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1. Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages

Author

Jean-Sélim Driouich, Maxime Cochin, Guillaume Lingas, Léa Luciani, Cécile Baronti, Ornéllie Bernadin, Magali Gilles, Paola Mariela Saba Villarroel, Grégory Moureau, Paul-Rémi Petit, Axelle Dupont, Jacques Izopet, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Dany Anglicheau, Morgane Cheminant, Stéphanie Nguyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Josephine Tine, Joe Miantezila Basilua, Denis Angoulvant, Coralie Tardivon, Gilles Blancho, Guillaume Martin-Blondel, Yazdan Yazdanpanah, France Mentré, Vincent Lévy, Franck Touret, Jérémie Guedj, Xavier de Lamballerie, and Antoine Nougairède

Subjects
Preclinical animal model, Monoclonal antibody, SARS-CoV-2, Omicron sublineages, AZD7442, Clinical therapeutics, Therapeutics. Pharmacology, RM1-950
Abstract

Therapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has been hampered by the emergence of new variants. To adapt the therapeutic landscape, health authorities have based their recommendations mostly on in vitro neutralization tests. However, these do not provide a reliable understanding of the changes in the dose-effect relationship and how they may translate into clinical efficacy. Taking the example of EvusheldTM (AZD7442), we aimed to investigate how in vivo data can provide critical quantitative results and project clinical effectiveness. We used the Golden Syrian hamster model to estimate 90 % effective concentrations (EC90) of AZD7442 in vivo against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5 variants. While our in vivo results confirmed the partial loss of AZD7442 activity for BA.1 and BA.2, they showed a much greater loss of efficacy against BA.5 than that obtained in vitro. We analyzed in vivo EC90s in perspective with antibody levels measured in a cohort of immunocompromised patients who received 300 mg of AZD7442. We found that a substantial proportion of patients had serum levels of anti-SARS-CoV-2 spike protein IgG above the estimated in vivo EC90 for BA.1 and BA.2 (21 % and 92 % after 1 month, respectively), but not for BA.5. These findings suggest that AZD7442 is likely to retain clinical efficacy against BA.2 and BA.1, but not against BA.5. Overall, the present study illustrates the importance of complementing in vitro investigations by preclinical studies in animal models to help predict the efficacy of monoclonal antibodies in humans.

Published
2024
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2. Living During COVID-19 While Immunocompromised: A Patient and Physician Perspective from France

Author

Elise Foudrat and Sophie Caillard

Subjects
COVID-19, Immunosuppressive drug, Kidney transplant, Patient’s perspective, Prophylactic monoclonal antibodies, SARS-CoV-2 vaccine, Infectious and parasitic diseases, RC109-216
Abstract

Abstract This article is co-authored by a kidney transplant recipient and her nephrologist. By sharing her personal experience of the coronavirus disease 2019 (COVID-19) pandemic, the patient illustrates the concerns of immunocompromised patients during this unprecedented health crisis. She describes the difficulties encountered at work, the omnipresent protective measures, and the need for appropriate information. The nephrologist, who follows a cohort of over 1700 kidney transplant recipients, recounts the medical team’s struggle to protect their vulnerable patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a veritable succession of hopes and disappointments. She describes the management of immunosuppression in kidney transplant recipients, the deployment of the COVID-19 vaccination program with the finding of poor immune responses in many patients including those receiving immunosuppressant drugs after kidney transplant, and the first use of prophylactic monoclonal antibodies. From both the patient’s and the physician’s perspectives, the COVID-19 pandemic has required continuous adaptation.

Published
2024
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3. In Vitro and In Vivo Neutralizing Efficacy of Monoclonal Antibodies Against Sars-Cov-2 Variants in Kidney Transplant Recipients

Author

Ilies Benotmane, Martin Jungbauer-Groznica, Isabelle Staropoli, Delphine Planas, Océane Dehan, Angela Brisebarre, Etienne Simon-Loriere, Samira Fafi-Kremer, Olivier Schwartz, Timothée Bruel, and Sophie Caillard

Subjects
sotrovimab, COVID-19, immunocompromised, kidney transplant recipients, monoclonal antibodies, SARS-CoV-2, Specialties of internal medicine, RC581-951
Published
2024
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4. Intrinsic capacity and frailty in older adults with end-stage kidney disease undergoing pre-kidney transplant comprehensive geriatric assessment

Author

Sarah Collette-Robert, Florent Guerville, Teddy Novais, Elodie Pongan, Emmanuel Morelon, Julien Vernaudon, Eloïse Francq, Lionel Couzi, Isabelle Bourdel-Marchasson, Sophie Caillard, Romain Pszczolinski, Damien Heitz, Thomas Gilbert, and Antoine Garnier-Crussard

Subjects
Comprehensive geriatric assessment, End-stage kidney disease, Frailty, Geronto-nephrology, Intrinsic capacity, Kidney transplantation., Internal medicine, RC31-1245
Abstract

Objective: Frailty has been extensively studied in end-stage kidney disease (ESKD) and kidney transplant (KT) patients. The identification of frailty is useful to predict adverse outcomes among ESKD and KT patients. The recent concept of intrinsic capacity (IC) appears as a good and easy-to-understand tool to screen for and monitor frailty in older adults with ESKD. This study aims to assess the relationships between frailty and IC in older adults with ESKD awaiting KT. Design: Cross-sectional study Setting and participants: 236 patients from a day-care geriatric unit undergoing pre-KT geriatric assessment between 2017 and 2022 were included in the main sample, and 151 patients in an independent multicentric replication sample. Measurements: Frailty was evaluated using the physical frailty phenotype (PFP) and IC measures using the World Health Organization’s screening (step 1) and diagnostic (step 2) tools for five IC domains (vitality, locomotion, audition, cognition, psychology). Multivariate regressions were run to assess relationships between PFP and IC domains, adjusted for age, sex, and comorbidities. Analyses were replicated using another independent multicenter cohort including 151 patients with ESKD to confirm the results. Results: Impairments in the locomotion, psychology, and vitality IC domains according to WHO screening tools were associated with frailty (odds ratio 9.62 [95% CI 4.09−24.99], 3.19 [95% CI 1.11–8.88], and 3.11 [95% CI 1.32–7.29], respectively). When IC were measured linearly with z-scores, all IC domains except hearing were inversely associated with frailty. In the replication cohort, results were overall similar, with a greater association between psychology domain and frailty. Conclusion: This study highlights the relationship between frailty and IC in ESKD patients. We assume that IC may be assessed and monitored in ESKD patients, to predict and prevent future frailty, and post-KT adverse outcomes.

Published
2024
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5. Aortobifemoral Bypass in Kidney Transplant Candidates: A Ten-Year Experience

Author

Pascaline Bonnin, Salomé Kuntz, Sophie Caillard, Nabil Chakfé, and Anne Lejay

Subjects
kidney transplantation, vascular calcification, vascular surgical procedures, blood vessel prosthesis, kidney, Specialties of internal medicine, RC581-951
Abstract

In patients with severe aorto-iliac calcifications, vascular reconstructions can be performed in order to allow kidney transplantation. The aim of this study was to analyze the outcomes of kidney transplant candidates who underwent an aortobifemoral bypass (ABFB) for aorto-iliac calcifications. A retrospective study including all kidney transplant candidates who underwent an ABFB between 2012 and 2022 was performed. Primary outcome was 30-day morbidity-mortality after ABFB. Secondary outcome was accessibility to kidney transplant waiting list. Twenty-two ABFBs were performed: 10 ABFBs in asymptomatic patients presenting severe aorto-iliac circumferential calcifications without hemodynamic consequences, and 12 ABFBs in symptomatic patients in whom aorto-iliac calcifications were responsible for claudication or critical limb threatening ischemia. Overall 30-day mortality was 0%. Overall 30-day morbidity was 22.7%: 1 femoral hematoma and 1 retroperitoneal hematoma requiring surgical drainage in the asymptomatic group, and 2 digestive ischemia requiring bowel resection and 1 femoral hematoma requiring surgical drainage in the symptomatic group. Among the 22 patients, 20 patients could access to kidney waiting list and 8 patients underwent a kidney transplantation, including 3 living-donor transplantations. Aorto-iliac revascularization can be an option to overcome severe calcifications contraindicating kidney transplantation.

Published
2024
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6. A Tubular Vena Cava Conduit Used to Lengthen a Kidney Transplant Renal Artery Injured During Organ Procurement

Author

Bogdan Bratu, Salomé Kuntz, Sophie Caillard, Nabil Chakfe, and Anne Lejay

Subjects
Kidney transplantation, Vascular surgical procedures, kidney, Diseases of the circulatory (Cardiovascular) system, RC666-701, Surgery, RD1-811
Abstract

Introduction: Organ transplantation is limited by the supply of transplantable organs, and the supply of organs cannot meet the needs of patients on the waiting list. Ensuring transplantation of any procured organ is therefore mandatory. Organ injury, mostly to the organ's vasculature, can occur during multi-organ procurement, preventing subsequent transplantation. In such a context, vascular reconstructions of arterial or venous organ injuries can be useful. Report: This report describes the case of an obese 64 year old female with a history of diabetic nephropathy who underwent a cadaveric kidney transplant (right kidney with one main renal artery, one inferior polar artery, one vein, and one ureter). The ex situ preparation of the graft revealed that the main renal artery was injured and cut close to the renal hilum (0.8 cm length, 6 mm diameter), not allowing graft implantation. In order to increase the length of the main renal artery, the donor inferior vena cava was used to create a tubular conduit, allowing subsequent graft implantation. Cold and warm ischaemic times were respectively 12 hours and 36 minutes, with immediate graft function. The patient was discharged on day 8 (serum creatinine level was 95 μmol/L). Twelve month follow up was uneventful (serum creatinine level was 108 μmol/L and duplex ultrasonography showed homogeneous blood flow throughout the graft). Discussion: This case report highlights the possibility of overcoming an injured kidney graft artery by creating a tubular vena cava conduit in order to allow subsequent transplantation. Vascular reconstructions of organs injured during procurement should be considered.

Published
2024
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7. Post-transplantation Burkitt lymphoma: a retrospective study of 55 patients

Author

Pierre Walczak, Sylvain Choquet, Jacques Dantal, David Boutboul, Felipe Suarez, Marine Baron, Veronique Morel, Thomas Cluzeau, Mohamed Touati, Michelle Elias, Emmanuel Bachy, Emmanuelle Nicolas-Virelizier, Roch Houot, Geoffroy Venton, Caroline Jacquet, Marie-Pierre Moles-Moreau, Fabrice Jardin, Eric Durot, Noureddine Balegroune, Laure Ecotiere, Romain Guieze, Nassim Kamar, Loic Ysebaert, Lionel Couzi, Hugo Gonzalez, Louise Roulin, Kevin Ou, Sophie Caillard, Heiner Zimmermann, Ralf Ulrich Trappe, and Damien Roos-Weil

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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9. Development and validation of multivariable prediction models of serological response to SARS-CoV-2 vaccination in kidney transplant recipients

Author

Bilgin Osmanodja, Johannes Stegbauer, Marta Kantauskaite, Lars Christian Rump, Andreas Heinzel, Roman Reindl-Schwaighofer, Rainer Oberbauer, Ilies Benotmane, Sophie Caillard, Christophe Masset, Clarisse Kerleau, Gilles Blancho, Klemens Budde, Fritz Grunow, Michael Mikhailov, Eva Schrezenmeier, and Simon Ronicke

Subjects
kidney transplantation, COVID-19, vaccination, clinical decision support, immunosuppression therapy, Immunologic diseases. Allergy, RC581-607
Abstract

Repeated vaccination against SARS-CoV-2 increases serological response in kidney transplant recipients (KTR) with high interindividual variability. No decision support tool exists to predict SARS-CoV-2 vaccination response to third or fourth vaccination in KTR. We developed, internally and externally validated five different multivariable prediction models of serological response after the third and fourth vaccine dose against SARS-CoV-2 in previously seronegative, COVID-19-naïve KTR. Using 20 candidate predictor variables, we applied statistical and machine learning approaches including logistic regression (LR), least absolute shrinkage and selection operator (LASSO)-regularized LR, random forest, and gradient boosted regression trees. For development and internal validation, data from 590 vaccinations were used. External validation was performed in four independent, international validation cohorts comprising 191, 184, 254, and 323 vaccinations, respectively. LASSO-regularized LR performed on the whole development dataset yielded a 20- and 10-variable model, respectively. External validation showed AUC-ROC of 0.840, 0.741, 0.816, and 0.783 for the sparser 10-variable model, yielding an overall performance 0.812. A 10-variable LASSO-regularized LR model predicts vaccination response in KTR with good overall accuracy. Implemented as an online tool, it can guide decisions whether to modulate immunosuppressive therapy before additional active vaccination, or to perform passive immunization to improve protection against COVID-19 in previously seronegative, COVID-19-naïve KTR.

Published
2022
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10. Atypical hemolytic and uremic syndrome due to C3 mutation in pancreatic islet transplantation: a case report

Author

Thibault Bahougne, Jérome Olagne, Marion Munch, Laura Braun-Parvez, Marie-Pierrette Chenard, Véronique Frémeaux-Bacchi, Sophie Caillard, Philippe Baltzinger, Michel Greget, Laurence Kessler, and Bruno Moulin

Subjects
Atypical hemolytic and uremic syndrome, Complement C3, Islets of Langerhans transplantation, Case report, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background We here report on the first observation of a C3 mutation that is related to atypical hemolytic and uremic syndrome (aHUS), which occurred in a pancreatic islet transplant patient. Immunosuppressive treatments, such as calcineurin inhibitors, have been linked to undesirable effects like nephrotoxicity. Case presentation A 40-year-old man with brittle diabetes, who was included in the TRIMECO trial, became insulin-independent 2 months after pancreatic islet transplantation. About 15 months after islet transplantation, the patient exhibited acute kidney injury due to aHUS. Despite plasma exchange and eculizumab treatment, the patient developed end-stage renal disease. A genetic workup identified a missense variant (p.R592Q) in the C3 gene. In vitro, this C3 variant had defective Factor I proteolytic activity with membrane proteins as cofactor proteins, which was thus classified as pathogenic. About 1 year after the aHUS episode, kidney transplantation was carried out under the protection of the specific anti-C5 monoclonal antibody eculizumab. The patient had normal kidney function, with preserved pancreatic islet function 4 years later. Conclusions Pancreatic islet transplantation could have triggered this aHUS episode, but this link needs to be clarified. Although prophylactic eculizumab maintains kidney allograft function, its efficacy still needs to be studied in larger populations.

Published
2020
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11. High Predictive Value of the Soluble ZEBRA Antigen (Epstein-Barr Virus Trans-Activator Zta) in Transplant Patients with PTLD

Author

Julien Lupo, Anne-Sophie Wielandts, Marlyse Buisson, CRYOSTEM Consortium, Mohammed Habib, Marwan Hamoudi, Patrice Morand, Frans Verduyn-Lunel, Sophie Caillard, and Emmanuel Drouet

Subjects
Epstein-Barr Virus, ZEBRA protein, BZLF1, PTLD, post-transplant lymphoproliferative disease, predictive biomarker, Medicine
Abstract

The ZEBRA (Z EBV replication activator) protein is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. An increasing body of studies have highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders, such as post-transplant lymphoproliferative disease (PTLD). We studied 108 transplanted patients (17 PTLD and 91 controls), retrospectively selected from different hospitals in France and in the Netherlands. The majority of PTLD were EBV-positive diffuse large B-cell lymphomas, five patients experienced atypical PTLD forms (EBV-negative lymphomas, Hodgkin’s lymphomas, and T-cell lymphomas). Fourteen patients among the seventeen who developed a pathologically confirmed PTLD were sZEBRA positive (soluble ZEBRA, plasma level above 20 ng/mL, measured by an ELISA test). The specificity and positive predictive value (PPV) of the sZEBRA detection in plasma were 98% and 85%, respectively. Considering a positivity threshold of 20 ng/mL, the sensitivity of the sZEBRA was 82.35% and the specificity was 94.51%. The mean of the sZEBRA values in the PTLD cases were significantly higher than in the controls (p < 0.0001). The relevance of the lytic cycle and, particularly, the role of ZEBRA in lymphomagenesis is a new paradigm pertaining to the prevention and treatment strategies for PTLD. Given the high-specificity and the predictive values of this test, it now appears relevant to investigate the lytic EBV infection in transplanted patients as a prognostic biomarker.

Published
2022
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12. Atypical focal segmental glomerulosclerosis associated with a new PODXL nonsense variant

Author

David Marx, Sophie Caillard, Jérôme Olagne, Bruno Moulin, Thierry Hannedouche, Guy Touchard, Arnaud Dupuis, Christian Gachet, Anne Molitor, Seiamak Bahram, and Raphael Carapito

Subjects
exome sequencing, focal segmental glomerulosclerosis, glomerular basement membrane duplication, membranoproliferative glomerulonephritis, podocalyxin, PODXL, Genetics, QH426-470
Abstract

Abstract Background Podocalyxin (PODXL) is a highly sialylated adhesion glycoprotein that plays an important role in podocyte's physiology. Recently, missense and nonsense dominant variants in the PODXL gene have been associated with focal segmental glomerulosclerosis (FSGS), a leading cause of nephrotic syndrome and kidney failure. Their histologic description, however, was superficial or absent. Methods We performed exome sequencing on a three‐generation family affected by an atypical glomerular nephropathy and characterized the disease by light and electron microscopy. Results The disease was characterized by FSGS features and glomerular basement membrane duplication. Six family members displayed chronic proteinuria, ranging from mild manifestations without renal failure, to severe forms with end‐stage renal disease. Exome sequencing of affected twin sisters, their affected mother, healthy father, and healthy maternal uncle revealed a new nonsense variant cosegregating with the disease (c.1453C>T, NM_001018111) in the PODXL gene, which is known to be expressed in the kidney and to cause nephropathy when mutated. The variant is predicted to lead to a premature stop codon (p.Q485*) that results in the loss of the intracytoplasmic tail of the protein. Conclusion This is the first description of a peculiar association combining a PODXL stop‐gain variant and both FSGS and membranoproliferative glomerulonephritis features, described by light and electron microscopy.

Published
2021
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13. Prediction of Vaccine Response and Development of a Personalized Anti-SARS-CoV-2 Vaccination Strategy in Kidney Transplant Recipients: Results from a Large Single-Center Study

Author

Ilies Benotmane, Gabriela Gautier-Vargas, Noëlle Cognard, Jérôme Olagne, Françoise Heibel, Laura Braun-Parvez, Jonas Martzloff, Peggy Perrin, Romain Pszczolinski, Bruno Moulin, Samira Fafi-Kremer, and Sophie Caillard

Subjects
kidney transplant recipients, COVID-19, anti-SARS-CoV-2 mRNA vaccine, serological response, prediction, Medicine
Abstract

Kidney transplant recipients (KTRs) displays marked inter-individual variations in magnitude of immune responses to anti-SARS-CoV-2 vaccination. The aim of this large single-center study was to identify the predictive factors for serological response to the mRNA-1273 vaccine in KTRs. We also devised a score to optimize prediction with the goal of implementing a personalized vaccination strategy. The study population consisted of 564 KTRs who received at least two doses of the mRNA-1273 vaccine. Anti-RBD IgG titers were quantified one month after each vaccine dose and until six months thereafter. A third dose vaccine was given when the antibody titer after the second dose was p < 0.0001) and the occurrence of a good antibody response (AUC = 0.785, p < 0.0001). Notably, antibody titers declined over time both after the second and third vaccine doses. In summary, a high burden of comorbidities and immunosuppression was correlated with a weaker antibody response. A fourth vaccine dose and/or pre-exposure prophylaxis with monoclonal antibodies should be considered for KTRs who remain unprotected.

Published
2022
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14. Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after Kidney Transplantation.

Author

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

Subjects
Medicine, Science
Abstract

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

Published
2021
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15. Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients

Author

Marion Cremoni, Sébastien Cuozzo, Emanuela Martinuzzi, Susana Barbosa, Nadia Ben Hassen, Filippo Massa, Elisa Demonchy, Matthieu Durand, Olivier Thaunat, Vincent Esnault, Moglie Le Quintrec, Sophie Caillard, Nicolas Glaichenhaus, and Antoine Sicard

Subjects
kidney transplantation, COVID-19, SARS-CoV-2, T lymphocytes, immune responsiveness, Microbiology, QR1-502
Abstract

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline (p = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients.

Published
2022
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16. Prospective Measures of Adherence by Questionnaire, Low Immunosuppression and Graft Outcome in Kidney Transplantation

Author

Mathilde Prezelin-Reydit, Valérie Dubois, Sophie Caillard, Anne Parissiadis, Isabelle Etienne, Françoise Hau, Laetitia Albano, Monique Pourtein, Benoît Barrou, Jean-Luc Taupin, Christophe Mariat, Léna Absi, Cécile Vigneau, Virginie Renac, Gwendaline Guidicelli, Jonathan Visentin, Pierre Merville, Olivier Thaunat, and Lionel Couzi

Subjects
adherence, immunosuppression, kidney transplantation, dnDSA, graft survival, Medicine
Abstract

Background: Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies (dnDSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for dnDSA generation, acute rejection and GF. Methods: We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of dnDSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models. Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed dnDSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with dnDSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with dnDSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, dnDSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were dnDSA occurrence, and acute rejection. Conclusions: Prospective serial monitoring of MNA using the Morisky scale does not predict dnDSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF.

Published
2021
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17. Avascular osteonecrosis in kidney transplant recipients: Risk factors in a recent cohort study and evaluation of the role of secondary hyperparathyroidism.

Author

Renaud Felten, Peggy Perrin, Sophie Caillard, Bruno Moulin, and Rose-Marie Javier

Subjects
Medicine, Science
Abstract

Avascular osteonecrosis (AVN) is a bone complication that indicates poor functional prognosis. Modern immunosuppressive and steroid-sparing drugs have significantly lowered the occurrence of AVN after kidney transplantation (KT). However, recent data on its incidence rates and risk factors are lacking. Using a large, recent cohort, we sought to investigate AVN incidence and risk factors, with a special focus on mineral and bone disorders. We conducted a cohort study in 805 patients who underwent KT between 2004 and 2014. AVN was identified in 32 patients (4%): before KT in 15 (1.8%) and after KT in 18 (2.2%) cases, including one patient with both. In the group with post-KT AVN, the median time intervals from KT to 1) first symptoms and 2) AVN diagnosis were 12 months [1-99] and 20 months [4-100], respectively. Being overweight/obese, having pre-transplant diabetes or hyperparathyroidism at transplantation, developing acute rejection, and receiving higher cumulative corticosteroid doses were associated with AVN occurrence. Multivariate analysis revealed that BMI ≥ 26 kg/m2 and higher cumulative corticosteroid doses were predictive of AVN. In conclusion, overweight/obesity is a strong risk factor for AVN. Despite a low maintenance dose, the use of corticosteroids-mostly for treatment of acute rejection-remains an independent risk factor.

Published
2019
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18. Risk and Severity of COVID-19 and ABO Blood Group in Transcatheter Aortic Valve Patients

Author

Marion Kibler, Laurent Dietrich, Mohamad Kanso, Adrien Carmona, Benjamin Marchandot, Kensuke Matsushita, Antonin Trimaille, Cécile How-Choong, Albane Odier, Gabrielle Gennesseaux, Ophélie Schramm, Antje Reydel, Sébastien Hess, Chisato Sato, Sophie Caillard, Laurence Jesel, Olivier Morel, and Patrick Ohlmann

Subjects
ABO blood group, coronavirus disease 2019, transcatheter aortic valve replacement, Medicine
Abstract

While cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have described its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Numerous observational studies have reported an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection. Our objective was to investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The occurrence and severity (hospitalization and/or death) of COVID-19 and their associations with the ABO blood group served as the main outcome measures. Of the 1125 patients who had undergone TAVR, 403 (36%) died before 1 January 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Of them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariable analysis identified the A blood group (vs. others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio (OR) = 6.32; 95% confidence interval (CI) = 2.11−18.92; p = 0.001). The A blood group (vs. others; OR = 8.27; 95% CI = 1.83−37.43, p = 0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64−15.27, p = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). We conclude that patients who have undergone TAVR frequently have a number of cardiovascular comorbidities that may work to increase the risk of COVID-19. The subgroup with the A blood group was especially prone to developing the disease and showed unfavorable outcomes.

Published
2020
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19. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort

Author

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

Subjects
kidney transplantation, belatacept, tacrolimus, opportunistic infections, CMV infection, pneumocystis pneumonia, Medicine
Abstract

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

Published
2020
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20. An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides.

Author

Pilar Domingo-Calap, Benjamin Schubert, Mélanie Joly, Morgane Solis, Meiggie Untrau, Raphael Carapito, Philippe Georgel, Sophie Caillard, Samira Fafi-Kremer, Nicodème Paul, Oliver Kohlbacher, Fernando González-Candelas, and Seiamak Bahram

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(-3)-10(-5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.

Published
2018
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21. Eculizumab for Thrombotic Microangiopathy Associated with Antibody-Mediated Rejection after ABO-Incompatible Kidney Transplantation

Author

Luca Lanfranco, Melanie Joly, Arnaud Del Bello, Laure Esposito, Noelle Cognard, Peggy Perrin, Bruno Moulin, Nassim Kamar, and Sophie Caillard

Subjects
Surgery, RD1-811
Abstract

Thrombotic microangiopathy is a form of antibody-mediated rejection (ABMR): it is the main complication of ABO-incompatible (ABOi) kidney transplantation (KT). Herein, we report on two cases of ABMR with biological and histological features of thrombotic microangiopathy (TMA) that were treated by eculizumab after ABOi KT. The first patient presented with features of TMA at postoperative day (POD) 13. Because of worsening biological parameters and no recovery of kidney function, despite seven sessions of immunoadsorption, a salvage therapy of eculizumab was started on POD 23. Kidney function slightly improved during the first 4 months after transplantation. Eculizumab was stopped at month 4. However, kidney function worsened progressively, leading to dialysis at month 13 after transplantation. The second patient presented with features of TMA at POD 1. In addition to immunoadsorption therapy, eculizumab was started on POD 6. Kidney function improved. Eculizumab was stopped on POD 64 and immunoadsorption sessions were stopped on POD 102. At the last follow-up (after 9 months), eGFR was at 43 mL/min/1.73 m2. Our case reports show the beneficial effect of eculizumab to treat ABMR after ABOi KT. However, it should be given early after diagnosing TMA associated with ABMR.

Published
2017
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22. Low to undetectable Omicron BQ.1.1 neutralization by patient’s sera a month after initiation of AZD7442 600 mg

Author

Franck Touret, Guillaume Martin-Blondel, Xavier de Lamballerie, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Dany Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N’Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Karine Barthélémy, Stéphane Priet, Elif Nurtop, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Amandine Le Bourgeois, and Vincent Lévy

Subjects
Microbiology (medical), Infectious Diseases
Published
2023

24. Expert Consensus on the Characteristics of Patients with Epstein–Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) for Whom Standard-Dose Chemotherapy May be Inappropriate: A Modified Delphi Study

Author

Sridhar Chaganti, Arie Barlev, Sophie Caillard, Sylvain Choquet, Kate Cwynarski, Anke Friedetzky, Eva González-Barca, Natalia Sadetsky, Stefan Schneeberger, Dhanalakshmi Thirumalai, Pier L. Zinzani, and Ralf U. Trappe

Subjects
Pharmacology (medical), General Medicine
Published
2023

25. Low serum neutralization of Omicron variants a month after AZD7442 prophylaxis initiation

Author

Xavier de Lamballerie, Guillaume Martin-Blondel, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Denis Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Vincent Lévy, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Microbiology (medical), Infectious Diseases, [SDV]Life Sciences [q-bio]
Published
2023

26. Isolated kidney transplantation under lumasiran therapy in primary hyperoxaluria type 1: a report of five cases

Author

Anne-Laure Sellier-Leclerc, Elisabeth Metry, Stéphanie Clave, Peggy Perrin, Cécile Acquaviva-Bourdain, Charlène Levi, Meindert Crop, Sophie Caillard, Bruno Moulin, Jaap Groothoff, Justine Bacchetta, Paediatric Nephrology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and ARD - Amsterdam Reproduction and Development

Subjects
Transplantation, Nephrology
Published
2022

27. Torque teno virus DNA load as a predictive marker of antibody response to a three-dose regimen of COVID-19 mRNA-based vaccine in lung transplant recipients

Author

Floriane Gallais, Benjamin Renaud-Picard, Morgane Solis, Elodie Laugel, Eric Soulier, Sophie Caillard, Romain Kessler, and Samira Fafi-Kremer

Subjects
Torque teno virus, Pulmonary and Respiratory Medicine, Vaccines, Synthetic, Transplantation, COVID-19 Vaccines, SARS-CoV-2, COVID-19, Antibodies, Viral, Antibodies, Neutralizing, Transplant Recipients, Immunoglobulin G, Antibody Formation, DNA, Viral, Humans, Surgery, RNA, Messenger, mRNA Vaccines, Cardiology and Cardiovascular Medicine, Lung, BNT162 Vaccine, Biomarkers, Retrospective Studies
Abstract

Previous studies have reported that lung transplant recipients (LTR) develop a poor response to two doses of COVID-19 vaccine, but data regarding the third dose are lacking. We investigated the antibody response after three doses of mRNA vaccine in LTR and its predictive factors.A total of 136 LTR, including 10 LTR previously infected and 126 COVID-19-naive LTR, were followed during and after three doses of mRNA vaccine. We retrospectively measured anti-receptor-binding domain (RBD) IgG response and neutralizing antibodies. In a posthoc analysis, we used a multivariate logistic regression model to assess the association between vaccine response and patient characteristics, including viral DNA load (VL) of the ubiquitous Torque teno virus (TTV) (optimal cut-off set by ROC curve analysis), which reflects the overall immunosuppression.After 3 doses, 47/126 (37.3%) COVID-19-naive LTR had positive anti-RBD IgG (responders) and 14/126 (11.1%) had antibody titers above 264 Binding Antibody Units/mL. None neutralized the omicron variant versus 7 of the 10 previously infected LTR. Nonresponse was associated with TTV VL ≥6.2 logCOVID-19-naive LTR respond poorly to three doses of mRNA vaccine, especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies.

Published
2022

28. A gain-of-function variant in the Wiskott-Aldrich syndrome gene is associated with a MYH9-related disease-like syndrome

Author

David Marx, Arnaud Dupuis, Anita Eckly, Anne Molitor, Jérôme Olagne, Guy Touchard, Sihem Kaaki, Cécile Ory, Anne-Laure Faller, Bénédicte Gérard, Melanie Cotter, Lisa Westerberg, Marton Keszei, Bruno Moulin, Christian Gachet, Sophie Caillard, Seiamak Bahram, and Raphaël Carapito

Subjects
Neutropenia, Myosin Heavy Chains, Gain of Function Mutation, Hearing Loss, Sensorineural, Mutation, Humans, Renal Insufficiency, Hematology, Thrombocytopenia, Actins, Wiskott-Aldrich Syndrome Protein, Wiskott-Aldrich Syndrome
Abstract

While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. In the present study, we report exome sequencing of individuals from 3 generations of a family with a dominant disease combining neutropenia, macrothrombocytopenia, and renal failure. We identified a heterozygous missense gain-of-function variant in the WAS gene (c.881T>C, p.I294T) that segregates with the disease and is already known to cause XLN. There was no pathogenic variant in MYH9, TUBB1, or ACTN1. This is the first report of a WAS gain-of-function variant associated with both the hematological phenotype of XLN (neutropenia, macrothrombocytopenia) and renal disease (proteinuria, renal failure) with glomerular tip lesion hyalinosis and actin condensations in effaced podocytes foot processes.

Published
2022

29. Evolution of humoral lesions on follow-up biopsy stratifies the risk for renal graft loss after antibody-mediated rejection treatment

Author

Antonin Bouchet, Brieuc Muller, Jerome Olagne, Thomas Barba, Mélanie Joly, Augustin Obrecht, Maud Rabeyrin, Frédérique Dijoud, Cécile Picard, Sarah Mezaache, Antoine Sicard, Alice Koenig, Anne Parissiadis, Valérie Dubois, Emmanuel Morelon, Sophie Caillard, and Olivier Thaunat

Subjects
Graft Rejection, Transplantation, Isoantibodies, Nephrology, Biopsy, Graft Survival, Humans, Kidney Transplantation, Antibodies, Retrospective Studies, Follow-Up Studies
Abstract

Background The standard-of-care protocol, based on plasma exchanges, high-dose intravenous immunoglobulin and optimization of maintenance immunosuppression, can slow down the evolution of antibody-mediated rejection (AMR), but with high interindividual variability. Identification of a reliable predictive tool of the response to AMR treatment is a mandatory step for personalization of the follow-up strategy and to guide second-line therapies. Methods Interrogation of the electronic databases of 2 French university hospitals (Lyon and Strasbourg) retrospectively identified 81 renal transplant recipients diagnosed with AMR without chronic lesions (cg score ≤1) at diagnosis and for whom a follow-up biopsy had been performed 3–6 months after initiation of therapy. Results The evolution of humoral lesions on follow-up biopsy (disappearance versus persistence versus progression) correlated with the risk for allograft loss (logrank test, P = .001). Patients with disappearance of humoral lesions had ∼80% graft survival at 10 years. The hazard ratio for graft loss in multivariate analysis was 3.91 (P = .04) and 5.15 (P = .02) for patients with persistence and progression of lesions, respectively. The non-invasive parameters classically used to follow the intensity of humoral alloimmune response (evolution of immunodominant DSA mean fluorescence intensity) and the decline of renal graft function (estimated glomerular filtration rate decrease and persistent proteinuria) showed little clinical value to predict the histological response to AMR therapy. Conclusion We conclude that invasive monitoring of the evolution of humoral lesions by the mean of follow-up biopsy performed 3–6 months after the initiation of therapy is an interesting tool to predict long-term outcome after AMR treatment.

Published
2022

30. Early Administration of Anti–SARS-CoV-2 Monoclonal Antibodies Prevents Severe COVID-19 in Kidney Transplant Patients

Author

Juliette Gueguen, Charlotte Colosio, Arnaud Del Bello, Anne Scemla, Yohan N’Guyen, Claire Rouzaud, Claudia Carvalho-Schneider, Gabriela Gautier Vargas, Pierre Tremolières, A. Jalal Eddine, Christophe Masset, Olivier Thaunat, Melchior Chabannes, Paulo Malvezzi, Pierre Pommerolle, Lionel Couzi, Nassim Kamar, Sophie Caillard, and Philippe Gatault

Subjects
Nephrology
Abstract

Kidney transplant recipients (KTRs) are prone to develop severe COVID-19 and are less well protected by vaccine than immunocompetent subjects. Thus, the use of neutralizing anti-SARS-CoV-2 monoclonal antibody (MoAb) to confer a passive immunity appears attractive in KTRs.We performed a French nationwide study to compare COVID-19-related hospitalization, 30-day admission to intensive care unit (ICU), and 30-day death between KTRs who received an early infusion of MoAb (MoAb group) and KTRs who did not (control group). Controls were identified from the COVID-SFT registry (NCT04360707) using a propensity score matching with the following covariates: age, sex, delay between transplantation and infection, induction and maintenance immunosuppressive therapy, initial symptoms, and comorbidities.A total of 80 KTRs received MoAb between February 2021 and June 2021. They were matched to 155 controls. COVID-19-related hospitalization, 30-day admission to ICU, and 30-day death were less frequently observed in the MoAb group (35.0% vs. 49.7%,The early use of MoAb in KTRs with a mild form of COVID-19 largely improved outcomes in KTRs.

Published
2022

31. Incidence of cytomegalovirus infection in seropositive kidney transplant recipients treated with everolimus: A randomized, open-label, multicenter phase 4 trial

Author

Hannah Kaminski, Nassim Kamar, Olivier Thaunat, Nicolas Bouvier, Sophie Caillard, Isabelle Garrigue, Dany Anglicheau, Jean-Philippe Rérolle, Yannick Le Meur, Antoine Durrbach, Thomas Bachelet, Hélène Savel, Roxane Coueron, Jonathan Visentin, Arnaud Del Bello, Isabelle Pellegrin, Julie Déchanet-Merville, Pierre Merville, Rodolphe Thiébaut, Lionel Couzi, Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, 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, Dialyse, Transplantations [CHU Limoges], CHU Limoges, 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), Hôpital Henri Mondor - Service de néphrologie et transplantation, Department of Nephrology, Transplantation and Dialysis, Bordeaux, France, Department of Nephrology, Transplantation and Dialysis, Bordeaux, Service d’information Médicale [CHU de Bordeaux] (Pôle de Santé Publique), Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux], Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
T cell biology, Transplantation, immunosuppressant - mechanistic target of rapamycin: everolimus, clinical research, nephrology, virus diseases, kidney transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunology and Allergy, clinical trial, Pharmacology (medical), infection and infectious agents - viral: Cytomegalovirus (CMV), practice
Abstract

International audience; Cytomegalovirus (CMV) persists as the most frequent opportunistic infection among solid organ transplant recipients. This multicenter trial aimed to test whether treatment with everolimus (EVR) could decrease the incidence of CMV DNAemia and disease. We randomized 186 CMV seropositive kidney transplant recipients in a 1:1 ratio to receive EVR or mycophenolic acid (MPA) in association with basiliximab, cyclosporin, and steroids and 87 in each group were analyzed. No universal prophylaxis was administered to either group. The composite primary endpoint was the presence of CMV DNAemia, CMV treatment, graft loss, death, and discontinuation of the study at 6 months posttransplant. In the modified intent-to-treat analysis, 42 (48.3%) and 70 (80.5%) patients in the EVR and MPA groups reached the primary endpoint (OR = 0.21, 95% CI: 0.11-0.43, p

Published
2022

32. C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features

Author

Melchior Chabannes, Marion Rabant, Carine El Sissy, Marie-Agnès Dragon-Durey, Paula Vieira Martins, Marie Sophie Meuleman, Alexandre Karras, David Buob, Frank Bridoux, Eric Daugas, Vincent Audard, Sophie Caillard, Jérôme Olagne, Christine Kandel, Sophie Ferlicot, Carole Philipponnet, Thomas Crepin, Eric Thervet, Didier Ducloux, Véronique Frémeaux-Bacchi, and Sophie Chauvet

Subjects
Nephrology
Published
2023

35. Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study

Author

François-Daniel Ardellier, Seyyid Baloglu, Magdalena Sokolska, Vincent Noblet, François Lersy, Olivier Collange, Jean-Christophe Ferré, Adel Maamar, Béatrice Carsin-Nicol, Julie Helms, Maleka Schenck, Antoine Khalil, Augustin Gaudemer, Sophie Caillard, Julien Pottecher, Nicolas Lefèbvre, Pierre-Emmanuel Zorn, Muriel Matthieu, Jean Christophe Brisset, Clotilde Boulay, Véronique Mutschler, Yves Hansmann, Paul-Michel Mertes, Francis Schneider, Samira Fafi-Kremer, Mickael Ohana, Ferhat Meziani, Nicolas Meyer, Tarek Yousry, Mathieu Anheim, François Cotton, Hans Rolf Jäger, Stéphane Kremer, Fabrice Bonneville, Gilles Adam, Guillaume Martin-Blondel, Jérémie Pariente, Thomas Geeraerts, Hélène Oesterlé, Federico Bolognini, Julien Messie, Ghazi Hmeydia, Joseph Benzakoun, Catherine Oppenheim, Jean-Marc Constans, Serge Metanbou, Adrien Heintz, Blanche Bapst, Imen Megdiche, Lavinia Jager, Patrick Nesser, Yannick Talla Mba, Thomas Tourdias, Juliette Coutureau, Céline Hemmert, Philippe Feuerstein, Nathan Sebag, Sophie Carre, Manel Alleg, Claire Lecocq, Emmanuel Schmitt, René Anxionnat, François Zhu, Géraud Forestier, Aymeric Rouchaud, Pierre-Olivier Comby, Frederic Ricolfi, Pierre Thouant, Sylvie Grand, Alexandre Krainik, Isaure de Beaurepaire, Grégoire Bornet, Audrey Lacalm, Patrick Miailhes, Julie Pique, Claire Boutet, Xavier Fabre, Béatrice Claise, Sonia Mirafzal, Laure Calvet, Hubert Desal, Jérome Berge, Grégoire Boulouis, Apolline Kazemi, Nadya Pyatigorskaya, Augustin Lecler, Suzana Saleme, Myriam Edjlali-Goujon, Basile Kerleroux, Jean-Christophe Brisset, Samir Chenaf, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University College of London [London] (UCL), Nouvel Hôpital Civil de Strasbourg, Département de Neuroradiology [Rennes], Neuroimagerie: méthodes et applications (EMPENN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), CHU Pontchaillou [Rennes], Service de Médecine Intensive et Réanimation [Strasbourg], CHU Strasbourg, Département de Radiologie [Bichat] (DR- 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Groupe d'Analyse des Itinéraires et des Niveaux Salariaux (GAINS), Le Mans Université (UM), Les Hôptaux universitaires de Strasbourg (HUS), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Louis Pasteur [Colmar] (CH Colmar), Hôpital Sainte-Anne [Paris], CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), SFNR-COVID Group, CHU Henri Mondor [Créteil], Hôpital Marie Madeleine [Forbach] (CHIC Unisanté+), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier de Haguenau, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital privé d’Antony, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Clermont-Ferrand, and Société Française de Neuroradiologie [Paris] (SFNR)

Subjects
Multicenter Study, Radiological and Ultrasound Technology, Cerebrovascular Circulation, COVID-19, Radiology, Nuclear Medicine and imaging, Neuroimaging, Neurology (clinical), Magnetic Resonance Imaging, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background and purpose: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences.Methods: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex.Results: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p=0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies.Conclusion: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

Published
2023

36. High‐flow arteriovenous fistula and hemodynamic consequences at 1 year after kidney transplantation

Author

Alexandra Monnier, Nicolas Keller, Bernard Geny, Samy Talha, Noëlle Cognard, Bruno Moulin, and Sophie Caillard

Subjects
medicine.medical_specialty, Cardiac output, business.industry, Fistula, Hemodynamics, Arteriovenous fistula, medicine.disease, Kidney Transplantation, Cohort Studies, Arteriovenous Shunt, Surgical, Renal Dialysis, Nephrology, Internal medicine, Arteriovenous Fistula, medicine, Cardiology, Humans, Prospective Studies, business, High flow, Pathological, Kidney transplantation, Cohort study
Abstract

INTRODUCTION There are only scarce data regarding the cardiovascular impact of arteriovenous fistula after kidney transplantation depending on fistula flow. METHODS We performed a single-center, prospective, cohort study including 49 patients with a functional fistula at 1 year from kidney transplantation. Patients were convened for a clinical work-up, a biological analysis, a fistula's Doppler ultrasonography and an echocardiography. Main judgment criterion was comparison of echocardiography parameters between patients with relative (fistula flow >1 L/min and a fistula flow/cardiac output ratio >20%), absolute high-flow fistula (fistula flow >2 L/min) and normal-flow fistula. RESULTS High-flow fistula frequency was 69%. Significantly higher left ventricular end-diastolic and systolic diameters were observed in this group compared with the normal-flow fistula group (53 ± 6 vs. 48 ± 7 mm; p = 0.04 and 33 ± 6 vs. 28 ± 8 mm; p = 0.02) and between the absolute and relative high-flow fistula subgroups (56 ± 6 vs. 51 ± 6 mm; p = 0.009 and 35 ± 6 vs. 31 ± 5 mm; p = 0.01). The study showed no other significant differences. CONCLUSIONS This study showed a significantly higher but not pathological left ventricular end-diastolic and systolic diameters values in patients with high-flow fistula compared with patients with normal-flow fistula and between patients with respectively absolute and relative high-flow fistula.

Published
2021

37. SARS-Cov-2 Seroprevalence in a French Kidney Transplant Center Located Within a 'High-risk' Zone

Author

Gabriela Gautier Vargas, Vanessa Jegou, Karima Kedjam, Jonas Martzloff, Bruno Moulin, Ilies Benotmane, Céline Meidinger, Audrey Desmarquets, Laura Braun, Lucille Steinmetz, Sophie Caillard, Sandra Ludwiller, Francoise Heibel, Noëlle Cognard, Murielle Morvan, Xavier Bassand, Dominique Schmitt, Danielle Roy, Amandine Bigot, Peggy Perrin, Anne Rihon, Jérôme Olagne, David Marx, and Samira Fafi Kremer

Subjects
Transplantation, medicine.medical_specialty, SARS-CoV-2, Transmission (medicine), business.industry, COVID-19, Outbreak, Seroepidemiologic Studies, Antibodies, Viral, medicine.disease, Kidney Transplantation, Asymptomatic, Covid, Serology, Internal medicine, Cohort, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, medicine, Humans, Seroprevalence, France, medicine.symptom, business, Kidney transplantation
Abstract

Supplemental Digital Content is available in the text., Background. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in kidney transplant recipients (KTRs) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France’s highest risk zone (Grand Est) for coronavirus disease 2019 (Covid-19) during the initial disease outbreak. Methods. To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTRs. Results. SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTRs had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTRs and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission. Conclusions. Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTRs living in one of the France’s highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. Rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.

Published
2021

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

Author

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

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

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

Published
2021

39. Impact of Covid-19 on kidney transplant and waiting list patients: Lessons from the first wave of the pandemic

Author

Benoit Barrou, Yannick Le Meur, L. Sebbag, Lionel Couzi, Lisa M. McElroy, Sophie Caillard, Yuval A. Patel, Scott Sanoff, Olivier Thaunat, Mathias Büchler, Gilles Blancho, Jérôme Dumortier, Marc Hazzan, Brian I. Shaw, Dany Anglicheau, Mariya L. Samoylova, Miriam Manook, Eric Epailly, Sacha Mussot, CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Duke University [Durham], CHU Strasbourg, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Louis Pradel [CHU - HCL], 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CarMeN, laboratoire, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)

Subjects
Male, medicine.medical_specialty, Waiting Lists, Patients, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Kidney, Kidney transplant, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Health care, Pandemic, Candidates, medicine, Humans, Pandemics, Kidney transplantation, Transplantation, business.industry, Communication, Patient Preference, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], Nephrology, Waiting list, Communicable Disease Control, Emergency medicine, Female, France, Covid-19, business, Attitude to Health
Abstract

International audience; BACKGROUND: The first wave of the Covid-19 pandemic resulted in a drastic reduction in kidney transplantation and a profound change in transplant care in France. It is critical for kidney transplant centers to understand the behaviors, concerns and wishes of transplant recipients and waiting list candidates. METHODS: French kidney patients were contacted to answer an online electronic survey at the end of the lockdown. RESULTS: At the end of the first wave of the pandemic in France (11 May 2020), 2112 kidney transplant recipients and 487 candidates answered the survey. More candidates than recipients left their home during the lockdown, mainly for health care (80.1% vs. 69.4%; P\textless0.001). More candidates than recipients reported being exposed to Covid-19 patients (2.7% vs. 1.2%; P=0.006). Many recipients and even more candidates felt inadequately informed by their transplant center during the pandemic (19.6% vs. 54%; P\textless0.001). Among candidates, 71.1% preferred to undergo transplant as soon as possible, 19.5% preferred to wait until Covid-19 had left their community, and 9.4% were not sure what to do. CONCLUSIONS: During the Covid-19 pandemic in France, the majority of candidates wished to receive a transplant as soon as possible without waiting until Covid-19 had left their community. Communication between kidney transplant centers and patients must be improved to better understand and serve patients' needs.

Published
2021

40. Covid-19 en transplantation rénale, leçons du registre français

Author

Sophie Caillard, Olivier Thaunat, and Marc Hazzan

Subjects
Male, medicine.medical_specialty, Waiting Lists, Coronavirus disease 2019 (COVID-19), 030232 urology & nephrology, Mortalité, Article, 03 medical and health sciences, 0302 clinical medicine, Facteurs de risqué, Pronostic, Humans, Medicine, Registries, Mortality, Kidney transplantation, Aged, Gynecology, business.industry, Renal transplantation, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Transplant Recipients, Hospitalization, Risk factors, Nephrology, Creatinine, Transplantation rénale, Female, France, Covid-19, business
Abstract

Résumé La pandémie Covid-19 frappe la population de transplantés français dès le 3 mars 2020. Très rapidement, un registre français s’est mis en place sous l’égide de la Société francophone de transplantation permettant de colliger les cas de Covid-19 confirmés survenant chez des patients transplantés de rein dans la quasi-totalité des centres français. L’analyse de ce registre conjointement à celle des données du registre Cristal de l’Agence de la Biomédecine a permis d’aboutir à des premiers résultats instructifs. Nous avons d’abord montré que l’incidence des formes sévères au sein des patients transplantés hospitalisés pour Covid-19 était de 46 % et que leur mortalité était de 22,8 %. Les facteurs de risque de formes sévères et de mortalité sont décrits. Nous avons ensuite montré, en comparant les transplantés à des patients immunocompétents appariés pour les principaux facteurs de gravité de cette maladie, que la mortalité des patients transplantés était plus élevée parmi des transplantés (17,9 % vs 11,4 % ; p

Published
2021

42. Tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients

Author

Ilies Benotmane, Jérôme Olagne, Gabriela Gautier Vargas, Noëlle Cognard, Francoise Heibel, Laura Braun-Parvez, Nicolas Keller, Jonas Martzloff, Peggy Perrin, Romain Pszczolinski, Bruno Moulin, Samira Fafi-Kremer, and Sophie Caillard

Abstract

ObjectiveThis single-center retrospective study evaluated the use of tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients (KTRs) during the omicron wave.MethodsKTRs were deemed at high risk for moderate-to-severe COVID-19 in presence of at least one comorbidity (age >60 years, diabetes, obesity, or cardiovascular disease) associated with a weak humoral response (ResultsOf the 61 KTRs at high risk, 26 received tixagevimab-cilgavimab. COVID-19-related hospitalizations (3.8% versus 34%, p=0.006) and oxygen need (3.8% versus 23%, p=0.04) were significantly less frequent in patients who received tixagevimab-cilgavimab. In addition, non-significant trends towards a lower number of ICU admissions (3.8% versus 14.3% p=0.17) and deaths (0 versus 3, p=0.13) were observed after administration of tixagevimab-cilgavimab. Ten of the 73 low-risk KTRs received tixagevimab-cilgavimab, and no significant clinical benefit was observed in this subgroup.ConclusionEarly administration of tixagevimab-cilgavimab may be clinically useful in high-risk KTRs with COVID-19; however, no major benefit was observed for low-risk patients.

Published
2022

43. 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

44. Persistence of SARS-CoV-2 antibodies in kidney transplant recipients

Author

Peggy Perrin, Sophie Caillard, Ilies Benotmane, Samira Fafi-Kremer, Marie-José Wendling, Aurélie Velay, and Gabriela Gautier Vargas

Subjects
Transplantation, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Kidney Transplantation, Kidney transplant, Virology, Transplant Recipients, Infectious disease (medical specialty), biology.protein, Humans, Immunology and Allergy, Medicine, Pharmacology (medical), Antibody, business, Immunosuppressive Agents
Published
2021

45. Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients

Author

Alexandre O, Gérard, Susana, Barbosa, Dany, Anglicheau, Lionel, Couzi, Marc, Hazzan, Olivier, Thaunat, Gilles, Blancho, Sophie, Caillard, Antoine, Sicard, and Faouzi, Saliba

Subjects
Male, Transplantation, Antimetabolites, TOR Serine-Threonine Kinases, Calcineurin Inhibitors, COVID-19, Middle Aged, Mycophenolic Acid, Kidney Transplantation, Transplant Recipients, Abatacept, Cohort Studies, Creatinine, Humans, Female, Immunosuppressive Agents
Abstract

Solid organ transplant recipients are at high risk for fatal forms of coronavirus disease 2019 (COVID-19). We conducted a cohort study among kidney transplant (KT) recipients from the French Solid Organ Transplant COVID-19 Registry to investigate the association between maintenance immunosuppressive drugs and 60-d mortality.Data from all KT recipients with COVID-19 included in the French Solid Organ Transplant COVID-19 Registry between February 28, 2020, and December 30, 2020, were retrieved. We evaluated associations between immunosuppressive drugs and death within 60 d using logistic regression, with all baseline characteristics considered to influence outcome or immunosuppressive regimen. The Benjamini-Hochberg correction was used for controlling false positive rate; 40 multiple imputations were performed. Adjusted P value0.05 was considered statistically significant.There were 1451 KT recipients included. Median age was 58 y, and 66.4% were men. Most frequent comorbidities were hypertension (81.9%), diabetes (34.5%), and cardiovascular disease (29.5%). Median time since transplant was 71 mo. Maintenance immunosuppression regimens included calcineurin inhibitors (1295, 89.2%), antimetabolites (1205, 83%), corticosteroids (1094, 75.4%), mammalian target of rapamycin inhibitors (144, 9.9%), and belatacept (58, 4.0%). Among 1451 transplant recipients, 201 (13.9%) died within 60 d. Older age and higher baseline serum creatinine were associated with mortality (odds ratios, 1.09 [1.07-1.11] and 1.01 [1.005-1.009], P0.001). Corticosteroid-free regimens were associated with a significantly lower risk of death (odds ratio, 0.48 [0.31-0.76]; P = 0.011).Corticosteroid-free regimens were associated with a lower risk of death in KT recipients with COVID-19. Long-term exposure to corticosteroids impairs immune functions and may predispose solid organ transplant recipients to severe forms of COVID-19.

Published
2022

46. Aetiology, clinical features, diagnostic studies, and outcomes of community-acquired pneumonia in kidney transplant recipients admitted to hospital: a multicenter retrospective French cohort study

Author

Benoît Schwartz, Vincent Dupont, Sandra Dury, Aline Carsin-Vu, null Thomas Guillard, Sophie Caillard, Luc Frimat, Stephane Sanchez, Betoul Schvartz, Firouzé Bani-Sadr, null Damien Jolly, null Philippe Rieu, and null Antoine Goury

Subjects
Microbiology (medical), Infectious Diseases, General Medicine
Abstract

To assess the aetiology, clinical features, diagnostic studies and outcomes of community-acquired pneumonia (CAP) in a French cohort of hospitalized kidney transplant recipients kidney transplant recipients.We performed a retrospective, multicenter study in kidney transplant recipients admitted to 10 French centers for CAP from January 2016 to December 2018. CAP discharge diagnoses were clinically and radiologically validated. We assessed a descriptive analysis of all confirmed CAP including medical ward and intensive care unit (ICU) admissions.165 CAP episodes in 132 patients were included. Median time from transplantation to admission was 6.4 [IQR, 1.6-12.3] years, with corticosteroid exposure in 112/165 (67.9%) cases. Sputum culture was performed in 47/165 (28.5%) cases including 7/47 (14.9%) positive samples. Bronchoscopy was performed in 87/165 (52.7%) cases with pathogens identified in 39/87 (44.8%) cases. Microbiological studies led to identify a respiratory pathogen in 64/165 (38.8%) CAP episodes including 11/64 (17.2%) polymicrobial cases. Among these 64 episodes, 75 micro-organisms were identified; 46/75 (61.3%) core respiratory pathogens and 29/75 (38.7%) opportunistic or drug-resistant organisms including Pneumocystis jirovecii 9/75 (12%), Pseudomonas aeruginosa 5/75 (6.7%), multidrug-resistant Enterobacteriaceae 4/75 (5.3%) and Aspergillus 4/75 (5.3%). Patients required ICU admission in 26/165 (15.8%) episodes, invasive ventilation in 20/165 (12.1%) cases and 22/165 (13.3%) needed in-hospital dialysis.CAP episodes occurred in KTR with a long history of immunosuppressive drug exposure. Diagnostic studies identified a micro-organism in more than one third of CAP episodes, including drug-resistant and opportunistic pathogens.

Published
2022

47. A rapid decline in the anti-receptor-binding domain of the SARS-CoV-2 spike protein IgG titer in kidney transplant recipients after tixagevimab-cilgavimab administration

Author

Ilies Benotmane, Aurélie Velay, Gabriela-Gautier Vargas, Jérôme Olagne, Noëlle Cognard, Françoise Heibel, Laura Braun-Parvez, Jonas Martzloff, Peggy Perrin, Romain Pszczolinski, Bruno Moulin, Samira Fafi-Kremer, and Sophie Caillard

Subjects
Nephrology, SARS-CoV-2, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Humans, COVID-19, Kidney Transplantation
Published
2022

48. Breakthrough COVID-19 cases despite prophylaxis with 150 mg of tixagevimab and 150 mg of cilgavimab in kidney transplant recipients

Author

Ilies Benotmane, Aurélie Velay, Gabriela Gautier-Vargas, Jérôme Olagne, Augustin Obrecht, Noëlle Cognard, Françoise Heibel, Laura Braun-Parvez, Nicolas Keller, Jonas Martzloff, Peggy Perrin, Romain Pszczolinski, Bruno Moulin, Samira Fafi-Kremer, Olivier Thaunat, and Sophie Caillard

Subjects
Transplantation, SARS-CoV-2, Immunology and Allergy, Humans, COVID-19, Pharmacology (medical), Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Antibodies, Viral, Kidney Transplantation, Antibodies, Neutralizing
Abstract

The cilgavimab-tixagevimab combination retains a partial in vitro neutralizing activity against the current SARS-CoV-2 variants of concern (omicron BA.1, BA.1.1, and BA.2). Here, we examined whether preexposure prophylaxis with cilgavimab-tixagevimab can effectively protect kidney transplant recipients (KTRs) against the omicron variant. Of the 416 KTRs who received intramuscular prophylactic injections of 150 mg tixagevimab and 150 mg cilgavimab, 39 (9.4%) developed COVID-19. With the exception of one case, all patients were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients (7.7%), respectively. Two KTRs died of COVID-19-related acute respiratory distress syndrome. SARS-CoV-2 sequencing was carried out in 15 cases (BA.1, n = 5; BA.1.1, n = 9; BA.2, n = 1). Viral neutralizing activity of the serum against the BA.1 variant was negative in the 12 tested patients, suggesting that this prophylactic strategy does not provide sufficient protection against this variant of concern. In summary, preexposure prophylaxis with cilgavimab-tixagevimab at the dose of 150 mg of each antibody does not adequately protect KTRs against omicron. Further clarification of the optimal dosing can assist in our understanding of how best to harness its protective potential.

Published
2022

49. A fourth dose of the mRNA-1273 SARS-CoV-2 vaccine improves serum neutralization against the Delta variant in kidney transplant recipients

Author

Olivier Schwartz, Delphine Planas, Ilies Benotmane, Samira Fafi-Kremer, Timothée Bruel, Sophie Caillard, CHU Strasbourg, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)

Subjects
Delta, Delta variant, COVID-19 Vaccines, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Alpha (ethology), kidney transplantation, neutralizing antibodies, Antibodies, Viral, fourth dose, Immune system, Neutralization test, Humans, Medicine, Neutralizing antibody, Messenger RNA, biology, business.industry, SARS-CoV-2, COVID-19, Antibodies, Neutralizing, Transplant Recipients, Titer, mRNA vaccine, Nephrology, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, business, 2019-nCoV Vaccine mRNA-1273
Abstract

In immunocompetent subjects, the effectiveness of SARS-CoV-2 vaccines against the delta variant appears three- to five-fold lower than that observed against the alpha variant. Additionally, three doses of SARS-CoV-2 mRNA-based vaccines might be unable to elicit a sufficient immune response against any variant in immunocompromised kidney transplant recipients. This study describes the kinetics of the neutralizing antibody (NAbs) response against the delta strain before and after a fourth dose of a mRNA vaccine in 67 kidney transplant recipients who had experienced a weak antibody response after three doses. While only 16% of patients harbored NAbs against the delta strain prior to the fourth injection – this percentage raised to 66% afterwards. We also found that, after the fourth dose, the NAbs titer increased significantly (p=0.0001) from

Published
2022

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

Author

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

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

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

Published
2020

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