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1. Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study

Author

Magali Giral, Philippe Grimbert, Baptiste Morin, Nicolas Bouvier, Matthias Buchler, Jacques Dantal, Valérie Garrigue, Dominique Bertrand, Nassim Kamar, Paolo Malvezzi, Karine Moreau, Yoni Athea, and Yannick Le Meur

Subjects
extended-release tacrolimus, LCPT, immunosuppression, kidney transplantation, tremor, C0/D ratio, Specialties of internal medicine, RC581-951
Abstract

Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients. The primary endpoint was change in The Essential Tremor Rating Assessment Scale (TETRAS) score; secondary endpoints included 12-item Short Form Survey (SF-12) scores, tacrolimus trough concentrations, neurologic symptoms, and safety assessments. Subgroup analyses were conducted to assess change in TETRAS score and tacrolimus trough concentration/dose (C0/D) ratio by prior tacrolimus formulation and tacrolimus metabolizer status. Among 221 patients, the mean decrease of TETRAS score after switch to LCPT was statistically significant (p < 0.0001 vs. baseline). There was no statistically significant difference in change in TETRAS score after switch to LCPT between patients who had received IR-TAC and those who had received PR-TAC before switch, or between fast and slow metabolizers of tacrolimus. The overall increase of C0/D ratio post-switch to LCPT was statistically significant (p < 0.0001) and from baseline to either M1 or M3 (both p < 0.0001) in the mITT population and in all subgroups. In the fast metabolizers group, the C0/D ratio crossed over the threshold of 1.05 ng/mL/mg after the switch to LCPT. Other neurologic symptoms tended to improve, and the SF-12 mental component summary score improved significantly. No new safety concerns were evident. In this observational study, all patients had a significant improvement of tremor, QoL and C0/D ratio post-switch to LCPT irrespective of the previous tacrolimus formulation administered (IR-TAC or PR-TAC) and irrespective from their metabolism status (fast or slow metabolizers).

Published
2024
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2. Belatacept inhibit human B cell germinal center development in immunodeficient mice

Author

Chloé Samson, Allan Thiolat, Anissa Moktefi, José L. Cohen, Caroline Pilon, and Philippe Grimbert

Subjects
Medicine, Science
Abstract

Abstract The humoral response mediated by alloantibodies directed against donor HLA molecules (DSAs) is one of the main causes of graft loss in kidney transplantation. Understanding the pathophysiology leading to humoral kidney rejection as the development of therapeutic tools is therefore a main objective in the field of solid organ transplantation and necessitate adapted experimental models. Among the immunosuppressive agents used in renal transplantation, belatacept, a fusion protein targeting T costimulatory molecules has shown its ability to prevent more efficiently the secretion of DSA by different mechanisms including a direct action on plasma cells but also on B lymphocytes and follicular helper T lymphocytes (Tfh) cooperation. This cellular cooperation occurs within germinal centers (GC), the seat of B lymphocytes differentiation. Here, we aimed to develop a dedicated mouse model in which human GC would be functional to study the effect of belatacept on GC formation and the ability of B lymphocytes to secrete immunoglobulin. We next demonstrate that belatacept inhibits the formation of these GCs, by inhibiting the frequency of Tfh and B lymphocytes. This alters the B maturation and therefore the generation of plasma cells and consequently, immunoglobulin secretion.

Published
2023
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3. Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database

Author

Léa Hoisnard, Bénédicte Lebrun-Vignes, Sébastien Maury, Matthieu Mahevas, Khalil El Karoui, Lydia Roy, Anissa Zarour, Marc Michel, José L. Cohen, Aurélien Amiot, Pascal Claudepierre, Pierre Wolkenstein, Philippe Grimbert, and Emilie Sbidian

Subjects
Medicine, Science
Abstract

Abstract Increasing number of Janus kinase (JAK) inhibitors have been approved for chronic haematopoietic neoplasms and inflammatory/autoimmune diseases. We aimed to assess safety of the first three approved JAK inhibitors: ruxolitinib, tofacitinib and baricitinib. In this retrospective observational study, pharmacovigilance data were extracted from the World Health Organization database. Adverse events are classified according to Medical Dictionary for Regulatory Activities hierarchy. Until February 28, 2021, all Individual Case Safety Reports [ICSRs] with the suspected drug ruxolitinib, tofacitinib or baricitinib were included. Disproportionality analysis was performed and the information component (IC) was estimated. Adverse events were considered a significant signal if the lower end of the 95% credibility interval of the IC (IC025) was positive. We identified 126,815 ICSRs involving JAK inhibitors. Ruxolitinib, tofacitinib and baricitinib were associated with infectious adverse events (IC025 1.7, especially with viral [herpes and influenza], fungal, and mycobacterial infectious disorders); musculoskeletal and connective tissue disorders (IC025 1.1); embolism and thrombosis (IC025 0.4); and neoplasms (IC025 0.8, especially malignant skin neoplasms). Tofacitinib was associated with gastrointestinal perforation events (IC025 1.5). We did not find a significant increase in the reporting of major cardiovascular events. We identified significant association between adverse events and ruxolitinib, tofacinitib and baricitinib in international pharmacovigilance database.

Published
2022
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4. Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study

Author

Antoine Morel, Yaniss Ouamri, Florence Canouï‐Poitrine, Sébastien Mulé, Cécile Maud Champy, Alexandre Ingels, Vincent Audard, Alain Luciani, Philippe Grimbert, Marie Matignon, Frédéric Pigneur, and Thomas Stehlé

Subjects
Myosteatosis, Kidney transplantation, Mortality risk factors, Prognosis, CT scan, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background Patients with end‐stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT). Methods In a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross‐sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross‐sectional area normalized for height2, reported in cm2/m2) and MD (mean attenuation of muscle cross‐sectional area, expressed in Hounsfield units). We determined age‐specific and sex‐specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival. Results Among the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm2/m2 in men and 42.3 ± 7.3 cm2/m2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22–12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30–10.7, P = 0.015), and body mass index > 25 kg/m2 (aOR 2.94, 95% CI: 1.4–6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06–4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02–4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03–1.09, P = 0.0003). Low SMI was not associated with mortality. Conclusions Myosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

Published
2022
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5. ATG-Fresenius increases the risk of red blood cell transfusion after kidney transplantation

Author

Maria Sebti, Camille Petit-Hoang, Btissam Chami, Étienne Audureau, Catherine Cordonnier-Jourdin, Muriel Paul, Franck Pourcine, Philippe Grimbert, Clément Ourghanlian, and Marie Matignon

Subjects
kidney transplantation, anti-thymocyte globulins, donor-specific anti-HLA antibodies, red blood cell transfusion, induction therapy, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionIn sensitized deceased donor kidney allograft recipients, the most frequent induction therapy is anti-thymocyte globulins (ATG), including Thymoglobulin® (Thymo) and ATG-Fresenius (ATG-F).MethodsWe conducted a 3-year monocentric observational study to compare the impact of ATGs on hematological parameters. We included adult kidney transplant recipients treated with ATG induction therapy, either Thymo or ATG-F, on a one-in-two basis. The primary endpoint was red blood cell (RBC) transfusions within 14 days after transplantation.ResultsAmong 309 kidney allograft recipients, 177 (57.2%) received ATG induction, 90 (50.8 %) ATG-F, and 87 (49.2%) Thymo. The ATG-F group received significantly more RBC transfusions (63.3% vs. 46% p = 0.02) and in bigger volumes (p = 0.01). Platelet transfusion was similar in both groups. Within 14 and 30 days after transplantation, older age, ATG-F induction, and early surgical complication were independently associated with RBC transfusion. Patient survival rate was 95%, and the death-censored kidney allograft survival rate was 91.5% at 12 months post-transplantation. There was no difference in the incidence of acute rejection and infections or in the prevalence of anti-HLA donor-specific antibodies.DiscussionIn conclusion, after kidney transplantation, ATG-F is an independent risk factor for early RBC transfusion and early thrombocytopenia without clinical and biological consequences. These new data should be clinically considered, and alternatives to ATG should be further explored.

Published
2022
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6. Longitudinal evaluation of the impact of immunosuppressive regimen on immune responses to COVID-19 vaccination in kidney transplant recipients

Author

Aurélie Wiedemann, Céline Pellaton, Manon Dekeyser, Lydia Guillaumat, Marie Déchenaud, Corinne Krief, Christine Lacabaratz, Philippe Grimbert, Giuseppe Pantaleo, Yves Lévy, and Antoine Durrbach

Subjects
COVID-19, immunocompromised, immunosuppressive regimen, mRNA vaccine, immune responses, Medicine (General), R5-920
Abstract

Immunocompromised patients have a high risk of death from SARS-CoV-2 infection. Vaccination with an mRNA vaccine may protect these patients against severe COVID-19. Several studies have evaluated the impact of immune-suppressive drug regimens on cellular and humoral responses to SARS-CoV-2 variants of concern in this context. We performed a prospective longitudinal study assessing specific humoral (binding and neutralizing antibodies against spike (S) and T-lymphocyte (cytokine secretion and polyfunctionality) immune responses to anti-COVID-19 vaccination with at least two doses of BNT162b2 mRNA vaccine in stable kidney transplant recipients (KTR) on calcineurin inhibitor (CNI)- or belatacept-based treatment regimens. Fifty-two KTR−31 receiving CNI and 21 receiving belatacept—were enrolled in this study. After two doses of vaccine, 46.9% of patients developed anti-S IgG. Anti-spike IgG antibodies were produced in only 21.4% of the patients in the belatacept group, vs. 83.3% of those in the CNI group. The Beta and Delta variants and, more importantly, the Omicron variant, were less well neutralized than the Wuhan strain. T-cell functions were also much weaker in the belatacept group than in the CNI group. Renal transplant patients have an impaired humoral response to BNT162b2 vaccination. Belatacept-based regimens severely weaken both humoral and cellular vaccine responses. Clinically, careful evaluations of at least binding IgG responses, and prophylactic or post-exposure strategies are strongly recommended for transplant recipients on belatacept-based regimens.

Published
2022
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7. Heart Transplantation, Either Alone or Combined With Liver and Kidney, a Viable Treatment Option for Selected Patients With Severe Cardiac Amyloidosis

Author

Soulef Guendouz, MD, Philippe Grimbert, MD, PhD, Costin Radu, MD, PhD, Daniel Cherqui, MD, PhD, Chady Salloum, MD, Nicolas Mongardon, MD, PhD, Sami Maghrebi, MD, Karim Belhadj, MD, Fabien Le Bras, MD, Emmanuel Teiger, MD, PhD, Jean-Paul Couetil, MD, PhD, Adriana Balan, MD, Mounira Kharoubi, MSc, Mélanie Bézard, MSc, Silvia Oghina, MD, Diane Bodez, MD, PhD, Luc Hittinger, MD, PhD, Vincent Audard, MD, PhD, Violaine Planté-Bordeneuve, MD, PhD, Alexandre De la Taille, MD, PhD, Eric Bergoend, MD, Valerie Frenkel, MD, PhD, Pascale Fanen, MD, PhD, Vincent Leroy, MD, PhD, Christophe Duvoux, MD, PhD, Maryvonnick Carmagnat, PharmD, Thierry Folliguet, MD, PhD, and Thibaud Damy, MD, PhD

Subjects
Surgery, RD1-811
Abstract

Background. Heart transplantation in cardiac amyloidosis (CA) patients is possible and generally considered for transplantation if other organs are not affected. In this study, we aimed to describe and assess outcome in patients following heart transplantations at our CA referral center. Methods. We assessed all CA patients that had heart transplantations at our center between 2005 and 2018. Patients with New York Heart Association status 3 out of 4, with poor short-term prognosis due to heart failure, despite treatment, and without multiple myeloma, systemic disease, severe neuropathic/digestive comorbidities, cancer, or worsening infections were eligible for transplantation. Hearts were transplanted by bicaval technique. Standard induction and immunosuppressive therapies were used. Survival outcome of CA patients after transplantation was compared with recipients with nonamyloid pathologies in France. Results. Between 2005 and 2018, 23 CA patients had heart transplants: 17 (74%) had light chain (light chain amyloidosis [AL]) and 6 (26%) had hereditary transthyretin (hereditary transthyretin amyloidosis [ATTRv]) CA. Also, 13 (57%) were male, and the mean age at diagnosis was 56.5 y (range, 47.7–62.8). Among AL patients, 13 had heart-only and 5 had heart-kidney transplantations. Among ATTRv patients, 1 had heart-only and 5 had heart-liver transplantations. The 1-y survival rate after transplantation was 78%, 70% with AL, and 100% with ATTRv. At 2 y, 74% were alive: 65% with AL and 100% with ATTRv. Conclusion. After heart transplantation, French CA and nonamyloid patients have similar survival outcomes. Among CA patients, ATTRv patients have better prognosis than those with AL, possibly due to the combined heart-liver transplantation. Selected CA patients should be considered for heart transplantations.

Published
2022
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8. Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside

Author

Guillaume Carteaux, Manuella Pons, François Morin, Samuel Tuffet, Arnaud Lesimple, Bilal Badat, Anne-Fleur Haudebourg, François Perier, Yvon Deplante, Constance Guillaud, Frédéric Schlemmer, Elena Fois, Nicolas Mongardon, Mehdi Khellaf, Karim Jaffal, Camille Deguillard, Philippe Grimbert, Raphaëlle Huguet, Keyvan Razazi, Nicolas de Prost, François Templier, François Beloncle, Alain Mercat, Laurent Brochard, Vincent Audard, Pascal Lim, Jean-Christophe Richard, Dominique Savary, and Armand Mekontso Dessap

Subjects
COVID-19, Acute hypoxemic respiratory failure, Continuous positive airway pressure, Frugal innovation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter (“Filter Frugal CPAP”, FF-CPAP) in and out the ICU. Methods (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. Results Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient’s work of breathing (6–34%) needed to sustain the tidal volume, depending on the filter’s resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p

Published
2021
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9. Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME)

Author

Thomas Kerforne, Christiane Mousson, Karim Asehnoune, Fanny Feuillet, Olivier Huet, Bertrand Rozec, Aude Garin, Alexandre Hertig, Jeremy Bourenne, Nassim Kamar, Emmanuel Morelon, Denis Glotz, Morgane Péré, Thierry Boulain, Jean Reignier, René Robert, Dominique Bertrand, Pierre-Yves Egreteau, Thierry Benard, Raphaëlle Larmet, Luc Frimat, Sophie Girerd, Mathias Büchler, Anne Renault, Patrice Tirot, Cécile Vigneau, Eric Delpierre, David Schnell, Olivier Lesieur, Lionel Rostaing, Mathieu Lesouhaitier, Laurent Martin-Lefevre, Antoine Durrbach, Noëlle Brulé, Emmanuel Canet, Maryvonne Hourmant, Agnes Duveau, Laurent Dube, Marc Pierrot, Stanislas Humbert, Jean-Marc Boyer, François Labadie, Antoine Thierry, Jean-François Vincent, Angelique Goepp, Pierre Bouju, Charlotte Quentin, Yannick Le Meur, Jean-Christophe Venhard, Olivier Michel, Marie-Hélène Voellmy, Fabien Herve, Anne Courte, Lucile Amrouche, Marc Hazzan, Valerie Moal, Moglie Le Quintrec-Donnette, Philippe Grimbert, Anne Elisabeth Heng, Pierre Merville, Christian Hiesse, Brice Fermier, Charlotte Guyot-Colosio, Nicolas Bouvier, Jean-Philippe Rerolle, Sarah Drouin, Sophie Caillard, Laetitia Albano, Pierre-Francois Westeel, Florent Montini, Dider Dorez, Eric Alamartine, Carole Ouisse, and Veronique Sebille

Subjects
Medicine
Abstract

Introduction Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysis HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and dissemination The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration number NCT03098706.

Published
2022
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10. Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients

Author

Elsa Feredj, Etienne Audureau, Anna Boueilh, Vincent Fihman, Slim Fourati, Jean-Daniel Lelièvre, Sébastien Gallien, Philippe Grimbert, Marie Matignon, and Giovanna Melica

Subjects
vaccination, pneumonia, kidney transplantation, Medicine
Abstract

Background: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined. Methods: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs. Results: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97–6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43–7.74)) and HCV (OR = 3.76 (1.58–8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26–0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.

Published
2023
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11. HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers

Author

Nizar Joher, Marie Matignon, and Philippe Grimbert

Subjects
anti-CD38, daratumumab, HLA desensitization, DSA, solid organ transplantation, Immunologic diseases. Allergy, RC581-607
Abstract

The presence of anti-human leucocyte antigen (HLA) antibodies in the potential solid organ transplant recipient’s blood is one of the main barriers to access to a transplantation. The HLA sensitization is associated with longer waitlist time, antibody mediated rejection and transplant lost leading to increased recipient’s morbidity and mortality. However, solid organ transplantation across the HLA immunological barriers have been reported in recipients who were highly sensitized to HLA using desensitization protocols. These desensitization regimens are focused on the reduction of circulating HLA antibodies. Despite those strategies improve rates of transplantation, it remains several limitations including persistent high rejection rate and worse long-term outcomes when compare with non-sensitized recipient population. Currently, interest is growing in the development of new desensitization approaches which, beyond targeting antibodies, would be based on the modulation of alloimmune pathways. Plasma cells appears as an interesting target given their critical role in antibody production. In the last decade, CD38-targeting immunotherapies, such as daratumumab, have been recognized as a key component in the treatment of myeloma by inducing an important plasma cell depletion. This review focuses on an emerging concept based on targeting CD38 to desensitize in the field of transplantation.

Published
2021
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12. Phenotypic and Transcriptomic Lymphocytes Changes in Allograft Recipients After Intravenous Immunoglobulin Therapy in Kidney Transplant Recipients

Author

Caroline Pilon, Jeremy Bigot, Cynthia Grondin, Allan Thiolat, Philippe Lang, José L. Cohen, Philippe Grimbert, and Marie Matignon

Subjects
kidney transplantation, high-dose intravenous immunoglobulin, donor specific antibodies, lymphocytes phenotype, immunomodulation, Immunologic diseases. Allergy, RC581-607
Abstract

High dose intravenous immunoglobulin (IVIG) are widely used after kidney transplantation and its biological effect on T and B cell phenotype in the context of maintenance immunosuppression was not documented yet. We designed a monocentric prospective cohort study of kidney allograft recipients with anti-HLA donor specific antibodies (DSA) without acute rejection on screening biopsies treated with prophylactic high-dose IVIG (2 g/kg) monthly for 2 months. Any previous treatment with Rituximab was an exclusion criterion. We performed an extensive analysis of phenotypic and transcriptomic T and B lymphocytes changes and serum cytokines after treatment (day 60). Twelve kidney transplant recipients who completed at least two courses of high-dose IVIG (2 g/kg) were included in a median time of 45 (12–132) months after transplant. Anti-HLA DSA characteristics were similar before and after treatment. At D60, PBMC population distribution was similar to the day before the first infusion. CD8+ CD45RA+ T cells and naïve B-cells (Bm2+) decreased (P = 0.03 and P = 0.012, respectively) whereas Bm1 (mature B-cells) increased (P = 0.004). RORγt serum mRNA transcription factor and CD3 serum mRNA increased 60 days after IVIG (P = 0.02 for both). Among the 25 cytokines tested, only IL-18 serum concentration significantly decreased at D60 (P = 0.03). In conclusion, high dose IVIG induced limited B cell and T cell phenotype modifications that could lead to anti-HLA DSA decrease. However, no clinical effect has been isolated and the real benefit of prophylactic use of IVIG after kidney transplantation merits to be questioned.

Published
2020
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13. Human Apoptotic Cells, Generated by Extracorporeal Photopheresis, Modulate Allogeneic Immune Response

Author

Caroline Pilon, Thomas Stehlé, Asma Beldi-Ferchiou, Marie Matignon, Allan Thiolat, Aude Burlion, Cynthia Grondin, Brigitte Birebent, France Pirenne, Hélène Rouard, Philippe Lang, Gilles Marodon, Philippe Grimbert, and José L. Cohen

Subjects
tolerance, NSG mice, immunomodulation, transplantation, apoptotic cell, Immunologic diseases. Allergy, RC581-607
Abstract

The induction of specific and sustainable tolerance is a challenging issue in organ transplantation. The discovery of the immunosuppressive properties of apoptotic cells in animal models has paved the way for their use in human transplantation. In this work, we aimed to define a stable, reproducible, and clinically compatible production procedure of human apoptotic cells (Apo-cells). Using a clinically approved extracorporeal photopheresis technique, we have produced and characterized phenotypically and functionally human apoptotic cells. These Apo-cells have immunosuppressive properties proved in vitro and in vivo in NOD/SCID/γC mice by their capacity to modulate an allogeneic response following both a direct and an indirect antigen presentation. These results brought the rationale for the use of Apo-cells in tolerance induction protocol for organ transplantation.

Published
2019
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14. Intravenous immunoglobulin therapy in kidney transplant recipients with de novo DSA: Results of an observational study.

Author

Marie Matignon, Caroline Pilon, Morgane Commereuc, Cynthia Grondin, Claire Leibler, Tomek Kofman, Vincent Audard, José Cohen, Florence Canoui-Poitrine, and Philippe Grimbert

Subjects
Medicine, Science
Abstract

Approximately 25% of kidney transplant recipients develop de novo anti-HLA donor-specific antibodies (dnDSA) leading to acute antibody-mediated rejection (ABMR) in 30% of patients. Preemptive therapeutic strategies are not available.We conducted a prospective observational study including 11 kidney transplant recipients. Inclusion criteria were dnDSA occurring within the first year after transplant and normal allograft biopsy. All patients were treated with high-dose IVIG (2 g/kg 0, 1 and 2 months post-dnDSA). The primary efficacy outcome was incidence of clinical and subclinical acute ABMR within 12 months after dnDSA detection as compared to a historical control group (IVIG-).Acute ABMR occurred in 2 or 11 patients in the IVIG+ group and in 1 of 9 patients in the IVIG- group. IVIG treatment did not affect either class I or class II DSA, as observed at the end of the follow-up. IVIG treatment significantly decreased FcγRIIA mRNA expression in circulating leukocytes, but did not affect the expression of any other markers of B cell activation.In this first pilot study including kidney allograft recipients with early dnDSA, preemptive treatment with high-dose IVIG alone did not prevent acute ABMR and had minimal effects on DSA outcome and B cell phenotype.

Published
2017
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15. Renal artery fibromuscular dysplasia in Pompe disease: A case report

Author

Evangelia Pappa, Constantinos Papadopoulos, Philippe Grimbert, Pascal Laforêt, and Guillaume Bassez

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Vascular involvement in Late Onset Pompe Disease, glycogen storage disease type II characterized by limb-girdle muscle and diaphragmatic weakness, is well documented. Abnormalities of posterior cerebral circulation have mostly been reported, whereas there are also cases of associated extracerebral arteriopathy. We report the case of a 42-year-old man diagnosed with LOPD a year after renal infarct due to renal artery fibromuscular dysplasia. We propose that the association of LOPD and arteriopathy should always be considered in clinical practice. Keywords: Muscle disease, Glycogenoses, Metabolic disease (inherited), All clinical neurology

Published
2018
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16. Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial

Author

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

Subjects
Transplantation, Immunology and Allergy, Pharmacology (medical)
Published
2023

18. Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study

Author

Julien Dang, Lauriane Segaux, Anissa Moktefi, Thomas Stehlé, Mounira Kharoubi, Khalil El Karoui, Philippe Rémy, Philippe Grimbert, Violaine Plante-Bordeneuve, Soulef Guendouz, Arnault Galat, Sophie Mallet, Silvia Oghina, Gagan Deep Singh Chadha, Amira Zaroui, Pascale Fanen, Florence Canoui-Poitrine, Thibaud Damy, and Vincent Audard

Subjects
Internal Medicine
Abstract

Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their

Published
2022

19. Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2– Recovered Dialysis Patients

Author

Philippe Attias, Imane Azzaoui, Khalil El Karoui, Andréa de La Selle, Aurélien Sokal, Pascal Chappert, Philippe Grimbert, Ignacio Fernandez, Magali Bouvier, Chloé Samson, Djamal Dahmane, Philippe Rieu, Patrice Nizard, Slim Fourati, Hamza Sakhi, and Matthieu Mahévas

Subjects
Vaccines, Synthetic, Transplantation, SARS-CoV-2, Epidemiology, Vaccination, Immunity, COVID-19, Antibodies, Viral, Critical Care and Intensive Care Medicine, Renal Dialysis, Nephrology, Immunoglobulin G, Humans, Original Article, mRNA Vaccines
Abstract

BACKGROUND AND OBJECTIVES: After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti–SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2–recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated the dynamics of antireceptor binding domain IgG titers and antireceptor binding domain memory B cells until 6 months after two and three doses (administered within 6 months after the second dose) of mRNA vaccine in SARS-CoV-2–recovered and virus-naive dialysis populations. Results were analyzed by ordinary one-way ANOVA, the Kruskal–Wallis test, or the Wilcoxon matched-pairs test as appropriate. RESULTS: In total, 108 individuals (59 patients on dialysis and 49 controls) were included. In virus-naive patients on dialysis, antireceptor binding domain IgG response was quantitatively lower after two doses compared with healthy controls, but IgG titers increased by three-fold after three doses (P=0.008). In SARS-CoV-2–recovered patients on dialysis, antireceptor binding domain IgG titers after two doses were significantly higher compared with virus-naive patients on dialysis but did not significantly increase after a third dose. Regarding memory B cell response, we detected receptor binding domain–specific memory B cells at similar proportions in virus-naive patients on dialysis and vaccinated controls after two doses. Moreover, a strong receptor binding domain–specific memory B cell expansion was observed after the third dose in virus-naive patients on dialysis (5.5-fold; P

Published
2022

20. Additional Benefits of Rituximab and Plasma Exchange on Top of Standard Induction Therapy in Kidney Transplant Recipients With a Negative CDC Crossmatch but High Preformed Donor Specific Antibody Titer

Author

Inna Mohamadou, Marie Matignon, Stéphanie Malard, Yannis Lombardi, David Buob, Anissa Moktefi, Matthieu Jamme, Nacera Ouali, Cedric Rafat, Hélène François, Camille Petit-Hoang, Eric Rondeau, Laurent Mesnard, Philippe Grimbert, Jean-Luc Taupin, and Yosu Luque

Subjects
Transplantation
Abstract

Optimal induction strategy in highly sensitized kidney transplant recipients (KTRs) is still a matter of debate. The place of therapies, such as plasma exchange and rituximab, with potential side effects and high cost, is not clearly established. We compared two induction strategies with (intensive) or without (standard) rituximab and plasma exchange in KTRs with high levels of preformed DSA transplanted between 2012 and 2019. Sixty KTRs with a mean age of 52.2 ± 12.2 years were included, 36 receiving standard and 24 intensive induction. Mean fluorescence intensity of immunodominant DSA in the cohort was 8,903 ± 5,469 pre-transplantation and similar in both groups. DSA level decrease was similar at 3 and 12 months after transplantation in the two groups. An intensive induction strategy was not associated with better graft or patient survival, nor more infectious complications. The proportion of patients with rejection during the first year was similar (33% in each group), but rejection occurred later in the intensive group (211 ± 188 days, vs. 79 ± 158 days in the standard group, p < 0.01). Our study suggests that an intensive induction therapy including rituximab and plasma exchanges in highly sensitized kidney recipients is not associated with better graft survival but may delay biopsy-proven rejection.

Published
2023

21. Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study

Author

Alexandre Ingels, Frédéric Pigneur, Florence Canoui-Poitrine, Yaniss Ouamri, Vincent Audard, Thomas Stehlé, Antoine Morel, Marie Matignon, Sébastien Mulé, Alain Luciani, Cécile Maud Champy, and Philippe Grimbert

Subjects
Adult, Male, CT scan, medicine.medical_specialty, Myosteatosis, Mortality risk factors, medicine.medical_treatment, Diseases of the musculoskeletal system, Kidney, Kidney transplantation, Risk Factors, Physiology (medical), Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, Renal replacement therapy, Risk factor, Aged, Retrospective Studies, business.industry, Hazard ratio, QM1-695, Retrospective cohort study, Odds ratio, Middle Aged, Allografts, medicine.disease, Prognosis, RC925-935, Sarcopenia, Cohort, Human anatomy, Female, business
Abstract

Background Patients with end‐stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT). Methods In a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross‐sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross‐sectional area normalized for height2, reported in cm2/m2) and MD (mean attenuation of muscle cross‐sectional area, expressed in Hounsfield units). We determined age‐specific and sex‐specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival. Results Among the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm2/m2 in men and 42.3 ± 7.3 cm2/m2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22–12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30–10.7, P = 0.015), and body mass index > 25 kg/m2 (aOR 2.94, 95% CI: 1.4–6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06–4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02–4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03–1.09, P = 0.0003). Low SMI was not associated with mortality. Conclusions Myosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

Published
2022

22. Development and validation of a new equation based on plasma creatinine and muscle mass assessed by CT scan to estimate glomerular filtration rate: a cross-sectional study

Author

Thomas Stehlé, Yaniss Ouamri, Antoine Morel, Emmanuelle Vidal-Petiot, Soraya Fellahi, Lauriane Segaux, Dominique Prié, Philippe Grimbert, Alain Luciani, Vincent Audard, Jean Philippe Haymann, Sébastien Mulé, Eric De Kerviler, Marie-Noëlle Peraldi, Anne Boutten, Marie Matignon, Florence Canouï-Poitrine, Martin Flamant, and Frédéric Pigneur

Subjects
Transplantation, Nephrology
Abstract

Background Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods The muscle mass–based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C–based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0–86.0] vs 51.5% (95% CI 39.0–64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0–55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7–66.0) for EKFC}. Difference in bias between Black and white subjects was −2.1 mL/min/1.73 m2 (95% CI −7.2 to 3.0), vs −8.4 mL/min/1.73 m2 (95% CI −13.2 to −3.6) for CKD-EPICr2021. Conclusion MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds.

Published
2023

23. Évaluation de la présence d’une infirmière en pratique avancée dans la prise en charge des transplantés rénaux

Author

Tiphanie Londero, Philippe Grimbert, Marie Matignon, and Cécile Boncourt

Subjects
03 medical and health sciences, 0302 clinical medicine, Nephrology, Political science, 030232 urology & nephrology, Humanities, Kidney transplant
Abstract

Resume L’implantation d’une nouvelle profession necessite d’anticiper sa plus-value et de definir son domaine d’intervention. Cet article explore les besoins d’un modele de soin en transplantation renale par l’etude de donnees epidemiologiques et d’une enquete exploratoire au sein d’un centre hospitalier universitaire d’Ile-de-France. Les resultats definissent les limites de la prise en charge actuelle et affirment la place de l’infirmiere en pratique avancee dans le secteur de la transplantation renale. Son role s’etablit aupres du patient et de son entourage, du centre de greffe et des professionnels de ville.

Published
2021

24. Face transplantation: A longitudinal histological study focusing on chronic active and mucosal rejection in a series with long-term follow-up

Author

Jean-Paul Meningaud, Philippe Grimbert, Laurent Lantieri, Mikael Hivelin, Barbara Papouin, C. Suberbielle, Emilie Sbidian, Maryvonnick Carmagnat, Romain Bosc, Anissa Moktefi, Pierre Wolkenstein, and Nicolas Ortonne

Subjects
Graft Rejection, medicine.medical_specialty, Face transplant, Biopsy, medicine.medical_treatment, Concordance, 030230 surgery, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), skin and connective tissue diseases, Transplantation, Mucous Membrane, integumentary system, medicine.diagnostic_test, Chronic Active, business.industry, FOXP3, Kidney Transplantation, Concomitant, Immunohistochemistry, business, Facial Transplantation, Follow-Up Studies
Abstract

The 2007 Banff working classification of skin-containing Tissue Allograft Pathology addressed only acute T cell-mediated rejection in skin. We report the longitudinal long-term histological follow-up of six face transplant recipients, focusing on chronic and mucosal rejection. We identified three patterns suggestive of chronic rejection (lichen planus-like, vitiligo-like and scleroderma-like). Four patients presented lichen planus-like and vitiligo-like chronic rejection at 52 ± 17 months posttransplant with severe concomitant acute T cell-mediated rejection. After lichen planus-like rejection, two patients developed scleroderma-like alterations. Graft vasculopathy with C4d deposits and de novo DSA led to subsequent graft loss in one patient. Chronic active rejection was frequent and similar patterns were noted in mucosae. Concordance between 124 paired skin and mucosal biopsies acute rejection grades was low (κ = 0.2, p = .005) but most grade 0/I mucosal rejections were associated with grade 0/I skin rejections. We defined discordant (grade≥II mucosal rejection and grade 0/I skin rejection) (n = 55 [70%]) and concordant (grade≥II rejection in both biopsies) groups. Mucosal biopsies of the discordant group displayed lower intra-epithelial GranzymeB/FoxP3 ratios suggesting a less aggressive phenotype (p = .08). The grading system for acute rejection in mucosa may require phenotyping. Whether discordant infiltrates reflect a latent allo-immune reaction leading to chronic rejection remains an open question.

Published
2021

26. Impact of pre‐eclampsia on renal outcome in sickle cell disease patients

Author

Edouard Lecarpentier, Frédéric Galactéros, Pablo Bartolucci, Anoosha Habibi, Marie-Isabelle Bornes, Emmanuelle Boutin, Elena Foïs, Philippe Remy, François Lionnet, Idris Boudhabhay, Thomas Stehlé, Florence Canoui-Poitrine, Dil Sahali, Khalil El Karoui, Philippe Grimbert, Bassam Haddad, Alexandre Hertig, and Vincent Audard

Subjects
Adult, medicine.medical_specialty, Cell, Renal function, Anemia, Sickle Cell, Disease, Kidney, Sickle cell nephropathy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pre-Eclampsia, Pregnancy, Internal medicine, medicine, Humans, In patient, Eclampsia, business.industry, Hematology, Odds ratio, medicine.disease, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Kidney Diseases, business, Follow-Up Studies, Glomerular Filtration Rate, 030215 immunology
Abstract

The long-term consequences of pre-eclampsia (PrE) for renal function have never been determined in patients with sickle cell disease (SCD). Between 2008 and 2015, we screened 306 pregnancies in women with SCD and identified 40 with PrE (13%). The control group consisted of 65 pregnant SCD patients without PrE. In multivariable analysis, PrE events were associated with an increase of 1 log of lactate dehydrogenase level (adjusted odds ratio, aOR = 3·83, P = 0·05), a decrease of 10 g/l of haemoglobin levels (aOR = 2·48, P = 0·006) and one or more vaso-occlusive crisis during pregnancy (aOR = 16·68, P = 0·002). Estimated glomerular filtration rate (eGFR) was similar in the two groups at steady state but was significantly lower in the PrE group after one year of follow-up and at last follow-up (130 vs 148 ml/min/1·73 m2 , P < 0·001 and 120 vs 130 ml/min/1·73 m2 , P < 0·001, respectively). In multivariable analysis, eGFR had returned to steady-state levels one year after pregnancy in patients without PrE but continued to decrease in patients with PrE (β = -18·15 ml/min/1·73 m2 , P < 0·001). This decline was more marked at the end of follow-up (β = -31·15 ml/min, P < 0·001). In conclusion, PrE episodes are associated with a significant risk of subsequent renal function decline in SCD patients.

Published
2021

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

Author

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

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

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

Published
2021

28. Belatacept-based immunosuppressive regimen in HIV-positive kidney transplant recipients

Author

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

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

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

Published
2020

29. The authors reply

Author

Nizar Joher, Anissa Moktefi, Philippe Grimbert, Eléonore Pagot, Narindra Jouan, Khalil El Karoui, Cécile Maud Champy, Marie Matignon, and Thomas Stehlé

Subjects
Nephrology
Published
2022

30. Comparison of the iliac, vaginal and umbilical graft extraction in robot-assisted laparoscopic living donor nephrectomy

Author

Alexandre de la Taille, Alexandre Ingels, Dimitri Vordos, C. Champy, Philippe Grimbert, Laurent Salomon, Philippe Le Corvoisier, Marie Matignon, Maher Abdessater, Jean Courcier, Tiphanie Londero, Jose Batista Da Costa, R. Yiou, and Andras Hoznek

Subjects
Nephrology, medicine.medical_specialty, Warm Ischemia Time, business.industry, Urology, Significant difference, 030232 urology & nephrology, Renal function, medicine.disease, Living donor nephrectomy, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Operative time, business, Kidney transplantation, Survival analysis
Abstract

To compare different extractions routes for robot-assisted living donor nephrectomy in terms of post-operative pain and renal function recovery. Live donor kidney transplantation data from our institution were reviewed from November 2011 to March 2017. Postoperative pain was estimated using cumulative painkillers consumption. Variables were compared between the 3 groups with ANOVA for continuous data, χ2 test for categorial data. A survival analysis with Kaplan–Meier curve assessing time to transplant recipient nadir was performed to compare the renal function recovery. Sixty-three RLDN were performed (23 iliac, 23 vaginal and 17 umbilical extractions). There was no significant difference between the three groups in terms of operative time, blood lost, warm ischemia time, cumulative painkiller consumption and renal function recovery time. Postoperative complications for Umbilical, Vaginal and Iliac were, respectively, of 0, 3 and 1. No major difference was found between the 3 groups beside a slightly longer hospital stay in the iliac group. Iliac incision might impact post-operative pain with a moderate but significant longer hospital stay. Vaginal extraction is an option when cosmetic outcomes present a real demand. The three options appeared to be safe and should be discussed with the patient in regard of the surgeon experience.

Published
2020

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

Author

Marie-Alice Macher, Lionel Badet, Nacera Ouali, Philippe Grimbert, Yann Neuzillet, Emilie Savoye, Renaud Snanoudj, Christophe Legendre, Myriam Pastural, Matthieu Durand, Camille Legeai, Marie-Noëlle Peraldi, François Kerbaul, Agence de la biomédecine [Saint-Denis la Plaine], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU AP-HP Centre Université de Paris, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

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

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

Published
2022

32. Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside

Author

Bilal Badat, Nicolas Mongardon, Keyvan Razazi, C. Deguillard, Frédéric Schlemmer, Mehdi Khellaf, Raphaëlle Huguet, Pascal Lim, Nicolas de Prost, François Templier, Karim Jaffal, Dominique Savary, Francois Morin, Elena Fois, Yvon Deplante, François Beloncle, François Perier, Constance Guillaud, Laurent Brochard, Philippe Grimbert, Armand Mekontso Dessap, Anne-Fleur Haudebourg, Jean-Christophe Richard, Samuel Tuffet, Manuella Pons, Vincent Audard, Arnaud Lesimple, Alain Mercat, Guillaume Carteaux, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de neurosciences (CHU Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, University of Toronto, Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Henri Mondor, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), 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 ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Chard-Hutchinson, Xavier, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
medicine.medical_specialty, medicine.medical_treatment, Continuous positive airway pressure, Context (language use), Respiratory physiology, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anesthesiology, medicine, Intubation, Tidal volume, Acute hypoxemic respiratory failure, Frugal innovation, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Oxygenation, 3. Good health, respiratory tract diseases, 030228 respiratory system, Emergency medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract

Background We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter (“Filter Frugal CPAP”, FF-CPAP) in and out the ICU. Methods (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. Results Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient’s work of breathing (6–34%) needed to sustain the tidal volume, depending on the filter’s resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p Conclusion Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.

Published
2021

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

Author

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

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

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

Published
2020

34. Infectious disease consultation is effective in boosting vaccine coverage in patients awaiting kidney transplantation: A French prospective study

Author

Florence Runyo, Camille Gomart, Philippe Grimbert, William Vindrios, Marie Matignon, Sébastien Gallien, Etienne Audureau, Giovanna Melica, Anna Boueilh, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), 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), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Adult, Male, medicine.medical_specialty, Vaccination schedule, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Interferon gamma release assay, kidney transplantation, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Tetanus Toxoid, medicine, latent tuberculosis, Humans, Infection control, Prospective Studies, Referral and Consultation, Immunization Schedule, Dialysis, Kidney transplantation, Aged, Transplantation, Latent tuberculosis, business.industry, Vaccination, Middle Aged, Hepatitis B, vaccine coverage, medicine.disease, Infectious Diseases, 030211 gastroenterology & hepatology, business, preventive strategies
Abstract

International audience; Recommended preventive strategies before kidney transplantation include screening and treatment of latent tuberculosis infection (LTBI), and updating of the recommended vaccines. We prospectively evaluated in dedicated infectious diseases consultations, from 2014 to 2018, the clinical and vaccination data of new adult kidney allograft candidates. Patients were offered an updated vaccination schedule, if appropriate, and were screened for LTBI using chest imaging and interferon gamma release assay (IGRA). Overall, 467 patients with median age of 58 [46-66] years were evaluated, of whom 302 patients (65%) were men (sex ratio 1.83), and 333 (71%) were on dialysis. Main causes of renal insufficiency were diabetes (25%) and autoimmune nephropathies (18%). The vaccination coverage was low and varied according to the different types of vaccines and patients. Vaccination or immunization rates were 24%, 6%, 54%, and 51% for tetanus-diphtheria-polio-acellular pertussis, Pneumococcus, hepatitis B, and seasonal influenza, respectively. ID consultation successfully rose patients' vaccinations coverage, in fulfillment with recommendations, in 465 (99%) patients. LTBI treatment was administered in 78 (16.7%) patients and caused drug-related adverse events in 9 (11%). A dedicated infectious disease consultation should become a critical tool for coordinating infection prevention strategies.

Published
2021

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

Author

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

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

International audience

Published
2021

39. Creatinine clearance after cimetidine administration in a new short procedure: comparison with plasma and renal clearances of iohexol

Author

Dominique Prié, Vincent Audard, Mehdi Sakka, Ahmad Ghadafi Ismail, Khalil El Karoui, Marie Matignon, Thomas Stehlé, Philippe Grimbert, and Florence Canoui-Poitrine

Subjects
medicine.medical_specialty, 030232 urology & nephrology, Urology, Renal function, GFR measurement, iohexol plasma clearance, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, creatinine clearance, Medicine, Cimetidine, AcademicSubjects/MED00340, Transplantation, business.industry, Limits of agreement, Original Articles, cimetidine, Confidence interval, Nephrology, Iohexol Clearance, iohexol renal clearance, Positive bias, Iohexol, business, Clearance, medicine.drug
Abstract

BackgroundCreatinine clearance after cimetidine administration (Cim-CreatClr) was once proposed as a method of glomerular filtration rate (GFR) measurement, but has been largely abandoned. We investigated whether a new short procedure for Cim-CreatClr determination could be considered an appropriate method for GFR measurement.MethodsA 150-min protocol involving oral cimetidine administration was developed to determine Cim-CreatClr. In total, 168 patients underwent simultaneous assessments of creatinine clearance before and after cimetidine administration [basal creatinine clearance (Basal-CreatClr) and Cim-CreatClr, respectively], renal iohexol clearance and plasma iohexol clearance (R-iohexClr and P-iohexClr, respectively). We compared the agreement between the various methods of GFR measurement, using Bland–Altman plots to determine biases, precisions (standard deviation of the biases) and accuracy (proportions of GFR values falling within 10, 15 and 30% of the mean: P10, P15 and P30, respectively).ResultsAfter cimetidine administration, Basal-CreatClr decreased by 19.8% [95% reference limits of agreement (95% LoA): −2.2 to 41.7%]. The bias between Cim-CreatClr and P-iohexClr was −0.6% (95% LoA −26.8 to 28%); the precision was 14.0%; P10, P15 and P30 were 57.1% [95% confidence interval (95% CI) 49.3 to 64.7%], 73.2% (95% CI 65.8 to 79.7%) and 97.0% (95% CI 93.2 to 99.0%), respectively. Due to the positive bias (16.7%; 95% LoA −3.6 to 36.9%) of Cim-CreatClr relative to R-iohexClr, accuracy of Cim-CreatClr relative to R-iohexClr was poor despite a good precision (10.3%).ConclusionsOur study shows a high level of agreement between Cim-CreatClr and P-iohexClr. These results suggest that this short Cim-CreatClr procedure is a valid method for GFR measurement, which might be useful, in particular, in situations in which P-iohexClr is not suitable or not available.

Published
2019

40. Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use

Author

Thibault Damy, Karim Belhadj, Brian Ezekian, Chantal Gautreau, Jaeberm Park, Vincent Audard, David Kheav, Jean Kwun, Marie Matignon, Bradley H. Collins, John S. Yi, Stuart J. Knechtle, Diane Bodez, Janghoon Yoon, Dong-Feng Chen, Alton B. Farris, Elsa Poullot, Philippe Grimbert, Mark D. Stegall, Miriam Manook, Laureline Faivre, Alyssa M. Bilewski, Dehbia Menouch, and Soulef Guendouz

Subjects
Adult, Graft Rejection, Male, 0301 basic medicine, Benzylamines, medicine.medical_specialty, medicine.drug_class, Urology, 030230 surgery, Plasma cell, CD38, Cyclams, Monoclonal antibody, T-Lymphocytes, Regulatory, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Heterocyclic Compounds, Isoantibodies, Animals, Humans, Medicine, Kidney transplantation, biology, business.industry, Plerixafor, Antibody-Dependent Cell Cytotoxicity, Antibodies, Monoclonal, Daratumumab, General Medicine, medicine.disease, ADP-ribosyl Cyclase 1, Kidney Transplantation, Macaca mulatta, Transplantation, Basic Research, 030104 developmental biology, medicine.anatomical_structure, Nephrology, biology.protein, Antibody, business, medicine.drug
Abstract

BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. METHODS: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. RESULTS: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P

Published
2019

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

Author

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

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

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

Published
2019

42. Évaluation de greffons de bigreffe transplantés en monogreffe

Author

Dimitrios Vordos, M. Such, A. De La Taille, M. Matignon, C. Chahwan, Philippe Grimbert, C. Champy, J. Klapp, A. Hoznek, N Merzeau, and L. Salomon

Subjects
Kidney, medicine.medical_specialty, urogenital system, business.industry, Urology, medicine.medical_treatment, 030232 urology & nephrology, Renal function, medicine.disease, Single kidney, Surgery, Transplantation, 03 medical and health sciences, surgical procedures, operative, 0302 clinical medicine, medicine.anatomical_structure, medicine, In patient, business, Kidney transplantation, Dialysis, Kidney disease
Abstract

Introduction Kidney transplantation is championed as the gold standard treatment for patients with end-stage kidney disease. According to the biomedical agency, there is an increasing number of patients waiting for kidney transplantation. Faced with organ shortage, the use of marginal grafts may well increase the number of available kidney grafts. Occasionally, during dual kidney graft transplantation, the poor quality of one of the two grafts, or other specific circumstances, may lead to transplantation of only one of the two grafts. We have compared patient outcome concerning single kidney transplantation from an initial dual kidney graft with respect to dual kidney graft transplantation. Material Among 67 patients enrolled for a dual kidney graft, 39 dual kidney grafts (group 1) were compared with 12 grafts performed with only one of the two kidneys of a dual kidney graft (group 2) as well as 15 grafts performed following a classic kidney graft protocol (group 3). Results The survival of grafts was respectively for groups 1, 2 and 3 of 100%, 72,5% and 75,4% (P=0.17). The survival of patients was respectively for groups 1, 2 and 3 of 78.3%, 89.9% and 87.8% (P=0.47). Conclusion Our study suggests that transplantation of a single kidney, initially proposed as dual kidney graft candidate, has satisfying results in terms of graft survival and patient mortality at the expense of poorer renal function in comparison to dual kidney graft. Indeed, there was no significant difference in the survival of patients and grafts. This seems promising taking into consideration that the aim of transplantation in elderly recipients is primarily to avoid dialysis, rather than having optimal post-transplantation kidney function. Level of evidence 4.

Published
2019

43. Costimulatory blockade molecules and B-cell–mediated immune response: current knowledge and perspectives

Author

Claire Leibler, Rebecca A. Elsner, Khalil El Karoui, Chloé Samson, Allan Thiolat, Philippe Grimbert, Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Graft Rejection, 0301 basic medicine, Isoantigens, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Autoimmunity, Cell Communication, Human leukocyte antigen, Kidney, Lymphocyte Activation, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Immune system, Costimulatory and Inhibitory T-Cell Receptors, Isoantibodies, medicine, Humans, Transplantation, Homologous, B cell, Autoimmune disease, B-Lymphocytes, biology, business.industry, Alloimmunity, T-Lymphocytes, Helper-Inducer, Allografts, medicine.disease, Kidney Transplantation, 3. Good health, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Immunology, biology.protein, Lymph Nodes, Antibody, business, Immunosuppressive Agents
Abstract

There is an urgent need for therapeutic agents that target humoral alloimmunity in solid organ transplantation. This includes sensitized patients with preformed donor-specific human leukocyte antigen antibodies and patients who develop de novo donor-specific antibodies, both of which are associated with acute and chronic antibody-mediated rejection and allograft loss. In the last decade, both experimental and clinical studies highlighted the major impact of costimulation molecules in the control of immune responses both in the field of transplantation and autoimmune disease. Although these molecules have been initially developed to control the early steps of T-cell activation, recent evidence also supports their influence at several steps of the humoral response. In this review, we aim to provide an overview of the current knowledge of the effects of costimulatory blockade agents on humoral responses in both autoimmune and allogeneic contexts. We first present the effects of costimulatory molecules on the different steps of alloantibody production. We then summarize mechanisms and clinical results observed using cytotoxic T lymphocyte antigen-4 (CTLA4)-Ig molecules both in transplantation and autoimmunity. Finally, we present the potential interest and implications of other costimulatory family members as therapeutic targets, with emphasis on combinatorial approaches, for the optimal control of the alloantigen-specific humoral response.

Published
2019

44. Les évènements indésirables associés aux inhibiteurs de Janus kinases : à propos de 126 815 rapports de pharmacovigilance du WHO

Author

Matthieu Mahevas, Léa Hoisnard, L. Roy, Aurelien Amiot, P. Claudepierre, José L. Cohen, Anissa Zarour, Emilie Sbidian, Philippe Grimbert, K. El Karoui, Sébastien Maury, Bénédicte Lebrun-Vignes, Marc Michel, and Pierre Wolkenstein

Subjects
Rheumatology
Abstract

Introduction Les inhibiteurs de Janus kinases (anti-JAK) sont des therapies ciblees qui bloquent la signalisation intracellulaire de plusieurs cytokines. Ils sont utilises dans le traitement de pathologies auto-inflammatoires et dysimmunitaires. Leur principal interet reside dans leur voie d’administration : orale et topique. Avec l’augmentation des indications ainsi que le developpement de nouvelles molecules, la securite d’utilisation de ces therapies ciblees est un element crucial. L’objectif de cette etude etait d’evaluer la securite des 3 premiers anti-JAK commercialises a partir des declarations de pharmacovigilance internationale. Materiels et methodes Dans cette etude observationnelle retrospective, les donnees de pharmacovigilance provenaient de la base de donnees de l’Organisation Mondiale de la Sante de declaration des evenements indesirables (VigiBase, 24 millions de declarations). Toutes les declarations comportant les medicaments suspects suivants ont ete incluses : ruxolitinib, tofacitinib et baricitinib. Chaque declaration comporte un/plusieurs evenements indesirables, classes selon la terminologie du Dictionnaire medical des affaires reglementaires MedDRA. Des analyses de disproportionnalite ont ete realisees afin d’estimer l’information component (IC). Un evenement indesirable est considere comme un signal de securite si la borne inferieure de l’intervalle de credibilite a 95 % (IC025) est positive. Resultats Nous avons identifie 126 815 declarations d’evenements indesirables impliquant un anti-JAK. Les traitements par ruxolitinib, tofacitinib et baricitinib etaient significativement associes avec la survenue d’infections (IC025 1,7 au niveau de la classe therapeutique, et plus precisement pour les infections virales [herpes et influenza], fongiques et mycobacteriennes) ; d’affections musculosquelettiques et du tissu conjonctif (IC025 1,1) ; d’embolies et de thromboses (IC025 0,4) ; de tumeurs malignes et benignes (IC025 0,8, et plus precisement les tumeurs malignes cutanees). Le tofacitinib etait associe avec la survenue de perforations gastro-intestinales (IC025 1,5). Nous n’avons pas identifie de signal concernant les evenements cardiovasculaires indesirables majeurs. Discussion La sous-declaration des evenements indesirables et l’absence de detail quant aux examens cliniques, biologiques ou d’imagerie ayant permis le diagnostic de l’evenement indesirable constituent les principales limites de cette etude. Un suivi plus long et de nouvelles etudes observationnelles pourront contribuer a l’amelioration de la connaissance des risques associes au traitement par anti-JAK au sein de differentes populations de patients selon la pathologie sous-jacente et les comorbidites. Conclusion Nous avons identifie des signaux de securite significatifs a partir des donnees de declaration internationale des evenements indesirables en lien avec les 3 premiers anti-JAK commercialises : evenements infectieux, embolies et thromboses, perforations gastro-intestinales et tumeurs malignes cutanees.

Published
2021

46. Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients withde novocarcinoma

Author

Christophe Tournigand, Corinne Haioun, Benoit Rousseau, Daniel Azoulay, Camille Tlemsani, Philippe Compagnon, Laurent Salomon, Jehan Dupuis, I. Cholley, Alexis Laurent, M. Matignon, Christophe Duvoux, Philippe Grimbert, Cindy Neuzillet, Aude Guillemin, Alexandre de la Taille, Chaddy Salloum, and Pierre Wolkenstein

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Kidney, business.industry, medicine.medical_treatment, Cancer, Immunosuppression, medicine.disease, Transplantation, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Immunosuppressive drug, 030220 oncology & carcinogenesis, Internal medicine, Cohort, Toxicity, medicine, Carcinoma, business
Abstract

Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients with de novo cancer (excluding nonmelanoma skin cancers) were selected from a monocentric cohort of 4,637 kidney and liver allograft recipients. We assessed oncologic treatment optimality according to guidelines and analyzed immunosuppressive drug modifications and oncologic treatment impacts on treatment feasibility, toxicities, and graft/patient survivals. A total of 180 patients with 205 cancers were included: mean age 60 years, median delay from transplantation to first de novo cancer 5 years. In 46% of cases, immunosuppressive therapy was modified after cancer diagnosis: 24% dose reduction and 22% mTOR inhibitor introduction. Optimal oncologic treatment was performed in 80% and 38% of patients with localized and advanced cancer respectively. Transplantation and immunosuppression hindered optimal oncologic treatment in 11% instances. Immunosuppressive therapy modifications did not affect oncologic treatment tolerance nor graft survival. In multivariate analysis, optimal oncologic treatment and mTOR inhibitor introduction improved survival of patients with de novo carcinoma. Optimal oncologic treatment is feasible in kidney and liver allograft recipients without safety concerns. Optimal oncologic treatment and mTOR inhibitor introduction seem to markedly improve survival of patients with de novo carcinoma.

Published
2018

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

Author

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

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

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

Published
2021

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

Author

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

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

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

Published
2021

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

Author

Valérie Moal, Véronique Leblond, Gilles Salles, Valérie Chatelet, Benoit Barrou, Alizée Maarek, Sophie Caillard, Christiane Mousson, Laurent Genestier, Luc Frimat, Antoine Durrbach, Vincent Pernin, Emmanuel Bachy, Philippe Rieu, Olivier Thaunat, Didier Ducloux, Valérie Dubois, Manon Charrier, Bénédicte Janbon, Thomas Barba, Dany Anglicheau, Antoine Thierry, Jacques Dantal, Gaelle Fossard, Anne-Elisabeth Heng, Mathias Büchler, Pierre-François Westeel, François Provôt, Denis Glotz, Elisabeth Cassuto, Jean-Philippe Rerolle, Philippe Grimbert, Philippe Gaulard, Jonathan M. Chemouny, Nacera Ouali, Christophe Mariat, and Emmanuel Morelon

Subjects
Adult, Male, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, Lymphoproliferative disorders, Disease, Lymphoma, T-Cell, Gastroenterology, Cohort Studies, hemic and lymphatic diseases, Internal medicine, Medicine, Humans, Prospective Studies, Aged, Transplantation, Chemotherapy, business.industry, Hazard ratio, Middle Aged, medicine.disease, Kidney Transplantation, surgical procedures, operative, Cohort, Registry data, Female, business, Cohort study
Abstract

BACKGROUND Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients. METHODS All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients. RESULTS T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001). CONCLUSIONS This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.

Published
2021

50. De Novo Focal and Segmental Glomerulosclerosis After COVID-19 in a Patient With a Transplanted Kidney From a Donor With a High-risk APOL1 Variant

Author

Aude Mausoleo, Marie Matignon, Julie Oniszczuk, Stephanie Malard-Castagnet, Anna Boueilh, Thomas Stehlé, David Buob, Marie Christine Verpont, Dil Sahali, Philippe Grimbert, Anissa Moktefi, Vincent Audard, Slim Fourati, Nicolas Pallet, Khalil El Karoui, 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), IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), service Anatomie et Cytologie Pathologique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Etablissement Français du Sang [Nantes], Department of Pathology [Cleveland, OH, USA] (School of Medicine), Case Western Reserve University [Cleveland], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor - Service de néphrologie et transplantation, Service de Néphrologie-Transplantation [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)

Subjects
Male, Pathology, medicine.medical_specialty, Apolipoprotein L1, [SDV]Life Sciences [q-bio], Context (language use), 030230 surgery, Kidney, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Genotype, medicine, Humans, Genotyping, ComputingMilieux_MISCELLANEOUS, Transplantation, biology, medicine.diagnostic_test, Glomerulosclerosis, Focal Segmental, SARS-CoV-2, business.industry, Not Otherwise Specified, COVID-19, Glomerulosclerosis, Middle Aged, medicine.disease, Kidney Transplantation, Tissue Donors, 3. Good health, biology.protein, 030211 gastroenterology & hepatology, Renal biopsy, business, Nephrotic syndrome
Abstract

There is compelling evidence that renal complications in a native kidney are a major concern in patients infected with severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19). The spectrum of renal lesions observed on renal grafts in this context remains to be determined.We report the case of a renal transplant recipient with non-severe COVID-19, who subsequently developed nephrotic syndrome associated with acute renal injury.Renal biopsy demonstrated focal and segmental glomerulosclerosis lesions classified as not otherwise specified histological variant. Genotyping for 2 risk alleles of the apolipoprotein L1 gene demonstrated that the donor was homozygous for the G2/G2 genotype.In renal transplant patients receiving kidneys from donors with high-risk apolipoprotein L1 variants, COVID-19 may promote acute glomerular injury in the form of focal and segmental glomerulosclerosis.

Published
2020
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