Search

Your search keyword '"Renaud Snanoudj"' showing total 140 results
Start Over Author "Renaud Snanoudj"
140 results on '"Renaud Snanoudj"'

1. A case report of Paracetamol related pyroglutamic acidosis: mind the gap in a malnourished patient

Author

Rita Eid, Emmanuel Zamparini, Younes Ouchrif, Renaud Snanoudj, Chris Ottolenghi, and Mohamad Zaidan

Subjects
High anion gap metabolic acidosis, Malnutrition, Paracetamol, Pyroglutamic acidosis, Case report, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Case presentation We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap. Conclusion This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

Published
2024
Full Text
View/download PDF

2. Antibody Mediated Rejection and T-cell Mediated Rejection Molecular Signatures Using Next-Generation Sequencing in Kidney Transplant Biopsies

Author

Esteban Cortes Garcia, Alessia Giarraputo, Maud Racapé, Valentin Goutaudier, Cindy Ursule-Dufait, Pierre de la Grange, Lucie Adoux, Marc Raynaud, Clément Couderau, Fariza Mezine, Jessie Dagobert, Oriol Bestard, Francesc Moreso, Jean Villard, Fabian Halleck, Magali Giral, Sophie Brouard, Richard Danger, Pierre-Antoine Gourraud, Marion Rabant, Lionel Couzi, Moglie Le Quintrec, Nassim Kamar, Emmanuel Morelon, François Vrtovsnik, Jean-Luc Taupin, Renaud Snanoudj, Christophe Legendre, Dany Anglicheau, Klemens Budde, Carmen Lefaucheur, Alexandre Loupy, and Olivier Aubert

Subjects
next generation sequencing, RNA-seq experiment, kidney biopsies, molecular signature, allograft rejection, kidney transplantation, Specialties of internal medicine, RC581-951
Abstract

Recently, interest in transcriptomic assessment of kidney biopsies has been growing. This study investigates the use of NGS to identify gene expression changes and analyse the pathways involved in rejection. An Illumina bulk RNA sequencing on the polyadenylated RNA of 770 kidney biopsies was conducted. Differentially-expressed genes (DEGs) were determined for AMR and TCMR using DESeq2. Genes were segregated according to their previous descriptions in known panels (microarray or the Banff Human Organ Transplant (B-HOT) panel) to obtain NGS-specific genes. Pathway enrichment analysis was performed using the Reactome and Kyoto Encyclopaedia of Genes and Genomes (KEGG) public repositories. The differential gene expression using NGS analysis identified 6,141 and 8,478 transcripts associated with AMR and TCMR. While most of the genes identified were included in the microarray and the B-HOT panels, NGS analysis identified 603 (9.8%) and 1,186 (14%) new specific genes. Pathways analysis showed that the B-HOT panel was associated with the main immunological processes involved during AMR and TCMR. The microarrays specifically integrated metabolic functions and cell cycle progression processes. Novel NGS-specific based transcripts associated with AMR and TCMR were discovered, which might represent a novel source of targets for drug designing and repurposing.

Published
2024
Full Text
View/download PDF

3. Use of a Belatacept-based Immunosuppression for Kidney Transplantation From Donors After Circulatory Death: A Paired Kidney Analysis

Author

Rita Eid, MD, Anne Scemla, MD, Magali Giral, MD, PhD, Nadia Arzouk, MD, Dominique Bertrand, MD, Marie-Noëlle Peraldi, MD, PhD, Laurent Mesnard, MD, PhD, Helene Longuet, MD, Mehdi Maanaoui, MD, PhD, Geoffroy Desbuissons, MD, Edouard Lefevre, MD, and Renaud Snanoudj, MD, PhD

Subjects
Surgery, RD1-811
Abstract

Background. Efficacy and safety of belatacept have not been specifically reported for kidney transplantations from donors after circulatory death. Methods. In this retrospective multicenter paired kidney study, we compared the outcome of kidney transplantations with a belatacept-based to a calcineurin inhibitor (CNI)-based immunosuppression. We included all kidney transplant recipients from donors after uncontrolled or controlled circulatory death performed in our center between February 2015 and October 2020 and treated with belatacept (n = 31). The control group included the recipients of the contralateral kidney that were treated with CNI in 8 other centers (tacrolimus n = 29, cyclosporine n = 2). Results. There was no difference in the rate of delayed graft function. A higher incidence of biopsy-proven rejections was noted in the belatacept group (24 versus 6 episodes). Estimated glomerular filtration rate (eGFR) was significantly higher in the belatacept group at 3-, 12-, and 36-mo posttransplant, but the slope of eGFR was similar in the 2 groups. During a mean follow-up of 4.1 y, 12 patients discontinued belatacept and 2 patients were switched from CNI to belatacept. For patients who remained on belatacept, eGFR mean value and slope were significantly higher during the whole follow-up. At 5 y, eGFR was 80.7 ± 18.5 with belatacept versus 56.3 ± 22.0 mL/min/1.73 m2 with CNI (P = 0.003). No significant difference in graft and patient survival was observed. Conclusions. The use of belatacept for kidney transplants from either uncontrolled or controlled donors after circulatory death resulted in a better medium-term renal function for patients remaining on belatacept despite similar rates of delayed graft function and higher rates of cellular rejection.

Published
2024
Full Text
View/download PDF

4. Invasive bacillary angiomatosis in a kidney transplant recipient: A challenging case on belatacept immunosuppression

Author

Rita Eid, Maureen Assayag, Edouard Lefevre, Lélia Escaut, Marwa Laifi, Albane Brodin-Sartorius, Mohamad Zaidan, and Renaud Snanoudj

Subjects
Bacillary angiomatosis, Bartonella, Kidney transplant recipient, Belatacept, Biopsy, Infectious and parasitic diseases, RC109-216
Abstract

ABSTRACT: Bacillary angiomatosis is a disseminated vascular proliferative disease caused by aerobic gram-negative bacilli Bartonella henselae or Bartonella quintana. Bacillary angiomatosis is mostly described in immunosuppressed patients with HIV infection and organ transplant recipients. We describe the case of a female aged 75 years who is a kidney transplant recipient who was admitted for a 3-month history of intermittent fever, chills, vomiting, and a 12-kg weight loss. The maintenance immunosuppression was based on prednisone, mycophenolate, and monthly infusions of belatacept. Physical examination was unremarkable. Laboratory investigations revealed elevated blood acute phase proteins but all blood cultures were negative. Serological tests for Bartonella were negative. Thoracoabdominal computed tomography scan and transesophageal echocardiography were normal. A Positron Emission Tomography scan showed a hypermetabolic mass in the duodenopancreatic region, with multiple hepatic and splenic lesions. Histological findings of spleen and pancreatic biopsies were not conclusive. The histopathological examination of a celiac lymph node biopsy finally demonstrated bacillary angiomatosis. The diagnosis of bacillary angiomatosis in immunocompromised patients is most often delayed in the absence of skin involvement. A high index of clinical suspicion is needed when interpreting negative results.

Published
2023
Full Text
View/download PDF

5. Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation

Author

Jean Marc Ayoubi, Marie Carbonnel, Niclas Kvarnström, Aurelie Revaux, Marine Poulain, Sarah Vanlieferinghen, Yves Coatantiec, Mathilde Le Marchand, Morgan Tourne, Paul Pirtea, Renaud Snanoudj, Morgan Le Guen, Pernilla Dahm-Kähler, Catherine Racowsky, and Mats Brännström

Subjects
uterus transplantation, immunotherapy, COVID-19, SARS-CoV-2, case report, Surgery, RD1-811
Abstract

Absolute uterus factor infertility, whether congenital or acquired, renders the woman unable to carry a child. Although uterus transplantation (UTx) is being increasingly performed as a non-vital procedure to address this unfortunate condition, the immunosuppression required presents risks that are further compounded by pregnancy and during the puerperium period. These vulnerabilities require avoidance of SARS-CoV-2 infection in pregnant UTx recipients especially during the third trimester, as accumulating evidence reveals increased risks of morbidity and mortality. Here we describe a successful UTx case with delivery of a healthy child, but in which both mother and neonate developed asymptomatic SARS-CoV-2 infection seven days after RNA vaccination, on day 35 post-partum. Although the patient was successfully treated with a combination therapy comprised of two monoclonal antibodies, this case highlights the challenges associated with performing UTx in the era of Covid-19. More broadly, the risks of performing non-vital organ transplantation during a pandemic should be discussed among team members and prospective patients, weighing the risks against the benefits in improving the quality of life, which were considerable for our patient who achieved motherhood with the birth of a healthy child.

Published
2022
Full Text
View/download PDF

6. COVID-19 in Patients on Maintenance Dialysis in the Paris Region

Author

Sarah Tortonese, Ivan Scriabine, Louis Anjou, Christopher Loens, Arthur Michon, Mohammed Benabdelhak, Sarah Ouali, Gabriel Morin, Marwa Laifi, Hélène Dobosziewicz, Matthieu Guillet, Manon Dekeyser, Liem Binh Luong Nguyen, Anne Grünenwald, Julien Dang, Geoffroy Desbuissons, Laurent Becquemont, Renaud Snanoudj, Christophe Legendre, Hadia Hebibi, Edouard Lefèvre, Séverine Beaudreuil, and Mohamad Zaidan

Subjects
coronavirus, COVID-19, hemodialysis, kidney, peritoneal dialysis, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Coronavirus disease 2019 (COVID-19) represents a serious threat to patients on maintenance dialysis. The clinical setting, mortality rate, and prognostic factors in these patients have not been well established. Methods: We included all dialyzed patients with COVID-19 referred to our dialysis center between March 11 and April 11, 2020. Data were obtained through the review of the medical records and were censored at the time of data cutoff, on May 11, 2020. Results: Forty-four patients on maintenance dialysis with COVID-19 were referred to our dialysis unit during the COVID-19 epidemic. Median age was 61 years (interquartile range [IQR]: 51.5–72.5); 65.9% were men. Comorbidities included hypertension (97.7%), diabetes mellitus (50%), and chronic cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (79.5%), shortness of breath (29.5%), cough (43.2%), and diarrhea (13.6%). Three profiles of severity were distinguished based on the World Health Organization (WHO) progression scale. Forty-one (93.2%) were hospitalized and only 3 were maintained on outpatient hemodialysis. Thirty-three (75%) patients required oxygen therapy, including 15 (45.5%) who were referred to the intensive care unit. Overall, 27.3% of patients died, and 58.5% were discharged from hospital, including only 2 (13.3%) of those admitted to the intensive care unit. By multivariate analysis, cough, thrombopenia 175 mg/l were significantly associated with death. Conclusion: A major outbreak of COVID-19 occurred in the Paris region, and spread among dialyzed patients. Our study underscores the severity of COVID-19 in these patients and identified prognostic markers.

Published
2020
Full Text
View/download PDF

7. Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France

Author

Laurène Tardieu, Gillian Divard, Olivier Lortholary, Anne Scemla, Éric Rondeau, Isabelle Accoceberry, Rémi Agbonon, Alexandre Alanio, Adela Angoulvant, Laetitia Albano, Philippe Attias, Anne Pauline Bellanger, Dominique Bertrand, Julie Bonhomme, Françoise Botterel, Nicolas Bouvier, Matthias Buchler, Taieb Chouaki, Thomas Crépin, Marie-Fleur Durieux, Guillaume Desoubeaux, Gary Doppelt, Loïc Favennec, Arnaud Fekkar, Ophélie Fourdinier, Marie Frimat, Jean-Pierre Gangneux, Claire Garandeau, Lilia Hasseine, Christophe Hennequin, Xavier Iriart, Nassim Kamar, Hannah Kaminski, Raphael Kormann, Laurence Lachaud, Christophe Legendre, Moglie Le Quintrec Donnette, Jordan Leroy, Charlène Levi, Marie Machouart, David Marx, Jean Menotti, Valérie Moal, Florent Morio, Natacha Mrozek, Muriel Nicolas, Philippe Poirier, Marie-Noelle Peraldi, Benjamin Poussot, Stéphane Ranque, Jean-Philippe Rerolle, Boualem Sendid, Renaud Snanoudj, Jérôme Tourret, Marc Vasse, Cécile Vigneau, Odile Villard, Laurent Mesnard, Fanny Lanternier, and Cédric Rafat

Subjects
cryptococcosis, opportunistic infection, transplant associated diseases, renal transplantation, cryptococcal meningitis, graft outcome, Medicine
Abstract

Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.

Published
2022
Full Text
View/download PDF

8. Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation

Author

Claire Tinel, Agathe Vermorel, Daniela Picciotto, Lise Morin, Arnaud Devresse, Virginia Sauvaget, Xavier Lebreton, Laïla Aouni, Dominique Prié, Séverine Brabant, Véronique Avettand-Fenoel, Anne Scemla, Marc Olivier Timsit, Renaud Snanoudj, Christophe Legendre, Fabiola Terzi, Marion Rabant, and Dany Anglicheau

Subjects
urinary chemokines, CXCL10, BK polyomavirus, kidney transplantation, prognostic biomarker, Immunologic diseases. Allergy, RC581-607
Abstract

BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08–2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.

Published
2020
Full Text
View/download PDF

9. Successful Outcome of a Corticodependent Henoch-Schönlein Purpura Adult with Rituximab

Author

Taylor Pindi Sala, Jean-Marie Michot, Renaud Snanoudj, Marion Dollat, Emmanuel Estève, Bernadette Marie, Yacine Taoufik, Jean-François Delfraissy, Thierry Lazure, and Olivier Lambotte

Subjects
Medicine
Abstract

Henoch-Schönlein purpura (HSP) is a systemic vasculitis involving small vessels with deposition of immunoglobulin A (IgA) complexes, usually affecting children. Compared with children, HSP in adults is more severe and frequently associated with cancer. We report the case of a 49-year-old woman with medical history of kidney transplantation for segmental glomerular hyalinosis. Eight years after the transplantation, while taking combined immunosuppressive therapy with tacrolimus and azathioprine indicated for the prevention against transplant rejection, she developed a Henoch-Schönlein purpura. Vasculitis involves skin and sciatic peroneal nerve and she received systemic corticosteroid treatment. Because of four relapses and corticosteroid dependence, the patient was treated with rituximab (two intravenous infusions of 1000 mg given two weeks apart). Successful outcome was observed along two years of follow-up. This new case of successful use of rituximab in HSP promotes more investigations of this treatment in clinical trials.

Published
2014
Full Text
View/download PDF

10. Home and Office Blood Pressure Monitoring in Renal Transplant Recipients

Author

Rebecca Sberro-Soussan, Marion Rabant, Renaud Snanoudj, Julien Zuber, Lynda Bererhi, Marie-France Mamzer, Christophe Legendre, and Eric Thervet

Subjects
Surgery, RD1-811
Abstract

Background. Arterial hypertension in renal transplant recipients (RTR) is associated with increased morbid mortality. In the general population, home blood pressure monitoring (HBPM) was found to be superior to office blood pressure (OBP) in identifying true hypertensive patients. The aim of this study was to investigate HBPM for the assessment of blood pressure profile in RTR. Methodology and Principal Findings. We included prospectively 87 stable RTR. Sitting OBP was measured during the outpatient clinic. HBPM was performed by measuring BP every morning and night for 4 days. The accepted limits for the OBP and HBPM, were respectively, 140/90 mmHg and 135/85 mmHg. Patients were classified as “normotensive,” “uncontrolled,” “white-coat hypertensive” and “masked hypertensive”, (OBP below the limit and HBPM above). During the study, 81 patients (55 males, age 48.5±14 years) were available for analysis. The mean OBP and HBP were 138/83±14/10 mmHg and 133/79±14/8 mmHg; 29% of patients were uncontrolled, 28% normotensive, 21% white coat, and 21% masked hypertensive. Age, glycemia, and number of antihypertensive drugs were associated with hypertension. Conclusion and Significance. In RTR, HBPM is well accepted and better define BP profile since there is 42% discrepancy between OBPM and HBPM. Whether this discrepancy is associated with worst outcome in the long term remains to be demonstrated.

Published
2012
Full Text
View/download PDF

11. Microbiology and outcomes of polymicrobial peritonitis associated with peritoneal dialysis: a register-based cohort study from the French Language Peritoneal Dialysis Registry

Author

Valentine Forté, Sophie Novelli, Mohamad Zaidan, Renaud Snanoudj, Christian Verger, and Séverine Beaudreuil

Subjects
Transplantation, Nephrology
Abstract

Background Previous studies have reported that polymicrobial peritonitis in peritoneal dialysis (PD) is associated with poor outcomes, but recent data from European cohorts are scarce. Methods We included from the French Language Peritoneal Dialysis Registry all patients ≥18 years of age who started PD between January 2014 and November 2020. We compared microbiology and patient characteristics associated with mono- and polymicrobial peritonitis. We assessed patient outcomes after a first polymicrobial peritonitis using survival analysis with competing events. We differentiated microorganisms isolated from dialysis effluent as enteric or non-enteric pathogens. Results A total of 8848 patients contributed 13 023 patient-years of follow-up and 3348 culture-positive peritonitis episodes, including 251 polymicrobial ones. This corresponded to rates of 0.32 and 0.02 episodes/patient-year, respectively. For most patients (72%) who experienced polymicrobial peritonitis, this was their first peritonitis episode. Enteric pathogens were more frequently isolated in polymicrobial than in monomicrobial peritonitis (57 versus 44%; P Conclusion Isolation of enteric pathogens, rather than the polymicrobial character of the peritonitis, is associated with poorer outcomes.

Published
2022

12. Pathological spectrum of hereditary transthyretin renal amyloidosis and clinicopathologic correlation: a French observational study

Author

Julien Dang, Sophie Ferlicot, Micheline Misrahi, Charlotte Mussini, Ilias Kounis, Philippe Rémy, Didier Samuel, Violaine Planté-Bordeneuve, David Adams, Benoit Funalot, Renaud Snanoudj, Thibaud Damy, Anissa Moktefi, Vincent Audard, and Mohamad Zaidan

Subjects
Transplantation, Nephrology
Abstract

Background Cardiac and neurological involvements are the main clinical features of hereditary transthyretin (ATTRv) amyloidosis. Few data are available about ATTRv amyloid nephropathy (ATTRvN). Methods We retrospectively included 30 patients with biopsy-proven ATTRvN [V30M (26/30) including two domino liver recipients, S77Y (2/30), V122I (1/30) and S50R (1/30) variants] from two French reference centers. We described the pathological features by comparing amyloid deposits distribution to patients with AL or AA amyloidosis, and sought to determine clinicopathological correlation with known disease-modifying factors such as TTR variant, gender and age at diagnosis. Results In comparison with AL and AA amyloidosis, ATTRv patients had similar glomerular, arteriolar and arterial amyloid deposits, but more cortical and medullary tubulointerstitial (33%, 44%, 77%, P = .03) involvement. While the presence of glomerular deposits is associated with the range of proteinuria, some patients with abundant glomerular ATTRv amyloidosis had no significant proteinuria. V30M patients had more glomerular (100% and 25%, odds ratio = 114, 95% confidence interval 3.85–3395.00, P = .001) deposits, and higher estimated glomerular filtration rate [50 (interquartile range 44–82) and 27 (interquartile range 6–31) mL/min/1.73 m², P = .004] than non-V30M patients. We did not find difference in amyloid deposition according to gender or age at diagnosis. Conclusion ATTRvN affects all kidney compartments, but compared with AL/AA amyloidosis, ATTRvN seems to involve more frequently tubulointerstitial areas. V30M patients represents the dominant face of the disease with a higher risk of glomerular/arteriolar involvement. ATTRvN should thus be considered in patients, and potential relatives, with ATTRv amyloidosis and kidney dysfunction, regardless of proteinuria level.

Published
2023

13. Natural Antibodies Are Associated With Rejection and Long-Term Renal Allograft Loss in a Multicenter International Cohort

Author

Sarah B. See, Xue Yang, Carole Burger, Baptiste Lamarthée, Renaud Snanoudj, Ronzon Shihab, Demetra S. Tsapepas, Poulomi Roy, Stéphanie Larivière-Beaudoin, Katia Hamelin, Aleixandra Mendoza Rojas, Nicole M. van Besouw, Amanda Bartosic, Nikita Daniel, Vasilescu E. Rodica, Sumit Mohan, David Cohen, Lloyd Ratner, Carla C. Baan, Jonathan S. Bromberg, Héloïse Cardinal, Dany Anglicheau, Yifei Sun, and Emmanuel Zorn

Subjects
Transplantation
Published
2023

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

Author

Bastien Berger, Marc Hazzan, Nassim Kamar, Hélène Francois, Marie Matignon, Clarisse Greze, Philippe Gatault, Luc Frimat, Pierre F. Westeel, Valentin Goutaudier, Renaud Snanoudj, Charlotte Colosio, Antoine Sicard, Dominique Bertrand, Christiane Mousson, Jamal Bamoulid, Antoine Thierry, Dany Anglicheau, Lionel Couzi, Jonathan M. Chemouny, Agnes Duveau, Valerie Moal, Yannick Le Meur, Gilles Blancho, Jérôme Tourret, Paolo Malvezzi, Christophe Mariat, Jean-Philippe Rerolle, Nicolas Bouvier, Sophie Caillard, Olivier Thaunat, Hospices Civils de Lyon (HCL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), OT is supported by the Etablissement Français du Sang and the Fondation pour la Recherche Médicale (PME20180639518)., Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Transplantation, Nephrology, [SDV]Life Sciences [q-bio], SARS-CoV2
Abstract

International audience; Introduction - SARS-CoV-2 pandemic evolved in 2 consecutive waves during 2020. Improvements in the management of COVID-19 led to a reduction in mortality rates among hospitalized patients during the second wave. Whether this progress benefited kidney transplant recipients (KTRs), a population particularly vulnerable to severe COVID-19, remained unclear. Methods - In France, 957 KTRs were hospitalized for COVID-19 in 2020 and their data were prospectively collected into the French Solid Organ Transplant (SOT) COVID registry. The presentation, management, and outcomes of the 359 KTRs diagnosed during the first wave were compared to those of the 598 of the second wave. Results - Baseline comorbidities were similar between KTRs of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs. 58.4%, < 0.001) or calcineurin inhibitor (32.1% vs. 16.6%, < 0.001) was less frequent during the second wave. Hydroxychloroquine and azithromycin that were commonly used during the first wave (21.7% and 30.9%, respectively) but were almost abandoned during the second wave. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, < 0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, = 0.48) and COVID-19 hospitalization period was not associated with death due to COVID-19 in multivariate analysis (Hazard ratio 0.89, 95% confidence interval 0.67-1.17, = 0.4). Conclusion - We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality among KTRs. Our data indirectly support the importance of vaccination and neutralizing monoclonal anti-SARS-CoV-2 antibodies to protect KTRS from severe COVID-19.

Published
2022

15. Pregnancies and Gynecological Follow-Up after Solid Organ Transplantation: Experience of a Decade

Author

Alice Bedin, Marie Carbonnel, Renaud Snanoudj, Antoine Roux, Sarah Vanlieferinghen, Claire Marchiori, Alexandre Hertig, Catherine Racowsky, and Jean-Marc Ayoubi

Subjects
pregnancy, organ transplantation, immunosuppression, kidney, lung, gynecology, General Medicine
Abstract

In recent years, solid organ transplantations, such as kidney or lung grafts, have been performed worldwide with an improvement of quality of life under immunosuppressive therapy and an increase in life expectancy, allowing young women to consider childbearing. In the current study, we conduct a retrospective study in two French centers for kidney and lung transplantations to evaluate the rate and outcomes of pregnancies, contraception and gynecological monitoring for women under 40 years old who underwent solid organ transplantation. Among 210 women, progestin was the most widely used contraceptive method. Of the 210 women, 24 (11.4%) conceived 33 pregnancies of which 25 (75.8%) were planned with an immunosuppressant therapy switch. Of the 33 pregnancies, 7 miscarried (21.2%) and 21 (63.7%) resulted in a live birth with a high rate of pre-eclampsia (50%). No graft rejections were observed during pregnancies. Among the deliveries, 19 were premature (90.5%, mostly due to induced delivery) and the C-section rate was high (52.4%). No particular pathology was identified among newborns. We conclude that pregnancies following solid organ transplantation are feasible, and while they are at an increased risk of pre-eclampsia and prematurity, they should still be permitted with close surveillance by a multidisciplinary care team.

Published
2022

16. Transplantation rénale du sujet âgé : un bénéfice pour tous ?

Author

Renaud Snanoudj

Subjects
Pediatrics, medicine.medical_specialty, business.industry, 030232 urology & nephrology, medicine.disease, Kidney transplant, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Waiting list, medicine, business, Contraindication, Kidney transplantation
Abstract

Age per se should not be a contraindication to kidney transplantation. The first studies have shown a benefit for the survival of elderly eligible patients getting a kidney transplant compared to be maintained on the waiting list. However, more recent data suggest that this benefit is not as constant, notably with a significant early mortality period. The eligibility of elderly patients for transplantation must be based on the usual consideration of co-morbidities, but should also include, for some patients, a geriatric evaluation to detect clinical symptoms of frailty. The decision to transplant an elderly recipient must also integrate the characteristics of the donors, since the use of donors with increasingly expanding criteria can have a negative impact on the survival of these patients.

Published
2021

17. COVID-19 in Patients on Maintenance Dialysis in the Paris Region

Author

Julien Dang, Geoffroy Desbuissons, Arthur Michon, Liêm Binh Luong Nguyen, Anne Grunenwald, Laurent Becquemont, Sarah Ouali, Renaud Snanoudj, Hadia Hebibi, Manon Dekeyser, Séverine Beaudreuil, Ivan Scriabine, Gabriel Morin, Christopher Loens, Mohammed Benabdelhak, Louis Anjou, Edouard Lefèvre, Marwa Laifi, Christophe Legendre, Sarah Tortonese, Mohamad Zaidan, Matthieu Guillet, Hélène Dobosziewicz, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Nephrocare Ile De France, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), We thank Ms. Val?rie G?rard and Ms. Nadia Corre, and all the colleagues and nurses of our department and institution who were involved in the management of patients during the recent epidemic. We also thank Marie Frank and J?r?my Laurent from the D?partement d'Information M?dicale Paris Saclay for supplying the data regarding the ICU mortality rate in our institution, Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and HAL UVSQ, Équipe

Subjects
kidney, medicine.medical_specialty, medicine.medical_treatment, coronavirus, 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Article, Peritoneal dialysis, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interquartile range, law, Oxygen therapy, Internal medicine, medicine, Dialysis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, hemodialysis, business.industry, Mortality rate, Medical record, COVID-19, lcsh:Diseases of the genitourinary system. Urology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Intensive care unit, 3. Good health, peritoneal dialysis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Nephrology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hemodialysis, business
Abstract

International audience; Introduction: Coronavirus disease 2019 (COVID-19) represents a serious threat to patients on maintenance dialysis. The clinical setting, mortality rate, and prognostic factors in these patients have not been well established. Methods: We included all dialyzed patients with COVID-19 referred to our dialysis center between March 11 and April 11, 2020. Data were obtained through the review of the medical records and were censored at the time of data cutoff, on May 11, 2020. Results: Forty-four patients on maintenance dialysis with COVID-19 were referred to our dialysis unit during the COVID-19 epidemic. Median age was 61 years (interquartile range [IQR]: 51.5–72.5); 65.9% were men. Comorbidities included hypertension (97.7%), diabetes mellitus (50%), and chronic cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (79.5%), shortness of breath (29.5%), cough (43.2%), and diarrhea (13.6%). Three profiles of severity were distinguished based on the World Health Organization (WHO) progression scale. Forty-one (93.2%) were hospitalized and only 3 were maintained on outpatient hemodialysis. Thirty-three (75%) patients required oxygen therapy, including 15 (45.5%) who were referred to the intensive care unit. Overall, 27.3% of patients died, and 58.5% were discharged from hospital, including only 2 (13.3%) of those admitted to the intensive care unit. By multivariate analysis, cough, thrombopenia 175 mg/l were significantly associated with death. Conclusion: A major outbreak of COVID-19 occurred in the Paris region, and spread among dialyzed patients. Our study underscores the severity of COVID-19 in these patients and identified prognostic markers.

Published
2020

18. Long-term survival benefit from dual kidney transplantation using kidneys from donors with very extended criteria-a French cohort between 2002 and 2014

Author

Marie-Alice Macher, Lionel Badet, Nacera Ouali, Philippe Grimbert, Yann Neuzillet, Emilie Savoye, Renaud Snanoudj, Christophe Legendre, Myriam Pastural, Matthieu Durand, Camille Legeai, Marie-Noëlle Peraldi, François Kerbaul, 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), GHU AP-HP Centre Université de Paris, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, Dual kidney transplantation, [SDV]Life Sciences [q-bio], dual kidney transplantation, Urology, Renal function, Context (language use), Extended criteria, Kidney, delayed graft function, Long term survival, medicine, Humans, Retrospective Studies, Transplantation, business.industry, Graft Survival, Retrospective cohort study, Kidney Transplantation, Delayed Graft Function, Tissue Donors, Treatment Outcome, Nephrology, Cohort, marginal donor, business, long-term survival
Abstract

Background This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). Methods Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. Results The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P Conclusions In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.

Published
2022

19. 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

20. CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant Recipients

Author

Marion Rabant, Jean Luc Taupin, Aniela Zablocki, Tifanie Blein, Soëli Charbonnier, Dany Anglicheau, Charlotte Leclaire, Baptiste Lamarthée, Carole Burger, Julien Zuber, Fabiola Terzi, Mélanie Hardy, Lise Morin, Xavier Lebreton, Béatrice Charreau, Claire Tinel, Christophe Legendre, Renaud Snanoudj, Emilie Lebraud, Morgan Gallazzini, Simon C. Satchell, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre européen des sciences de la transplantation et de l'immunologie [CHU Nantes] (IHU CESTI), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut de transplantation urologie-néphrologie (ITUN), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), University of Bristol [Bristol], and Le Bihan, Sylvie

Subjects
Adult, Graft Rejection, Male, Reoperation, CRISPR-Cas systems, Non hla antibodies, [SDV]Life Sciences [q-bio], Kidney Glomerulus, Bristol Heart Institute, kidney transplantation, Human leukocyte antigen, Kidney transplant, kidney rejection, Clinical Research, HLA Antigens, Isoantibodies, endothelial, Medicine, CRISPR, Humans, antibodies, Cells, Cultured, Aged, Retrospective Studies, business.industry, Nuclear Proteins, General Medicine, Middle Aged, Tissue Donors, endothelial cells, non-HLA antibodies, [SDV] Life Sciences [q-bio], Nephrology, inflammation, Immunology, Trans-Activators, antibody-mediated rejection, Female, endothelial inflammation, business, beta 2-Microglobulin, Gene Deletion
Abstract

International audience; Background After kidney transplantation, donor-specific antibodies against human leukocyte antigen donor-specific antibodies (HLA-DSAs) drive antibody-mediated rejection (ABMR) and are associated with poor transplant outcomes. However, ABMR histology (ABMRh) is increasingly reported in kidney transplant recipients (KTRs) without HLA-DSAs, highlighting the emerging role of non-HLA antibodies (Abs). Methods W e designed a non-HLA Ab detection immunoassay (NHADIA) using HLA class I and II–deficient glomerular endothelial cells (CiGEnC Δ HLA) that had been previously generated through CRISPR/Cas9-induced B2M and CIITA gene disruption. Flow cytometry assessed the reactivity to non-HLA antigens of pretransplantation serum samples from 389 consecutive KTRs. The intensity of the signal observed with the NHADIA was associated with post-transplant graft histology assessed in 951 adequate biopsy specimens. Results W e sequentially applied CRISPR/Cas9 to delete the B2M and CIITA genes to obtain a CiGEnC Δ HLA clone. CiGEnC Δ HLA cells remained indistinguishable from the parental cell line, CiGEnC, in terms of morphology and phenotype. Previous transplantation was the main determinant of the pretransplantation NHADIA result ( P

Published
2021

21. 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

22. Conversion From Calcineurin Inhibitors to Belatacept in HLA-sensitized Kidney Transplant Recipients With Low-level Donor-specific Antibodies

Author

Renaud Snanoudj, Dany Anglicheau, Christophe Legendre, Marc-Olivier Timsit, Camilo E Ulloa, Anne Scemla, Frank Martinez, and Rebecca Sberro-Soussan

Subjects
Adult, Graft Rejection, Male, Isoantigens, Biopsy, Calcineurin Inhibitors, Human leukocyte antigen, 030230 surgery, Pharmacology, Kidney, Kidney transplant, Belatacept, Nephrotoxicity, Abatacept, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Isoantibodies, Humans, Medicine, Renal Insufficiency, Aged, Transplantation, biology, medicine.diagnostic_test, Drug Substitution, business.industry, Donor specific antibodies, Middle Aged, Allografts, Kidney Transplantation, body regions, Calcineurin, Treatment Outcome, biology.protein, Female, 030211 gastroenterology & hepatology, Antibody, business, Glomerular Filtration Rate, medicine.drug
Abstract

Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA).We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept.Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m to 40.7 ± 12.3 mL/min/1.73 m (P0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection.We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.

Published
2019

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

Author

Bénédicte Janbon, Sophie Caillard, Isabelle Jollet, Elisabeth Cassuto, Elodie Bailly, Bruno Hurault de Ligny, Michel Delahousse, Marc Hazzan, Anne Devys, Antoine Thierry, Pierre Merville, Sophie Girerd, Renaud Snanoudj, Dany Anglicheau, Vincent Vuiblet, Nassim Kamar, Kahina Amokrane, Philippe Grimbert, Eric Rondeau, Gabriel Choukroun, Alexandre Hertig, Marie Metzger, Jean-Luc Taupin, Yann Le Meur, Christophe Legendre, Emmanuel Morelon, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie [Amiens], CHU Amiens-Picardie-hôpital Sud, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Etablissement français du sang [Angers], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Foch [Suresnes], Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)

Subjects
Adult, Graft Rejection, Male, 0301 basic medicine, Isoantigens, Allosensitization, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, kidney transplantation, Human leukocyte antigen, acute rejection, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA-DQ Antigens, immunosuppression minimization, Humans, Transplantation, Homologous, Medicine, Everolimus, education, Kidney transplantation, education.field_of_study, biology, Drug Substitution, business.industry, Histocompatibility Testing, Patient Selection, Graft Survival, Immunosuppression, Middle Aged, epitopes, medicine.disease, HLA mismatching, 3. Good health, 030104 developmental biology, Nephrology, Immunology, Cyclosporine, antibody-mediated rejection, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies
Abstract

International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.

Published
2019

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

Author

Nathalie Chavarot, Bruno Moulin, Valérie Moal, Olivier Thaunat, Marc Hazzan, Jamal Bamoulid, Antoine Durrbach, Christiane Mousson, Nassim Kamar, Yannick Lemeur, Charlotte Kaeuffer, Clarisse Greze, Philippe Grimbert, Ilies Benotmane, Dominique Bertrand, Antoine Thierry, Tristan Legris, Gilles Blancho, Pierre François Westeel, Mariam Jdidou, Hélène François, Sophie Caillard, Marie Matignon, Yvon Ruch, Morgane Solis, Antoine Sicard, Dany Anglicheau, Philippe Gatault, Valentin Goutaudier, François Danion, Lionel Couzi, Charlotte Colosio, Renaud Snanoudj, Christophe Masset, Agnès Duveau, Jonathan M. Chemouny, Luc Frimat, CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Tours (UT), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Aix Marseille Université (AMU), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Bourgogne (UB), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Poitiers, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), University of Lille, This study was supported by the Strasbourg University Hospital (COVIS-HUS Study- HUS number 7760), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP Hôpital Tenon [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University Hospital of Montpellier, Hôpital Bicêtre, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), PINIER, CHRISTINE, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Registries, Aucun, MESH: Comorbidity, 030230 surgery, law.invention, chemistry.chemical_compound, 0302 clinical medicine, law, cardiovascular disease, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, clinical research / practice, Immunology and Allergy, Cumulative incidence, Pharmacology (medical), kidney transplantation / nephrology, MESH: Incidence, MESH: Aged, Univariate analysis, MESH: France / epidemiology, MESH: Middle Aged, MESH: Transplant Recipients / statistics & numerical data, Acute kidney injury, Intensive care unit, 3. Good health, MESH: COVID-19 / epidemiology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, glomerular filtration rate (GFR), kidney failure / injury, medicine.medical_specialty, infection and infectious agents - viral, infectious disease, Brief Communication, MESH: Graft Rejection / prevention & control, 03 medical and health sciences, Internal medicine, Diabetes mellitus, MESH: Severity of Illness Index, MESH: COVID-19 / diagnosis, medicine, Humans, MESH: SARS-CoV-2, Mechanical ventilation, Creatinine, Transplantation, MESH: Humans, business.industry, SARS-CoV-2, MESH: Graft Rejection / epidemiology, COVID-19, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, Transplant Recipients, MESH: Male, immunosuppressive regimens, MESH: Immunosuppressive Agents / therapeutic use, MESH: Pandemics, MESH: Propensity Score, chemistry, Reinfection, MESH: Immunosuppression / methods, MESH: Intensive Care Units, business, MESH: Female, MESH: Kidney Transplantation
Abstract

International audience; There are no studies which have compared the risk of severe Covid-19 and related mortality between transplant recipients and non-transplant patients. We enrolled two groups of patients hospitalized for Covid-19, i.e., kidney transplant recipients from the French Registry of Solid Organ Transplant (n=306) and a single-center cohort of non-transplant patients (n=795). An analysis was performed among subgroups matched for age and risk factors for severe Covid-19 or mortality. Severe Covid-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death.Transplant recipients were younger and had more comorbidities compared to non-transplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe Covid-19 did not differ between KTR and non-transplant patients; however, 30-day Covid-19-related mortality was significantly higher in KTR (17.9% versus 11.4%, respectively, p=0.038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe Covid-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR=1.55), and creatinine level >115 µmol/L (HR=2.32) were associated with Covid-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. Kidney transplant recipients had a higher Covid-19-related mortality compared to non-transplant hospitalized patients.

Published
2021

25. The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury and/or proteinuria

Author

David Buob, Ap-Hp, Renaud Snanoudj, Matthieu Jamme, Marie-Christine Verpont, Guillaume Geri, Nicolas Pallet, Christian Richard, Olivia May, Hélène François, Thomas Sthelé, Arthur Michon, Xavier Belenfant, Anne Grunenwald, Vincent Audard, Ziad A. Massy, Anissa Moktefi, François Gaillard, Christophe Legendre, Mohamad Zaidan, Fabrizio Andreelli, Julie Oniszczuk, Ophelie Le Monnier, Hassane Izzedine, Charlotte Mussini, Hélène Dobosziewicz, Albane Brodin-Sartorius, Universities, Marie Essig, Edouard Lefèvre, Zahir Amoura, Manon Dekeyser, Sophie Ferlicot, Aurélie Sannier, Alexis Mathian, Aymeric Couturier, Eric Daugas, Matthieu Guillet, Romain Arrestier, Isabelle Brocheriou-Spelle, Camille Petit-Hoang, and Nadine Maroun

Subjects
kidney, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Diabetes mellitus, Internal medicine, medicine, Renal replacement therapy, AcademicSubjects/MED00340, Dialysis, focal segmental glomerulosclerosis, Kidney, Transplantation, collapsing glomerulopathy, medicine.diagnostic_test, business.industry, Acute kidney injury, COVID-19, Fast Track Original Article, medicine.disease, acute tubular injury, medicine.anatomical_structure, Nephrology, Renal biopsy, business
Abstract

Background The coronavirus disease 2019 (COVID-19) may be associated with kidney injury, which may impact patient's prognosis. Methods We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury (AKI) and/or proteinuria and underwent a kidney biopsy in Paris and its metropolitan area. Results Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between 8 March and 19 May 2020 were included. The median age was 63 years (interquartile range 52–69). Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney disease (25.5%), cardiac diseases (38.6%) and respiratory diseases (27.3%). Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%) and diarrhoea (23.4%). Almost all patients developed AKI (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy (CG) and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while 8 (17%) had an alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and CG was only observed in patients harbouring a combination of APOL1 risk variants. At the last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 had died. Conclusions This study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Published
2021
Full Text
View/download PDF

26. Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD-preliminary results

Author

Lynda Cheddani, Marie Metzger, Ziad A. Massy, Maryvonne Hourmant, Marie Essig, Tilman B. Drüeke, C. Kerleau, Christian Jacquelinet, Renaud Snanoudj, Sophie Liabeuf, Beverley Balkau, Nantes Kidney, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Foch [Suresnes], Agence de la biomédecine [Saint-Denis la Plaine], 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), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Ambroise Paré [AP-HP], Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Risk Factors, Internal medicine, Risk of mortality, Humans, Medicine, Prospective Studies, Renal Insufficiency, Chronic, education, Dialysis, Kidney transplantation, Aged, Transplantation, education.field_of_study, business.industry, Mortality rate, Hazard ratio, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Transplant Recipients, Survival Rate, Cardiovascular Diseases, Nephrology, Case-Control Studies, Female, business, Glomerular Filtration Rate, Kidney disease
Abstract

BackgroundAlthough kidney transplantation prolongs survival relative to dialysis, it is associated with a higher death rate than in the general population. The objective of the present study was to assess and compare the risk of mortality and frequency of non-lethal cardiovascular (CV) events in kidney transplant recipients (KTRs) beyond 1 year after successful transplantation versus patients with chronic kidney disease (CKD) using propensity score–matched analysis of estimated glomerular filtration rate (eGFR) and other parameters.MethodsAfter propensity score matching, we studied 340 KTRs from the French Données Informatisées et Validées en Transplantation cohort and 605 non-transplant patients with CKD (CKDps) from the French Chronic Kidney Disease–Renal Epidemiology and Information Network cohort. The mean ± standard deviation eGFR was 42 ± 13 and 41 ± 12 mL/min/ 1.73 m2, respectively (P = 0.649). Descriptive data were completed by a survival analysis with Cox regression models.ResultsAfter a median follow-up period of 2.8 years (KTRs 2.0 years, CKDp 2.9 years), 71 deaths were recorded (31 and 40 in the KTR and CKD groups, respectively). Univariate analysis showed that KTRs had a significantly greater risk of mortality than CKDps. In multivariable analysis, KTRs were found to have a 2.7-fold greater risk of mortality [hazard ratio 2.7 (95% confidence interval 1.6–4.7); P = 0.005]. There was no between-group difference concerning the risk of CV events (P = 0.448). CV death rates in KTRs (29.0%) approximated those of CKDps (22.5%), whereas death rates due to infections were higher in KTRs (19.4% versus 10.0%).ConclusionBeyond 1 year after transplantation, KTRs, who possibly had a longer CKD history, had a significantly greater mortality risk than eGFR-matched CKDps. The excess risk was not associated with CV events.

Published
2021

27. 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

28. COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities

Author

Delphine Mika, Nathalie Chavarot, Renaud Snanoudj, Guillaume Bonnet, Laura Geneste, Olivier Aubert, Rebecca Sberro-Soussan, Antonin Trimaille, Théo Pezel, Charles Fauvel, Lucile Amrouche, Michel Delahousse, Anne Scemla, Antoine Deney, Julien Zuber, Mohamad Zaidan, Carole Burger, Vassili Panagides, Dany Anglicheau, Ariel Cohen, Christophe Legendre, Juliette Gueguen, Mariam Jdidou, Willy Sutter, Joffrey Celier, Claire Aguilar, Wassima Marsou, Orianne Weizman, and Thibaut Pommier

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Comorbidity, 030230 surgery, Letter to the Editors, law.invention, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Interquartile range, law, COVID‐19, Internal medicine, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Pandemics, Letter to the Editor, solid organ transplantation, Kidney transplantation, Aged, Retrospective Studies, Transplantation, business.industry, SARS-CoV-2, COVID-19, Immunosuppression, Retrospective cohort study, Middle Aged, medicine.disease, Intensive care unit, Kidney Transplantation, Transplant Recipients, Intensive Care Units, Cohort, Female, business, Body mass index
Abstract

Higher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3-73.1) in three French transplant centers. After a median follow-up of 13 days (7-30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2-14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.

Published
2020

29. Kidney transplantation improves the clinical outcomes of Acute Intermittent Porphyria

Author

Bruno Moulin, Valérie Chatelet, Laurent Gouya, Sophie Caillard, Nassim Kamar, Renaud Snanoudj, Luc Frimat, Jonathan Maurice Chemouny, Charlène Levi, Nicolas Pallet, Neila Talbi, Alexandre Karras, Hervé Puy, Clément Vachey, Caroline Schmitt, Thibaud Lefebvre, Hélène Lazareth, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Strasbourg, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Foch [Suresnes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Porphobilinogen, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Heme, 030105 genetics & heredity, Kidney, Biochemistry, End stage renal disease, End-stage renal disease, 03 medical and health sciences, Young Adult, Acute Intermittent Porphyria, 0302 clinical medicine, Endocrinology, Chronic kidney disease, Internal medicine, Genetics, medicine, Humans, Porphyria cutanea tarda, Molecular Biology, Kidney transplantation, Dialysis, Acute intermittent porphyria, Porphyrin precursors, business.industry, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Transplantation, Porphyria, Treatment Outcome, Porphyria, Acute Intermittent, Kidney Failure, Chronic, Female, Aminolevulinic acid, business, 030217 neurology & neurosurgery, Kidney disease
Abstract

International audience; Background - Acute Intermittent Porphyria (AIP) is a rare inherited autosomal dominant disorder of heme biosynthesis. Porphyria-associated kidney disease occurs in more than 50% of the patients with AIP, and end stage renal disease (ESRD) can be a devastating complication for AIP patients. The outcomes of AIP patients after kidney transplantation are poorly known. Methods - We examined the outcomes of 11 individuals with AIP, identified as kidney transplant recipients in the French Porphyria Center Registry. Results - AIP had been diagnosed on average 19 years before the diagnosis of ESRD except for one patient in whom the diagnosis of AIP had been made 5 years after the initiation of dialysis. Median follow-up after transplantation was 9 years. A patient died 2 months after transplantation from a cardiac arrest and a patient who received a donation after cardiac death experienced a primary non-function. No rejection episode and no noticeable adverse event occurred after transplantation. Serum creatinine was on average 117 μmol/l, and proteinuria

Published
2020

30. Uterus Transplantation with Live Donors: Screening Candidates in One French Center

Author

Marie Carbonnel, Morgan Le Guen, Dominique de Ziegler, Elena Menzhulina, Renaud Snanoudj, Aurélie Revaux, Jean-Marc Ayoubi, and Lea Karpel

Subjects
Pediatrics, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, uterus, business.industry, screening, lcsh:R, lcsh:Medicine, uterine, General Medicine, Limiting, Article, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Uterus transplantation, Medicine, transplant, 030212 general & internal medicine, business, transplantation
Abstract

We report our experience regarding the profile and screening process of potential recipients (R) and their live donors (D) in our Uterus transplantation (UTx) trial from 2014 to 2020. The initial screening was performed using medical questionnaires and consultations. The second step of the screening consisted of two individual interviews with an independent multidisciplinary committee. Then, a complete medical, biological and imaging assessment of the directed living D, the R, and her partner was performed over a two-day hospitalization. A total of 239 women contacted our department: 165 potentials R and 74 potentials D. During the first step of screening, 141 R and 45 D were excluded. Only 12 R/D pairs were pursued. During inclusion, 10 R/D pairs were excluded. One R/D pair is still under evaluation. Finally, only 1 R/D pair was definitively included (0.6%), which led us to perform the first French UTx in March 2019 with a successful graft. The primary limiting factors of inclusion were due to very strict criteria and difficulty of having a suitable directed living D. The International Society of UTx (ISUTx) guidelines based on worldwide results of trials can help ease our inclusion criteria in the future while remaining safe for patients.

Published
2020

31. Predictive value of mixed antigen screen beads in pre-transplant assessment of HLA immunization in solid organ transplant recipients

Author

Jérémy Siemowski, Sophie Caillat-Zucman, Jean-Luc Taupin, Renaud Snanoudj, Christophe Legendre, Pierre Galichon, Michel Delahousse, Elizabeth Amankwa, Marie Matignon, Nadia Arzouk, and Vissal-David Kheav

Subjects
Graft Rejection, medicine.medical_specialty, Human leukocyte antigen, 030230 surgery, Organ transplantation, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA Antigens, Isoantibodies, Medicine, Humans, Transplantation, medicine.diagnostic_test, biology, business.industry, Histocompatibility Testing, Organ Transplantation, Predictive value, Immunization, Immunoassay, Immunology, biology.protein, 030211 gastroenterology & hepatology, Antibody, business
Abstract

Pre-transplant serum screening of anti-HLA antibodies is recommended for solid organ transplantations. Many laboratories use the less expensive bead-based screening assay as the main technique and, if positive, turn to single-antigen beads (SAB). We studied the correlations between these two immunoassays. We re-analyzed the raw data of the two assays in 3030 first organ transplant recipients, explored with the two tests. We performed a ROC curve analysis of the screening ratio to predict a positive SAB assay. The AUC were 0.72 and 0.64 for class I and class II. The optimal thresholds of screening ratios were 3.28 (class I) and 2.11 (class II). Whatever the class, the negative predictive value was low, around 40%, with 36% of discordant sera, as defined by negative screening and positive SAB. Testing class I discordant sera on acid-treated SAB showed that 54% of antibodies reacted against denatured HLA molecules. However, these screening-negative sera may contain donor-specific antibodies in 13.9% and 28.7% of cases for class I and class II, respectively, involved in antibody-mediated rejection with the same frequency as non-discordant sera. Given the low predictive value of screening, both assays should be performed at least once on the same serum before transplantation.

Published
2020

32. Development and validation of an optimized integrative model using urinary chemokines for noninvasive diagnosis of acute allograft rejection

Author

Renaud Snanoudj, Marie Essig, Maarten Naesens, Agathe Vermorel, Arnaud Devresse, Dany Anglicheau, Jérôme Olagne, David Marx, Sophie Caillard, Fabiola Terzi, Virginia Sauvaget, Pierre Marquet, Claire Tinel, Marion Rabant, Wilfried Gwinner, Marc Olivier Timsit, Bruno Moulin, Lucile Amrouche, Véronique Avettand-Fenoel, Christophe Legendre, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie

Subjects
Graft Rejection, medicine.medical_specialty, Urinary system, Urology, Renal function, 030230 surgery, medicine.disease_cause, Chemokine CXCL9, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Transplantation, Creatinine, Polyomavirus Infections, business.industry, Area under the curve, medicine.disease, Allografts, Kidney Transplantation, Confidence interval, BK virus, Chemokine CXCL10, Tumor Virus Infections, chemistry, BK Virus, business, Viral load
Abstract

The urinary chemokines CXCL9 and CXCL10 are promising noninvasive diagnostic markers of acute rejection (AR) in kidney recipients, but their levels might be confounded by urinary tract infection (UTI) and BK virus (BKV) reactivation. Multiparametric model development and validation addressed these confounding factors in a training set of 391 samples, optimizing the diagnostic performance of urinary chemokines. CXCL9/creatinine increased in UTI and BKV viremia with or without nephropathy (BKVN) (no UTI/leukocyturia/UTI: -0.10/1.61/2.09, P = .0001 and no BKV/viremia/BKVN: -0.10/1.90/2.29, P

Published
2020

33. Trends and Outcomes with Kidney Failure from Antineoplastic Treatments and Urinary Tract Cancer in France

Author

Renaud Snanoudj, Bénédicte Stengel, Clémence Béchade, Cécile Vigneau, Nadia Haddy, Mathilde Lassalle, Christian Jacquelinet, Florent de Vathaire, Natalia Alencar de Pinho, Imene Mansouri, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Agence de la biomédecine [Saint-Denis la Plaine], 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), 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 ), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Ministère de l'Enseignement Supérieur et de la Recherche, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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
Male, Time Factors, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, urologic neoplasms, Critical Care and Intensive Care Medicine, renal insufficiency, 0302 clinical medicine, Risk Factors, end-stage kidney disease, antineoplastic agents, nephrectomy, humans, Kidney transplantation, confidence intervals, Kidney, Incidence (epidemiology), nephrotoxicity, Age Factors, Middle Aged, Nephrectomy, 3. Good health, urinary tract cancer, comorbidity, medicine.anatomical_structure, Treatment Outcome, Nephrology, 030220 oncology & carcinogenesis, renal dialysis, diabetes mellitus, Female, France, Adult, information services, medicine.medical_specialty, Urinary system, kidney transplantation, Risk Assessment, survival, 03 medical and health sciences, Sex Factors, Internal medicine, Diabetes mellitus, medicine, cancer, Dialysis, Aged, Transplantation, business.industry, waiting lists, Editorials, registries, Original Articles, medicine.disease, radiation, Case-Control Studies, incidence, Kidney Failure, Chronic, business
Abstract

International audience; Background and objectives - Cancer survival is improving along with an increase in the potential for adverse kidney effects from antineoplastic treatments or nephrectomy. We sought to describe recent trends in the incidence of kidney failure related to antineoplastic treatments and urinary tract cancers and evaluate patient survival and kidney transplantation access. Design, setting, participants, & measurements - We used the French Renal Epidemiology and Information Network registry to identify patients with kidney failure related to antineoplastic treatments or urinary tract cancer from 2003 to 2015. We identified 287 and 1157 cases with nephrotoxin- and urinary tract cancer-related kidney failure, respectively. The main study outcomes were death and kidney transplantation. After matching cases to two to ten controls (=11,678) with other kidney failure causes for age, sex, year of dialysis initiation, and diabetes status, we estimated subdistribution hazard ratios (SHR) of each outcome separately for patients with and without active malignancy. Results - The mean age- and sex-adjusted incidence of nephrotoxin-related kidney failure was 0.43 (95% CI, 0.38 to 0.49) per million inhabitants and 1.80 (95% CI, 1.68 to 1.90) for urinary tract cancer-related kidney failure; they increased significantly by 5% and 2% annually, respectively, during 2006-2015. Compared with matched controls, age-, sex-, and comorbidity-adjusted SHRs for mortality in patients with nephrotoxin-related kidney failure were 4.2 (95% CI, 3.2 to 5.5) and 1.4 (95% CI, 1.0 to 2.0) for those with and without active malignancy, respectively; for those with urinary tract cancer, SHRs were 2.0 (95% CI, 1.7 to 2.2) and 1.1 (95% CI, 0.9 to 1.2). The corresponding SHRs for transplant wait-listing were 0.19 (95% CI, 0.11 to 0.32) and 0.62 (95% CI, 0.43 to 0.88) for nephrotoxin-related kidney failure cases and 0.28 (95% CI, 0.21 to 0.37) and 0.47 (95% CI, 0.36 to 0.60) for urinary tract cancer cases. Once on the waiting list, access to transplantation did not differ significantly between cases and controls. Conclusions - Cancer-related kidney failure is slowly but steadily increasing. Mortality does not appear to be increased among patients without active malignancy at dialysis start, but their access to kidney transplant remains limited.

Published
2020

34. SO058IGG4-RELATED KIDNEY DISEASE : A FRENCH NATIONWIDE RETROSPECTIVE COHORT STUDY

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Chaba, Anis, Zaidan, Mohamad, Jean Jacques, BOFFA, Alexandre, KARRAS, Vincent, Audard, RENAUD, SNANOUDJ, Thaunat, Olivier, NOUVIER, Mathilde, Devresse, Arnaud, Joly, Dominique, Halimi, Jean Michel, CARTERY, CLAIRE, Daugas, Eric, Peraldi, Marie-Noelle, Mathieu, LEGENDRE, Julie, BELLIERE, Faguer, Stanislas, Dimitri, TITECA, William, HANF, Petitclerc, Thierry, Guillaume, HANOUNA, Chemouny, Jonathan, Nabila, GOUMRI, Simon, DUQUENNOY, Vilaine, Eve, 57TH ERA-EDTA VIRTUAL CONGRESS, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Chaba, Anis, Zaidan, Mohamad, Jean Jacques, BOFFA, Alexandre, KARRAS, Vincent, Audard, RENAUD, SNANOUDJ, Thaunat, Olivier, NOUVIER, Mathilde, Devresse, Arnaud, Joly, Dominique, Halimi, Jean Michel, CARTERY, CLAIRE, Daugas, Eric, Peraldi, Marie-Noelle, Mathieu, LEGENDRE, Julie, BELLIERE, Faguer, Stanislas, Dimitri, TITECA, William, HANF, Petitclerc, Thierry, Guillaume, HANOUNA, Chemouny, Jonathan, Nabila, GOUMRI, Simon, DUQUENNOY, Vilaine, Eve, and 57TH ERA-EDTA VIRTUAL CONGRESS

Published
2020

35. Midterm Outcomes of 12 Renal Transplant Recipients Treated With Eculizumab to Prevent Atypical Hemolytic Syndrome Recurrence

Author

Magali Devriese, Anne Scemla, Lucile Amrouche, Véronique Frémeaux-Bacchi, Arnaud Mejean, Renaud Snanoudj, Julien Zuber, Christophe Legendre, Rebecca Sberro-Soussan, Marion Rabant, and Charlène Levi

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Biopsy, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, urologic and male genital diseases, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Recurrence, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Young adult, Kidney transplantation, Atypical Hemolytic Uremic Syndrome, Transplantation, biology, medicine.diagnostic_test, business.industry, Complement C5, Complement C3, Middle Aged, Eculizumab, medicine.disease, Kidney Transplantation, Treatment Outcome, Renal transplant, Mutation, Monoclonal, biology.protein, Kidney Failure, Chronic, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies, medicine.drug
Abstract

Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab.Twelve renal transplant recipients with aHUS-related end-stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25). Clinical and histological features, complement assessment, and free eculizumab measurements were analyzed. The median follow-up was 24.6 months.Five patients had failed at least 1 previous renal transplant from aHUS. A genetic mutation was identified in 9 patients, anti-H antibodies were found in 2. No patient demonstrated biological recurrence of thrombotic microangiopathy under treatment. Three antibody-mediated rejections (AMRs) occurred without detectable C5 residual activity. AMR was associated with subclinical thrombotic microangiopathy in 2 patients. One patient lost his graft after several complications, including AMR. One patient experienced posttransplant C3 glomerulonephritis. The last median serum creatinine was 128.2 ± 40.8 μmol/L.These data confirm that eculizumab is highly effective in preventing posttransplantation aHUS recurrence, yet may not fully block AMR pathogenesis.

Published
2017

36. Identification des déterminants de la mauvaise observance et de son impact sur l’échec de greffe

Author

Thomas Janssoone, Renaud Snanoudj, A. Brodin Sartorius, P. Sinel-Boucher, Pierre Rinder, Clémence Bic, and Pierre Hornus

Subjects
Nephrology
Abstract

Introduction Plusieurs etudes indiquent qu’une bonne observance des patients transplantes renaux limite le risque d’echec de la greffe mais les donnees d’observance sont difficilement accessibles. Nous avons mobilise les donnees du Systeme National des Donnees de Sante pour etudier la correlation entre observance et echec de greffe sur 16 000 patients. Description L’etude vise a identifier les determinants d’une mauvaise observance des patients et l’impact de cette mauvaise observance sur l’echec de la greffe. Nous avons eu acces aux donnees de remboursements des 16 000 transplantes entre janvier 2013 et decembre 2017. Ces donnees comprennent l’âge, le sexe, le detail des sejours hospitaliers des patients (avant, pendant et apres la greffe) ainsi que l’ensemble des visites en pharmacie et les traitements delivres lors de ces visites. Methodes Nous avons construit un indicateur “proxy” de l’observance des patients a partir de la frequence des visites en pharmacie pour les traitements chroniques lies a leur pathologie, cette frequence est attendue a une fois par mois au minimum. Pour estimer les determinants d’une mauvaise observance (frequence de visite en pharmacie en dessous de 9 fois par an), nous avons utilise des modeles classiques (modeles de Cox et regression logistique) ainsi que de modeles d’intelligence artificielle, notamment pour mieux estimer les interactions entre les variables explicatives. Resultats Le modele construit presente de bons resultats et les principaux determinants identifies sont le temps depuis le dernier achat, le sexe et l’index de Charlson de l’annee pre-transplantation. Les modeles d’IA sont legerement plus robustes que les modeles classiques, mais apparaissent peu interpretables. Apres ajustement sur les variables disponibles, il apparait que la mauvaise observance a un impact significatif sur l’echec de greffe. Conclusion Un enrichissement de la base de donnees avec les donnees de prescription et d’analyse biologique est actuellement en cours.

Published
2021

37. SO058IGG4-RELATED KIDNEY DISEASE : A FRENCH NATIONWIDE RETROSPECTIVE COHORT STUDY

Author

Chaba, Anis, primary, Zaidan, Mohamad, primary, Jean Jacques, BOFFA, primary, Alexandre, KARRAS, primary, Vincent, Audard, primary, RENAUD, SNANOUDJ, primary, Thaunat, Olivier, primary, NOUVIER, Mathilde, primary, Arnaud, DEVRESSE, primary, Joly, Dominique, primary, Halimi, Jean Michel, primary, CARTERY, CLAIRE, primary, Daugas, Eric, primary, Peraldi, Marie-Noelle, primary, Mathieu, LEGENDRE, primary, Julie, BELLIERE, primary, Faguer, Stanislas, primary, Dimitri, TITECA, primary, William, HANF, primary, Petitclerc, Thierry, primary, Guillaume, HANOUNA, primary, Chemouny, Jonathan, primary, Nabila, GOUMRI, primary, Simon, DUQUENNOY, primary, and Vilaine, Eve, primary

Published
2020
Full Text
View/download PDF

38. Central nervous system complications in adult cystinosis patients

Author

Dany Anglicheau, Herve Lemaitre, Ana Saitovitch, Corinne Antignac, Clément Pontoizeau, Aude Servais, Aurélie Hummel, Anne Scemla, Nathalie Boddaert, Benoît Funalot, Renaud Snanoudj, Christophe Legendre, Jennifer Boisgontier, and Rebecca Sberro-Soussan

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Cysteamine, Central nervous system, Cystinosis, Renal function, Neurological examination, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, Nephropathic Cystinosis, Central Nervous System Diseases, Internal medicine, Genetics, medicine, Middle frontal gyrus, Humans, Gray Matter, Genetics (clinical), 030304 developmental biology, Aged, 0303 health sciences, medicine.diagnostic_test, business.industry, 030305 genetics & heredity, Middle Aged, medicine.disease, Fanconi Syndrome, Magnetic Resonance Imaging, medicine.anatomical_structure, chemistry, Cerebral blood flow, Case-Control Studies, Cerebrovascular Circulation, Cystine, Female, business
Abstract

Little is known about the long-term progression of adult nephropathic cystinosis patients. Our objective was to study central nervous system complications in cystinosis patients in the era of early cysteamine treatment, using advanced neuroimaging techniques. Neurological examination and multimodal brain 3 Tesla MRI were performed in 21 adult cystinosis patients, including 18 infantile cystinosis patients, 20 controls matched for age and renal function, and 12 healthy controls. Differences in gray matter volume and rest cerebral blood flow (CBF) using arterial spin labeling sequence were investigated using whole-brain voxel-based approach. Median age was 33.8 years (18.7-65.8). Seven patients (38.9%) presented with at least one central nervous system clinical abnormality: two (11.1%) with seizures, three (16.7%) with memory defects, five (27.8%) with cognitive defect, and one (5.5%) with stroke-like episode. These patients had a worse compliance to treatment (compliance score 2 vs 1, P = .03) and received a lower median cysteamine dose (0.9 g/day vs 2.1 g/day, P = .02). Among patients with infantile cystinosis, 13 (72.2%) showed cortical atrophy, which was absent in controls, but it was not correlated with symptoms. Cystinosis patients showed a significant gray matter decrease in the middle frontal gyrus compared with healthy controls and a significant negative correlation between the cystine blood level and rest CBF was observed in the right superior frontal gyrus, a region associated with executive function. Compliance to cysteamine treatment is a major concern in these adult patients and could have an impact on the development of neurological and cognitive complications.

Published
2019

39. No clinical benefit of rapid versus gradual tapering of immunosuppression to treat sustained BK virus viremia after kidney transplantation: a single-center experience

Author

Lise Morin, Agathe Vermorel, Arnaud Devresse, Dany Anglicheau, Marion Rabant, Lucile Amrouche, Julien Zuber, Anne Scemla, Claire Tinel, Véronique Avettand-Fenoel, Christophe Legendre, Renaud Snanoudj, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie

Subjects
Adult, Male, medicine.medical_specialty, Basiliximab, medicine.medical_treatment, Urology, Viremia, 030230 surgery, medicine.disease_cause, Drug Administration Schedule, Tacrolimus, Mycophenolic acid, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Kidney transplantation, Aged, Retrospective Studies, Immunosuppression Therapy, Polyomavirus Infections, Transplantation, business.industry, Graft Survival, Immunosuppression, Middle Aged, Mycophenolic Acid, medicine.disease, Kidney Transplantation, BK virus, Immunosuppressive drug, BK Virus, Multivariate Analysis, Female, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, medicine.drug
Abstract

Immunosuppressive drug tapering is currently the recommended treatment of BK virus (BKV) viremia after kidney transplantation; however, its exact modalities remain unclear. We retrospectively compared two consecutive strategies in 111 patients with sustained viremia: a gradual monitoring/tapering group (GT, n = 57) before 2012 and a rapid monitoring/tapering group (RT, n = 54) after 2012. At viremia diagnosis, the dose of mycophenolic acid (MPA) and tacrolimus levels (T0 ) were similar among patient groups. However, following onset, the dose of MPA at 1 month (P = 0.002) and 3 months (P = 0.005) and Tac T0 at 1 month (P = 0.030) and 3 months (P = 0.006) were lower in the RT group. This rapid minimization shortened BKV viremia (P < 0.001) and resulted in a better protection of graft function in patients with confirmed BKV-associated nephropathy (P = 0.033) without impacting 5-year graft survival. Survival without rejection was similar (P = 0.571), but the RT group had increased the development of de novo donor-specific antibodies (dnDSAs; P < 0.001). Multivariate Cox analysis identified basiliximab versus Thymoglobulin® induction [hazard ratio (HR), 3.090; P = 0.001] and the RT strategy (HR, 6.021; P = 0.002) as independently associated with dnDSAs. Compared to a gradual tapering, rapid immunosuppression tapering to treat sustained BKV viremia does not improve medium-term clinical outcome but increases the risk of developing dnDSAs.

Published
2019

40. Baseline graft status is a critical predictor of kidney graft failure after diarrhoea

Author

Fanny Lanternier, Lise Morin, Florence Aulagnon, Frank Martinez, L Bererhi, Renaud Snanoudj, Adel A Aidoud, Rebecca Sberro-Soussan, Xavier Lebreton, Lucile Amrouche, Anne Scemla, Dany Anglicheau, Jean-Luc Taupin, Véronique Avettand-Fenoel, Julien Zuber, Olivier Lortholary, O. Aubert, Arnaud Devresse, Claire Tinel, Christophe Legendre, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie

Subjects
Adult, Diarrhea, Graft Rejection, Male, medicine.medical_specialty, Time Factors, 030232 urology & nephrology, Renal function, 030230 surgery, Gastroenterology, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Kidney transplantation, Retrospective Studies, Kidney, Transplantation, business.industry, Incidence, Graft Survival, Hazard ratio, Acute kidney injury, Retrospective cohort study, Middle Aged, medicine.disease, Kidney Transplantation, medicine.anatomical_structure, Nephrology, Kidney Failure, Chronic, Female, France, medicine.symptom, business, Glomerular Filtration Rate
Abstract

Background Diarrhoea is one of the most frequent complications after kidney transplantation (KT). Non-infectious diarrhoea has been associated with reduced graft survival in kidney transplant recipients. However, the risk factors for renal allograft loss following diarrhoea remain largely unknown. Methods Between January 2010 and August 2011, 195 consecutive KT recipients who underwent standardized microbiological workups for diarrhoea at a single centre were enrolled in this retrospective study. Results An enteric pathogen was readily identified in 91 patients (47%), while extensive microbiological investigations failed to find any pathogen in the other 104. Norovirus was the leading cause of diarrhoea in these patients, accounting for 30% of the total diarrhoea episodes. The baseline characteristics were remarkably similar between non-infectious and infectious diarrhoea patients, with the exception that the non-infectious group had significantly lower graft function before diarrhoea (P = 0.039). Infectious diarrhoea was associated with a longer duration of symptoms (P = 0.001) and higher rates of acute kidney injury (P = 0.029) and hospitalization (P Conclusion Our study shows that pre-existing conditions (re-transplantation, chronic graft dysfunction and late occurrence) determine the primary functional long-term consequences of post-transplant diarrhoea.

Published
2019

41. Nouveaux aspects de la compatibilité HLA en transplantation

Author

Renaud Snanoudj and Christophe Legendre

Subjects
medicine.medical_specialty, Histocompatibility Testing, Human leukocyte antigen, 030230 surgery, Biology, Epitope, Organ transplantation, Transplantation, Isoantibodies, 03 medical and health sciences, 0302 clinical medicine, Antigen, Nephrology, Immunology, medicine, biology.protein, Antibody, 030215 immunology
Abstract

In organ transplantation, HLA compatibility between a donor and a recipient is currently assessed through the comparison of their HLA antigens and the sole count of incompatible HLA antigens. Similarly, antibodies were originally described as antigenic-specific. With solid phase assays detection of anti-HLA antibodies and crystallographic studies, it is now recognized that anti-HLA antibodies are not specific for antigens, but for epitopes, i.e. short polymorphic sequences of amino acids that are more often in positions accessible to allo-antibodies. These epitopes, due to the distribution of HLA molecules polymorphism, may be shared by different HLA antigens. This explains why an immunization towards a given HLA antigen can lead to synthesis of antibodies reactive towards other antigens sharing one or more epitopes. Similarly, structural comparison of the HLA molecules of a recipient and his donor defines the epitope load, i.e. the number of incompatible epitopes. This epitope load is correlated with the risk of developing antibodies specific for the donor after transplantation. New tools, such as the HLAMatchmaker software, allow to determine the epitopic load and to analyze the epitopic specificity of alloantibodies. These tools will possibly lead to rethink the method of graft allocation, or at least to take differently into account HLA compatibility in allocation algorythms.

Published
2016

42. La transplantation rénale améliore le cours des porphyries aiguës intermittentes

Author

Valérie Chatelet, Renaud Snanoudj, Sophie Caillard, N. Kamar, Hélène Lazareth, C. Levi, Luc Frimat, Jonathan Maurice Chemouny, Nicolas Pallet, and Hervé Puy

Subjects
Nephrology
Abstract

Introduction La porphyrie aigue intermittente (PAI) est une maladie secondaire a une mutation de l’hydroxymethylbilane synthase (HMBS), qui participe a la biosynthese de l’heme. La PAI se caracterise par des crises neuroviscerales accompagnees de l’excretion urinaire de precurseurs de porphyrines, le porphobilinogene (PBG) et d’acide aminolevulinique (ALA). Une atteinte renale est retrouvee chez plus de 50 % des patients porteurs de PAI symptomatique. La survenue d’une insuffisance renale terminale (IRCT) est une complication rare mais severe de la maladie qui mene a l’accumulation de precurseurs des porphyrines et precipite les crises. Il n’existe pas de donnees concernant le devenir des patients apres transplantation renale. Methodes Etude retrospective portant sur les patients porteurs de PAI, identifies comme transplantes renaux par le Centre francais des porphyries (CRMR porphyries, hopital Louis-Mourier, Colombes). Resultats Onze patients porteurs de PAI ont beneficie d’une transplantation renale. Le diagnostic de PAI etait porte en moyenne 19 ans avant la survenue de l’IRCT a l’exception d’un patient pour lequel le diagnostic de PAI avait ete porte 5 ans apres l’initiation de la dialyse. Le suivi median apres transplantation etait de 9 ans. Un patient est decede deux mois apres la greffe d’un arret cardio-respiratoire. Aucun episode de rejet, aucune perte de greffon ou autre evenement indesirable n’a ete retrouve. Au dernier suivi, la creatininemie mediane etait de 117 μmol/L en moyenne et la proteinurie etait Fig. 1 ). Conclusion La transplantation renale apparait comme le traitement de choix de l’IRCT chez les patients porteurs de PAI. Elle permet de reduire considerablement l’activite de la maladie chez ces patients.

Published
2020

43. Étude de cohorte rétrospective sur l’expérience francophone dans l’atteinte rénale de la maladie à IgG4

Author

Mohamad Zaidan, M. Tim Ebbo, A. Chaba, A. Karras, A. Devresse, Renaud Snanoudj, Vincent Audard, Mathilde Nouvier, and Jean-Jacques Boffa

Subjects
Nephrology
Abstract

Introduction La maladie associee aux IgG4 est une pathologie fibro-inflammatoire pouvant affecter potentiellement tous les organes. L’atteinte renale represente une de ses principales manifestations. Description Cette etude presente les differentes caracteristiques diagnostiques, therapeutiques ainsi que les marqueurs associes a la rechute et au declin de la fonction renale. Methodes Nous avons conduit une etude observationnelle retrospective portant sur les patients atteints d’une nephropathie s’inscrivant dans le cadre d’une maladie associee aux IgG4 dans 41 centres francais et 2 centres belges. Resultats Soixante-quatorze patients, 64 hommes et 10 femmes avec une nephropathie associee a une maladie a IgG4 ont ete inclus. L’âge moyen au diagnostic etait 65,2 ans. L’atteinte renale etait inaugurale dans 63 % des cas mais seulement 12 % patients avaient une atteinte renale isolee au diagnostic. Quatre-vingt-deux pour cent des patients ont beneficie d’une biopsie renale revelant une atteinte tubulo-interstitielle chez l’ensemble des patients avec en plus 16 % glomerulopathies associees. L’analyse de survie multivariee permettait de retenir ≥ 4 organes atteins (p = 0,01), la consommation de C3 et C4 (p = 0,003) ainsi que l’administration de rituximab (p = 0,04) comme associes de facon independante a la survenue de rechute. En regression logistique multivariee l’âge (p = 0,008), le pic de creatinine (p = 0,004) mais aussi un taux d’IgG4 serique superieur a 5 g/L (p = 0,063) semblaient etre de bon marqueurs pronostics ( Fig. 1 ). Conclusion La NIgG4 se presente le plus souvent comme une nephrite tubulo-interstitielle aigue. La reponse a la corticotherapie est favorable. Le taux de rechute est de 30 % et le risque d’evolution vers l’insuffisance renale chronique concerne une majorite de patients. La consommation du complement, le nombre d’organe atteins et l’administration de rituximab sont predictifs de rechute. L’âge, le pic de creatinine et le taux d’IgG4 sont des marqueurs de severite de l’atteinte renale.

Published
2020

44. Benefits of kidney transplantation for a national cohort of patients aged 70 years and older starting renal replacement therapy

Author

Marc Bauwens, Renaud Snanoudj, Roland M Andrianasolo, Camille Legeai, Maryvonne Hourmant, Marie-Alice Macher, Olivier Moranne, Joaquim Soares, Cécile Couchoud, Christian Jacquelinet, Agence de la biomédecine [Saint-Denis la Plaine], 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), Hôpital Foch [Suresnes], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Graft Rejection, Male, Pediatrics, Time Factors, medicine.medical_treatment, 030232 urology & nephrology, kidney transplantation/nephrology, Comorbidity, 030230 surgery, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, Postoperative Complications, 0302 clinical medicine, Risk Factors, Epidemiology, Immunology and Allergy, Medicine, Pharmacology (medical), organ transplantation in general, Kidney transplantation, Geriatrics, Graft Survival, Prognosis, 3. Good health, Renal Replacement Therapy, Survival Rate, Female, medicine.medical_specialty, Waiting Lists, recipient selection, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, clinical research/practice, comorbidities, 03 medical and health sciences, patient survival, Renal Dialysis, Humans, Renal replacement therapy, Dialysis, Aged, Transplantation, geriatrics, business.industry, Perioperative, medicine.disease, health services and outcomes research, Kidney Transplantation, Kidney Failure, Chronic, registry/registry analysis, business, Follow-Up Studies
Abstract

International audience; Our objectives were to evaluate kidney transplantation survival benefit in people aged ≥70 who were receiving renal replacement therapy (RRT) and to identify their risk factors for posttransplant mortality. This study included all patients in the national French Renal Epidemiology and Information Network registry who started RRT between 2002 and 2013 at age ≥70. Mortality risk was compared between patients with transplants; on the waiting list; and on dialysis matched for age, gender, comorbidities, and time on dialysis. Of the 41 716 elderly patients starting RRT, 1219 (2.9%) were on the waiting list and 877 (2.1%) underwent transplantation during the follow-up. Until month 3, transplant patients had a risk of death triple that of the wait-listed group. Although the risk was halved at month 9, the perioperative risk was still not offset by month 36. Compared with matched dialysis patients (n = 2183), transplant patients were not at significantly increased perioperative risk and had a lower mortality risk starting at month 3. Risk factors for posttransplant mortality were diabetes, cardiovascular comorbidities, and dialysis duration >2 years. Among older dialysis patients, 20% had neither cardiovascular comorbidity nor diabetes. Systematic early assessment of the eligibility of elderly patients for kidney transplantation is recommended to expand registration to patients with poor survival on dialysis and no cardiovascular comorbidity.

Published
2018

45. Efficacité et tolérance du fébuxostat chez 73 patients goutteux avec une insuffisance rénale chronique stade 4/5 : étude rétrospective de 10 centres

Author

Frédéric Lioté, Pierre-Antoine Juge, Evangeline Pillebout, Cécile Vigneau, Gérard Chalès, Marie-Elise Truchetet, Alain Saraux, Thierry Schaeverbeke, Philippe Dieudé, Renaud Snanoudj, Thomas Bardin, Sébastien Ottaviani, Emilie Cornec-Le Gall, Tristan Pascart, Hang-Korng Ea, Pascal Richette, René-Marc Flipo, Divi Cornec, Florian Bailly, Clotilde Loustau, Centre Viggo-Petersen, service de rhumatologie, Hôpital Lariboisière-APHP, Service de rhumatologie, CHU Bordeaux [Bordeaux], Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de rhumatologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie adultes [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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHRU - Service de néphrologie, dialyse et transplantation rénale, Département de Rhumatologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Rhumatologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service de rhumatologie [Rennes] = Rheumatology [Rennes], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Département de Rhumatologie ( BORDEAUX - Rhumato ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques ( BIOSCAR ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Sud, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Service de Rhumatologie [CHU Pitié Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, 030232 urology & nephrology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract

Resume Objectif Les doses maximales de l’allopurinol sont limitees en cas d’insuffisance renale chronique, particulierement aux stades 4/5. Le febuxostat possede un metabolisme hepatique et son utilisation a ete autorisee sans modification posologique chez les patients insuffisants renaux stades 1 a 3. Notre objectif etait d’etudier la tolerance et l’efficacite du febuxostat chez les patients insuffisants renaux chroniques stades 4/5. Methodes Dans cette etude retrospective, nous avons inclus les patients presentant (1) un diagnostic de goutte, (2) un traitement par febuxostat, (3) un debit de filtration glomerulaire ≤ 30 mL/min/1,73m 2 (formule MDRD) lors de l’initiation du febuxostat et (4) un suivi d’au moins 3 mois apres le debut du traitement par febuxostat. L’efficacite, la tolerance et la variation de la fonction renale ont ete analysees. Resultats Nous avons inclus 73 patients goutteux (âge moyen 70,2 ± 11,8 ans, 61 hommes, 31 patients avec nephrangiosclerose et 18 patients transplantes renaux) provenant de 10 centres universitaires. L’uricemie a l’initiation etait de 9,86 ± 2,85 mg/dL, la duree devolution moyenne de la goutte etait de 6,2 ± 7,0 ans. Les comorbidites etaient constituees d’insuffisance cardiaque (17,8 %), d’hypertension arterielle (98,6 %), de diabete (30,1 %), de dyslipidemie (64,8 %) et d’antecedents d’evenements thromboemboliques (38,4 %). Lors de la derniere visite (suivi moyen de 68,5 ± 64,8 semaines), la dose de febuxostat etait de 40 mg/j pour 7 patients (10,5 %), 80 mg/j pour 50 (74,6 %) et 120 mg/j pour 10 patients (14,9 %). L’uricemie etait Conclusion Le febuxostat semble etre efficace chez les patients goutteux insuffisants renaux chroniques stades 4/5. Cependant, la tolerance concernant la fonction renale n’est pas certaine. De plus grandes etudes sont necessaires pour la determiner.

Published
2018

46. Response to: 'Renal allograft histology at 10 years after transplantation in the tacrolimus era: Evidence of pervasive chronic injury'

Author

Christophe Legendre and Renaud Snanoudj

Subjects
Transplantation, medicine.medical_specialty, business.industry, Urology, Histology, 030230 surgery, Chronic injury, Kidney, Kidney Transplantation, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, Renal allograft, Immunology and Allergy, Medicine, Transplantation, Homologous, Pharmacology (medical), business, Drug toxicity
Published
2017

47. Dramatic Improvement of Severe Cryptococcosis-Induced Immune Reconstitution Syndrome With Adalimumab in a Renal Transplant Recipient

Author

Olivier Lortholary, Anne Scemla, Perrine Parize, S. Gerber, Dany Anglicheau, Marie-Elisabeth Bougnoux, M. Zuber, Alyette Duquesne, F. Martinez, Renaud Snanoudj, and C. Legendre

Subjects
Adult, medicine.medical_treatment, Anti-Inflammatory Agents, Meningitis, Cryptococcal, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Immune system, Immune reconstitution inflammatory syndrome, Immune Reconstitution Inflammatory Syndrome, Adalimumab, Humans, Immunology and Allergy, Medicine, Pharmacology (medical), Transplantation, Tumor Necrosis Factor-alpha, business.industry, Brain, Immunosuppression, Cryptococcosis, medicine.disease, Kidney Transplantation, Magnetic Resonance Imaging, Transplant Recipients, Discontinuation, Treatment Outcome, Immunology, Monoclonal, Female, business, Complication, Immunosuppressive Agents, medicine.drug
Abstract

In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.

Published
2015

48. Efficacy and safety of febuxostat in 73 gouty patients with stage 4/5 chronic kidney disease: A retrospective study of 10 centers

Author

Thierry Schaeverbeke, Frédéric Lioté, Thomas Bardin, Renaud Snanoudj, Cécile Vigneau, Tristan Pascart, Marie-Elise Truchetet, Hang-Korng Ea, Philippe Dieudé, René-Marc Flipo, Pierre-Antoine Juge, Florian Bailly, Emilie Cornec-Le Gall, Gérard Chalès, Divi Cornec, Alain Saraux, Pascal Richette, Evangeline Pillebout, Sébastien Ottaviani, Clotilde Loustau, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunology and Allergy, University Hospital and School of Medicine, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Service de rhumatologie, CHU Bordeaux [Bordeaux], 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), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Foch [Suresnes], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), UFR Médicale, Université Paris Diderot - Paris 7 (UPD7), Service Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [Rennes] = Rheumatology [Rennes], Service de Rhumatologie [Lariboisière], 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 ), 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), CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), 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 ), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Hôpital Sud, Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques ( BIOSCAR ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service de néphrologie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], LabEX IGO Immunothérapie Grand Ouest, Service de Rhumatologie [CHU de la Cavale-Blanche], Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière, Foie, métabolismes et cancer, and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -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
Male, Gout, 030232 urology & nephrology, Comorbidity, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Chronic kidney disease, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Academic Medical Centers, Incidence, Age Factors, Middle Aged, 3. Good health, Survival Rate, Treatment Outcome, Female, Febuxostat, France, Patient Safety, medicine.drug, Glomerular Filtration Rate, medicine.medical_specialty, Allopurinol, Renal function, Statistics, Nonparametric, Gout Suppressants, 03 medical and health sciences, Sex Factors, Rheumatology, Diabetes mellitus, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Aged, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, medicine.disease, Surgery, Transplantation, business, Dyslipidemia, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease, Follow-Up Studies
Abstract

International audience; Objectives - The allopurinol dose is limited in chronic kidney disease, particularly stage 4/5 chronic kidney disease. Febuxostat has a hepatic metabolism and has been approved without dose adaptation in gouty patients with stage 1-3 chronic kidney disease. We aimed to study the safety and efficacy of febuxostat for stage 4/5 chronic kidney disease. Methods - In this retrospective study, we included patients with (1) a diagnosis of gout, (2) febuxostat treatment, (3) estimated glomerular filtration rate≤30mL/min/1.73m (Modification of Diet in Renal Disease formula) at febuxostat initiation and (4) follow-up for at least 3 months after febuxostat initiation. Efficacy, safety and variation in estimated glomerular filtration rate were analyzed. Results - We included 73 patients (mean age 70.2±11.8, 61 men, 31 with vascular chronic kidney disease and 18 renal transplantation) with gout (baseline serum uric acid level=9.86±2.85mg/dL, mean gout duration 6.2±7.0 years) from 10 academic centers. Comorbidities included cardiac failure (17.8%), hypertension (98.6%), diabetes mellitus (30.1%), dyslipidemia (64.8%) and history of cardiovascular events (38.4%). At the last visit (mean follow-up 68.5±64.8 weeks), the daily dose of febuxostat was 40mg for 7 patients (10.5%), 80mg for 50 (74.6%) and 120mg for 10 (14.9%). Serum uric acid level was

Published
2017

49. Long-term Outcomes of Kidney Transplantation in Patients With High Levels of Preformed DSA: The Necker High-Risk Transplant Program

Author

Olivier Aubert, Ruy Cavalcanti, Jean-Paul Duong Van Huyen, Renaud Snanoudj, Frank Martinez, Lionel Lamhaut, Marion Rabant, Caroline Suberbielle, Rebecca Sberro-Soussan, Alexandre Loupy, Claire Tinel, Anne Scemla, Marc-Olivier Timsit, Julien Zuber, Dany Anglicheau, Lucile Amrouche, and Christophe Legendre

Subjects
Adult, Graft Rejection, Male, Pediatrics, medicine.medical_specialty, Paris, Time Factors, 030232 urology & nephrology, Kaplan-Meier Estimate, 030230 surgery, Risk Assessment, Donor Selection, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Isoantibodies, Risk Factors, medicine, Long term outcomes, Humans, In patient, Kidney transplantation, Transplantation, business.industry, Donor selection, Graft Survival, Middle Aged, medicine.disease, Allografts, Kidney Transplantation, Histocompatibility, Surgery, Treatment Outcome, Renal transplant, Female, business, Risk assessment, Biomarkers, Immunosuppressive Agents, Program Evaluation
Abstract

There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (AMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required.Our high immunologic risk program included 95 patients with high peak or day 0 DSA levels (mean fluorescence intensity [MFI]3000) with a complement-dependent cytotoxicity-negative crossmatch, who received a posttransplant desensitization protocol starting at day 0 with high-dose intravenous immunoglobulin, plasma exchanges, and eventually rituximab. Their characteristics were compared with a control group including 39 patients with a lower immunologic risk (MFI between 500 and 3000 at day 0) who received the same posttransplant desensitization.The median MFI of the immunodominant class I or II DSA in the peak or day 0 serum was 9421 (interquartile range, 4959-12 610). An AMR occurred during the first posttransplant year in 31 patients (32.6%), and at one year, the rate of chronic AMR was 39.5%. The 1-, 3-, 5- and 7-year death-censored allograft survival rates were 98%, 91%, 86%, and 78%, respectively, with concomitant recipient survival rates of 97%, 93%, 85%, and 79%, respectively.These results suggest that DSA-sensitized patients with high MFI levels can receive transplantation across the HLA-barrier, with the use of an intensified posttransplant immunosuppressive therapy starting at day 0 combined with close clinical, immunologic, and histologic monitoring.

Published
2017

50. List of Contributors

Author

Michael Abecassis, Ahmed Abed, Massimo Abelli, Sarwat Ahmad, Mario Alessiani, Aynaa Alsharidi, Fiorella Altruda, Gabriella Amorese, Andrea Angeletti, Mario Angelico, Roberta Angelico, Maria L. Angelotti, Robert J. Applegate, Anthony Atala, Chiara Attanasio, David Axelrod, Yanik Bababekov, Joydeep Basu, Francesca Becherucci, P. Matthew Belford, Enrico Benedetti, Valentina Benedetti, Ariela Benigni, Timothy A. Bertram, Oriol Bestard, Joshua Blake, Ugo Boggi, Lauren Brasile, Jonathan S. Bromberg, Sophie Brouard, Matthew Brovold, George W. Burke, Mirela Busic, Zeeshan Butt, Silvia Caddeo, Stefano Calzone, Josep M. Campistol, Irene Carmagnola, Fiona Carty, Diego Castanares-Zapatero, Christos E. Chadjichristos, Brooke E. Chambers, Sindhu Chandran, Christos Chatziantoniou, Ashton Chen, Linda Chen, Xiwu Chen, Valeria Chiono, Manuel Chiusa, Gaetano Ciancio, Gianluca Ciardelli, Gino Coletti, Elisabeth Coll, Christine Collienne, Robert B. Colvin, Monica Cortinovis, A. Benedict Cosimi, Paolo Cravedi, Giuseppe D’Amico, Stefano Da Sacco, Richard Danger, Jacques Dantal, Alan J. Davidson, Letizia De Chiara, Johannes W. De Fijter, Gloria de la Rosa, Francis L. Delmonico, Junhong Deng, Corinne Deurdulian, Abritee Dhal, Paolo Dionigi, Beatriz Domínguez-Gil, Marek Drozdzik, Jean-Claude Dussaule, Lauren Edgar, Maria Francesca Egidi, Hany El Hennawy, Karen English, Matthew J. Everly, Sharmila Fagoonee, Elvira Smeralda Famulari, Alan C. Farney, Marina Figliuzzi, Marialuisa Framarino-dei-Malatesta, David E. Fumo, Elena Gagliardini, Lorenzo Gallon, Sanjay K. Gandhi, Michael D. Gautreaux, Anna Geraedts, Domenico Giannese, Pier C. Giulianotti, Michael S. Goligorsky, Adam Griesemar, Josep M. Grinyó, Angelika C. Gruessner, Rainer W.G. Gruessner, Bulang He, Eliot Heher, Bing Ho, Sarah A. Hosgood, Kiyohiko Hotta, Atul Humar, H. David Humes, Giuseppe Iaria, Barbara Imberti, Juan Carlos Izpisua Belmonte, Ina Jochmans, Ravi Katari, Panagiotis Kavvadas, Tatsuo Kawai, Carlos Kengla, Tristan Keys, Amritha Kidiyoor, Kengo Kidokoro, Deepali Kumar, Michael A. Kutcher, Quirino Lai, Pierre-François Laterre, Céleste Lebbé, Christophe Legendre, Rachel Lennon, Peng Li, Jen-Jar Lin, Melissa H. Little, Xiongbing Lu, John W. Ludlow, Beatriz Mahíllo, Rosalinde Masereeuw, Rafael Matesanz, Mirjana S. Matovinovic, Benedetta Mazzinghi, Serge Cedrick Mbiandjeu Toya, Scott McEwen, Fabio Melandro, Loredana Melchiorri, Madhav C. Menon, Majid Mirzazadeh, Samantha Montag, Robert A. Montgomery, Virginie Montiel, Nuria Montserrat, Marina Morigi, Christian C. Morrill, Michel Mourad, Sean V. Murphy, Patricia Murray, Tiziana Nardo, Paolo A. Netti, Mark Nguyen, Michael L. Nicholson, John M. O’Callaghan, Linda Ohler, Giuseppe Orlando, Kenji Osafune, Tetsu Oura, Anna Peired, Andrea Peloso, Zhenzhen Peng, Norberto Perico, Laura Perin, Vittorio Perrone, Paul Persad, János Peti-Peterdi, Astgik Petrosyan, Andrea Pietrabissa, Christopher J. Pino, Jacques Pirenne, Francesco Pisani, Rutger J. Ploeg, Esteban Porrini, Ambra Pozzi, Alberto Pugliese, Luigi Pugliese, Ton J. Rabelink, Teresa Rampino, Michael A. Rees, Marlies E.J. Reinders, Andrea Remuzzi, Giuseppe Remuzzi, Anne Riquier-Brison, Raquel G. Roca, Jeffrey Rogers, Paola Romagnani, Ivy A. Rosales, Norman D. Rosenblum, Cinzia Rota, Piero Ruggenenti, Francesca Ruini, Junichiro Sageshima, Fadi El Salem, Shaifali Sandal, Veronika Sander, Ilaria Santeramo, Renato M. Santos, Minnie Sarwal, Jigesh Shah, Aneesha A. Shetty, Lorenzo Silengo, Eric Siskind, Anton Skaro, Renaud Snanoudj, Shay Soker, Andrew M. South, Goce Spasovski, Robert J. Stratta, Charles Strom, Bart Stubenitsky, Riccardo Tamburrini, Qizhi Tang, Ekamol Tantissattamo, Masayuki Tasaki, Hisham Tchelepi, Elena Ticozzelli, Opas Traitanon, Matias Trillini, Ivo Tzvetanov, María O. Valentín, Flavio Vincenti, Fabio Vistoli, Jelle Vriend, Stephen J. Walker, Jason A. Wertheim, David F. Williams, Bettina Wilm, Martijn J. Wilmer, Rebecca A. Wingert, Xavier Wittebole, Yun Xia, Christodoulos Xinaris, Kazuhiko Yamada, Takashi Yokoo, Shinya Yokote, Maarten L. Zandvliet, Roy Zent, Yuanyuan Zhang, David X. Zhao, Lihui Zhao, and Susan Y. Zhao

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results