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1. The value of extracorporeal photopheresis as an immunosuppression-modifying approach in solid organ transplantation: a potential solution to an unmet medical need

Author

Jean-François Augusto, Christian Benden, Fritz Diekmann, and Andreas Zuckermann

Subjects
allograft rejection, calcineurin inhibitors, extracorporeal photopheresis, immunosuppression, solid organ transplantation, Immunologic diseases. Allergy, RC581-607
Abstract

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.

Published
2024
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2. Immune‐mediated thrombotic thrombocytopenic purpura prognosis is affected by blood pressure

Author

Adrien Joseph, Martin Eloit, Elie Azoulay, Gilles Kaplanski, François Provot, Claire Presne, Alain Wynckel, Steven Grangé, Éric Rondeau, Frédéric Pène, Yahsou Delmas, Alexandre Lautrette, Christelle Barbet, Christiane Mousson, Jean‐Philippe Coindre, Pierre Perez, Matthieu Jamme, Jean‐François Augusto, Pascale Poullin, Frédéric Jacobs, Khalil El Karoui, Cécile Vigneau, Marc Ulrich, Tarik Kanouni, Moglie Le Quintrec, Mohamed Hamidou, Simon Ville, Anne Charvet‐Rumpler, Mario Ojeda‐Uribe, Pascal Godmer, Véronique Fremeaux‐Bacchi, Agnès Veyradier, Jean‐Michel Halimi, and Paul Coppo

Subjects
ADAMTS13, blood pressure, complement, hemolytic uremic syndrome, hypertension, prognosis, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Background The prevalence, prognostic role, and diagnostic value of blood pressure in immune‐mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. Methods Using a national cohort of iTTP (n = 368), Shigatoxin‐induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension‐related thrombotic microangiopathy (n = 25), we sought to compare the cohort’s blood pressure profile to assess its impact on prognosis and diagnostic performances. Results Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118–143] vs 161 [IQR 142–180] mmHg) and diastolic (76 [IQR 69–83] vs 92 [IQR 79–105] mmHg, both p

Published
2022
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4. Assessment of Renal Risk Score and Histopathological Classification for Prediction of End-Stage Kidney Disease and Factors Associated With Change in eGFR After ANCA-Glomerulonephritis Diagnosis

Author

Benoit Brilland, Charlotte Boud’hors, Marie-Christine Copin, Pierre Jourdain, Nicolas Henry, Samuel Wacrenier, Assia Djema, Clément Samoreau, Jean-Philippe Coindre, Maud Cousin, Jeremie Riou, Anne Croue, Jean-Paul Saint-André, Jean-François Subra, Giorgina Barbara Piccoli, and Jean-François Augusto

Subjects
ANCA, glomerulonephritis, end-stage kidney disease, eGFR, kidney biopsy, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionThe “Renal Risk Score” (RRS) and the histopathological classification have been proposed to predict the risk of end-stage kidney disease (ESKD) in ANCA-associated glomerulonephritis (ANCA-GN). Besides, factors associated with kidney function recovery after ANCA-GN onset remain to be more extensively studied. In the present study, we analyzed the value of the RRS and of the histopathological classification for ESKD prediction. Next, we analyzed factors associated with eGFR change within the first 2 years following ANCA-GN diagnosis.Materials and MethodsWe included patients from the Maine–Anjou ANCA-associated vasculitis registry with at least 6 months of follow-up. The values of ANCA-GN, histopathological classification, and RRS, and the factors associated with eGFR variations between ANCA-GN diagnosis and 2 years of follow-up were assessed.ResultsThe predictive values of the histopathological classification and RRS were analyzed in 123 patients. After a median follow-up of 42 months, 33.3% patients developed ESKD. The predictive value of RRS for ESKD was greater than that of the histopathological classification. Determinants of eGFR variation were assessed in 80/123 patients with complete eGFR measurement. The median eGFR increased from ANCA-GN diagnosis to month 6 and stabilized thereafter. The only factor associated with eGFR variation in our study was eGFR at ANCA-GN diagnosis, with higher eGFR at diagnosis being associated with eGFR loss (p

Published
2022
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6. Serum Interleukin-26 Is a New Biomarker for Disease Activity Assessment in Systemic Lupus Erythematosus

Author

Benoit Brilland, Maxime Bach-Bunner, Christopher Nunes Gomes, Vincent Larochette, Etienne Foucher, Marc Plaisance, Patrick Saulnier, Nathalie Costedoat-Chalumeau, Pascale Ghillani, Cristina Belizna, Yves Delneste, Jean-François Augusto, and Pascale Jeannin

Subjects
IL-26, SLEDAI, Proteinuria, anti-DNA antibodies, complement consumption, systemic lupus erythematosus, Immunologic diseases. Allergy, RC581-607
Abstract

ObjectiveInterleukin-26 (IL-26) has a unique ability to activate innate immune cells due to its binding to circulating double-stranded DNA. High levels of IL-26 have been reported in patients with chronic inflammation. We aimed to investigate IL-26 levels in patients with systemic lupus erythematosus (SLE).MethodsIL-26 serum levels were quantified by ELISA for 47 healthy controls and 109 SLE patients previously enrolled in the PLUS study. Performance of IL-26 levels and classical markers (autoantibodies or complement consumption) to identify an active SLE disease (SLE disease activity index (SLEDAI) score > 4) were compared.ResultsIL-26 levels were significantly higher in SLE patients than in controls (4.04 ± 11.66 and 0.74 ± 2.02 ng/mL; p = 0.005). IL-26 levels were also significantly higher in patients with active disease than those with inactive disease (33.08 ± 21.06 vs 1.10 ± 3.80 ng/mL, p < 0.0001). IL-26 levels correlated with SLEDAI score and the urine protein to creatinine ratio (uPCR) (p < 0.001). Patients with high IL-26 levels had higher SLEDAI score, anti-DNA antibodies levels, and uPCR (p < 0.05). They presented more frequently with C3 or C4 complement consumption. Lastly, IL-26 showed stronger performance than classical markers (complement consumption or autoantibodies) for active disease identification.ConclusionsOur results suggest that, in addition to classical SLE serological markers, the measurement of IL-26 levels may be a useful biomarker for active disease identification in SLE patients.

Published
2021
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7. Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

Author

Marie Lemerle, Anne-Sophie Garnier, Anne Croue, Alain Chevailler, Jean-Paul Saint-André, Jean-François Subra, Jean-François Augusto, and Julien Demiselle

Subjects
Lupus glomerulonephritis, ANCA, Immunology, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background The value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain. Case presentation We report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation. Conclusion This case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis.

Published
2019
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8. Anti-Pentraxin Antibodies in Autoimmune Diseases: Bystanders or Pathophysiological Actors?

Author

Benoit Brilland, Emeline Vinatier, Jean-François Subra, Pascale Jeannin, Jean-François Augusto, and Yves Delneste

Subjects
pentraxins, autoimmunity, systemic lupus erythematosus, ANCA-associated vasculitis, anti-pentraxin autoantibodies, Immunologic diseases. Allergy, RC581-607
Abstract

Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including the prototypic long pentraxin PTX3. Pentraxins act mainly as bridging molecules favoring the clearance of microbes and dead cells. They are also involved in many other biological processes, such as regulation of complement activation, inflammation and tissue homeostasis. Autoantibodies directed against pentraxins have been reported in various autoimmune diseases, especially in systemic lupus erythematosus and ANCA-associated vasculitis. In this review, we review the main biological characteristics and functions of pentraxins and summarize data concerning autoantibodies directed against pentraxins in the context of autoimmune diseases and discuss their potential pathological role.

Published
2021
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9. Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study

Author

Nicolas Henry, Chloé Mellaza, Nicolas Fage, François Beloncle, Franck Genevieve, Guillaume Legendre, Corentin Orvain, Anne-Sophie Garnier, Maud Cousin, Virginie Besson, Jean-François Subra, Agnès Duveau, Jean-François Augusto, and Benoit Brilland

Subjects
Thrombotic microangiopathies, etiology, primary, secondary, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, Medicine (General), R5-920
Abstract

Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice.Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes.Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death.Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.

Published
2021
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10. Refractory Auto-Immune Thrombotic Thrombocytopenic Pupura Successfully Treated With Caplacizumab

Author

Chloé Mellaza, Nicolas Henry, Pierre-Marie Fayolle, Satar Mortaza, Jean-François Subra, Agnès Veyradier, Paul Coppo, and Jean-François Augusto

Subjects
thrombotic thrombocitopenic purpura, caplacizumab, refractor, case report, platelet, Medicine (General), R5-920
Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by mechanical hemolytic anemia, profound thrombocytopenia, and neurological manifestations. Acquired auto-immune TTP, the most prevalent cause of TTP, is induced by the presence of inhibitory anti-ADAMTS13 auto-antibodies. Modern treatment of acquired TTP relies on plasma exchange, rituximab, and steroids. Caplacizumab (Cablivi®), a humanized single-variable domain immunoglobulin that targets the A1 domain of the ultra-large von Willebrand factor, inhibits the interaction between ultra-large vWFand platelets. In two clinical trials, caplacizumab, in addition to conventional treatment, shortened the delay to platelet count normalization in comparison to conventional treatment plus placebo, without increasing significantly hemorrhagic complications. Moreover, caplacizumab was associated with reduced occurrence of a secondary endpoint associating death, TTP recurrence, and major thromboembolic events. Here, we report the off-label use of caplacizumab in a 68-year-old patient with confirmed acquired TTP, severe thrombocytopenia, and generalized tonic–clonic seizures requiring mechanical ventilation and admission in the intensive care unit. Conventional treatment was rapidly started. Despite the intensification of plasma exchange treatment with twice-daily sessions, steroid continuation, and a second rituximab infusion on day 6, thrombotic microangiopathy worsened with thrombocytopenia at 21 g/L on day 8 from admission. We also considered using caplacizumab, which we could obtain and start on day 12 from admission, as it was available under a temporary authorization use in France. As soon as 12 h after caplacizumab initiation, we observed a significant increase of platelet count and improvement of other hemolytic parameters. We observed resolution of encephalopathy and complete recovery of motor paralysis, allowing us to stop mechanical ventilation on day 14. Caplacizumab was maintained for 128 days until day 139 from initial admission. The patient is going well 10 months after initial admission, without any neurological sequelae, and TTP did not relapse. To the best of our knowledge, this is the first reported use of caplacizumab in such a condition. This case report suggests that caplacizumab use may help to reduce the rate of refractory TTP episodes.

Published
2020
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11. T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

Author

Benoit Brilland, Céline Beauvillain, Gery Mazurkiewicz, Pierre Rucay, Yves Roquelaure, Julie Tabiasco, Emeline Vinatier, Jérémie Riou, Pascale Jeannin, Gilles Renier, Jean-François Subra, and Jean-François Augusto

Subjects
crystalline silica, occupational diseases, auto-immune diseases, activated T cells, regulatory T cells, auto-antibodies, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS.Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively.Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for

Published
2019
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12. Patients with ANCA-associated vasculitis admitted to the intensive care unit with acute vasculitis manifestations: a retrospective and comparative multicentric study

Author

Julien Demiselle, Johann Auchabie, François Beloncle, Philippe Gatault, Steven Grangé, Damien Du Cheyron, Jean Dellamonica, Sonia Boyer, Dimitri Titeca Beauport, Lise Piquilloud, Julien Letheulle, Christophe Guitton, Nicolas Chudeau, Guillaume Geri, François Fourrier, René Robert, Emmanuel Guérot, Julie Boisramé-Helms, Pierre Galichon, Pierre-François Dequin, Alexandre Lautrette, Pierre-Edouard Bollaert, Ferhat Meziani, Loïc Guillevin, Nicolas Lerolle, and Jean-François Augusto

Subjects
Anti-neutrophil cytoplasmic antibody, ANCA-associated vasculitis, Intensive care unit, Mortality, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Purpose Data for ANCA-associated vasculitis (AAV) patients requiring intensive care are scarce. Methods We included 97 consecutive patients with acute AAV manifestations (new onset or relapsing disease), admitted to 18 intensive care units (ICUs) over a 10-year period (2002–2012). A group of 95 consecutive AAV patients with new onset or relapsing disease, admitted to two nephrology departments with acute vasculitis manifestations, constituted the control group. Results In the ICU group, patients predominantly showed granulomatosis with polyangiitis and proteinase-3 ANCAs. Compared with the non-ICU group, the ICU group showed comparable Birmingham vasculitis activity score and a higher frequency of heart, central nervous system and lungs involvements. Respiratory assistance, renal replacement therapy and vasopressors were required in 68.0, 56.7 and 26.8% of ICU patients, respectively. All but one patient (99%) received glucocorticoids, 85.6% received cyclophosphamide, and 49.5% had plasma exchanges as remission induction regimens. Fifteen (15.5%) patients died during the ICU stay. The following were significantly associated with ICU mortality in the univariate analysis: the need for respiratory assistance, the use of vasopressors, the occurrence of at least one infection event in ICU, cyclophosphamide treatment, sequential organ failure assessment at admission and simplified acute physiology score II. After adjustment on sequential organ failure assessment or infection, cyclophosphamide was no longer a risk factor for mortality. Despite a higher initial mortality rate of ICU patients within the first hospital stay (p

Published
2017
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13. Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation.

Author

Anne-Sophie Garnier, Martin Planchais, Jérémie Riou, Clément Jacquemin, Laurence Ordonez, Jean-Paul Saint-André, Anne Croue, Abdelhadi Saoudi, Yves Delneste, Anne Devys, Isabelle Boutin, Jean-François Subra, Agnès Duveau, and Jean-François Augusto

Subjects
Medicine, Science
Abstract

BackgroundBiological biomarkers to stratify cancer risk before kidney transplantation are lacking. Several data support that tumor development and growth is associated with a tolerant immune profile. T cells expressing low levels of CD45RC preferentially secrete regulatory cytokines and contain regulatory T cell subset. In contrast, T cells expressing high levels of CD45RC have been shown to secrete proinflammatory cytokines, to drive alloreactivity and to predict acute rejection (AR) in kidney transplant patients. In the present work, we evaluated whether pre-transplant CD45RClow T cell subset was predictive of post-transplant cancer occurrence.MethodsWe performed an observational cohort study of 89 consecutive first time kidney transplant patients whose CD45RC T cell expression was determined by flow cytometry before transplantation. Post-transplant events including cancer, AR, and death were assessed retrospectively.ResultsAfter a mean follow-up of 11.1±4.1 years, cancer occurred in 25 patients (28.1%) and was associated with a decreased pre-transplant proportion of CD4+CD45RChigh T cells, with a frequency below 51.9% conferring a 3.7-fold increased risk of post-transplant malignancy (HR 3.71 [1.24-11.1], p = 0.019). The sensibility, specificity, negative predictive and positive predictive values of CD4+CD45RChigh52.1% were 94.5, 68.0, 34.7 and 98.6% respectively. Frequency of CD4+CD45RChigh T cells was positively correlated with those of CD8+CD45RChigh (pConclusionHigh frequency of CD45RChigh T cells was associated with AR, while low frequency was associated with cancer. Thus, CD45RC expression on T cells appears as a double-edged sword biomarker of promising interest to assess both cancer and AR risk before kidney transplantation.

Published
2019
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14. Incidence and Risk Factors of Venous Thromboembolic Events in Patients with ANCA-Glomerulonephritis: A Cohort Study from the Maine-Anjou Registry

Author

Nicolas Henry, Benoit Brilland, Samuel Wacrenier, Assia Djema, Anne Sophie Garnier, Renaud Gansey, Jean-Philippe Coindre, Virginie Besson, Agnès Duveau, Jean-François Subra, Maud Cousin, Giorgina Barbara Piccoli, and Jean-François Augusto

Subjects
venous thromboembolism, ANCA glomerulonephritis, statins, risk factor, Medicine
Abstract

(1) Introduction: The incidence of venous thromboembolisms (VTE) has not been extensively analyzed in patients with antineutrophil cytoplasmic antibody (ANCA)-glomerulonephritis (ANCA-GN). Thus, the aim of the present study was to assess the frequency and the risk factors of VTE in patients with ANCA-GN. (2) Methods: Patients from the Maine-Anjou ANCA-associated vasculitis (AAV) registry with a biopsy showing pauci-immune glomerulonephritis were included. VTE events, site, and interval from AAV diagnosis were analyzed. (3) Results: 133 patients fulfilled the inclusion criteria of the study and were analyzed. VTE episodes were diagnosed in 23/133 (17.3%) patients at a median delay of 3 months from ANCA-GN diagnosis. Patients with VTE had lower serum albumin (p = 0.040), were less frequently on statin therapy (p = 0.009) and had less frequently proteinase-3 (PR3)-ANCAs (p = 0.078). Univariate analysis identified higher age (p = 0.022), lower serum albumin (p = 0.030), lack of statin therapy (p = 0.009), and rituximab treatment (p = 0.018) as significant risk factors of VTE. In multivariate analysis, only lack of statin therapy (HR 4.873; p = 0.042) was significantly associated with VTE. (4) Conclusion: Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. Our results suggest that statin therapy is associated with a lower risk of VTE in ANCA-GN patients.

Published
2020
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15. High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin

Author

Anne-Sophie Garnier, Juliette Dellamaggiore, Benoit Brilland, Laurence Lagarce, Pierre Abgueguen, Alain Furber, Erick Legrand, Jean-François Subra, Guillaume Drablier, and Jean-François Augusto

Subjects
amoxicillin, crystalluria, acute kidney injury, incidence, Medicine
Abstract

Background: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is considered as a rare complication of high dose intravenous (IV) AMX administration. However, recently, its incidence seems to be increasing based on French pharmacovigilance centers. Occurrence of AICN has been observed mainly with IV administration of AMX and mostly under doses over 8 g/day. Given that pharmacovigilance data are based on declaration, the real incidence of AICN may be underestimated. Thus, the primary objective of the present study was to determine the incidence of AICN in the current practice. Materials and Methods: We conducted a retrospective study between 1 January 2015 and 31 December 2017 in Angers University Hospital. Inclusion criteria were age over 18 years-old and IV AMX administration of at least 8 g/day for more than 24 h. Patients admitted directly into the intensive care units were excluded. Medical records of patients that developed Kidney Disease:Improving Global Outcome (KDIGO) stage 2–3 acute kidney injury (AKI) were reviewed by a nephrologist and a specialist in pharmacovigilance. AICN was retained if temporality analysis was conclusive, after exclusion of other causes of AKI, in absence of other nephrotoxic drug administration. Results: A total of 1303 patients received IV AMX for at least 24 h. Among them, 358 (27.5%) were exposed to AMX doses of at least 8 g/day and were included. Patients were predominantly males (68.2%) with a mean age of 69.1 years-old. AMX was administered for a medical reason in 78.5% of cases. Patients received a median dose of AMX of 12 g/day (152.0 mg/kg/day). Seventy-three patients (20.4%) developed AKI, 42 (56.8%) of which were KDIGO stage 2 or 3. Among the latter, AICN diagnosis was retained in 16 (38.1%) patients, representing an incidence of 4.47% of total patients exposed to high IV AMX doses. Only female gender was associated with an increased risk of AICN. AMX dose was not significantly associated with AICN development. Conclusion: This study suggests a high incidence of AICN in patients receiving high IV AMX doses, representing one third of AKI causes in our study. Female gender appeared as the sole risk factor for AICN in this study.

Published
2020
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16. Early post-transplant serum IgA level is associated with IgA nephropathy recurrence after kidney transplantation.

Author

Anne-Sophie Garnier, Agnès Duveau, Julien Demiselle, Anne Croué, Jean-François Subra, Johnny Sayegh, and Jean-François Augusto

Subjects
Medicine, Science
Abstract

IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p

Published
2018
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17. CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

Author

Marie Lemerle, Anne-Sophie Garnier, Martin Planchais, Benoit Brilland, Yves Delneste, Jean-François Subra, Odile Blanchet, Simon Blanchard, Anne Croue, Agnès Duveau, and Jean-François Augusto

Subjects
kidney transplantation, acute rejection, lymphocyte, CD45RC, Medicine
Abstract

Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.

Published
2019
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18. Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry

Author

Fanny Guibert, Anne-Sophie Garnier, Samuel Wacrenier, Giorgina Piccoli, Assia Djema, Renaud Gansey, Julien Demiselle, Benoit Brilland, Maud Cousin, Virginie Besson, Agnès Duveau, Khuzama El Nasser, Jean-Philippe Coindre, Anne Croue, Jean-Paul Saint-André, Alain Chevailler, Jean-François Subra, and Jean-François Augusto

Subjects
ANCA, vasculitis, connective tissue disease, glomerulonephritis, Medicine
Abstract

Background and objectives: The overlap between antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (ANCA-GN) and connective tissue diseases (CTD) has been reported mainly as case series in the literature. Frequency of this association, as well as presentation and outcomes are unknown. Materials and Methods: Patients from the Maine-Anjou ANCA-associated vasculitides (AAV) registry with ANCA-GN diagnosed between 01/01/2000 and 01/01/2018, ANCA positivity, and at least six months of follow-up, were included. Results: 106 out of 142 patients fulfilled the inclusion criteria and were analyzed. CTD was present at ANCA-GN diagnosis in 16 (15.1%) patients. The most common CTD were rheumatoid arthritis, Sjogren syndrome and systemic sclerosis. Compared to the control group, females were more represented in the CTD group (75%, p = 0.001). Renal presentation was comparable between groups, including the pathological analysis of renal biopsies. Patients of CTD group presented a higher rate of non-renal relapse (25% versus 7.7%, p = 0.037), and experienced more frequently a venous thrombotic event (31.2% versus 10%, p = 0.021). No difference between groups was observed according to major outcomes. Conclusion: Association between CTD and ANCA-GN is not a rare condition and predominantly affects females. While AAV presentation is not significantly different, CTD patients experience more frequently non-renal relapse and venous thrombotic events.

Published
2019
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19. Detection of Anti-Pentraxin-3 Autoantibodies in ANCA-Associated Vasculitis.

Author

Amélie Simon, Jean-François Subra, Philippe Guilpain, Pascale Jeannin, Pascale Pignon, Simon Blanchard, Erwan Garo, Sébastien Jaillon, Alain Chevailler, Gilles Renier, Xavier Puéchal, Barbara Bottazzi, Alberto Mantovani, Yves Delneste, and Jean-François Augusto

Subjects
Medicine, Science
Abstract

Pentraxin 3 (PTX3), in common with myeloperoxidase and proteinase 3, is stored in human neutrophil granules and is expressed on apoptotic neutrophil surface. We therefore investigated the presence of anti-PTX3 autoantibodies (aAbs) in the sera of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients.Presence of anti-PTX3 autoantibodies was analysed by a specific enzyme-linked immunosorbent assay in sera from 150 patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), and in sera of 227 healthy subjects (HS), 40 systemic sclerosis (SSc) patients, and 25 giant cell arteritis patients (GCA). Using indirect immunofluorescence on fixed human neutrophils, we also analyzed the staining pattern associated with the presence of anti-PTX3 aAbs.Anti-PTX3 aAbs were detected in 56 of 150 (37.3%) of the AAV patients (versus 12 of 227 (5.3%) of HS, p

Published
2016
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20. Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis.

Author

Jean-François Augusto, Virginie Langs, Julien Demiselle, Christian Lavigne, Benoit Brilland, Agnès Duveau, Caroline Poli, Alain Chevailler, Anne Croue, Frederic Tollis, Johnny Sayegh, and Jean-François Subra

Subjects
Medicine, Science
Abstract

Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes.We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3

Published
2016
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21. Serum Magnesium after Kidney Transplantation: A Systematic Review

Author

Anne-Sophie Garnier, Agnès Duveau, Martin Planchais, Jean-François Subra, Johnny Sayegh, and Jean-François Augusto

Subjects
Magnesium-Kidney, transplantation-New-onset, diabetes after transplantation-cardiovascular risk, Nutrition. Foods and food supply, TX341-641
Abstract

Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence linking hypomagnesemia to clinical consequences in these specific populations. After a brief summary of the main mechanisms involved in Mg regulation and of Mg status in end-stage renal disease, the review focuses on the relationship between hypomagnesemia and cardiovascular risk in kidney transplant recipients. A body of evidence in recent studies points to a negative impact of hypomagnesemia on post-transplant diabetes mellitus (PTDM) and cardiovascular risk, which currently represent the main threat for morbidity and mortality in kidney transplantation. Deleterious biological mechanisms induced by hypomagnesemia are also discussed. While data analysis enables us to conclude that hypomagnesemia is linked to the development of PTDM, studies prospectively evaluating the impact of hypomagnesemia correction after kidney transplantation are still lacking and needed.

Published
2018
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22. A higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.

Author

Laurence Ordonez, Isabelle Bernard, Marianne Chabod, Jean-François Augusto, Valerie Lauwers-Cances, Christelle Cristini, Maria-Cristina Cuturi, Jean-François Subra, and Abdelhadi Saoudi

Subjects
Medicine, Science
Abstract

Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC) on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion. We then investigated whether the frequency of the recipients CD45RC T cell subsets before transplantation would predict acute graft rejection in a cohort of 89 patients who had undergone their first kidney transplantation. We showed that patients exhibiting more than 54.7% of CD8 CD45RC(high) T cells before transplantation had a 6 fold increased risk of acute kidney graft rejection. In contrast, the proportions of CD4 CD45RC T cells were not predictive. Thus, a higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.

Published
2013
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23. Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience

Author

Jean-François, Augusto, Elie, Azoulay, Virginie, Barbay, Ygal, Benhamou, Jaccard, Arnaud, Anne, Charvet-Rumpler, Dominique, Chauveau, Gabriel, Choukroun, Jean-Philippe, Coindre, Paul, Coppo, Yahsou, Delmas, Salanoubat, Celia, Antoine, Dossier, Ville, Simon, Véronique, Frémeaux-Bacchi, Lionel, Galicier, Steven, Grangé, Bertrand, Guidet, Jean-Michel, Halimi, Neel, Antoine, Miguel, Hié, Frédéric, Jacobs, Bérangère, Joly, Tarik, Kanouni, Gilles, Kaplanski, Rieu, Virginie, Véronique, Le Guern, Bruno, Moulin, Jean-Michel, Rebibou, Mario, Ojeda Uribe, Nathalie, Parquet, Frédéric, Pène, Pierre, Perez, Pascale, Poullin, Claire, Pouteil-Noble, Claire, Presne, François, Provôt, Mesnard, Laurent, Samir, Saheb, Amélie, Seguin, Aude, Servais, Alain, Stépanian, Agnès, Veyradier, Cécile, Vigneau, Alain, Wynckel, Patricia, Zunic, Thierry, Krummel, Marc, Ulrich, Alexandre, Hertig, Suzon, Benoît, Gilardin, Laurent, Moglie, Le Quintrec, Theresa, Kwon, Valérie, Chatelet, Damien, Ducheyron, Nihal, Martis, Manon, Marie, David, Ribes, Anne-Marie, Ronchetti, Béranger, Nicolas, Coppo, Paul, Tsatsaris, Vassilis, Boisseau, Pierre, Provôt, François, Delmas, Yahsou, Poullin, Pascale, Vanhoorelbeke, Karen, Veyradier, Agnès, and Joly, Bérangère S.

Published
2024
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25. Study of Post-Kidney Transplantation Parietal Complications and Presarcopenia

Author

Marion Beau, Julien Barbieux, Pierre Bigot, Jean Piquet, Gauthier Aupert, Agnes Duveau, Souhil Lebdai, Martin Planchais, Jean-François Augusto, and Thibaut Culty

Subjects
Transplantation, Surgery
Abstract

Sarcopenia is defined as a loss of muscle mass and strength. Its effects on postoperative outcomes in oncology and geriatrics have already been shown. Approximately 40% of patients in end-stage renal failure are affected with sarcopenia. A recent study suggests that sarcopenia could predict surgical complications after renal transplantation in obese patients. The aim of this study was to evaluate the effect of sarcopenia on parietal complications (eg, wound healing, lymphocele, hematoma).Two indices of muscle fat infiltration (intra-muscular adipose content [IMAC], Hounsfield unit average calculation [HUAC]) and 3 of muscle mass index (total psoas index [TPI], visceral fat area/total abdominal muscle area [VFA/TAMA], and skeletal muscle mass index [SMMI]) were retrospectively measured on pretransplant computed tomography scans for patients undergoing kidney transplantation between 2007 and 2017. Patients were considered sarcopenic when the index was above the third quartile for muscle fat infiltration (IMAC, HUAC) and VFA/TAMA, and under the first quartile for muscle mass (TPI, SMMI). The occurrence of wound healing, collection (hematoma and lymphocele), and acute rejection were compared between sarcopenic and nonsarcopenic patients.Of 484 transplanted patients, 117 patients had a computed tomography scan before transplantation. Patients with a high HUAC had significantly more collections (P = .02) and total parietal complications (P = .09). Patients with a high IMAC had significantly more acute rejection (P = .001).Muscle fat infiltration appears to influence the outcome of renal transplantation. The management of sarcopenia in pretransplantation should be a subject of further research.

Published
2023

26. Association between kinetic of anti-neutrophil cytoplasmic antibody (ANCA), renal survival and relapse risk in ANCA glomerulonephritis

Author

Clément Samoreau, Giorgina Barbara Piccoli, Cécile Martin, Philippe Gatault, Emeline Vinatier, Frank Bridoux, Jérémie Riou, Alice Desouche, Pierre Jourdain, Jean-Philippe Coindre, Samuel Wacrenier, Fanny Guibert, Nicolas Henry, Odile Blanchet, Anne Croué, Assia Djema, Lise-Marie Pouteau, Marie-Christine Copin, Céline Beauvillain, Jean-François Subra, Jean-François Augusto, and Benoit Brilland

Subjects
Transplantation, Nephrology
Abstract

Background Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies have focused on its association with renal prognosis. Thus we aimed to investigate the relationship between ANCA specificity and the evolutive profile and renal outcomes. Methods This multicentric retrospective study included patients diagnosed with ANCA-GN since 1 January 2000. Patients without ANCA at diagnosis and with fewer than three ANCA determinations during follow-up were excluded. We analysed estimated glomerular filtration rate (eGFR) variation, renal-free survival and relapse-free survival according to three ANCA profiles (negative, recurrent and persistent) and to ANCA specificity [myeloperoxidase (MPO) or proteinase 3 (PR3)]. Results Over a follow-up of 56 months [interquartile range (IQR) 34–101], a median of 19 (IQR 13–25) ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free survival (P = .019) and tended to have a lower renal survival (P = .053) compared with those with a negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (P = .015) and those with a recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (P = .013) compared with other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a 2-fold increase in eGFR at 2 years [odds ratio 6.79 (95% confidence interval 1.78–31.4), P = .008]). Conclusion ANCA kinetic after an ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus ANCA kinetics may help identify patients with a smouldering disease.

Published
2022

27. Clusterin Neutralizes the Inflammatory and Cytotoxic Properties of Extracellular Histones

Author

Jean-François Augusto, Céline Beauvillain, Caroline Poli, Léa Paolini, Isabelle Tournier, Pascale Pignon, Simon Blanchard, Laurence Preisser, Raffaella Soleti, Chloé Delépine, Marine Monnier, Isabelle Douchet, Pierre Asfar, François Beloncle, Olivier Guisset, Renaud Prével, Alain Mercat, Emeline Vinatier, Julien Goret, Jean-François Subra, Dominique Couez, Mark R Wilson, Patrick Blanco, Pascale Jeannin, and Yves Delneste

Subjects
Pulmonary and Respiratory Medicine, Critical Care and Intensive Care Medicine
Published
2023

28. Kidney injury molecule 1 (KIM-1): a potential biomarker of acute kidney injury and tubulointerstitial injury in patients with ANCA-glomerulonephritis

Author

Benoît Brilland, Charlotte Boud'hors, Samuel Wacrenier, Simon Blanchard, Jérôme Cayon, Odile Blanchet, Giorgina Barbara Piccoli, Nicolas Henry, Assia Djema, Jean-Philippe Coindre, Pascale Jeannin, Yves Delneste, Marie-Christine Copin, and Jean-François Augusto

Subjects
Transplantation, Nephrology
Abstract

Background Kidney injury molecule 1 (KIM-1) is a transmembrane glycoprotein expressed by proximal tubular cells, recognized as an early, sensitive and specific urinary biomarker for kidney injury. Blood KIM-1 was recently associated with the severity of acute and chronic kidney damage but its value in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis with glomerulonephritis (ANCA-GN) has not been studied. Thus, we analyzed its expression at ANCA-GN diagnosis and its relationship with clinical presentation, kidney histopathology and early outcomes. Methods We assessed KIM-1 levels and other pro-inflammatory molecules (C-reactive protein, interleukin-6, tumor necrosis factor α, monocyte chemoattractant protein-1 and pentraxin 3) at ANCA-GN diagnosis and after 6 months in patients included in the Maine-Anjou registry, which gathers data patients from four French Nephrology Centers diagnosed since January 2000. Results Blood KIM-1 levels were assessed in 54 patients. Levels were elevated at diagnosis and decreased after induction remission therapy. KIM-1 was associated with the severity of renal injury at diagnosis and the need for kidney replacement therapy. In opposition to other pro-inflammatory molecules, KIM-1 correlated with the amount of acute tubular necrosis and interstitial fibrosis/tubular atrophy (IF/TA) on kidney biopsy, but not with interstitial infiltrate or with glomerular involvement. In multivariable analysis, elevated KIM-1 predicted initial estimated glomerular filtration rate (β = –19, 95% CI –31, –7.6, P = .002). Conclusion KIM-1 appears as a potential biomarker for acute kidney injury and for tubulointerstitial injury in ANCA-GN. Whether KIM-1 is only a surrogate marker or is a key immune player in ANCA-GN pathogenesis remain to be determined.

Published
2023

29. Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience

Author

Béranger, Nicolas, Coppo, Paul, Tsatsaris, Vassilis, Boisseau, Pierre, Provôt, François, Delmas, Yahsou, Poullin, Pascale, Vanhoorelbeke, Karen, Veyradier, Agnès, Joly, Bérangère S., Jean-François, Augusto, Elie, Azoulay, Virginie, Barbay, Ygal, Benhamou, Jaccard, Arnaud, Anne, Charvet-Rumpler, Dominique, Chauveau, Gabriel, Choukroun, Jean-Philippe, Coindre, Paul, Coppo, Yahsou, Delmas, Salanoubat, Celia, Antoine, Dossier, Ville, Simon, Véronique, Frémeaux-Bacchi, Lionel, Galicier, Steven, Grangé, Bertrand, Guidet, Jean-Michel, Halimi, Neel, Antoine, Miguel, Hié, Frédéric, Jacobs, Bérangère, Joly, Tarik, Kanouni, Gilles, Kaplanski, Rieu, Virginie, Véronique, Le Guern, Bruno, Moulin, Jean-Michel, Rebibou, Mario, Ojeda Uribe, Nathalie, Parquet, Frédéric, Pène, Pierre, Perez, Pascale, Poullin, Claire, Pouteil-Noble, Claire, Presne, François, Provôt, Mesnard, Laurent, Samir, Saheb, Amélie, Seguin, Aude, Servais, Alain, Stépanian, Agnès, Veyradier, Cécile, Vigneau, Alain, Wynckel, Patricia, Zunic, Thierry, Krummel, Marc, Ulrich, Alexandre, Hertig, Suzon, Benoît, Gilardin, Laurent, Moglie, Le Quintrec, Theresa, Kwon, Valérie, Chatelet, Damien, Ducheyron, Nihal, Martis, Manon, Marie, David, Ribes, and Anne-Marie, Ronchetti

Abstract

•Three distinct entities of pregnancy-onset TTP are singled out: iTTP, uTTP, and cTTP, with fetal outcome closely linked to gestational age.•In the context of pregnancy, most iTTP and uTTP are shown to have an open ADAMTS13 conformation at acute phase.

Published
2024
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31. Immunoglobulin A Vasculitis Following COVID-19: A French Multicenter Case Series

Author

Yanis Ramdani, Jean Marc Galempoix, Jean François Augusto, Eva Dekmeer, Laurent Perard, Nicole Ferreira, Adrien Bigot, Julie Magnant, Stéphanie Jobard, Elisabeth Diot, Marie Charlotte Besse, Hélène Henrique, François Maillot, and Alexandra Audemard-Verger

Subjects
Male, Vasculitis, COVID-19 Vaccines, IgA Vasculitis, SARS-CoV-2, Immunology, COVID-19, Middle Aged, Immunoglobulin A, Rheumatology, Immunology and Allergy, Humans, Female, Retrospective Studies
Abstract

ObjectiveImmunoglobulin A vasculitis (IgAV) usually occurs following viral respiratory tract infection. In the context of the global coronavirus disease 2019 (COVID-19) pandemic, we describe a case series of patients who developed IgAV following SARS-CoV-2 infection.MethodsThis national multicenter retrospective study included patients with IgAV following SARS-CoV-2 infection from January 1, 2020, to January 1, 2022. Patients had histologically proven IgAV and reverse transcription PCR (RT-PCR)-proven SARS-CoV-2 infection. The interval between infection and vasculitis onset had to be < 4 weeks.ResultsWe included 5 patients, 4 of whom were women with a mean age of 45 years. Four patients had paucisymptomatic infections and 1 required a 48-hour low-flow oxygen treatment. All 5 patients had purpuric skin involvement. Arthritis was observed in 2 patients, 3 had IgA glomerulonephritis, and 2 had digestive involvement. Three renal biopsies were performed and showed mesangial IgA deposits without any extracapillary proliferation. Median C-reactive protein was 180 (range 15.1-225) mg/L, median serum creatinine level was 65 (range 41-169) µmol/L, and 2 patients had a glomerular filtration rate < 60 mL/min. Four patients received first-line treatment with glucocorticoids. All patients had a favorable progression and 2 patients experienced minor skin relapses, one after COVID-19 vaccination.ConclusionThis series describes the emergence of IgAV closely following COVID-19; we were not able to eliminate an incidental link between these events. Their disease outcomes were favorable. In most of our patients, the SARS-CoV-2 infection was paucisymptomatic, and we recommend RT-PCR tests to look for COVID-19 in patients without any evident triggers for IgAV.

Published
2022

32. Low Complement C3 Levels at Diagnosis of ANCA-Associated Glomerulonephritis, a Specific Subset of Patients to Target With Anti-C5aR Therapy?

Author

Fanny Guibert, Nicolas Henry, Giorgina Barbara Piccoli, Jean-François Augusto, Benoit Brilland, and Samuel Wacrenier

Subjects
High probability, Kidney, Anca associated glomerulonephritis, business.industry, Glomerulonephritis, Activity index, medicine.disease, medicine.anatomical_structure, Nephrology, Pauci-immune, Immunology, medicine, medicine.symptom, Treatment resistance, Low Complement, business, Letter to the Editor
Published
2021

34. Diagnosis and Risk Factors for Intracranial Aneurysms in Autosomal Polycystic Kidney Disease: A cross-sectional study from the Genkyst Cohort

Author

Siriane, Lefèvre, Marie-Pierre, Audrézet, Jean-Michel, Halimi, Hélène, Longuet, Frank, Bridoux, Laure, Ecotière, Jean-François, Augusto, Agnès, Duveau, Eric, Renaudineau, Cécile, Vigneau, Thierry, Frouget, Christophe, Charasse, Lorraine, Gueguen, Régine, Perrichot, Grégoire, Couvrat, Guillaume, Seret, Yannick, Le Meur, Emilie, Cornec-Le Gall, S, Martin, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CH de Saint-Malo [Broussais], 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre hospitalier Saint-Brieuc, Centre Hospitalier Intercommunal de Cornouaille (CHIC), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Association ECHO [Expansion des Centres d’Hémodialyse de l’Ouest], 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), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Chard-Hutchinson, Xavier

Subjects
Male, subarachnoid hemorrhage, PKD2, PKD1, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Humans, risk factors, genetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, autosomal dominant polycystic kidney disease (ADPKD), Polycystic Kidney Diseases, Transplantation, intracranial aneurysms, Intracranial Aneurysm, Estrogens, Polycystic Kidney, Autosomal Dominant, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, female genital diseases and pregnancy complications, Cross-Sectional Studies, Nephrology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Background Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyse the risk factors associated with the occurrence of IAs in ADPKD patients. Methods A cross-sectional study was performed in 26 nephrology centres from the western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes. Results Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9%, 6.2% and 8.1% at 50, 60 and 70 years, respectively. While this risk appeared to be similar in male and female individuals 2-fold higher in PKD1 compared with PKD2, with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension Conclusions This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of oestrogen.

Published
2022

35. Ifosfamide nephrotoxicity in adult patients

Author

Dominique Nochy, Jean-François Augusto, Rémi Boudet, Gaël Ensergueix, Alexandre Karras, Sophie Chauvet, Eric Thervet, Claire Trivin, Hélène Lazareth, Marie Essig, Charlène Levi, Nicolas Pallet, Dominique Joly, Guy Touchard, and Hail Aboudagga

Subjects
Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Gastroenterology, Nephrotoxicity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, mitochondrial toxicity, AcademicSubjects/MED00340, Acute tubular necrosis, chronic kidney injury, Transplantation, Kidney, Chemotherapy, Ifosfamide, ifosfamide, business.industry, nephrotoxicity, Acute kidney injury, Original Articles, medicine.disease, medicine.anatomical_structure, acute kidney injury, 030220 oncology & carcinogenesis, business, proximal tubular dysfunction, medicine.drug, Kidney disease
Abstract

BackgroundIfosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients.MethodsThe aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity.ResultsWe report 34 patients (median age: 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration.

Published
2019

36. Patients of 75 years and over with ANCA-associated vasculitis have a lower relapse risk than younger patients: A multicentre cohort study

Author

Carole Philipponnet, Christian Pagnoux, R. Mesbah, Claire Blanchard-Delaunay, Guillaume Beinse, Alexandre Karras, Eric Liozon, Jean-François Augusto, Mohamed Hamidou, Sara Thietart, Perrine Smets, Xavier Puéchal, Karim Sacre, Pierre-Louis Carron, Pascal Cohen, François Maurier, Benjamin Terrier, Dimitri Titeca-Beauport, Luc Mouthon, Khalil El Karoui, Alex Kostianovsky, and Loïc Guillevin

Subjects
medicine.medical_specialty, Multivariate analysis, Proportional hazards model, business.industry, Granulomatosis with Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, medicine.disease, Antibodies, Antineutrophil Cytoplasmic, Cohort Studies, Maintenance therapy, Recurrence, Internal medicine, Censoring (clinical trials), Internal Medicine, medicine, Humans, Granulomatosis with polyangiitis, business, Vasculitis, Microscopic polyangiitis, Cohort study, Aged, Retrospective Studies
Abstract

Little is known about antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in older patients. We aim to study relapse risk of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in patients diagnosed after 75 years and compare it with those of patients aged 65-75 years.Data from AAV patients aged ≥65 years were extracted from the French Vasculitis Study Group (FVSG) database and from a call for observation to FVSG members. Cox and Fine-Gray models were used to assess relapse risk, taking death into account either as a censoring or a competing event, respectively.The analysis included 219 patients aged ≥75 years (median 79) and 80 patients aged 65-75 years (median 70), of those 155 had GPA (52%), 136 MPA (45%), with 95 (32%) anti-proteinase 3 positivity and 179 (61%) anti-myeloperoxidase. Patients aged ≥75 years had a lower relapse risk in multivariate analysis (cause-specific hazards ratio [CSHR] 0.54, 95% CI [0.33-0.89], p = 0.016, Cox model; subdistribution hazard ratio [SHR] 0.46, 95% CI [0.29-0.74], p = 0.001, Fine-Gray model) after taking into account vasculitis type. Patients aged ≥75 years had a lower probability of being treated for remission maintenance with a combination of glucocorticoids and immunosuppressants (vs. glucocorticoids alone, HR 0.28, 95% CI [0.11-0.68], p = 0.005) after adjusting to Five Factor Score, although relapse-free survival was significantly longer when receiving such combination (CSHR 0.40, 95% [CI 0.24-0.67], p 0.001).AAV patients ≥75 years have a lower relapse risk than patients aged 65-75 years despite a lower probability of having received maintenance therapy with a combination of glucocorticoids and immunosuppressants, but they still benefit from such treatment regimen.

Published
2021

37. Humoral response to a third injection of BNT162b2 vaccine in patients on maintenance haemodialysis

Author

Marine Dekervel, Marine Asfar, Sophie Blanchi, Virginie Besson, Anne-Sophie Garnier, Giorgina Barbara Piccoli, Lise-Marie Pouteau, Jean-François Augusto, Massimo Torreggiani, Chloé Mellaza, Alexandra Ducancelle, Jean-Paul Imiela, Amaury Dujardin, Nicolas Henry, Axelle Paquin, Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Laval (CH Laval), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie-Dialyse-Transplantation [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)

Subjects
medicine.medical_specialty, SARS-Cov-2, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, immunogenicity, Immunoglobulin G, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Seroconversion, education, AcademicSubjects/MED00340, 030203 arthritis & rheumatology, Transplantation, education.field_of_study, BNT162b2 vaccine, biology, business.industry, Immunogenicity, COVID-19, 3. Good health, Vaccination, haemodialysis, Nephrology, Cohort, biology.protein, Original Article, Antibody, business
Abstract

Background Humoral response against sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after two doses of BNT162b2 (Pfizer-BioNTech) has been proven to be less intense in maintenance dialysis patients as compared with healthy subjects, leading the French authorities to recommend a third injection in this population. Here we investigated the response to the third injection in two cohorts of haemodialysis (HD) patients. Methods Data from two prospective observational cohorts were collected. In the first (‘systematic’) cohort, patients from two HD centres (n = 66) received a third injection of BNT162b2, regardless of the response after two injections. In the second (‘conditional’) cohort, the injection was only prescribed to patients (n = 34) with no or low response to the previous two doses. In both cohorts, the third dose was injected 1–2 months after the second dose. Serology was performed after the second and third doses to assess anti-Spike immunoglobulin G (S IgG) antibody titre. Results In the systematic cohort, anti-S IgG was found in 83.3 and 92.4% of patients after the second and third doses of BNT162b2, respectively. In this cohort, 6/11 (54.5%) and 20/21 (95.2%) patients switched from non-responder to low responder and from low responder to high responder, respectively. In low and high responders to two doses, 50/55 (90.9%) at least doubled their anti-S IgG titre. Similar trends were observed in the conditional cohort. Conclusions In maintenance HD patients, humoral response against SARS-CoV-2 was boosted after a third dose of BNT162b2, allowing seroconversion in more than half of non-responders. These data may support an intensified vaccination protocol with a third dose of BNT162b2 in dialysis patients., Graphical Abstract Graphical Abstract

Published
2021

38. 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

39. Successful treatment of acute kidney allograft rejection using extracorporeal photopheresis in the context of post‐transplant lymphoproliferative diseases: three successive cases

Author

Johnny Sayegh, Jean-François Subra, Jean-François Augusto, Philippe Gatault, Elodie Merieau, Agnès Duveau, Matthias Büchler, Anne-Sophie Garnier, Elodie Bailly, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université d'Angers (UA), and Augusto, jean-françois

Subjects
Graft Rejection, medicine.medical_specialty, extracorporeal photopheresis, education, Urology, kidney transplantation, Context (language use), Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Graft function, fluids and secretions, hemic and lymphatic diseases, Extracorporeal Photopheresis, medicine, Humans, Kidney transplantation, Transplantation, business.industry, Allografts, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Post transplant, surgical procedures, operative, medicine.anatomical_structure, Methylprednisolone, Allograft rejection, Photopheresis, Acute rejection, business, medicine.drug
Abstract

International audience; We reported 3 kidney transplant patients with PTLD who developed mixed AR following IS treatment minimization. AR episodes were treated with extracorporeal photopheresis (ECP), methylprednisolone and IVIG. In all patients, graft function improved under ECP and stabilized in the long term. These observations suggest that ECP is safe and efficient for treatment of AR in the context of PTLD.

Published
2021
Full Text
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40. Impact of aging on phenotype and prognosis in IgA vasculitis

Author

Stanislas Faguer, Noémie Le Gouellec, François Maurier, Bertrand Lioger, Patrice Cacoub, Noémie Jourde-Chiche, Sébastien Sanges, Christian Lavigne, Benjamin Terrier, Julie Goutte, Geoffrey Urbanski, Zahir Amoura, Aurélie Hummel, Evangeline Pillebout, Sophie Deriaz, Loic Raffray, Alban Deroux, Alexandra Audemard-Verger, Elisabeth Diot, Guillaume Moulis, Nicole Feirreira-Maldent, Johan Chanal, François Maillot, A. Baldolli, Loïc Guillevin, Jean-François Augusto, Eric Thervet, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LUNAM Université [Nantes Angers Le Mans], Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), 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 [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Biomarqueurs d’urgence et de réanimation (GRC 14 - BIOSFAST), Sorbonne Université (SU), Centre d'investigation clinique de Toulouse (CIC 1436), 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)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Ambroise Paré [AP-HP], Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), 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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Vasculaire [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Plateforme Histologie, Immunomarquage et Microdissection laser [Institut Cochin] (HistIM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Immunoglobulin A, Adult, Male, Vasculitis, medicine.medical_specialty, Aging, Henoch-Schonlein purpura, Disease, 03 medical and health sciences, IgA vasculitis, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Aged, Retrospective Studies, 030203 arthritis & rheumatology, biology, business.industry, Age Factors, Retrospective cohort study, Middle Aged, medicine.disease, renal involvement, Purpura, 030104 developmental biology, Phenotype, Quartile, age, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biology.protein, outcome, Kidney Failure, Chronic, Female, prognosis, medicine.symptom, business, Henoch–Schönlein purpura
Abstract

Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P 6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.

Published
2021

41. 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

43. Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Author

Sara, Thietart, Alexandre, Karras, Jean-François, Augusto, Carole, Philipponnet, Pierre-Louis, Carron, Xavier, Delbrel, Rafik, Mesbah, Gilles, Blaison, Pierre, Duffau, Khalil, El Karoui, Perrine, Smets, Jonathan, London, Luc, Mouthon, Loïc, Guillevin, Benjamin, Terrier, Xavier, Puéchal, and Stéphane, Vinzio

Subjects
Cohort Studies, Treatment Outcome, Recurrence, Humans, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Female, General Medicine, Rituximab, Glucocorticoids, Aged, Antibodies, Antineutrophil Cytoplasmic
Abstract

Older patients are underrepresented in studies of rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Little is known about outcomes and adverse events associated with the use of rituximab therapy among patients 75 years and older with ANCA-associated vasculitis.To examine outcomes and adverse events associated with the use of rituximab therapy in patients 75 years and older with ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).This multicenter cohort study involved 93 patients 75 years and older with ANCA-associated vasculitis from 36 university and nonuniversity hospitals in France. Data were obtained from the French Vasculitis Study Group database between January 1, 2000, and July 1, 2018, and a call for observation sent to French Vasculitis Study Group members on June 6, 2019. Data analysis was performed from November 15 to December 31, 2021. Inclusion criteria included a diagnosis of GPA or MPA according to European Medicines Agency classification criteria and receipt of treatment with rituximab after age 75 years. Patients were excluded if they were missing relevant clinical or biological data. Data on race and ethnicity were not reported because inclusion of this information was not authorized by the ethics committee.At least 1 infusion of rituximab as induction or maintenance therapy.Occurrence of remission, relapse, drug discontinuation, death, and serious infections (including types of serious infections).Of 238 patients screened, 93 were included (median [IQR] age, 79.4 [76.7-83.1] years; 51 women [54.8%]); 52 patients (55.9%) had a diagnosis of GPA, and 41 (44.1%) had a diagnosis of MPA. Thirty patients (32.3%) received rituximab as induction therapy in combination with high-dose glucocorticoid regimens, 27 (29.0%) received rituximab as maintenance therapy, and 36 (38.7%) received rituximab as both induction and maintenance therapy. The median (IQR) follow-up was 2.3 (1.1-4.0) years. Among 66 patients who received rituximab as induction therapy, 57 (86.4%) achieved remission, and 2 (3.0%) experienced relapses. The incidence of serious infection was significantly higher when rituximab was used as induction therapy vs maintenance therapy (46.6 [95% CI, 24.8-79.7] per 100 patient-years vs 8.4 [95% CI, 3.8-15.9] per 100 patient-years; P = .004). Most infections (12 of 22 [54.5%]) were gram-negative bacterial infections. The incidence of death was 19.7 (95% CI, 7.2-42.9) per 100 patient-years among those who received rituximab as induction therapy and 5.3 (95% CI, 1.9-11.6) per 100 patient-years among those who received rituximab as maintenance therapy.In this cohort study, rituximab therapy was associated with achievement and maintenance of remission in most patients 75 years and older with ANCA-associated vasculitis. The incidence of serious infections and death was high when rituximab was used as induction therapy in combination with high-dose glucocorticoid regimens but not when rituximab was used as maintenance therapy. Efforts might focus on reducing serious infections during the first months of therapy.

Published
2022

44. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP

Author

Jean-François Augusto, Naïke Bigé, Lionel Galicier, Alain Wynckel, Nihal Martis, Michael Bubenheim, Ygal Benhamou, Antoine Dossier, Claire Presne, Elie Azoulay, Virginie Rieu, Agnès Veyradier, Sandrine Malot, François Provôt, Christelle Barbet, Miguel Hie, Amélie Seguin, Sten de Witte, Pascale Poullin, M. Ulrich, Paul Coppo, Thierry Krummel, François Lhote, Yahsou Delmas, Pierre Perez, Anne Charvet Rumpler, Ruben Benainous, Olivier Moranne, Salvy-Córdoba, Nathalie, Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine] (Cnr-mat), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], 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), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [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), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie [Hôpital Albert Calmette], Hôpital Albert Calmette [Lille], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [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)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Brabois, CHU, Partenaires INRAE, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Libourne, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Normandie Université (NU)-Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Compassionate Use Trials, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Combined Modality Therapy, MESH: Von Willebrand Factor, medicine.medical_treatment, Plenary Paper, Salvage therapy, 030204 cardiovascular system & hematology, Severity of Illness Index, Biochemistry, MESH: Historically Controlled Study, 0302 clinical medicine, Adrenal Cortex Hormones, Prospective Studies, Thiamine, Prospective cohort study, MESH: Treatment Outcome, MESH: Middle Aged, Plasma Exchange, MESH: Compassionate Use Trials, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Immunosuppression, Hematology, Middle Aged, MESH: Plasma Exchange, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Combined Modality Therapy, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Treatment Outcome, MESH: Thromboembolism, 030220 oncology & carcinogenesis, Disease Progression, Drug Therapy, Combination, Female, MESH: Disease Progression, Rituximab, MESH: Rituximab, MESH: Hemorrhage, medicine.drug, Adult, medicine.medical_specialty, MESH: Purpura, Thrombotic Thrombocytopenic, Immunology, Thrombotic thrombocytopenic purpura, ADAMTS13 Protein, Hemorrhage, MESH: Single-Domain Antibodies, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, Thromboembolism, MESH: Severity of Illness Index, Internal medicine, von Willebrand Factor, medicine, Humans, MESH: Platelet Count, MESH: ADAMTS13 Protein, Adverse effect, Immunosuppression Therapy, MESH: Humans, Purpura, Thrombotic Thrombocytopenic, Platelet Count, business.industry, Historically Controlled Study, MESH: Adult, Cell Biology, Single-Domain Antibodies, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Drug Therapy, Combination, Regimen, Caplacizumab, business, MESH: Female
Abstract

The anti–von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Published
2021

45. MO259LYMPHOPENIA AT ANCA-GLOMERULONEPHRITIS DIAGNOSIS IS CORRELATED WITH SEVERITY AND RENAL PROGNOSIS

Author

Wacrenier, Samuel, primary, Riou, Jeremie, additional, Jourdain, Pierre, additional, Guibert, Fanny, additional, HENRY, NICOLAS, additional, Assia, DJEMA, additional, Coindre, Jean Philippe, additional, Crochette, Romain, additional, Cousin, Maud, additional, Croue, Anne, additional, Jean François, SUBRA, additional, Piccoli, Giorgina, additional, Jean François, AUGUSTO, additional, and Brilland, Benoit, additional

Published
2021
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46. Lymphopaenia at diagnosis of anti-neutrophil cytoplasmic antibody-vasculitis with renal involvement is correlated with severity and renal prognosis

Author

Giorgina Barbara Piccoli, Assia Djema, Samuel Wacrenier, Fanny Guibert, Pierre Jourdain, Jean-François Augusto, Jean-François Subra, Benoit Brilland, Romain Crochette, Jean-Philippe Coindre, Jérémie Riou, Nicolas Henry, Anne Croue, and Maud Cousin

Subjects
0301 basic medicine, Nephrology, medicine.medical_specialty, Lymphocyte, Renal function, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Kidney, Gastroenterology, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Lymphopenia, medicine, Humans, Retrospective Studies, 030203 arthritis & rheumatology, Transplantation, Anca vasculitis, business.industry, Glomerulonephritis, medicine.disease, Prognosis, 030104 developmental biology, medicine.anatomical_structure, Biomarker (medicine), Kidney Failure, Chronic, Vasculitis, business, Kidney disease
Abstract

Background Lymphopaenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) only a few small-scale studies have been targeted towards this issue. Research has not yet focused on AAV with renal involvement (AAV-RI). Thus the aim of this study was to analyse the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients. Methods We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French nephrology centres, recorded since January 2000. We analysed clinical, biological and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analysed. Event-free survival was also assessed. Results Among the 145 patients included in the study, those with lymphopaenia at diagnosis had a lower renal function at baseline [estimated glomerular filtration rate (eGFR) 13 versus 26 mL/min; P = 0.002] and were more likely to require kidney replacement therapy (51% versus 25%; P = 0.003). Lymphopaenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (P = 0.0027). ESKD-free survival was lower in lymphopaenic patients (P Conclusions Lymphopaenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopaenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis.

Published
2021

47. Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes

Author

Nora Schwotzer, Noémie Jourde-Chiche, Fadi Fakhouri, Simon Ville, Jean-François Augusto, Awena Le Fur, Hélène Perrochia, Laurent Daniel, Jean-Michel Goujon, Stanislas Bataille, Viviane Gnemmi, Sébastien Kissling, François Provôt, Samuel Rotman, Moglie Le Quintrec, Anne Moreau, Alexandre Karras, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), 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), 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 d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), 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 universitaire de Poitiers (CHU Poitiers), Prémilleux, Annick, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CHU Montpellier, and Hôpital Lapeyronie [Montpellier] (CHU)

Subjects
Nephrology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030204 cardiovascular system & hematology, Myelodysplastic syndromes, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Clinical Research, Internal medicine, medicine, Minimal change disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, acute tubulointerstitial nephritis, autoimmunity, myelodysplastic syndromes, business.industry, Acute kidney injury, Glomerulonephritis, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV] Life Sciences [q-bio], IgA vasculitis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract

Introduction Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients. Methods We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres. Results Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman’s capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died. Conclusions MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN., Graphical abstract

Published
2020

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

Author

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

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

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

Published
2020

49. Incidence and Risk Factors of Venous Thromboembolic Events in Patients with ANCA-Glomerulonephritis: A Cohort Study from the Maine-Anjou Registry

Author

Jean-François Augusto, Nicolas Henry, Virginie Besson, Jean-François Subra, Maud Cousin, Jean-Philippe Coindre, Samuel Wacrenier, Anne Sophie Garnier, Giorgina Barbara Piccoli, Assia Djema, Renaud Gansey, Agnès Duveau, Benoit Brilland, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Le Mans (CH Le Mans), CH Cholet, Centre Hospitalier de Laval (CH Laval), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
medicine.medical_specialty, venous thromboembolism, lcsh:Medicine, ANCA glomerulonephritis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, Lower risk, Article, statins, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, risk factor, Internal medicine, Medicine, cardiovascular diseases, Risk factor, 10. No inequality, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, Univariate analysis, business.industry, Incidence (epidemiology), lcsh:R, General Medicine, medicine.disease, equipment and supplies, 3. Good health, Rituximab, business, Vasculitis, Cohort study, medicine.drug
Abstract

(1) Introduction: The incidence of venous thromboembolisms (VTE) has not been extensively analyzed in patients with antineutrophil cytoplasmic antibody (ANCA)-glomerulonephritis (ANCA-GN). Thus, the aim of the present study was to assess the frequency and the risk factors of VTE in patients with ANCA-GN. (2) Methods: Patients from the Maine-Anjou ANCA-associated vasculitis (AAV) registry with a biopsy showing pauci-immune glomerulonephritis were included. VTE events, site, and interval from AAV diagnosis were analyzed. (3) Results: 133 patients fulfilled the inclusion criteria of the study and were analyzed. VTE episodes were diagnosed in 23/133 (17.3%) patients at a median delay of 3 months from ANCA-GN diagnosis. Patients with VTE had lower serum albumin (p = 0.040), were less frequently on statin therapy (p = 0.009) and had less frequently proteinase-3 (PR3)-ANCAs (p = 0.078). Univariate analysis identified higher age (p = 0.022), lower serum albumin (p = 0.030), lack of statin therapy (p = 0.009), and rituximab treatment (p = 0.018) as significant risk factors of VTE. In multivariate analysis, only lack of statin therapy (HR 4.873, p = 0.042) was significantly associated with VTE. (4) Conclusion: Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. Our results suggest that statin therapy is associated with a lower risk of VTE in ANCA-GN patients.

Published
2020

50. Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study

Author

Benoit Brilland, Nicolas Fage, Maud Cousin, Jean-François Augusto, François Beloncle, Chloé Mellaza, Corentin Orvain, Franck Geneviève, Guillaume Legendre, Agnès Duveau, Virginie Besson, Jean-François Subra, Nicolas Henry, and Anne-Sophie Garnier

Subjects
medicine.medical_specialty, HELLP syndrome, etiology, Thrombotic thrombocytopenic purpura, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Atypical hemolytic uremic syndrome, primary, Medicine, real-life, thrombotic thrombocytopenic purpura, Original Research, lcsh:R5-920, business.industry, Retrospective cohort study, General Medicine, Odds ratio, medicine.disease, ADAMTS13, Transplantation, 030220 oncology & carcinogenesis, Etiology, hemolytic uremic syndrome, Thrombotic microangiopathies, business, lcsh:Medicine (General), secondary
Abstract

Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice.Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes.Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death.Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.

Published
2020

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