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1. Success of Pregnancy in a Patient on High-Volume Hemodiafiltration with Citrate-Acidified Dialysate

Author

Gaelle Pelle, Arwa Jalal Eddine, Philippe Rieu, Julie Attias, Stephanie Fay, and Alexandre Hertig

Subjects
pregnancy, dialysis, high-volume online hemodiafiltration, citrate, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Although pregnancy in dialysis patients is rare, recent reports in the literature have shown improvement in pregnancy outcome in this population. Increasing doses of dialysis have led to improvement in fetal prognosis, but recommendations are still lacking, and there are few documented reports of pregnant woman on high-volume online hemodiafiltration. Here, we report the first successful pregnancy in a 28-year-old patient on daily high-volume online post-dilution hemodiafiltration with a citrate dialysate. At 37 weeks and 1 day, she delivered a healthy 2.3 kg baby that did not require neonatal intensive care. This case report suggests that hemodiafiltration with a dialysate acidified with citrate is safe in pregnancy. Further reports and a registry are necessary to confirm that high-volume online hemodiafiltration with a citrate dialysate should be the preferred dialysis modality in pregnant women.

Published
2023
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2. Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease

Author

Pauline Caillard, Cécile Vigneau, Jean-Michel Halimi, Marc Hazzan, Eric Thervet, Morgane Heitz, Laurent Juillard, Vincent Audard, Marion Rabant, Alexandre Hertig, Jean-François Subra, Vincent Vuiblet, Dominique Guerrot, Mathilde Tamain, Marie Essig, Thierry Lobbedez, Thomas Quemeneur, Mathieu Legendre, Alexandre Ganea, Marie-Noëlle Peraldi, François Vrtovsnik, Maïté Daroux, Raïfah Makdassi, Gabriel Choukroun, and Dimitri Titeca-Beauport

Subjects
anti-glomerular basement membrane disease, complement C3, C3 glomerular deposits, kidney biopsy, kidney prognosis, kidney survival, Immunologic diseases. Allergy, RC581-607
Abstract

Background and objectivesActivation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease.MethodsWe conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3

Published
2023
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3. Conversion to belatacept after lung transplantation: Report of 10 cases.

Author

Olivier Brugière, Alexandre Vallée, Quentin Raimbourg, Marie-Noelle Peraldi, Sylvie Colin de Verdière, Laurence Beaumont, Abdulmonem Hamid, Mathilde Zrounba, Antoine Roux, Clément Picard, François Parquin, Matthieu Glorion, Julie Oniszczuk, Alexandre Hertig, Hervé Mal, and Vincent Bunel

Subjects
Medicine, Science
Abstract

BackgroundCalcineurin inhibitors (CNIs) remain the cornerstone of maintenance immunosuppression (IS) after lung transplantation (LTx), although CNI-related life-threatening toxic effects may occur. Belatacept, a novel immunosuppressant that blocks a T-cell co-stimulation pathway, is a non-nephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, there are only a few reports of belatacept conversion as a CNI-free or CNI-sparing IS treatment.MethodsWe reviewed a series of 10 LTx recipients with conversion to a CNI-free belatacept IS regimen within the first year post-LTx (n = 7) or a belatacept/low-dose CNI combination after the first year (n = 3).ResultsUse of belatacept was triggered by severe renal failure in 9 patients and under-IS with previous other IS-related toxicities in 1 patient. Mean estimated glomerular filtration rate after starting belatacept significantly improved at 6 months after initiation and at the last-follow-up (p = 0.006, and p = 0.002 respectively). The incidence of recurrent and/or severe acute cellular rejection (ACR) episodes was high in patients with CNI-free belatacept-based IS (n = 4/7). Chronic graft allograft dysfunction developed in 2 of 9 recipients under belatacept IS. Belatacept was stopped in 6 patients because of recurrent/severe ACR (n = 3), recurrent opportunistic infections (n = 1), center modified policy (n = 1), or other cause (n = 1).ConclusionEarly conversion to CNI-free belatacept-based IS improved renal function in this series but was counterbalanced by a high incidence of recurrent ACR, including life-threatening episodes. Other studies are needed to better determine the indications for its use after LTx, possibly with lower immunological risk IS regimens, such as CNI-sparing belatacept.

Published
2023
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4. Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Author

Aude Gibelin, Guillaume Dumas, Sandrine Valade, Marc Pineton de Chambrun, François Bagate, Mathilde Neuville, Francis Schneider, Loredana Baboi, Matthieu Groh, Jean-Herlé Raphalen, Jean-Daniel Chiche, Nicolas De Prost, Charles-Edouard Luyt, Claude Guérin, Eric Maury, Etienne de Montmollin, Alexandre Hertig, Antoine Parrot, Raphaël Clere-Jehl, and Muriel Fartoukh

Subjects
Vasculitis, Diffuse alveolar hemorrhage, Intensive care, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.

Published
2021
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5. Shiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017

Author

Benoît Travert, Antoine Dossier, Matthieu Jamme, Aurélie Cointe, Yahsou Delmas, Sandrine Malot, Alain Wynckel, Amélie Seguin, Claire Presne, Miguel Hie, Ygal Benhamou, David Ribes, Gabriel Choukroun, Steven Grangé, Alexandre Hertig, Emilie Cornec Le Gall, Lionel Galicier, Eric Daugas, Lila Bouadma, François-Xavier Weill, Elie Azoulay, Fadi Fakhouri, Agnès Veyradier, Stéphane Bonacorsi, Julien Hogan, Véronique Frémeaux-Bacchi, Eric Rondeau, Patricia Mariani-Kurkdjian, and Paul Coppo

Subjects
hemolytic uremic syndrome, Shiga toxin, thrombotic microangiopathy, Escherichia coli, E. coli, bacteria, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin–producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009–2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

Published
2021
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6. Plasticity of natural killer cells in pregnant patients infected with SARS-CoV-2 and their neonates during childbirth

Author

Marie Carbonnel, Camille Daclin, Nadine Tarantino, Olivia Groiseau, Véronique Morin, Alice Rousseau, Marc Vasse, Alexandre Hertig, Titouan Kennel, Jean Marc Ayoubi, and Vincent Vieillard

Subjects
natural killer cells, pregnancy, neonates, SARS-CoV-2, COVID-19, Immunologic diseases. Allergy, RC581-607
Abstract

The COVID-19 pandemic has occurred due to infection caused by the SARS-CoV-2 coronavirus, which impacts gestation and pregnancy. In SARS-CoV-2 infection, only very rare cases of vertical transmission have been reported, suggesting that fetal immune imprinting due to a maternal infection is probably a result of changes in maternal immunity. Natural killer (NK) cells are the leading maternal immune cells that act as a natural defense system to fight infections. They also play a pivotal role in the establishment and maintenance of pregnancy. While peripheral NK cells display specific features in patients infected with SARS-CoV-2 in the general population, information remains elusive in pregnant mothers and neonates. In the present study, we analyzed the characteristics of NK cells isolated from both neonatal umbilical cord blood and maternal peripheral blood close to the time of delivery. Phenotype and functions were compared in 18 healthy pregnant women and 34 COVID-19 patients during pregnancy within an ongoing infection (PCR+; N = 15) or after recovery (IgG+PCR−; N = 19). The frequency of NK cells from infected women and their neonates was correlated with the production of inflammatory cytokines in the serum. The expression of NKG2A and NKp30, as well as degranulation of NK cells in pregnant women with ongoing infection, were both negatively correlated to estradiol level. Furthermore, NK cells from the neonates born to infected women were significantly decreased and also correlated to estradiol level. This study highlights the relationship between NK cells, inflammation, and estradiol in patients with ongoing infection, providing new insights into the impact of maternal SARS-CoV-2 infection on the neonate.

Published
2022
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7. Severe HELLP syndrome masquerading as thrombocytopenic thrombotic purpura: a case report

Author

Cyril Mousseaux, Bérangère S. Joly, Inna Mohamadou, Romain Arrestier, Alexandre Hertig, and Cédric Rafat

Subjects
Acute liver failure, HELLP syndrome, Therapeutic plasma exchange, Thrombotic microangiopathy, Thrombotic thrombocytopenic purpura, Case report, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Thrombotic microangiopathies (TMAs) occurring in the postpartum period may be difficult to manage. They present as the combination of mechanical hemolytic anemia and consumption thrombocytopenia due to endothelial dysfunction. The cause of this endothelial aggression can be multiple: thrombocytopenic thrombotic purpura (TTP), HELLP syndrome, antiphospholipid syndrome, atypical hemolytic and uremic syndrome or acute fatty liver of pregnancy. TTP results from a severe deficiency of ADAMTS13, which is a protease cleaving specifically von Willebrand factor chiefly produced by liver cells. There are two main causes, the production of anti-ADAMTS13 auto-antibodies and, more rarely, a genetic deficiency in ADAMTS13. First-line treatment is based on plasma exchange. HELLP syndrome occurs in the third trimester of pregnancy usually in association with preeclampsia and represents a form of TMA characterized by damage to the sinusoidal capillaries of the liver. Prompt delivery is the main treatment. We present a case illustrating the challenges in discriminating between different postpartum TMAs, with a focus on the distinction between TTP and HELLP syndrome. Specifically, we highlight how acute liver failure (ALF) stemming from HELLP may lead to TTP with a spectacular response to plasma exchanges. Case A 28-year-old, 33 + 4 weeks pregnant woman presented with severe preeclampsia complicated by ALF in the setting of partial liver necrosis, disseminated intravascular coagulation, microangiopathic hemolytic anemia and acute kidney injury. Greatly diminished levels of ADAMTS13 (

Published
2020
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8. Cell stress response impairs de novo NAD+ biosynthesis in the kidney

Author

Yohan Bignon, Anna Rinaldi, Zahia Nadour, Virginie Poindessous, Ivan Nemazanyy, Olivia Lenoir, Baptiste Fohlen, Pierre Weill-Raynal, Alexandre Hertig, Alexandre Karras, Pierre Galichon, Maarten Naesens, Dany Anglicheau, Pietro E. Cippà, and Nicolas Pallet

Subjects
Metabolism, Nephrology, Medicine
Abstract

The biosynthetic routes leading to de novo nicotinamide adenine dinucleotide (NAD+) production are involved in acute kidney injury (AKI), with a critical role for quinolinate phosphoribosyl transferase (QPRT), a bottleneck enzyme of de novo NAD+ biosynthesis. The molecular mechanisms determining reduced QPRT in AKI, and the role of impaired NAD+ biosynthesis in the progression to chronic kidney disease (CKD), are unknown. We demonstrate that a high urinary quinolinate-to-tryptophan ratio, an indirect indicator of impaired QPRT activity and reduced de novo NAD+ biosynthesis in the kidney, is a clinically applicable early marker of AKI after cardiac surgery and is predictive of progression to CKD in kidney transplant recipients. We also provide evidence that the endoplasmic reticulum (ER) stress response may impair de novo NAD+ biosynthesis by repressing QPRT transcription. In conclusion, NAD+ biosynthesis impairment is an early event in AKI embedded with the ER stress response, and persistent reduction of QPRT expression is associated with AKI to CKD progression. This finding may lead to identification of noninvasive metabolic biomarkers of kidney injury with prognostic and therapeutic implications.

Published
2022
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9. B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization

Author

David Cucchiari, Valeria Tubita, Jordi Rovira, Maria J. Ramirez-Bajo, Elisenda Banon-Maneus, Marta Lazo-Rodriguez, Natalia Hierro-Garcia, Francesc E. Borràs, Pedro Ventura-Aguiar, Gastón J. Piñeiro, Jaume Martorell, Lluís Peri, Mireia Musquera, Alexandre Hertig, Federico Oppenheimer, Josep M. Campistol, Fritz Diekmann, and Ignacio Revuelta

Subjects
B cells, kidney transplantation, desensitization, HLA-incompatibility, extracellular vesicles (EV), exosomes, Medicine (General), R5-920
Abstract

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs).Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization.Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable.Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting.

Published
2021
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10. Immunosuppressive Treatment in Children With IgA Nephropathy and the Clinical Value of Podocytopathic Features

Author

Alexandra Cambier, Marion Rabant, Michel Peuchmaur, Alexandre Hertig, Georges Deschenes, Cecile Couchoud, Anne Kolko, Remi Salomon, Julien Hogan, and Thomas Robert

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: There is a need for treatment guidelines and prognostic factor identification in children with primary IgA nephropathy. We analyzed the causative effect of steroids and the applicability of the Oxford classification. Methods: A total of 82 consecutive children (mean 10.6 years; median follow-up 3.3 years) were reviewed; 21 patients (25.6%) presented with acute kidney injury, and 6 (7.3%) with nephrotic syndrome. Renal biopsies were scored for Oxford classification and podocytopathic features in 2 groups: a group treated with steroid therapy (some in association with cyclophosphamide) and supportive care (renin angiotensin system blockade) and a group treated by supportive care alone. Results: The 2 groups were not comparable because baseline clinical data were different. Estimated glomerular filtration rate (eGFR) in immunosupressive group significantly improved between M0 (at onset) and M6 (6 months after treatment) from 89.9 [61.2–114.5] to 110.5 [93.7–120] ml/min per 1.73 m2, P

Published
2018
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11. Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury

Author

Aurélien Bataille, Pierre Galichon, Nadjim Chelghoum, Badreddine Mohand Oumoussa, Marie-Julia Ziliotis, Iman Sadia, Sophie Vandermeersch, Noémie Simon-Tillaux, David Legouis, Raphaël Cohen, Yi-Chun Xu-Dubois, Morgane Commereuc, Eric Rondeau, Stéphane Le Crom, and Alexandre Hertig

Subjects
Acute Kidney Injury, Epithelium, Fibrosis, Chronic Kidney Disease, Fatty Acid Oxidation, Physiology, QP1-981, Biochemistry, QD415-436
Abstract

Background/Aims: Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this decrease was a strong determinant of renal fibrogenesis, hence a focus for therapeutic interventions. Nevertheless, whether persistently differentiated renal tubules, surviving in a pro-fibrotic environment, also suffer from a decrease in FAO, is currently unknown. Methods: To address this question, we isolated proximal tubules captured ex vivo on the basis of the expression of an intact brush border antigen (Prominin-1) in C57BL6/J mice subjected to a controlled, two-hit model of renal fibrosis (reversible ischemic acute kidney injury (AKI) or sham surgery, followed by angiotensin 2 administration). A transcriptomic high throughput sequencing was performed on total mRNA from these cells, and on whole kidneys. Results: In contrast to mice subjected to sham surgery, mice with a history of AKI displayed histologically more renal fibrosis when exposed to angiotensin 2. High throughput RNA sequencing, principal component analysis and clustering showed marked consistency within experimental groups. As expected, FAO transcripts were decreased in whole fibrotic kidneys. Surprisingly, however, up- rather than down-regulation of metabolic pathways (oxidative phosphorylation, fatty acid metabolism, glycolysis, and PPAR signalling pathway) was a hallmark of the differentiated tubules captured from fibrotic kidneys. Immunofluorescence co-staining analysis confirmed that the expression of FAO enzymes was dependent of tubular trophicity. Conclusions: These data suggest that in differentiated proximal tubules energetic hyperactivity is promoted concurrently with organ fibrogenesis.

Published
2018
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12. Red urine, updated for the nephrologist: a case report

Author

Alexandre Le Joncour, Laurent Mesnard, Alexandre Hertig, and Thomas Robert

Subjects
Sickle cell trait, Hematuria, Kidney concentrating ability, Proteinuria, Kidney papillary necrosis, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Sickle cell trait is not completely benign, and some renal complications can occur. The baseline rate of admission for gross hematuria in normal males carrying the sickle cell trait is 2%. Case presentation A 35-year-old non-smoking African man experienced a 2-week history of painless, profuse and persistent gross hematuria. Laboratory tests showed normal renal function, hematuria and mild proteinuria. Abdominal ultrasonography and computed tomography angiography revealed no renal abnormalities; the bladder appeared pristine under cystoscopy. The diagnosis of sickle cell trait associated with gross hematuria was made using hemoglobin electrophoresis; renal biopsy and its complications were avoided. Urine was clear after 2 weeks of oral hydration and gamma epsilon-aminocaproic acid. Conclusion Hemoglobin electrophoresis should be performed in cases of gross hematuria. Coupled with other non-invasive evaluation, this could avoid renal biopsy and its associated complications.

Published
2018
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13. Prognostic Factors in Anti-glomerular Basement Membrane Disease: A Multicenter Study of 119 Patients

Author

Cindy Marques, Julien Carvelli, Lucie Biard, Stanislas Faguer, François Provôt, Marie Matignon, Jean-Jacques Boffa, Emmanuelle Plaisier, Alexandre Hertig, Maxime Touzot, Olivier Moranne, Xavier Belenfant, Djillali Annane, Thomas Quéméneur, Jacques Cadranel, Hassan Izzedine, Nicolas Bréchot, Patrice Cacoub, Alexis Piedrafita, Noémie Jourde-Chiche, and David Saadoun

Subjects
anti-glomerular basement membrane disease, Goodpasture's disease, glomerulonephritis, vasculitis, outcome, mortality, Immunologic diseases. Allergy, RC581-607
Abstract

We report the overall and renal outcome in a French nationwide multicenter cohort of 119 patients with anti-glomerular basement membrane (anti-GBM) disease. Sixty-four patients (54%) had an exclusive renal involvement, 7 (6%) an isolated alveolar hemorrhage and 48 (40%) a combined renal and pulmonary involvement. Initial renal replacement therapy (RRT) was required in 78% of patients; 82% received plasmapheresis, 82% cyclophosphamide, and 9% rituximab. ANCA positive (28%) patients were older (70 vs. 47 years, p < 0.0001), less frequently smokers (26 vs. 54%, p = 0.03), and had less pulmonary involvement than ANCA- patients. The 5 years overall survival was 92%. Risk factors of death (n = 11, 9.2%) were age at onset [HR 4.10 per decade (1.89–8.88) p = 0.003], hypertension [HR 19.9 (2.52–157 0.2) p = 0.005], dyslipidemia [HR 11.1 (2.72–45) p = 0.0008], and need for mechanical ventilation [HR 5.20 (1.02–26.4) p = 0.047]. The use of plasmapheresis was associated with better survival [HR 0.29 (0.08–0.98) p = 0.046]. At 3 months, 55 (46%) patients had end-stage renal disease (ESRD) vs. 37 (31%) ESRD-free and 27 (23%) unevaluable with follow-up < 3 months. ESRD patients were older, more frequently female and had a higher serum creatinine level at presentation than those without ESRD. ESRD-free survival was evaluated in patients alive without ESRD at 3 months (n = 37) using a landmark approach. In conclusion, this large French nationwide study identifies prognosis factors of renal and overall survival in anti-GBM patients.

Published
2019
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14. Lymphocyte-depleting induction and steroid minimization after kidney transplantation: A review

Author

Maarten Naesens, Stefan Berger, Luigi Biancone, Marta Crespo, Arjang Djamali, Alexandre Hertig, Robert Öllinger, José Portolés, Andreas Zuckermann, and Julio Pascual

Subjects
Induction, Depletion, Steroid sparing, Steroid avoidance, Kidney transplantation, ATG, Rabbit antithymocyte globulin, Thymoglobulin, Alemtuzumab, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular risk factors, improved growth in pediatric patients, and improved compliance with the immunosuppression regimen. Steroid avoidance (i.e. no steroids after the first week) is generally favored compared to later withdrawal. Induction therapy is routine in this setting, frequently rabbit antithymocyte globulin (rATG, Thymoglobulin®) or off-license use of alemtuzumab. Direct comparisons of steroid minimization regimens versus standard steroid regimens are rare. However, the available data show that the risk of acute rejection is low when rATG or alemtuzumab induction is given to support steroid-avoidance regimens after kidney transplantation. Steroid avoidance may be inadvisable in patients at high immunological risk or at risk of recurrent glomerular disease. Steroid withdrawal after day 8 may be possible without additional risk of rejection in patients given rATG induction, but while encouraging, the data are too sparse for firm conclusions. In summary, steroid avoidance may be beneficial for patients after renal transplantation, with the potential to avoid or reduce steroid-related comorbidities. Whilst depleting induction therapy could be the treatment of choice, results of prospective randomized, controlled studies are eagerly awaited.

Published
2016
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15. Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

Author

Adrien Joseph, Aurélie Cointe, Patricia Mariani Kurkdjian, Cédric Rafat, and Alexandre Hertig

Subjects
shiga toxin, escherichia coli, hemolytic uremic syndrome, thrombotic microangiopathy, Medicine
Abstract

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure.

Published
2020
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16. 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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18. Notch3 expression in capillary pericytes predicts worse graft outcome in human renal grafts with antibody‐mediated rejection

Author

Yichun Xu‐Dubois, Panagiotis Kavvadas, Zela Keuylian, Alexandre Hertig, Eric Rondeau, and Christos Chatziantoniou

Subjects
Graft Rejection, Inflammation, Biopsy, Endothelial Cells, Humans, Molecular Medicine, Cell Biology, Pericytes, Receptor, Notch3, Antibodies, Biomarkers
Abstract

Microvasculature consisting of endothelial cells and pericytes is the main site of injury during antibody-mediated rejection (ABMR) of renal grafts. Little is known about the mechanisms of activation of pericytes in this pathology. We have found recently that activation of Notch3, a mediator of vascular smooth muscle cell proliferation and dedifferentiation, promotes renal inflammation and fibrosis and aggravates progression of renal disease. Therefore, we studied the pericyte expression of Notch3 in 49 non-selected renal graft biopsies (32 for clinical cause, 17 for graft surveillance). We analysed its relationship with patients' clinical and morphological data, and compared with the expression of partial endothelial mesenchymal transition (pEndMT) markers, known to reflect endothelial activation during ABMR. Notch3 was de novo expressed in pericytes of grafts with ABMR, and was significantly correlated with the microcirculation inflammation scores of peritubular capillaritis and glomerulitis and with the expression of pEndMT markers. Notch3 expression was also associated with graft dysfunction and proteinuria at the time of biopsy and in the long term. Multivariate analysis confirmed pericyte expression of Notch3 as an independent risk factor predicting graft loss. These data suggest that Notch3 is activated in the pericytes of renal grafts with ABMR and is associated with poor graft outcome.

Published
2022

19. 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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20. Insuffisance rénale aiguë chez la femme enceinte

Author

Alexandre Hertig, Marie Carbonnel, and Charles Cerf

Subjects
Emergency Medicine, Emergency Nursing
Abstract

La prise en charge en réanimation des complications rénales graves observées chez la femme enceinte ou immédiatement après la délivrance implique de connaître la grande susceptibilité de l’endothélium maternel induite par la présence d’un placenta sécrétant, notamment, des facteurs anti-angiogéniques. Le mécanisme le plus fréquent de l’insuffisance rénale aiguë observée au décours de complications obstétricales graves (préeclampsie sévère, hémorragie de la délivrance, embolie amniotique…) est de loin la nécrose tubulaire aiguë, vraisemblablement ischémique. La plus grande difficulté est le diagnostic différentiel des insuffisances rénales aiguës contemporaines du HELLP syndrome (Hemolysis Enzyme Liver Low Platelets), car c’est une microangiopathie thrombotique : d’autres causes existent, qui sont exceptionnelles mais qui imposent de bien mesurer l’effet du temps, et de considérer des traitements beaucoup plus spécifiques que la seule délivrance du placenta.

Published
2022

21. Long-term health-related quality of life outcomes of adults with pediatric onset of frequently relapsing or steroid-dependent nephrotic syndrome

Author

Antoine Durrbach, Philippe Zaoui, Aurélie Bourmaud, Olivia Boyer, Alexandre Hertig, Olivier Fritz, Isabelle Tostivint, Agnès Dumas, Vincent L.M. Esnault, Alain Wynckel, Jacques Dantal, Moglie Le Quintrec, S. Guilmin-Crépon, Dominique Chauveau, Dil Sahali, Corinne Alberti, Dominique Guerrot, Claire Dossier, Marie-Sophie Meuleman, Stéphane Burtey, Alexandre Karras, Claire Rigothier, François Provôt, Philippe Remy, Eric Daugas, Karine Dahan, Vincent Audard, Hélène Mellerio, Marie-Pascale Morin, Aurélie Hummel, Ziad A. Massy, Fallou Leye, CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Toulouse [Toulouse], 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 Conception [CHU - APHM] (LA CONCEPTION), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Ambroise Paré [AP-HP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], CHU Pontchaillou [Rennes], CHU Grenoble, Centre Hospitalier de La Rochelle (CHR), 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), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Necker - Enfants Malades [AP-HP], CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Urgences néphrologiques et transplantation rénale [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP]

Subjects
Adult, Male, Quality of life, Pediatrics, medicine.medical_specialty, Nephrotic Syndrome, Multivariate analysis, Population, Family life, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Education, Idiopathic nephrotic syndrome, Recurrence, medicine, Humans, Prospective Studies, Long-term outcomes, Child, education, Prospective cohort study, Fatigue, education.field_of_study, business.industry, Standardized mortality ratio, Socioprofessional status, Nephrology, Marital status, Female, Steroids, business, Psychosocial, Immunosuppressive Agents
Abstract

International audience; Background: Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined.Methods: In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being.Results: In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32 years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = - 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS.Conclusions: This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.

Published
2021

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

Author

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

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

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

Published
2021

23. Lessons from the impact of COVID-19 on medical educational continuity and practices

Author

Alexandre Hertig, Alain Carrié, Noémie Simon-Tillaux, Marie-Christine Renaud, Isabelle Jéru, and Camille Vatier

Subjects
020205 medical informatics, Physiology, Distance education, Curriculum Development and Assessment, 02 engineering and technology, Computer-assisted web interviewing, Education, Digital media, Likert scale, 03 medical and health sciences, 0302 clinical medicine, 0202 electrical engineering, electronic engineering, information engineering, ComputingMilieux_COMPUTERSANDEDUCATION, 030212 general & internal medicine, Set (psychology), Curriculum, Multiple choice, Medical education, teachers, business.industry, COVID-19, General Medicine, undergraduate student, Scale (social sciences), digital resources, business, Psychology, remote learning
Abstract

The COVID-19 crisis necessitated abrupt transition to remote learning in medical schools. We aimed to assess the impact of COVID-19 on French undergraduate students and teachers, to identify practice changes, and to evaluate successes and areas for improvement of this remote learning experience. Data from 2 online questionnaires were analyzed with 509 participants among students and 189 among teachers from Sorbonne University. Responses to multiple choice, Likert response scale, and open-ended questions were evaluated. COVID-19 had negative impact on teaching continuity. Sixty-seven percent of students were in a dropout situation, and many suffered from psychological stress, leading to set up of a psychological support unit. Although most teachers (81%) and students (72%) had limited knowledge of digital resources, distance learning was quickly implemented, with a predominant use of Zoom. The analysis of several parameters revealed that students were significantly more satisfied than teachers by remote learning. Nevertheless, both students and teachers agreed to replace classical lectures by digital media and to promote in-person teaching in small interactive groups. This paper shares tips for faculty rapidly establishing remote learning. This comparative study of the students’ and teachers’ points of view underlines that new medical curricula should include more digital contents. We make recommendations regarding general university organization, equipment, and curricular development for long-term implementation of digital resources with reinforced relationships between faculty and students.

Published
2021

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

Author

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

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

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

Published
2021

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

Author

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

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

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

Published
2022

26. Are script concordance tests suitable for the assessment of undergraduate students? A multicenter comparative study

Author

Damien Roux, Alexandre Hertig, Olivier Palombi, Marie-Christine Renaud, Zahir Amoura, Thomas Papo, Alexandre Duguet, M. Braun, Olivier Steichen, and F. Cohen Aubart

Subjects
medicine.medical_specialty, Students, Medical, 020205 medical informatics, Concordance, Gastroenterology, Clinical reasoning, Reproducibility of Results, 02 engineering and technology, Test (assessment), 03 medical and health sciences, 0302 clinical medicine, 0202 electrical engineering, electronic engineering, information engineering, Internal Medicine, medicine, Humans, Medical physics, Clinical Competence, Educational Measurement, 030212 general & internal medicine, Psychology, Reliability (statistics), Education, Medical, Undergraduate, Multiple choice
Abstract

Introduction Script concordance tests (SCTs) have been developed to assess clinical reasoning in uncertain situations. Their reliability for the evaluation of undergraduate medical students has not been evaluated. Methods Twenty internal medicine SCT cases were implemented in undergraduate students of two programs. The results obtained on the SCTs were compared to those obtained by the same students on clinical-based classical multiple-choice questions (MCQs). Results A total of 551/883 students (62%) answered the SCTs. The mean aggregate score (based on a total 20 points) was 11.54 (3.29). The success rate and mean score for each question did not differ depending on the modal response but the discrimination rate did. The results obtained by the students on the SCT test correlated with their scores on the MCQ tests. Among students, 446/517 (86%) considered the SCTs to be more difficult than classical MCQs, although the mean score did not differ between the SCT and MCQ tests. Conclusion The use of SCTs is a feasible option for the evaluation of undergraduate students. The SCT scores correlated with those obtained on classical MCQ tests.

Published
2021

27. Shiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017

Author

Stéphane Bonacorsi, Matthieu Jamme, Alexandre Hertig, Elie Azoulay, David Ribes, Lila Bouadma, François-Xavier Weill, Julien Hogan, Aurélie Cointe, Antoine Dossier, Alain Wynckel, Eric Daugas, Benoit Travert, Agnès Veyradier, Yahsou Delmas, Patricia Mariani-Kurkdjian, Paul Coppo, Eric Rondeau, Gabriel Choukroun, Claire Presne, Miguel Hie, Emilie Cornec-Le Gall, Lionel Galicier, Steven Grangé, Sandrine Malot, Ygal Benhamou, Fadi Fakhouri, Véronique Frémeaux-Bacchi, and Amélie Seguin

Subjects
food-borne infections, Epidemiology, medicine.medical_treatment, Shiga toxin–producing Escherichia coli, Infectious and parasitic diseases, RC109-216, 0302 clinical medicine, 030212 general & internal medicine, bacteria, Immunodeficiency, Escherichia coli Infections, biology, Shiga-Toxigenic Escherichia coli, Hazard ratio, Shiga toxin, Eculizumab, thrombotic microangiopathy, STEC, food safety, Infectious Diseases, Cohort, Medicine, France, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Thrombotic microangiopathy, 030231 tropical medicine, 03 medical and health sciences, Internal medicine, medicine, Escherichia coli, Humans, HUS, Dialysis, Retrospective Studies, business.industry, Research, enteric infections, E. coli, Retrospective cohort study, medicine.disease, Shiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017, Hemolytic-Uremic Syndrome, biology.protein, hemolytic uremic syndrome, business
Abstract

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

Published
2021

28. Recovery of kidney function in patients treated with maintenance dialysis—a report from the ERA-EDTA Registry

Author

Julia Kerschbaum, Lucile Mercadal, Anders Åsberg, Marlies Noordzij, Carmen Santiuste de Pablos, Runolfur Palsson, Alexandre Hertig, Anneke Kramer, Samira Bell, Carmen Díaz-Corte, Manuel Benítez Sánchez, Lily Jakulj, Jaakko Helve, Mustafa Arici, Marc H Hemmelder, Ziad A. Massy, Kitty J Jager, Johan De Meester, Frederic Collart, HUS Abdominal Center, Nefrologian yksikkö, Department of Medicine, Nephrology, Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Quality of Care, APH - Methodology, APH - Global Health, and ACS - Diabetes & metabolism

Subjects
medicine.medical_specialty, medicine.medical_treatment, Renal function, Kidney, maintenance dialysis, Peritoneal dialysis, INITIATION, Renal Dialysis, Internal medicine, recovery of kidney function, medicine, Humans, FAILURE, Registries, PREDICTORS, Dialysis, Aged, PERITONEAL-DIALYSIS, OUTCOMES, Transplantation, business.industry, MYELOMA, Hazard ratio, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, Discontinuation, haemodialysis, medicine.anatomical_structure, peritoneal dialysis, Nephrology, 3121 General medicine, internal medicine and other clinical medicine, SURVIVAL, Kidney Failure, Chronic, Hemodialysis, business, RENAL-FUNCTION RECOVERY, Kidney disease
Abstract

Background Literature on recovery of kidney function (RKF) in patients with end-stage kidney disease treated with maintenance dialysis (i.e. >90 days) is limited. We assessed the incidence of RKF and its associated characteristics in a European cohort of dialysis patients. Methods We included adult patients from the European Renal Association–European Dialysis and Transplant Association Registry who started maintenance dialysis in 1997–2016. Sustained RKF was defined as permanent discontinuation of dialysis. Temporary discontinuation of ≥30 days (non-sustained RKF) was also evaluated. Factors associated with RKF adjusted for potential confounders were studied using Cox regression analyses. Results RKF occurred in 7657 (1.8%) of 440 996 patients, of whom 71% experienced sustained RKF. Approximately 90% of all recoveries occurred within the first 2 years after Day 91 of dialysis. Of patients with non-sustained RKF, 39% restarted kidney replacement therapy within 1 year. Sustained RKF was strongly associated with the following underlying kidney diseases (as registered by the treating physician): tubular necrosis (irreversible) or cortical necrosis {adjusted hazard ratio [aHR] 20.4 [95% confidence interval (CI) 17.9–23.1]}, systemic sclerosis [aHR 18.5 (95% CI 13.8–24.7)] and haemolytic uremic syndrome [aHR 17.3 (95% CI 13.9–21.6)]. Weaker associations were found for haemodialysis as a first dialysis modality [aHR 1.5 (95% CI 1.4–1.6)] and dialysis initiation at an older age [aHR 1.8 (95% CI 1.6–2.0)] or in a more recent time period [aHR 2.4 (95% CI 2.1–2.7)]. Conclusions Definitive discontinuation of maintenance dialysis is a rare and not necessarily an early event. Certain clinical characteristics, but mostly the type of underlying kidney disease, are associated with a higher likelihood of RKF.

Published
2020

29. [Nutritionnal complications and patients follow-up after bariatric surgery]

Author

Alexandre, Nuzzo, Sébastien, Czernichow, Alexandre, Hertig, Séverine, Ledoux, Tigran, Poghosyan, Didier, Quilliot, Maude, Le Gall, André, Bado, and Francisca, Joly

Subjects
Weight Loss, Bariatric Surgery, Humans, Follow-Up Studies, Obesity, Morbid
Abstract

NUTRITIONNAL COMPLICATIONS AND PATIENTS FOLLOW-UP AFTER BARIATRIC SURGERYBariatric surgery is the most consistently effective method for sustained weight reduction and can result in a substantial improvement in overall survival in patients with severe obesity. Complex mechanisms underlying metabolic benefits could also drive preventable, but potentially life-threatening, long-term nutritional complications. Consequently, physicians should be familiar with the lifelong monitoring of patients after bariatric surgery and the potential long-term complications in this paradoxical situation where the long-awaited weight loss can lead to severe nutritional complications.COMPLICATIONS NUTRITIONNELLES DE LA CHIRURGIE BARIATRIQUE ET SURVEILLANCE DES PATIENTS OPÉRÉS La chirurgie bariatrique est le traitement le plus efficace en termes de perte pondérale durable et de réduction de la morbi-mortalité en cas d’obésité sévère. Cependant, les modifications profondes de la physiologie digestive qui sous-tendent ces bénéfices métaboliques peuvent entraîner des carences nutritionnelles qui peuvent induire des complications sévères et irréversibles. La population des patients bariatriques étant en constante augmentation, tout médecin peut être amené à prendre un charge un patient opéré. Il devrait donc connaître les principes de la surveillance à vie et les possibles complications à long terme dans cette situation si paradoxale où la perte de poids tant attendue peut aussi s’associer à des carences potentiellement sévères.

Published
2022

30. Transplantation Outcome in Recipients Engrafted With Organs Recovered From the First French Deceased Donor With a SARS-COV-2 Vaccine-induced Thrombotic Thrombocytopenia

Author

Yanish Soorojebally, Caroline Pettenati, Mathilde Lefebvre, Thibaut d'Izarny Gargas, Albane Sartorius-Brodin, Michel Delahousse, Alexandre Hertig, Matthieu Jamme, Mickael Vourc'h, Filomena Conti, Ismail Elalamy, Marion Rabant, Sophie Ferlicot, Adrien Tissot, and Eva Desire

Subjects
Transplantation, 2019-20 coronavirus outbreak, Deceased donor, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Donor selection, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Treatment outcome, Organ transplantation, Immunology, Medicine, business
Published
2021

31. Clinical and histological differences between adults and children in new onset IgA nephropathy

Author

Alexandra Cambier, Alexandre Hertig, Rémi Salomon, Thomas Robert, Michel Peuchmaur, Marion Rabant, Aude Servais, Georges Deschênes, Khalil El Karoui, and Julien Hogan

Subjects
Adult, Male, Nephrology, medicine.medical_specialty, Tubular atrophy, Biopsy, Kidney Glomerulus, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Interstitial fibrosis, Severity of Illness Index, Gastroenterology, Nephropathy, New onset, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Child, Glucocorticoids, Retrospective Studies, Kidney, Proteinuria, medicine.diagnostic_test, Glomerulosclerosis, Focal Segmental, business.industry, Age Factors, Glomerulonephritis, IGA, medicine.disease, Treatment Outcome, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Follow-Up Studies, Glomerular Filtration Rate
Abstract

Previous reports suggest initial presentation of IgA nephropathy (IgAN) in children is different from adults. No systematic comparison of clinical, biological, and histological childhood- and adult-onset IgAN is currently available. We compared pediatric and adult clinical and histological characteristics at IgAN diagnosis. Data on 211 consecutive patients from two different centers in Paris (82 children, 129 adults) were reviewed. Kidney biopsies were scored for Oxford classification and podocytopathic (P1) features. We report higher eGFR at diagnosis in children compared to adults (89.5 vs. 64 ml/min/1.73 m2; p = 0.0001) but no difference in proteinuria. Histological analysis of kidney biopsy found higher proportions of mesangial (M1) and endocapillary (E1) hypercellularity in children compared with adults (M1 [80.7% vs. 27.9%, p = 0.0001]; E1 [71.3% vs. 30%, p = 0.0001]). Focal glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis ≥ 25% (T1), and P1 were more frequent in adults (S1 [81.5% vs. 61.3%, p = 0.0012], T1 [49.5% vs. 1.35%, p = 0.0001], P1 [33.8% vs. 16.4%, p = 0.008). Proteinuria associated with M1, E1, and C1 in children (M1, p = 0.0001; E1, p = 0.0005; C1, p = 0.0014) but S1, P1, and T1 in adults (S1, p = 0.0001; P1, p = 0.0001; T1, p = 0.001). After steroid treatment (41 children and 28 adults), proteinuria decreased in children (p < 0.001, follow-up 38 months) and adults (p < 0.001, follow-up 76.9 months), whereas eGFR remained stable in adults but increased significantly in children (90.6 to 110 ml/min/1.73m2). Proteinuria in children with IgAN is a marker of glomerular proliferative lesions whereas its presence in adults often reflects the presence of chronic lesions. This suggests the need for histological assessment.

Published
2020

32. Acute interstitial nephritis: aetiology and management

Author

Juliet Schurder, Eric Thervet, David Buob, Alexandre Karras, Peggy Perrin, and Alexandre Hertig

Subjects
Transplantation, Acute interstitial nephritis, Pathology, medicine.medical_specialty, Kidney, business.industry, MEDLINE, medicine.anatomical_structure, Nephrology, Acute Disease, medicine, Etiology, Humans, Nephritis, Interstitial, business
Published
2020

33. Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Author

François Bagate, Matthieu Groh, Etienne de Montmollin, Aude Gibelin, Alexandre Hertig, Loredana Baboi, Guillaume Dumas, Mathilde Neuville, Raphaël Clere-Jehl, Charles-Edouard Luyt, Francis Schneider, Eric Maury, Jean-Herlé Raphalen, Nicolas de Prost, Muriel Fartoukh, Marc Pineton de Chambrun, Sandrine Valade, Claude Guérin, Jean-Daniel Chiche, Antoine Parrot, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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], CHU Henri Mondor, Hôpital Foch [Suresnes], CHU Necker - Enfants Malades [AP-HP], Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de Réanimation Médicale [CHU Pitié-Salpétrière], 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 Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Réanimation Médicale [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), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Service d'Anesthésie réanimation [CHU Tenon], Gestionnaire, HAL Sorbonne Université 5, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Département de Néphrologie [CHU Tenon] (Néphrologie et dialyse), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de Pneumologie, Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S)

Subjects
Vasculitis, medicine.medical_specialty, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Acute respiratory failure, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Anesthesiology, Intensive care, medicine, 030212 general & internal medicine, RC86-88.9, Proportional hazards model, business.industry, Diffuse alveolar hemorrhage, Research, Medical emergencies. Critical care. Intensive care. First aid, Immunosuppression, Retrospective cohort study, medicine.disease, Intensive care unit, 3. Good health, 030228 respiratory system, Etiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract

Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.

Published
2021

34. 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

35. Reply to Morje et al

Author

Camille Vatier, Marie-Christine Renaud, Isabelle Jéru, Alexandre Hertig, Alain Carrié, and Noémie Simon-Tillaux

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Physiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), General Medicine, Sociology, Virology, Letter to the Editor, Education
Published
2021

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

Author

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

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

International audience

Published
2021

37. Markers of graft microvascular endothelial injury may identify harmful donor-specific anti-HLA antibodies and predict kidney allograft loss

Author

Alexandre Hertig, Matthieu Jamme, Jean-Luc Taupin, Nacera Ouali, Eric Rondeau, Isabelle Brocheriou, Yi-Chun Xu-Dubois, Marie Audouin, Chantal Jouanneau, Yosu Luque, David Buob, and Kevin Louis

Subjects
Graft Rejection, Male, Pathology, Biopsy, Vimentin, 030230 surgery, Kidney, 0302 clinical medicine, HLA Antigens, Immunology and Allergy, Pharmacology (medical), Renal Insufficiency, biology, medicine.diagnostic_test, Histocompatibility Testing, Microfilament Proteins, Middle Aged, Allografts, Tissue Donors, medicine.anatomical_structure, Immunohistochemistry, Female, Antibody, Adult, Reoperation, medicine.medical_specialty, Human leukocyte antigen, Antibodies, Endothelial activation, 03 medical and health sciences, Complement C4b, medicine, Humans, HSP47 Heat-Shock Proteins, Aged, Antilymphocyte Serum, Retrospective Studies, Fascin, Transplantation, business.industry, Microcirculation, Kidney Transplantation, Peptide Fragments, body regions, biology.protein, Endothelium, Vascular, Carrier Proteins, business, Biomarkers, Follow-Up Studies
Abstract

Graft microvasculature is a major target of donor-specific antibodies (DSA) and endothelial damage is direct evidence of antibody-mediated rejection (ABMR). Using immunohistochemistry, we analyzed the expression of three microvascular endothelial activation markers (fascin, vimentin, and hsp47), suggestive of endothelial-to-mesenchymal transition (EndMT) in 351 graft biopsies from 248 kidney recipients, with concomitant screening of circulating antihuman leukocyte antigen (HLA) DSA at the time of the biopsy. The factors associated with EndMT marker expression were DSA and the presence of microvascular inflammation (MI). EndMT expressing grafts had significantly more allograft loss compared to EndMT negative grafts (P < .0001). The expression of EndMT markers positively correlated with anti-HLA DSA class II mean fluorescence intensity (MFI) levels and especially identified DQ and DR antibodies as being more closely associated with microvascular injury. Moreover, only DSA linked to positive EndMT score affected allograft survival, regardless of DSA MFI levels or presence of C4d deposition. Thus, EndMT markers could represent a clinically relevant tool for early identification of ongoing endothelial injury, harmful DSA, and patients at high risk for allograft failure.

Published
2019

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

Author

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

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

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

Published
2019

39. Timing of Renal Replacement Therapy for Severe Acute Kidney Injury in Critically Ill Patients

Author

Didier Dreyfuss, David Hajage, Jean-Pierre Quenot, Saber Barbar, Jean-Damien Ricard, Stéphane Gaudry, and Alexandre Hertig

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Hyperkalemia, medicine.medical_treatment, Renal function, urologic and male genital diseases, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, 030212 general & internal medicine, Renal replacement therapy, Intensive care medicine, business.industry, Acute kidney injury, medicine.disease, Pulmonary edema, female genital diseases and pregnancy complications, 030228 respiratory system, Observational study, medicine.symptom, business, Watchful waiting
Abstract

Acute kidney injury (AKI) affects many ICU patients and is responsible for increased morbidity and mortality. Although lifesaving in many situations, renal replacement therapy (RRT) may be associated with complications, and the appropriate timing of its initiation is still the subject of intense debate. An early initiation strategy can prevent some metabolic complications, whereas a delayed one may allow for renal function recovery in some patients without need for this costly and potentially dangerous technique. For years, most of the knowledge on this issue stemmed from observational studies or small randomized controlled trials. Recent randomized controlled trials have indicated that a watchful waiting strategy (in the absence of life-threatening conditions such as severe hyperkalemia or pulmonary edema) during severe AKI allowed many patients to escape RRT and did not seem to adversely affect survival compared with a strategy of immediate RRT. In addition, data suggest that a delayed strategy may reduce the rate of complications (such as catheter infection) and favor renal function recovery. Ongoing studies will have to both confirm these conclusions and clarify to what extent the delay in initiating RRT can be prolonged. Pending those results, the bulk of evidence suggests that, in the absence of potential severe complications of AKI, delaying RRT is a valid and safe strategy that may also allow for considerable cost savings.

Published
2019

40. Post-partum acute kidney injury: sorting placental and non-placental thrombotic microangiopathies using the trajectory of biomarkers

Author

Luc Frimat, Alain Wynckel, Vassilis Tsatsaris, Cédric Rafat, Anne-Sophie Ducloy-Bouthors, Jean-Michel Rebibou, Julien Darmian, Jérôme Lambert, Alexandre Hertig, Mercedes Jourdain, Matthieu Jamme, François Provôt, Véronique Frémeaux-Bacchi, Eric Rondeau, Yahsou Delmas, Paul Coppo, Fleuria Meibody, and Pierre Perez

Subjects
Adult, medicine.medical_specialty, Thrombotic microangiopathy, Placenta, 030232 urology & nephrology, Thrombotic thrombocytopenic purpura, urologic and male genital diseases, Gastroenterology, Preeclampsia, 03 medical and health sciences, 0302 clinical medicine, Renal cortical necrosis, Pregnancy, Internal medicine, Intensive care, Atypical hemolytic uremic syndrome, medicine, Humans, 030212 general & internal medicine, Retrospective Studies, Transplantation, Platelet Count, Thrombotic Microangiopathies, business.industry, Postpartum Period, Acute kidney injury, Acute Kidney Injury, medicine.disease, Haemolysis, female genital diseases and pregnancy complications, Nephrology, Female, business, Biomarkers
Abstract

Background Among the severe complications of preeclampsia (PE), acute kidney injury (AKI) is problematic if features of thrombotic microangiopathy (TMA) are present. Although a haemolysis enzyme liver low-platelets syndrome is considerably more frequent, it is vital to rule out a flare of atypical haemolytic and uraemic syndrome (aHUS). Our objective was to improve differential diagnosis procedures in post-partum AKI. Methods A total of 105 cases of post-partum AKI, admitted to nine different regional French intensive care units from 2011 to 2015, were analysed. Analysis included initial and final diagnosis, renal features, haemostasis and TMA parameters, with particular focus on the dynamics of each component within the first days following delivery. A classification and regression tree (CART) was used to construct a diagnostic algorithm. Results AKI was attributed to severe PE (n = 40), post-partum haemorrhage (n = 33, including 13 renal cortical necrosis) and ‘primary’ TMA (n = 14, including 10 aHUS and 4 thrombotic thrombocytopenic purpura). Congruence between initial and final diagnosis was low (63%). The dynamics of haemoglobin, haptoglobin and liver enzymes were poorly discriminant. In contrast, the dynamic pattern of platelets was statistically different between primary TMA-related AKI and other groups. CART analysis independently highlighted the usefulness of platelet trajectory in the diagnostic algorithm. Limitations of this study include that only the most severe cases were included in this retrospective study, and the circumstantial complexity is high. Conclusion Trajectory of platelet count between admission and Day 3 helps to guide therapeutic decisions in cases of TMA-associated post-partum AKI. Our study also strongly suggests that during the post-partum period, there may be a risk of transient, slowly recovering TMA in cases of severe endothelial injury in women without a genetic mutation known to induce aHUS.

Published
2019

42. LDL-apheresis to decrease sFlt-1 during early severe preeclampsia: Report of two cases from a discontinued phase II trial

Author

Jean Guibourdenche, Samir Saheb, Eric Rondeau, Anthony Corchia, Cédric Rafat, Marie Bornes, Vassilis Tsatsaris, Bassam Haddad, Camille Petit-Hoang, Alexandre Hertig, Guillaume Lefèvre, Edouard Lecarpentier, Thomas Robert, Tabassome Simon, Alexandra Rousseau, Frederic Richard, CHI Créteil, Service de gynécologie et obstétrique [Créteil], Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
Adult, medicine.medical_specialty, Gestational Age, sFlt-1, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030204 cardiovascular system & hematology, Preeclampsia, Sepsis, 03 medical and health sciences, Fatal Outcome, 0302 clinical medicine, Pre-Eclampsia, Pregnancy, LDL-apheresis, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Vascular Endothelial Growth Factor Receptor-1, business.industry, Obstetrics, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, medicine.disease, 3. Good health, Lipoproteins, LDL, Apheresis, Reproductive Medicine, LDL apheresis, Hypertension, Blood Component Removal, Premature Birth, Gestation, Female, business
Abstract

International audience; Objective: Severe preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival.Study Design: A phase II prospective study. Adult women were included if they had very early (

Published
2018

43. Development of a practical prediction score for chronic kidney disease after cardiac surgery

Author

Anne Boutten, J-L Hanouz, Matthieu Jamme, Sophie Provenchère, Pierre Galichon, D Buklas, David Legouis, and Alexandre Hertig

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Operative Time, Renal function, Renal Insufficiency, Chronic/diagnosis/etiology, 030204 cardiovascular system & hematology, urologic and male genital diseases, Risk Assessment, law.invention, Cohort Studies, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, law, Internal medicine, Cardiopulmonary bypass, Humans, Medicine, Cardiac Surgical Procedures, Renal Insufficiency, Chronic, Aged, Retrospective Studies, Cardiopulmonary Bypass, Framingham Risk Score, ddc:617, business.industry, Age Factors, Acute kidney injury, Postoperative Complications/diagnosis, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Cardiac Surgical Procedures/adverse effects, Cardiac surgery, 030104 developmental biology, Anesthesiology and Pain Medicine, Cohort, Female, business, Forecasting, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract

Background: Chronic kidney disease (CKD) is a frequent and serious complication of cardiac surgery. This study was designed to establish a scoring system, calculated in the immediate postoperative period, to assess the risk of CKD at 1 yr in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: We conducted a cohort study including patients with preoperative estimated glomerular filtration rate above 60 ml min-1 (1.73 m)-2 who underwent cardiac surgery with cardiopulmonary bypass. We identified risk factors for de novo CKD at 1 yr using logistic regression. We derived a risk score for CKD, and externally validated this score in a second cohort. Results: The incidence of CKD was 18% and 23% in the derivation and validation cohorts, respectively. We developed a scoring system that included (i) the occurrence of postoperative acute kidney injury according to the Kidney Disease: Improving Global Outcomes criteria, (ii) age older than 65 yr, (iii) preoperative glomerular filtration rate

Published
2018

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

Author

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

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

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

Published
2021

45. Prevention and treatment of nutritional complications after bariatric surgery

Author

Didier Quilliot, Séverine Ledoux, Alexandre Nuzzo, Maude Le Gall, Alexandre Hertig, Sébastien Czernichow, André Bado, Francisca Joly, Tigran Poghosyan, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris Cité (UPCité), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier

Subjects
medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Gastrointestinal Diseases, Population, MEDLINE, Bariatric Surgery, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Metabolic Diseases, Weight loss, Intervention (counseling), Pandemic, Weight Loss, medicine, Humans, education, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, Hepatology, business.industry, Public health, Malnutrition, Gastroenterology, Severe obesity, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Obesity, 3. Good health, Surgery, Obesity, Morbid, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.symptom, business
Abstract

International audience; Obesity and the corresponding burden of related diseases is a major public health issue worldwide that is reaching pandemic proportions. Bariatric surgery is the only intervention that has been shown to result in substantial and lasting weight loss, and a decrease in overall mortality for patients with severe obesity. Consequently, the population of patients having undergone this procedure is increasing. Multifactorial weight-dependent and independent mechanisms underlying metabolic diseases could also drive preventable, but potentially life-threatening, long-term nutritional complications. However, given post-bariatric patients are prone to functional gastrointestinal symptoms and substantial weight loss, nutritional complications might be challenging. This Review is focused on the prevention and treatment of nutritional complications after bariatric surgery in the clinical setting.

Published
2021

46. 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

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

Author

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

Subjects
Graft Survival, Humans, Multicenter Studies as Topic, Transplants, Hypothermia, General Medicine, Kidney, Kidney Transplantation, Tissue Donors, Randomized Controlled Trials as Topic
Abstract

IntroductionExpanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysisHYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and disseminationThe trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration numberNCT03098706.

Published
2022

48. Author Correction: Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality

Author

Sandrine Placier, David Legouis, Pierre-Yves Martin, Maarten Naesens, Karim Gariani, Sophie de Seigneux, Anna Faivre, Sven-Erick Ricksten, Kari Koppitch, Alexandre Hertig, Marylise Fernandez, Jérôme Pugin, Charles Verney, Lena Berchtold, Andrew P. McMahon, Thomas Verissimo, Pietro E. Cippà, Pierre Galichon, and Eric Féraille

Subjects
medicine.medical_specialty, Tubular cell, business.industry, Endocrinology, Diabetes and Metabolism, Acute kidney injury, Cell Biology, Carbohydrate metabolism, medicine.disease, Endocrinology, Physiology (medical), Internal medicine, Internal Medicine, medicine, business
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

49. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality

Author

Andrew P. McMahon, Maarten Naesens, Karim Gariani, Pietro E. Cippà, Eric Féraille, Pierre Galichon, Sven-Erick Ricksten, Marylise Fernandez, Pierre-Yves Martin, Lena Berchtold, Jérôme Pugin, Anna Faivre, Thomas Verissimo, Sophie de Seigneux, Charles Verney, Sandrine Placier, Kari Koppitch, David Legouis, and Alexandre Hertig

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Renal function, Carbohydrate metabolism, urologic and male genital diseases, OXYGEN, VIVO, Endocrinology & Metabolism, HYPOGLYCEMIA, Physiology (medical), Internal medicine, Internal Medicine, medicine, ddc:612, RENAL-REPLACEMENT THERAPY, ddc:616, THIAMINE-DEFICIENCY, SLICES, Kidney, Renal circulation, Science & Technology, ddc:617, business.industry, urogenital system, Acute kidney injury, Cell Biology, Metabolism, GLUCONEOGENESIS, medicine.disease, female genital diseases and pregnancy complications, Endocrinology, medicine.anatomical_structure, Gluconeogenesis, Thiamine, business, Life Sciences & Biomedicine
Abstract

Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance are impaired during human and experimental AKI by using renal arteriovenous catheterization in patients, lactate tolerance testing in mice and glucose isotope labelling in rats. Single-cell transcriptomics reveal that gluconeogenesis is impaired in proximal tubule cells during AKI. In a retrospective cohort of critically ill patients, we demonstrate that altered glucose metabolism during AKI is a major determinant of systemic glucose and lactate levels and is strongly associated with mortality. Thiamine supplementation increases lactate clearance without modifying renal function in mice with AKI, enhances glucose production by renal tubular cells ex vivo and is associated with reduced mortality and improvement of the metabolic pattern in a retrospective cohort of critically ill patients with AKI. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism under stress conditions, delineates general mechanisms of AKI-associated mortality and introduces a potential intervention targeting metabolism for a highly prevalent clinical condition with limited therapeutic options. ispartof: NATURE METABOLISM vol:2 issue:8 pages:732-+ ispartof: location:Germany status: published

Published
2020

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