study, percentiles of mGFR in EKD were calculated from a development cohort of French and Belgian EKD younger than 65 years (n=1983). From the French kidney donor study, 147 EKD older than 65 years were considered as the internal validation cohort. In an external validation cohort, data on mGFR of subjects older than 65 years, either EKD or HP from the general population (from Germany, Sweden (2), Norway, Netherlands and France, n=2459) were included. Data were fully anonymized and this retrospective study was approved by the respective ethics committees. Percentiles were derived for the development database, using quantiles modeled as cubic splines with two linear parts joining at one age-knot of 40 years. The median quantile had a constant first part (slope of zero) and a second part with a negative slope of -0.88235 mL/min/1.73m² per year. To maintain consistency, all quantiles were adjusted to show the same shape as the medium quantile. Above 65 years, the percentile values were extrapolated using the same mathematical model. We then calculated the percentage of results from the internal and external validation cohorts that were within the 5th extrapolated percentile (P5) and 95th percentile (P95). A sensitivity analysis including the EKD only was performed. Results Individuals in the development cohort were younger than in the internal or external validation cohort (47.3±10.5 years vs. 68.8±2.9 years and 71.4±6.4 years; respectively, both p Conclusion We demonstrate that extrapolated percentiles of mGFR (calculated in individuals younger than 65) fits well with the distribution of mGFR in individuals older than 65. Extrapolation of percentiles to individuals older than 65 is useful to define age-adapted GFR thresholds for older individuals.

Published
2021
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32. Apheresis in Adult With Refractory Idiopathic Nephrotic Syndrome on Native Kidneys

Author

Christophe Mariat, Jean-Michel Halimi, Vincent Audard, Christiane Mousson, Fatouma Touré, Olivier Moranne, Noémie Jourde-Chiche, Lise Marie Pouteau, Lacraz Adeline, Alexandre Cez, Cyril Garrouste, Yahsou Delmas, Léa Moret, Bertrand Knebelman, Alexandre Ganea, Jean François Subra, Olivier Fritz, Myriam Dao, Johan Noble, Charlotte Laurent, Aurélie Hummel, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Limoges, Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Rouen, Normandie Université (NU), Centre Hospitalier de la Côte Basque (CHCB), CHU Bordeaux [Bordeaux], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de La Rochelle (CHR), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Laval (CH Laval), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Trousseau [Tours], EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Le CHCB, Centre Hospitalier de la Côte Basque, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Renal function, apheresis, 030204 cardiovascular system & hematology, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Refractory, Clinical Research, Internal medicine, minimal change nephrotic syndrome, medicine, Dialysis, focal segmental glomerulosclerosis, Proteinuria, business.industry, nephrotic syndrome, medicine.disease, Transplantation, Apheresis, Nephrology, medicine.symptom, business, Nephrotic syndrome
Abstract

Background Apheresis is the gold standard for idiopathic nephrotic syndrome (INS) relapse after transplantation, but it remains unknown whether such treatment is useful for adults with refractory INS on native kidneys. Methods This retrospective study included patients older than 16 years with biopsy-proven refractory (persistent nephrotic syndrome on corticosteroids plus at least 1 immunosuppressive drug) INS treated by apheresis and followed for at least 3 months. Results Between September 1997 and January 2020, 21 patients (focal segmental glomerulosclerosis: 12, minimal change nephrotic syndrome: 9, men: 67%, median age: 34 years) were identified. At last follow-up (12 months), 7 of 21 patients were in complete or partial remission. Remission was associated with older age (51 vs. 30 years, P = 0.05), lower proteinuria (3.9 vs. 7.3 g/d, P = 0.03), and lower estimated glomerular filtration rate (eGFR) (28.0 vs. 48.5 ml/min per 1.73 m2, P = 0.05) at apheresis. The need for dialysis before apheresis (odds ratio [OR] 22.0 [1.00–524], P = 0.026), age ≥50 years (OR: 22.6 [1.00–524], P = 0.006), a marked (>4.5 g/d) decrease in proteinuria (OR: 9.17 [1.15–73.2], P = 0.041), and a short (, Graphical abstract

Published
2021
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33. Management of Immunosuppression After Kidney Transplant Failure: Effect on Patient Sensitization

Author

Marine Freist, Céline Lambert, Dominique Bertrand, Julien Aniort, Cyril Garrouste, Matthias Büchler, Richard Lemal, Elodie Bailly, Paul Rouzaire, Anne Elisabeth Heng, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)

Subjects
Adult, Graft Rejection, Male, Reoperation, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Calcineurin Inhibitors, 030232 urology & nephrology, 030230 surgery, Gastroenterology, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Isoantibodies, Internal medicine, medicine, Humans, Sensitization, Dialysis, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Immunosuppression Therapy, Transplantation, business.industry, Immunosuppression, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Odds ratio, Middle Aged, Kidney Transplantation, Confidence interval, 3. Good health, Calcineurin, medicine.anatomical_structure, Female, Surgery, business, Immunosuppressive Agents
Abstract

Background Immunosuppressive treatment is often interrupted in the first months following kidney transplant failure (KTF) to limit side effects. The aim of this study was to assess the effect of prolonged treatment (PT) of more than 3 months’ duration after KTF on HLA sensitization and treatment tolerance. Methods We performed a retrospective observational study involving 119 patients with KTF in 3 French kidney transplant centers between June 2007 and June 2017. Sensitization was defined as the development of HLA donor-specific antibodies (DSA). Results In the PT group receiving calcineurin inhibitor (CNI) treatment, 30 of 52 patients (57.7%) were sensitized vs 52 of 67 patients (77.6%) who had early cessation of treatment (P = .02). The results were confirmed by multivariate analysis (odds ratio [OR] = 0.39, 95% confidence interval [CI] [0.16; 0.98], P = .04). The development of de novo DSAs after CNI treatment (n = 63/90 [70.0%]) was significantly more frequent than during CNI treatment, (n = 18/52 [34.6%], P = .01). Panel-reactive antibody ≥85% was lower in the PT group in multivariate analysis (OR = 0.28, 95% CI [0.10; 0.78], P = .02). No differences in the rates of infection, cardiovascular complications, neoplasia, and deaths were observed between the 2 groups. In multivariate analysis, continuation of corticosteroid treatment had no influence on sensitization but was associated with a higher rate of infection (OR = 2.66, 95% CI [1.09; 6.46], P = .03). Conclusion Maintenance of CNI treatment after return to dialysis in patients requesting a repeat transplant could avoid the development of anti-HLA sensitization with a good tolerance.

Published
2021
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34. Temporal trends in living kidney donation in France between 2007 and 2017

Author

Nicolas Bouvier, Valérie Moal, Antoine Durrbach, Michel Delahousse, Julien Allard, Alexandre Hertig, Cyril Garrouste, Lionel Couzi, Lionel Rostaing, Claire Pouteil-Noble, Laetitia Albano, Christophe Legendre, Marc Hazzan, Mathias Büchler, Cécile Vigneau, Bruno Moulin, Lola Jacquemont, Luc Frimat, Christophe Mariat, Marie Alice Macher, Christiane Mousson, François Gaillard, Moglie Le Quintrec, Isabelle Etienne, Veena Roberts, Dimitri Titeca-Beauport, Nassim Kamar, Antoine Thierry, Didier Ducloux, Philippe Rieu, Philippe Grimbert, Maryvonne Hourmant, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie, Hôpital Pasteur [Nice] (CHU), Laboratoire de Physiologie, Faculté de médecine Rangueil, Sciences Pour l'Oenologie (SPO), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de transplantation rénale, Hôpital Foch [Suresnes], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), U542, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Néphrologie et Transplantation, CHU Strasbourg, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Reims (CHU Reims), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Montpellier 1 (UM1)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, 030232 urology & nephrology, Renal function, 030230 surgery, Body Mass Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, temporal trends, Risk Factors, Internal medicine, medicine, Living Donors, Humans, Registries, 2. Zero hunger, Transplantation, Kidney, business.industry, Incidence, Kidney donation, Middle Aged, medicine.disease, Obesity, Kidney Transplantation, living kidney donors, Young age, Increased risk, medicine.anatomical_structure, Nephrology, Donation, Tissue and Organ Harvesting, Kidney Failure, Chronic, Female, France, business, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Glomerular Filtration Rate
Abstract

Background Long-term studies have demonstrated a slight increased risk for end-stage renal disease (ESRD) for living kidney donors (LKD). In France, living kidney donation doubled within the past 10 years. We investigated the change in characteristics of LKD between 2007 and 2017 and the adequacy of follow-up. Methods Data were obtained from the national registry for LKD. We compared characteristics of LKD between two study periods: 2007–11 and 2012–17, and stratified donors by age and relation to recipient. We aggregated four characteristics associated with higher ESRD risk [young age, first-degree relation to recipient, obesity, low glomerular filtration rate (GFR) for age] in a single risk indicator ranging from 0 to 4. Results We included 3483 donors. The proportion of unrelated donors >56 years of age increased significantly. The proportion of related donors Conclusions An increase in living kidney donation in France does not seem to be associated with the selection of donors at higher risk of ESRD and the proportion of donors with adequate annual follow-up significantly increased.

Published
2021
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35. Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E [version 1; referees: 4 approved]

Author

Xavier Moisset, Nicolas Vitello, Elodie Bicilli, Romain Courtin, Anna Ferrier, Frederic Taithe, Clément Lahaye, Ali Ait Hssain, Cyril Garrouste, and Clavelou Pierre

Subjects
Case Report, Articles, Musculoskeletal Pain & Analgesia, Neuromuscular Diseases, Viral Infections (without HIV), Amyotrophic neuralgia, Hepatitis E, dysphagia
Abstract

Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. Case report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding. A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has not yet been determined.

Published
2013
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37. Microsporidiosis after liver transplantation: A French nationwide retrospective study

Author

Jérôme, Dumortier, Sylvie, Radenne, Nassim, Kamar, Filomena, Conti, Armand, Abergel, Audrey, Coilly, Claire, Francoz, Pauline, Houssel-Debry, Claire, Vanlemmens, Noémie, Laverdure, Christophe, Duvoux, Xavier, Iriart, Marc, Thellier, Adela, Angoulvant, Nicolas, Argy, Brice, Autier, Anne-Pauline, Bellanger, Françoise, Botterel, Cyril, Garrouste, Meja, Rabodonirina, Philippe, Poirier, Perraud, Estelle, Hospices Civils de Lyon (HCL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030230 surgery, Liver transplantation, Microsporidiosis, Gastroenterology, Tacrolimus, Albendazole, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Fumagillin, Child, Dialysis, Retrospective Studies, Transplantation, liver transplantation, business.industry, Retrospective cohort study, Organ Transplantation, Middle Aged, medicine.disease, 3. Good health, Diarrhea, Infectious Diseases, microsporidiosis, Cyclosporine, 030211 gastroenterology & hepatology, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract

International audience; Background: Microsporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients.Methods: Through the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France.Results: We identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5-83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1-18.9) years post-transplant. Median duration of diarrhea before diagnosis was 22 days (12-45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients received specific therapy against microsporidiosis: fumagillin (n = 11) or albendazole (n = 4). Median duration of treatment was 14 days (8-45 days). Finally, 7 patients had immunosuppressive treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in one case. Two patients had infection relapse. No patient presented proven rejection within the 3 months after microsporidiosis. None of the patients died within the 3 months after microsporidiosis.Conclusions: Microsporidiosis is a very rare infection after liver transplantation but can induce severe dehydration and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes.

Published
2021
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38. Assessment of a Multiplex PCR for the Simultaneous Diagnosis of Intestinal Cryptosporidiosis and Microsporidiosis

Author

Cyril Garrouste, Frédéric Dalle, Frédéric Delbac, Loïc Favennec, Céline Nourrisson, Maxime Moniot, Philippe Poirier, Charlotte Faure, CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
030231 tropical medicine, Microsporidiosis, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Multiplex polymerase chain reaction, parasitic diseases, Medicine, Multiplex, Enterocytozoon bieneusi, 0303 health sciences, biology, 030306 microbiology, business.industry, fungi, Cryptosporidium, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, biology.organism_classification, Virology, Encephalitozoon intestinalis, 3. Good health, Microsporidia, Molecular Medicine, Encephalitozoon, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience; Microsporidiosis and cryptosporidiosis are associated with chronic diarrhea in immunocompromised patients. The objectives of this study were to: i) assess a multiplex quantitative PCR assay targeting Cryptosporidium spp and the microsporidian Enterocytozoon bieneusi and Encephalitozoon spp, and ii) provide an update on the epidemiology of these pathogens. A prospective study was conducted from January 2017 to January 2019. Performance of the assay was assessed, and all cryptosporidia and microsporidia isolates were genotyped. The sensitivity of the multiplex PCR method reached 1 copy/μL for each targeted pathogen. The sensitivity of co-proantigen testing in the diagnosis of cryptosporidiosis was 73%. The sensitivity of microscopy in the diagnosis of cryptosporidiosis was 64%, and microsporidiosis, 50%. Among the 456 patients included, 14 were positive for Cryptosporidium spp (4 different species); 5, for E. bieneusi; and 2, for Encephalitozoon intestinalis. The overall prevalence of cryptosporidia was 3.1%, and of microsporidia, 1.5%; in kidney transplant recipients (n = 82), corresponding values were 7.3% and 2.4% (6 and 2 patients), respectively. Two cases of E. intestinalis infection were diagnosed in children who had traveled to the tropics. This study is the first to assess a multiplex quantitative PCR method for the simultaneous diagnosis of intestinal microsporidiosis and cryptosporidiosis. The highest prevalences of both pathogens were observed in kidney transplant recipients

Published
2021
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39. An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants

Author

Sophie Caillard, Dany Anglicheau, Marie Matignon, Antoine Durrbach, Clarisse Greze, Luc Frimat, Olivier Thaunat, Tristan Legris, Valerie Moal, Pierre Francois Westeel, Nassim Kamar, Philippe Gatault, Renaud Snanoudj, Antoine Sicard, Dominique Bertrand, Charlotte Colosio, Lionel Couzi, Jonathan M. Chemouny, Christophe Masset, Gilles Blancho, Jamal Bamoulid, Agnes Duveau, Nicolas Bouvier, Nathalie Chavarot, Philippe Grimbert, Bruno Moulin, Yannick Le Meur, Marc Hazzan, Samira Fafi-Kremer, Alexandre Hertig, Jérôme Tourret, Benoit Barrou, Emmanuel Morelon, Pierre Merville, Valérie Moal, Pierre-François Westeel, Maïté Jaureguy, Didier Ducloux, Michel Tsimaratos, Florentine Garaix-Gilardo, Jérôme Dumortier, Sacha Mussot, Antoine Roux, Laurent Sebbag, Hélène Francois, Eric Rondeau, Christiane Mousson, Matthias Buchler, Jean-François Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, Jonathan Chemouny, Leonard Golbin, Betoul Schvartz, Paolo Malvezzi, Christophe Mariat, Antoine Thierry, Moglie Le Quintrec, Jean Philippe Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba, CHU Amiens-Picardie, Nouvel Hôpital Civil de Strasbourg, Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'investigation clinique [Nancy] (CIC), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, Hôpital Pasteur [Nice] (CHU), CHU Bordeaux [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université d'Angers (UA), Université de Caen Normandie (UNICAEN), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Immunosuppression Therapy, law.invention, chemistry.chemical_compound, 0302 clinical medicine, MESH: Aged, 80 and over, law, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, education.field_of_study, MESH: France / epidemiology, immunosuppression, Mortality rate, Immunosuppression, MESH: Kidney Transplantation / mortality, Intensive care unit, 3. Good health, Nephrology, MESH: Young Adult, Covid-19, medicine.medical_specialty, MESH: COVID-19 / complications, MESH: Postoperative Complications / virology, Population, kidney transplantation, Article, 03 medical and health sciences, Tocilizumab, Internal medicine, Diabetes mellitus, education, MESH: Pandemics / statistics & numerical data, business.industry, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Deprescriptions, mortality, 030104 developmental biology, chemistry, prognosis, business, MESH: Female
Abstract

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging., Graphical abstract

Published
2020
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40. Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

Author

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

Subjects
0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodialysis, Home, Disease, MESH: COVID-19 / therapy, registry, Ambulatory Care Facilities, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Aged, 80 and over, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, 80 and over, Prevalence, covid, dialysis, epidemiology, mortality, Aged, Aged, 80 and over, COVID-19, Case-Control Studies, Critical Care, Female, France, Humans, Incidence, Middle Aged, Patient Acuity, Protective Factors, Registries, Renal Dialysis, SARS-CoV-2, Sex Factors, Hypoalbuminemia, MESH: France / epidemiology, education.field_of_study, Incidence (epidemiology), 3. Good health, MESH: COVID-19 / epidemiology, Nephrology, Hemodialysis, medicine.medical_specialty, Population, Lower risk, Article, 03 medical and health sciences, MESH: Sex Factors, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Renal Dialysis / statistics & numerical data, education, Dialysis, Vascular disease, business.industry, medicine.disease, Former Smoker, MESH: Critical Care / statistics & numerical data, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Home, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Hemodialysis, Home / statistics & numerical data
Abstract

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

Published
2020
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41. Kidney Transplantation With a Sickle Cell Disease Donor

Author

Mohammed Hadj-Abdelkader, Jean-Louis Kemeny, Cyril Garrouste, Carole Philipponnet, Julien Aniort, Anne-Elisabeth Heng, Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and Service d'Anatomie Pathologique [CHU Clermont-Ferrand]

Subjects
business.industry, [SDV]Life Sciences [q-bio], Cell, 030232 urology & nephrology, MEDLINE, Disease, 030230 surgery, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, medicine.disease, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Text mining, Nephrology, Medicine, business, Nephrology Rounds, Kidney transplantation
Published
2020
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42. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort

Author

Rebecca Sberro, Antoine Thierry, Johan Noble, Anne Grall-Jezequel, Paolo Malvezzi, Johnny Sayegh, Nicolas Bouvier, Sophie Caillard, Florian Terrec, Maïté Jauréguy, Cyril Garrouste, Leonard Golbin, Eric Thervet, Thomas Jouve, Lionel Rostaing, Jean-Philippe Rerolle, Nathalie Chavarot, Philippe Gatault, Charlotte Colosio, Bénédicte Janbon, Dominique Bertrand, and Isabelle Etienne

Subjects
medicine.medical_specialty, 030232 urology & nephrology, Renal function, kidney transplantation, lcsh:Medicine, 030230 surgery, Pneumocystis pneumonia, Belatacept, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Cumulative incidence, tacrolimus, Kidney transplantation, belatacept, business.industry, Incidence (epidemiology), pneumocystis pneumonia, lcsh:R, General Medicine, opportunistic infections, medicine.disease, Cohort, business, CMV infection, medicine.drug, Cohort study
Abstract

Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13&ndash, 431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/&minus, 13 months. OPIs developed in 42(9.3%) patients after 14 +/&minus, 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%, p &lt, 0.001, and 11.6% vs. 2.4%, p &lt, 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person&ndash, years. Incidence of CMV disease was 2.8/100 person&ndash, years, of pneumocystis pneumonia 1.6/100 person&ndash, years, and of aspergillosis 0.2/100 person&ndash, years. Multivariate analyses showed that estimated glomerular filtration (eGFR) &lt, 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 &minus, 10.3), p &lt, 0.001). The incidence of EBV DNAemia was 17.3 events /100 person&ndash, years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/&minus, 18 mL/min/1.73 m2 to 42.2 +/&minus, 18 mL/min/1.73 m2 (p &lt, 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.

Published
2020

43. Prospects for improved glomerular filtration rate estimation based on creatinine-results from a transnational multicentre study

Author

Christophe Mariat, Christophe Legendre, Pierre Delanaye, Cyril Garrouste, Marie Courbebaisse, Andrew D. Rule, Edmund J. Lamb, Anders Grubb, Lola Jacquemont, Magnus Hansson, Anna Åkesson, Natalie Ebert, Elke Schaeffner, Hans Pottel, Stephen T. Turner, Jonas Björk, François Gaillard, Lionel Rostaing, Lionel Couzi, Bjørn Odvar Eriksen, R Neil Dalton, Toralf Melsom, Karin Littmann, Laurence Dubourg, Ulf Nyman, Ian Jones, Nassim Kamar, and Per-Ola Sundin

Subjects
medicine.medical_specialty, renal failure, ACCURACY, CKD-EPI, 030232 urology & nephrology, Urology, kidney function tests, Renal function, IOHEXOL CLEARANCE, GFR ESTIMATION, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Epidemiology, medicine, In patient, Young adult, AcademicSubjects/MED00340, Estimation, Transplantation, Creatinine, glomerular filtration rate, Science & Technology, CYSTATIN C, SERUM CREATININE, business.industry, creatinine, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, Original Articles, Urology & Nephrology, PERFORMANCE, medicine.disease, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, female genital diseases and pregnancy complications, RENAL-DISEASE, chemistry, Nephrology, RATE-ESTIMATING EQUATIONS, Cohort, business, Life Sciences & Biomedicine, chronic kidney disease, LUND-MALMO, Kidney disease
Abstract

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation. Results 7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels Conclusions None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.

Published
2020

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

Author

Matthias Büchler, Nicolas Maillard, Nicolas Bouvier, Céline Lambert, Dany Anglicheau, Camille Lanaret, Vincent Pernin, Clarisse Greze, Coralie Poulain, Audard Vincent, Antoine Thierry, Paolo Malvezzi, Rérolle Jean-Philippe, Nassim Kamar, Didier Ducloux, Anne Elisabeth Heng, Lionel Couzi, Sophie Ohlmann, Dominique Bertrand, Betoul Schvartz, Leonard Golbin, Cyril Garrouste, and Frank Martinez

Subjects
Transplantation, medicine.medical_specialty, business.industry, Primary Focal Segmental Glomerulosclerosis, medicine.medical_treatment, ADRENAL CORTICOSTEROIDS, Urology, medicine.disease, Hypogammaglobulinemia, Study report, Nephrology, Medicine, Rituximab, Plasmapheresis, business, Survival rate, Kidney transplantation, medicine.drug
Abstract

Background and Aims The indication of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation (KT) remains controversial. The objective of our study was to evaluate the benefit and tolerability of adding RTX to the standard of care (SOC) comprising plasmapheresis (PP), corticosteroids, and high-dose anticalcineurins for the treatment of FSGS recurrence after KT. Method This retrospective, multicenter study reports on 148 patients, transplanted between 31 December 2004 and 31 December 2018, aged 39.9 + 13.4 years, who developed FSGS recurrence at 7 [3–23] days. In all 109 patients received a SOC (Group 1). RTX was introduced in this group after more than 28 days of SOC for failure or for therapeutic intensification (n = 19, Group 1a), or for early discontinuation of PP (n = 12, Group 1b); 39 patients received RTX associated at the outset with SOC (Group 2). Results We observed 46.6% complete remission (CR) and 33.1% partial remission (PR). Ten-year graft survival was 65.6% [51.4–76.6] and 13.4% [3.4–30.0] in responders and non-responders respectively. There was no difference in CR + PR rate between G1 (82.5%) and G2 (71.8%), p = 0.08, confirmed by propensity score +4.3% (95% CI [−9.0%-17.5%], p = 0.53). Following addition of RTX (Group 1a), we observed a CR rate of 26.3% and a PR rate of 31.6%. Patients with and without RTX experienced similar rejection rates (18.6% and 28.2%, p = 0.17) and infection rates (71.4% and 79.5%, p = 0.40). In multivariate analysis, the infections were associted with hypogammaglobulinemia Conclusion Rituximab could be used in cases of SOC failure or in remission patients for early weaning of plasmapheresis, without increasing infectious risk.

Published
2020
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45. Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study

Author

Thomas Crepin, Joseph Rivalan, Anne Croue, Aurélie Hummel, Sophie Felix, Dominique Nochy, Emmanuelle Blanchard, Cyril Garrouste, Alexandre Karras, Charlotte Jaulerry, Marion Rabant, Marie-Christine Machet, David Buob, Christelle Barbet, Maud Cousin, François Pourreau, Jean-Michel Goujon, Jean-Michel Halimi, Sébastien Eymieux, Karine Renaudin, Didier Ducloux, Nolwenn Rabot, Catherine Albert, Clément Deltombe, Laurent Doucet, Emilie Cornec-Le Gall, Elodie Miquelestorena-Standley, Nathalie Rioux-Leclerc, and Nora Szlavik

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Histology, Adolescent, Endocapillary proliferative glomerulonephritis, Tubular atrophy, Staphylococcus, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Kidney, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Biopsy, Epidemiology, lcsh:Pathology, medicine, Humans, Child, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Research, Diabetes, Infant, Glomerulonephritis, IGA, Glomerulonephritis, Bacterial Infections, General Medicine, Middle Aged, Staphylococcal Infections, medicine.disease, medicine.anatomical_structure, Child, Preschool, Female, France, Renal biopsy, Infection, business, IgA, lcsh:RB1-214, Rare disease
Abstract

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007–2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Published
2020
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46. Clinical features and outcome of infection-related glomerulonephritis with IgA deposits

Author

Elodie Miquelestorena-Standley, Alexandre Karras, Thomas Crepin, Nathalie Rioux-Leclerc, Sophie Felix, David Buob, Jean-Michel Halimi, Dominique Nochy, Laurent Doucet, Marion Rabant, Marie-Christine Machet, Cyril Garrouste, Christelle Barbet, Charlotte Jaulerry, Didier Ducloux, Catherine Albert, Nolwenn Rabot, Joseph Rivalan, Maud Cousin, Clément Deltombe, Nora Szlavik, Karine Renaudin, Jean-Michel Goujon, Aurélie Hummel, Anne Croue, Emilie Cornec-Le Gall, and François Pourreau

Subjects
medicine.medical_specialty, Text mining, business.industry, Internal medicine, medicine, Glomerulonephritis, medicine.disease, business, Outcome (game theory)
Abstract

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Published
2020
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47. Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients

Author

Marine Freist, Elodie Gentes, Carole Philipponnet, Mohamed Hadj Abdelkader, Bruno Pereira, Aurélien Piraud, Cyril Garrouste, Anne-Elisabeth Heng, Julien Aniort, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Emile Roux [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Dept Clin Nutr, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Unité de Biostatistiques, Direction de la Recherche Clinique (DRCI)

Subjects
Male, 0301 basic medicine, dialyse, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030232 urology & nephrology, Muscle Proteins, Biochemistry, protéasome, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, 0302 clinical medicine, Medicine and Health Sciences, 2. Zero hunger, Multidisciplinary, Protein energy wasting, Muscle Analysis, Middle Aged, C-Reactive Proteins, Muscle atrophy, atrophie musculaire, 3. Good health, Hospitalization, Bioassays and Physiological Analysis, Nephrology, Creatinine, Medicine, Female, patient, Hemodialysis, medicine.symptom, Research Article, Proteasome Endopeptidase Complex, medicine.medical_specialty, Science, Nutritional Status, Circulating Proteasome, Research and Analysis Methods, Protein-Energy Malnutrition, 03 medical and health sciences, Signs and Symptoms, Renal Dialysis, Internal medicine, Medical Dialysis, medicine, Humans, Mortality, Survival rate, Nutrition, Aged, Wasting Syndrome, business.industry, Biology and Life Sciences, Proteins, Protein Complexes, Proteasomes, medicine.disease, perte d'énergie, Patient Outcome Assessment, 030104 developmental biology, Proteasome, Clinical Medicine, Atrophy, Complication, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract

International audience; Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40 [0.26-0.55] mu g/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.

Published
2020
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48. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment

Author

Sunil Babu, Guilia Antognoli, Elena Gutierréz, Yoshitaka Miyakawa, Moglie Le Quintrec, Jan Menne, David J. Kavanagh, Tatiana Kirsanova, Edwin K.S. Wong, Maria Vinogradova, Philip Campbell, Guillaume Favre, Michael Fischereder, Spero R. Cataland, Iino Fumie, Hermann Haller, Vladimir A. Dobronravov, Paramit Chowdhury, Guillaume Jeantet, Marie Scully, Sonia Boyer-Suavet, Thomas D. Barbour, Yosu Luque, Leonardo Caroti, Stephan Ortiz, Shashi K. Nagaraj, Cyril Garrouste, Masayoshi Okumi, Anja Gaeckler, Maria Cappuccilli, Chiu-Ching Huang, Anja Muhlfeld, Gema Ariceta, Gaetano La Manna, Eric Rondeau, Nils Heyne, Giorgia Comai, Natalia Ramos Terrada, Eric Goffin, Paola Rodriguez, Gregory Greenwood, Eugene Swenson, Barbara Seitz-Polski, Nilufer Broeders, Gowthami M. Arepally, Manuel Praga Terente, Marc Vallee, Johan Morelle, Siân V. Griffin, Nicole Lietar, Doyeun Oh, Theo Kasimatis, I-Ru Chen, Ulf Schönermarck, Susan Huang, Jin Seok Kim, Fiona G. Brown, François Provôt, Lino Cirami, Sung-Soo Yoon, Yahsou Delmas, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Sorbonne Université (SU), The Ohio State University Press, and Hannover Medical School [Hannover] (MHH)

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Thrombotic microangiopathy, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Antibodies, Monoclonal, Humanized, Gastroenterology, 03 medical and health sciences, Complement inhibitor, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Atypical hemolytic uremic syndrome, medicine, Clinical endpoint, Humans, complement, Adverse effect, Atypical Hemolytic Uremic Syndrome, Creatinine, business.industry, Thrombotic Microangiopathies, atypical hemolytic uremic syndrome, Complement System Proteins, Eculizumab, medicine.disease, ravulizumab, 3. Good health, thrombotic microangiopathy, 030104 developmental biology, Complement Inactivating Agents, chemistry, Nephrology, hemolytic uremic syndrome, eculizumab, business, medicine.drug
Abstract

Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. In this global, phase 3, single arm study in complement inhibitor-naive adults (18 years and older) who fulfilled diagnostic criteria for atypical hemolytic uremic syndrome, enrolled patients received ravulizumab through a 26-week initial evaluation period. The primary endpoint was complete thrombotic microangiopathy response defined as normalization of platelet count and lactate dehydrogenase and 25% or more improvement in serum creatinine. Secondary endpoints included changes in hematologic variables and renal function. Safety was also evaluated. Ravulizumab treatment resulted in an immediate, complete, and sustained C5 inhibition in all patients. Complete thrombotic microangiopathy response was achieved in 53.6% of patients. Normalization of platelet count, lactate dehydrogenase and 25% or more improvement in serum creatinine was achieved in 83.9%, 76.8% and 58.9% of patients, respectively. Improvement in estimated glomerular filtration rate by one or more stage was achieved in 68.1% of patients by day 183. No unexpected adverse events were reported across a safety analysis set of 58 patients. Four deaths occurred (three within one month of study initiation, including one in a patient excluded based on eligibility criteria after the first dose) with none considered treatment-related by the study investigator. Thus, treatment with ravulizumab once every eight weeks resulted in rapidly improved hematologic and renal endpoints with no unexpected adverse events in adults with atypical hemolytic uremic syndrome.

Published
2020
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49. Spondyloarthritis-Associated IgA Nephropathy

Author

Gabriel Choukroun, Thierry Lobbedez, Cécile Vigneau, Khalil El Karoui, Cyril Garrouste, Thomas Guincestre, Eric Thervet, Philippe Remy, Frédéric Lioté, Fadi Fakhouri, Nicolas Champtiaux, Alexandre Karras, Corinne Miceli, Evangeline Pillebout, Eric Toussirot, Marion Rabant, Alain Wynckel, Laurent Veillon, Emilie Cornec-Le Gall, Vincent Vuiblet, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Henri Mondor, CHU Amiens-Picardie, Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Clermont-Ferrand, Hopital Saint-Louis [AP-HP] (AP-HP), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Gestionnaire, Hal Sorbonne Université, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)

Subjects
medicine.medical_specialty, renal failure, NSAIDs, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, IgA nephropathy, TNF-alpha blockers, ankylosing spondylitis, spondyloarthritis, Internal medicine, medicine, 10. No inequality, Kidney, Ankylosing spondylitis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Proteinuria, medicine.diagnostic_test, business.industry, TNF-α blockers, Retrospective cohort study, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Nephrology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Renal biopsy, medicine.symptom, business, Kidney disease
Abstract

International audience; Introduction: IgA nephropathy (IgAN) can be associated with spondyloarthritis (SpA). The course of SpA-associated IgAN remains largely unknown due to the absence of large cohorts.Methods: This retrospective study included patients with biopsy-proven IgAN and definite SpA. Kidney biopsies were centrally examined and scored according to the IgAN Oxford Classification. Thirty-two patients fulfilled the inclusion criteria, with a male:female ratio of 9:1 and median age of 27 and 37 years at SpA and IgAN diagnosis, respectively. HLA-B27 was positive in 90% of cases, and most patients (60%) presented with ankylosing spondylitis. The mean baseline estimated glomerular filtration rate (eGFR) was 84 ± 26 ml/min per 1.73 m2, and the urine protein-to-creatinine ratio was 0.19 g/mmol.Results: Renal biopsy revealed frequent presence of crescents (33%) and interstitial inflammation (18%). Despite almost constant use of renin-angiotensin system inhibitors, combined with steroids in 13 of 32 patients, renal outcome was particularly poor. After a median follow-up of 5.9 years, 4 patients (12.5%) reached end-stage renal disease and 41% of patients experienced a >50% decrease of eGFR. The mean annual eGFR decline rate was -4.3 ± 6.7 ml/min per 1.73 m2. The risk of reaching class IV or V chronic kidney disease (CKD) stage during follow-up was associated with the presence of hypertension, level of proteinuria, and baseline S- and T-scores of the Oxford.Conclusion: SpA-associated IgAN is associated with a poor renal outcome, despite frequent use of steroids. Tumor necrosis factor (TNF)-α blockade did not appear to influence the rate of eGFR decline in this setting.

Published
2020
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50. Impact de l’obésité en transplantation rénale : étude monocentrique de cohorte et revue de la littérature

Author

Laurent Guy, Cyril Garrouste, Yves Boirie, Anne-Elisabeth Heng, Bruno Pereira, and Clarisse Greze

Subjects
medicine.medical_specialty, business.industry, 030232 urology & nephrology, Retrospective cohort study, 030230 surgery, medicine.disease, Obesity, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Weight loss, Internal medicine, medicine, Graft survival, medicine.symptom, business, Complication, Survival rate, Kidney transplantation, Cohort study
Abstract

Post-kidney transplantation outcomes in obese patients remain uncertain. The aim of this study is to compare patient and graft survival and post-transplant complications in obese patients and non-obese patients. We performed a retrospective analysis of a sample of 245kidney transplantations performed between 2008 and 2014 in Clermont-Ferrand. Obese patients and non-obese patients have been compared. Then we compared obese patients who have lost at least 5% of their weight (OPP) with obese patients who did not lose weight (OPS), and non-obese patients who have lost at least 5% of their weight (NOPP) with non-obese patients who did not lose weight (NOPS). Patient survival at 5years is similar between obese and non obese (84.06% versus 90.96%; P=0.49), between OPP and OPS (88.89% versus 81.82%; P=0.34) and between NOPP and NOPS (89.19% versus 91.05%; P=0.73). At 5years, graft survival is also comparable between obese and non obese (88.82% versus 81.86%; P=0.58), between OPP and OPS (85.56% versus 91.06%; P=0.98) and between NOPP and NOPS (88% versus 80.12%; P=0.31). The length of hospitalization and the rate of complications seem similar between obese and non obese and between OPP and OPS. Post-transplantation outcomes are similar between obese and non-obese patients and a weight loss for obese patients does not seem to decrease the risk of post-transplant complication.

Published
2018
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