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La COVID-19 est une affection due à un virus à ARN, le SARS-CoV-2. Elle se caractérise par une atteinte touchant essentiellement l’appareil respiratoire. Il existe une atteinte rénale qui se caractérise par trois atteintes principales, une nécrose tubulaire aiguë survenant dans les cas les plus sévères, une tubulopathie proximale, qui est un marqueur pronostique de la maladie, et une hyalinose segmentaire et focale survenant sur un terrain génétiquement prédisposé. La physiopathologie de l’atteinte rénale du SARS-CoV-2 n’est pas encore définie. Le rôle direct du virus est discuté alors que la tempête cytokinique et les complications hypoxiques et thrombotiques semblent plus importantes. Le devenir à long terme des atteintes rénales paraît plutôt bon. Un suivi à long terme permettra de dire si l’atteinte rénale fait partie du COVID long. COVID-19 is a disease caused by the RNA virus SARS-CoV-2. It is characterised by an attack mainly affecting the respiratory system. There is renal involvement which is characterised by three main types of damage, acute tubular necrosis occurring in the most severe cases, proximal tubulopathy which is a prognostic marker of the disease and segmental and focal hyalinosis occurring in a genetically predisposed terrain. The pathophysiology of SARS-CoV-2 renal involvement is not yet defined. The direct role of the virus is debated, whereas the cytokine storm and the hypoxic and thrombotic complications seem more important. The long-term outcome of the renal damage appears to be quite good. Long-term follow-up will allow us to say whether the renal damage is part of the long COVID.
Stéphane Burtey; Marion Sallée. Les atteintes rénales de la COVID-19. Néphrologie & Thérapeutique 2021, 17, 203 -207.
AMA StyleStéphane Burtey, Marion Sallée. Les atteintes rénales de la COVID-19. Néphrologie & Thérapeutique. 2021; 17 (4):203-207.
Chicago/Turabian StyleStéphane Burtey; Marion Sallée. 2021. "Les atteintes rénales de la COVID-19." Néphrologie & Thérapeutique 17, no. 4: 203-207.
Background Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)–dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats. Methods Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49. Results Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67). Conclusions 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.
Mickaël Bobot; Guillaume Hache; Anaïs Moyon; Samantha Fernandez; Laure Balasse; Laurent Daniel; Philippe Garrigue; Pauline Brige; Sophie Chopinet; Françoise Dignat-George; Philippe Brunet; Stéphane Burtey; Benjamin Guillet. Renal SPECT/CT with 99mTc–dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency. Nephrology Dialysis Transplantation 2020, 36, 804 -810.
AMA StyleMickaël Bobot, Guillaume Hache, Anaïs Moyon, Samantha Fernandez, Laure Balasse, Laurent Daniel, Philippe Garrigue, Pauline Brige, Sophie Chopinet, Françoise Dignat-George, Philippe Brunet, Stéphane Burtey, Benjamin Guillet. Renal SPECT/CT with 99mTc–dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency. Nephrology Dialysis Transplantation. 2020; 36 (5):804-810.
Chicago/Turabian StyleMickaël Bobot; Guillaume Hache; Anaïs Moyon; Samantha Fernandez; Laure Balasse; Laurent Daniel; Philippe Garrigue; Pauline Brige; Sophie Chopinet; Françoise Dignat-George; Philippe Brunet; Stéphane Burtey; Benjamin Guillet. 2020. "Renal SPECT/CT with 99mTc–dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency." Nephrology Dialysis Transplantation 36, no. 5: 804-810.
Background: Daily management to shield chronic dialysis patients from SARS-CoV-2 contamination makes patient care cumbersome. There are no screening methods to date and a molecular biology platform is essential to perform RT-PCR for SARS-CoV-2; however, accessibility remains poor. Our goal was to assess whether the tools routinely used to monitor our hemodialysis patients could represent reliable and quickly accessible diagnostic indicators to improve the management of our hemodialysis patients in this pandemic environment. Methods: In this prospective observational diagnostic study, we recruited patients from La Conception hospital. Patients were eligible for inclusion if suspected of SARS-CoV-2 infection when arriving at our center for a dialysis session between March 12th and April 24th 2020. They were included if both RT-PCR result for SARS-CoV-2 and cell blood count on the day that infection was suspected were available. We calculated the area under the curve (AUC) of the receiver operating characteristic curve. Results: 37 patients were included in the final analysis, of which 16 (43.2%) were COVID-19 positive. For the day of suspected COVID-19, total leukocytes were significantly lower in the COVID-19 positive group (4.1 vs. 7.4 G/L, p = 0.0072) and were characterized by lower neutrophils (2.7 vs. 5.1 G/L, p = 0.021) and eosinophils (0.01 vs. 0.15 G/L, p = 0.0003). Eosinophil count below 0.045 G/L identified SARS-CoV-2 infection with AUC of 0.9 [95% CI 0.81—1] (p < 0.0001), sensitivity of 82%, specificity of 86%, a positive predictive value of 82%, a negative predictive value of 86% and a likelihood ratio of 6.04. Conclusions: Eosinophil count enables rapid routine screening of symptomatic chronic hemodialysis patients suspected of being COVID-19 within a range of low or high probability.
Romain Vial; Marion Gully; Mickael Bobot; Violaine Scarfoglière; Philippe Brunet; Dammar Bouchouareb; Ariane Duval; He-Oh Zino; Julien Faraut; Océane Jehel; Yaël Berdad-Haddad; Stéphane Burtey; Pierre-André Jarrot; Guillaume Lano; Thomas Robert. Triage of Patients Suspected of COVID-19 in Chronic Hemodialysis: Eosinophil Count Differentiates Low and High Suspicion of COVID-19. Journal of Clinical Medicine 2020, 10, 4 .
AMA StyleRomain Vial, Marion Gully, Mickael Bobot, Violaine Scarfoglière, Philippe Brunet, Dammar Bouchouareb, Ariane Duval, He-Oh Zino, Julien Faraut, Océane Jehel, Yaël Berdad-Haddad, Stéphane Burtey, Pierre-André Jarrot, Guillaume Lano, Thomas Robert. Triage of Patients Suspected of COVID-19 in Chronic Hemodialysis: Eosinophil Count Differentiates Low and High Suspicion of COVID-19. Journal of Clinical Medicine. 2020; 10 (1):4.
Chicago/Turabian StyleRomain Vial; Marion Gully; Mickael Bobot; Violaine Scarfoglière; Philippe Brunet; Dammar Bouchouareb; Ariane Duval; He-Oh Zino; Julien Faraut; Océane Jehel; Yaël Berdad-Haddad; Stéphane Burtey; Pierre-André Jarrot; Guillaume Lano; Thomas Robert. 2020. "Triage of Patients Suspected of COVID-19 in Chronic Hemodialysis: Eosinophil Count Differentiates Low and High Suspicion of COVID-19." Journal of Clinical Medicine 10, no. 1: 4.
Background Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD). Methods We conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality. Results Among the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses. Conclusions COVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.
Guillaume Lano; Antoine Braconnier; Stanislas Bataille; Guilhem Cavaille; Julie Moussi-Frances; Bertrand Gondouin; Pascal Bindi; Magued Nakhla; Janette Mansour; Pascale Halin; Bénédicte Levy; Eric Canivet; Khaled Gaha; Isabelle Kazes; Natacha Noel; Alain Wynckel; Alexandre Debrumetz; Noemie Jourde-Chiche; Valerie Moal; Romain Vial; Violaine Scarfoglière; Mickael Bobot; Marion Gully; Tristan Legris; Marion Pelletier; Marion Sallee; Stephane Burtey; Philippe Brunet; Thomas Robert; Philippe Rieu. Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort. Clinical Kidney Journal 2020, 13, 878 -888.
AMA StyleGuillaume Lano, Antoine Braconnier, Stanislas Bataille, Guilhem Cavaille, Julie Moussi-Frances, Bertrand Gondouin, Pascal Bindi, Magued Nakhla, Janette Mansour, Pascale Halin, Bénédicte Levy, Eric Canivet, Khaled Gaha, Isabelle Kazes, Natacha Noel, Alain Wynckel, Alexandre Debrumetz, Noemie Jourde-Chiche, Valerie Moal, Romain Vial, Violaine Scarfoglière, Mickael Bobot, Marion Gully, Tristan Legris, Marion Pelletier, Marion Sallee, Stephane Burtey, Philippe Brunet, Thomas Robert, Philippe Rieu. Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort. Clinical Kidney Journal. 2020; 13 (5):878-888.
Chicago/Turabian StyleGuillaume Lano; Antoine Braconnier; Stanislas Bataille; Guilhem Cavaille; Julie Moussi-Frances; Bertrand Gondouin; Pascal Bindi; Magued Nakhla; Janette Mansour; Pascale Halin; Bénédicte Levy; Eric Canivet; Khaled Gaha; Isabelle Kazes; Natacha Noel; Alain Wynckel; Alexandre Debrumetz; Noemie Jourde-Chiche; Valerie Moal; Romain Vial; Violaine Scarfoglière; Mickael Bobot; Marion Gully; Tristan Legris; Marion Pelletier; Marion Sallee; Stephane Burtey; Philippe Brunet; Thomas Robert; Philippe Rieu. 2020. "Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort." Clinical Kidney Journal 13, no. 5: 878-888.
Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.
Christophe Guervilly; Stephane Burtey; Florence Sabatier; Raphaël Cauchois; Guillaume Lano; Evelyne Abdili; Florence Daviet; Laurent Arnaud; Philippe Brunet; Sami Hraiech; Noémie Jourde-Chiche; Marie Koubi; Romaric Lacroix; Léa Pietri; Yaël Berda; Thomas Robert; Clara Degioanni; Mélanie Velier; Laurent Papazian; Gilles Kaplanski; Françoise Dignat-George. Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19. The Journal of Infectious Diseases 2020, 222, 1789 -1793.
AMA StyleChristophe Guervilly, Stephane Burtey, Florence Sabatier, Raphaël Cauchois, Guillaume Lano, Evelyne Abdili, Florence Daviet, Laurent Arnaud, Philippe Brunet, Sami Hraiech, Noémie Jourde-Chiche, Marie Koubi, Romaric Lacroix, Léa Pietri, Yaël Berda, Thomas Robert, Clara Degioanni, Mélanie Velier, Laurent Papazian, Gilles Kaplanski, Françoise Dignat-George. Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19. The Journal of Infectious Diseases. 2020; 222 (11):1789-1793.
Chicago/Turabian StyleChristophe Guervilly; Stephane Burtey; Florence Sabatier; Raphaël Cauchois; Guillaume Lano; Evelyne Abdili; Florence Daviet; Laurent Arnaud; Philippe Brunet; Sami Hraiech; Noémie Jourde-Chiche; Marie Koubi; Romaric Lacroix; Léa Pietri; Yaël Berda; Thomas Robert; Clara Degioanni; Mélanie Velier; Laurent Papazian; Gilles Kaplanski; Françoise Dignat-George. 2020. "Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19." The Journal of Infectious Diseases 222, no. 11: 1789-1793.
Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)—derived from tryptophan metabolism—accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial dysfunction implicated in cardiovascular morbidity and mortality during CKD. In this review, we describe clinical and experimental evidence for IS endothelial toxicity and focus on the various molecular pathways implicated. In patients with CKD, plasma concentrations of IS correlate with cardiovascular events and mortality, with vascular calcification and atherosclerotic markers. Moreover, IS induces a prothrombotic state and impaired neovascularization. IS reduction by AST-120 reverse these abnormalities. In vitro, IS induces endothelial aryl hydrocarbon receptor (AhR) activation and proinflammatory transcription factors as NF-κB or AP-1. IS has a prooxidant effect with reduction of nitric oxide (NO) bioavailability. Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients.
Guillaume Lano; Stéphane Burtey; Marion Sallée. Indoxyl Sulfate, a Uremic Endotheliotoxin. Toxins 2020, 12, 229 .
AMA StyleGuillaume Lano, Stéphane Burtey, Marion Sallée. Indoxyl Sulfate, a Uremic Endotheliotoxin. Toxins. 2020; 12 (4):229.
Chicago/Turabian StyleGuillaume Lano; Stéphane Burtey; Marion Sallée. 2020. "Indoxyl Sulfate, a Uremic Endotheliotoxin." Toxins 12, no. 4: 229.
Cardiovascular complications observed in chronic kidney disease (CKD) are associated with aryl hydrocarbon receptor (AhR) activation by tryptophan-derived uremic toxins—mainly indoxyl sulfate (IS). AhR is a ligand-activated transcription factor originally characterized as a receptor of xenobiotics involved in detoxification. The aim of this study was to determine the role of AhR in a CKD mouse model based on an adenine diet. Wild-type (WT) and AhR−/− mice were fed by alternating an adenine-enriched diet and a regular diet for 6 weeks. Our results showed an increased mortality rate of AhR−/− males. AhR−/− females survived and developed a less severe renal insufficiency that WT mice, reflected by urea, creatinine, and IS measurement in serum. The protective effect was related to a decrease of pro-inflammatory and pro-fibrotic gene expression, an attenuation of tubular injury, and a decrease of 2,8-dihydroxyadenine crystal deposition in the kidneys of AhR−/− mice. These mice expressed low levels of xanthine dehydrogenase, which oxidizes adenine into 2,8-dihydroxyadenine, and low levels of the IS metabolism enzymes. In conclusion, the CKD model of adenine diet is not suitable for AhR knockout mice when studying the role of this transcription factor in cardiovascular complications, as observed in human CKD.
Camélia Makhloufi; Fanny Nicolas; Nathalie McKay; Samantha Fernandez; Guillaume Hache; Philippe Garrigue; Philippe Brunet; Benjamin Guillet; Stéphane Burtey; Stéphane Poitevin. Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease. International Journal of Molecular Sciences 2020, 21, 2483 .
AMA StyleCamélia Makhloufi, Fanny Nicolas, Nathalie McKay, Samantha Fernandez, Guillaume Hache, Philippe Garrigue, Philippe Brunet, Benjamin Guillet, Stéphane Burtey, Stéphane Poitevin. Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease. International Journal of Molecular Sciences. 2020; 21 (7):2483.
Chicago/Turabian StyleCamélia Makhloufi; Fanny Nicolas; Nathalie McKay; Samantha Fernandez; Guillaume Hache; Philippe Garrigue; Philippe Brunet; Benjamin Guillet; Stéphane Burtey; Stéphane Poitevin. 2020. "Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease." International Journal of Molecular Sciences 21, no. 7: 2483.
Endogenous agonists of the transcription factor aryl hydrocarbon receptor (AHR) such as the indolic uremic toxin, indoxyl sulfate (IS), accumulate in patients with chronic kidney disease. AHR activation by indolic toxins has prothrombotic effects on the endothelium, especially via tissue factor (TF) induction. In contrast, physiological AHR activation by laminar shear stress (SS) is atheroprotective. We studied the activation of AHR and the regulation of TF by IS in cultured human umbilical vein endothelial cells subjected to laminar fluid SS (5 dynes/cm2). SS and IS markedly increased the expression of AHR target genes PTGS2 (encoding for COX2), AHRR, CYP1A1, and CYP1B1, as well as F3 (encoding for TF), in an AHR-dependent way. IS amplified SS-induced TF mRNA and protein expression and upregulation of AHR target genes. Interestingly, tyrosine kinase inhibition by genistein decreased SS- but not IS-induced TF expression. Finally, the increase in TF expression induced by laminar SS was not associated with increased TF activity. In contrast, IS increased TF activity, even under antithrombotic SS conditions. In conclusion, IS and SS induce AHR activation and AHR-dependent TF upregulation by different mechanisms. Impairment of the antithrombotic properties of shear stressed endothelium by toxic AHR agonists could favor cardiovascular diseases in CKD.
Guillaume Lano; Manon Laforêt; Clarissa Von Kotze; Justine Perrin; Tawfik Addi; Philippe Brunet; Stéphane Poitevin; Stéphane Burtey; Laetitia Dou. Aryl Hydrocarbon Receptor Activation and Tissue Factor Induction by Fluid Shear Stress and Indoxyl Sulfate in Endothelial Cells. International Journal of Molecular Sciences 2020, 21, 2392 .
AMA StyleGuillaume Lano, Manon Laforêt, Clarissa Von Kotze, Justine Perrin, Tawfik Addi, Philippe Brunet, Stéphane Poitevin, Stéphane Burtey, Laetitia Dou. Aryl Hydrocarbon Receptor Activation and Tissue Factor Induction by Fluid Shear Stress and Indoxyl Sulfate in Endothelial Cells. International Journal of Molecular Sciences. 2020; 21 (7):2392.
Chicago/Turabian StyleGuillaume Lano; Manon Laforêt; Clarissa Von Kotze; Justine Perrin; Tawfik Addi; Philippe Brunet; Stéphane Poitevin; Stéphane Burtey; Laetitia Dou. 2020. "Aryl Hydrocarbon Receptor Activation and Tissue Factor Induction by Fluid Shear Stress and Indoxyl Sulfate in Endothelial Cells." International Journal of Molecular Sciences 21, no. 7: 2392.
Muscle strength is frequently altered in hemodialysis patients. In the present work, five potential muscle biomarkers have been studied in their ability to assess muscular strength, muscular mass and to predict mortality of hemodialysis patients: activin-A, procollagen III N-terminal peptide, follistatin, myostatin and insulin-like growth factor-1 (IGF-1). Three independent cohorts of prevalent hemodialysis patients (2 from Liège, Belgium and 1 from Marseille, France) were considered in this observational prospective study. The biomarkers were first measured in the Liege1 cohort. Two of them, myostatin and IGF-1, were then assessed in the whole population of patients (Liege1, Liege2 and Marseille). Muscle strength was assessed with handgrip strength (HGS) and muscle mass with bioimpedance analysis. One-year mortality predictive value of biomarkers was also studied in the Liège1 and Marseille cohorts. In the Liège1 cohort (n=67), HGS was only associated with concentrations of myostatin and IGF-1. These associations were confirmed in the whole population of 204 patients (r=0.37, P<0.001 and r=0.46, P<0.001, respectively) and remained significant (P<0.05) in multivariable models. The association between muscle mass and concentrations of myostatin and IGF-1were also significant. The ability of myostatin, IGF-1 and serum creatinine to detect a low HGS compared by Receiver Operating Characteristic curves analysis were not significantly different. Both myostatin and IGF-1 had a significant and comparable area under the curve to predict one-year mortality: 0.73 (95% CI: 0.64 to 0.83) and 0.72 (95% CI: 0.61 to 0.82), respectively. Our results suggest that myostatin and IGF-1 are two biomarkers of interest to assess muscle status of dialysis patients. Both biomarkers are associated with HGS, muscular mass, and one-year mortality.
Pierre Delanaye; Stanislas Bataille; Kevin Quinonez; Fanny Buckinx; Xavier Warling; Jean-Marie Krzesinski; Hans Pottel; Stéphane Burtey; Olivier Bruyère; Etienne Cavalier. Myostatin and Insulin-Like Growth Factor 1 Are Biomarkers of Muscle Strength, Muscle Mass, and Mortality in Patients on Hemodialysis. Journal of Renal Nutrition 2019, 29, 511 -520.
AMA StylePierre Delanaye, Stanislas Bataille, Kevin Quinonez, Fanny Buckinx, Xavier Warling, Jean-Marie Krzesinski, Hans Pottel, Stéphane Burtey, Olivier Bruyère, Etienne Cavalier. Myostatin and Insulin-Like Growth Factor 1 Are Biomarkers of Muscle Strength, Muscle Mass, and Mortality in Patients on Hemodialysis. Journal of Renal Nutrition. 2019; 29 (6):511-520.
Chicago/Turabian StylePierre Delanaye; Stanislas Bataille; Kevin Quinonez; Fanny Buckinx; Xavier Warling; Jean-Marie Krzesinski; Hans Pottel; Stéphane Burtey; Olivier Bruyère; Etienne Cavalier. 2019. "Myostatin and Insulin-Like Growth Factor 1 Are Biomarkers of Muscle Strength, Muscle Mass, and Mortality in Patients on Hemodialysis." Journal of Renal Nutrition 29, no. 6: 511-520.
Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.
Jitske Jansen; Katja Jansen; Ellen Neven; Ruben Poesen; Amr Othman; Alain van Mil; Joost Sluijter; Javier Sastre Toraño; Esther A. Zaal; Celia R. Berkers; Diederik Esser; HJ Wichers; Karin van Ede; Majorie van Duursen; Stéphane Burtey; Marianne C. Verhaar; Björn Meijers; Rosalinde Masereeuw. Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion. Proceedings of the National Academy of Sciences 2019, 116, 16105 -16110.
AMA StyleJitske Jansen, Katja Jansen, Ellen Neven, Ruben Poesen, Amr Othman, Alain van Mil, Joost Sluijter, Javier Sastre Toraño, Esther A. Zaal, Celia R. Berkers, Diederik Esser, HJ Wichers, Karin van Ede, Majorie van Duursen, Stéphane Burtey, Marianne C. Verhaar, Björn Meijers, Rosalinde Masereeuw. Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion. Proceedings of the National Academy of Sciences. 2019; 116 (32):16105-16110.
Chicago/Turabian StyleJitske Jansen; Katja Jansen; Ellen Neven; Ruben Poesen; Amr Othman; Alain van Mil; Joost Sluijter; Javier Sastre Toraño; Esther A. Zaal; Celia R. Berkers; Diederik Esser; HJ Wichers; Karin van Ede; Majorie van Duursen; Stéphane Burtey; Marianne C. Verhaar; Björn Meijers; Rosalinde Masereeuw. 2019. "Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion." Proceedings of the National Academy of Sciences 116, no. 32: 16105-16110.
Arteriovenous fistula (AVF) and arteriovenous graft (AVG) is the vascular access (VA) of 78% of hemodialysis patients (HD) in France. VA dysfunction corresponding to either stenosis requiring angioplasty or acute thrombosis is responsible for 30% of hospitalizations. Mean platelet volume (MPV) is a biological marker of cardiovascular events. We studied MPV in a cohort of HD patients as a predictive marker of VA dysfunction. We conducted a prospective monocentric cohort study that included patients with AVF or AVG on chronic HD (n = 153). The primary outcome was the incidence of VA dysfunction regarding MPV value. The median MPV was 10.8 fL (7.8–13.5), and four groups were designed according to MPV quartiles. Fifty-four patients experienced the first event of VA dysfunction. The incidence of VA dysfunction was higher in patients with the highest MPV: 59% (23 events), 34% (14 events), 27% (11 events), and 18% (6 events), respectively, for the fourth, third, second, and first quartiles (p = 0.001). Multivariate analysis confirmed an independent association between MPV and VA dysfunction—OR 1.52 (1.13–2.07), p < 0.001. VA dysfunction is predicted by MPV level. Patients with the highest MPV have the highest risk of VA events.
Guillaume Lano; Marion Sallée; Marion Pelletier; Stanislas Bataille; Megan Fraisse; Yaël Berda-Haddad; Philippe Brunet; Stéphane Burtey. Mean Platelet Volume Predicts Vascular Access Events in Hemodialysis Patients. Journal of Clinical Medicine 2019, 8, 608 .
AMA StyleGuillaume Lano, Marion Sallée, Marion Pelletier, Stanislas Bataille, Megan Fraisse, Yaël Berda-Haddad, Philippe Brunet, Stéphane Burtey. Mean Platelet Volume Predicts Vascular Access Events in Hemodialysis Patients. Journal of Clinical Medicine. 2019; 8 (5):608.
Chicago/Turabian StyleGuillaume Lano; Marion Sallée; Marion Pelletier; Stanislas Bataille; Megan Fraisse; Yaël Berda-Haddad; Philippe Brunet; Stéphane Burtey. 2019. "Mean Platelet Volume Predicts Vascular Access Events in Hemodialysis Patients." Journal of Clinical Medicine 8, no. 5: 608.
Chronic kidney disease (CKD) is a major public health problem, since 300,000,000 people in the world display a glomerular filtration rate (GFR) below 60 mL/min/1.73m2. Patients with CKD have high rates of complications and comorbidities. Thus, they require the prescription of numerous medications, making the management of patients very complex. The prescription of numerous drugs associated with an altered renal- and non-renal clearance makes dose adjustment challenging in these patients, with frequent drug-related adverse events. However, the mechanisms involved in this abnormal drug clearance during CKD are not still well identified. We propose here that the transcription factor, aryl hydrocarbon receptor, which is the cellular receptor for indolic uremic toxins, could worsen the metabolism and the excretion of drugs in CKD patients.
Tacy Santana Machado; Claire Cerini; Stéphane Burtey. Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease. Toxins 2019, 11, 209 .
AMA StyleTacy Santana Machado, Claire Cerini, Stéphane Burtey. Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease. Toxins. 2019; 11 (4):209.
Chicago/Turabian StyleTacy Santana Machado; Claire Cerini; Stéphane Burtey. 2019. "Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease." Toxins 11, no. 4: 209.
Marion Sallée; Stéphane Burtey. Myeloma cast nephropathy: the dusk of high cutoff haemodialysis. The Lancet Haematology 2019, 6, e174 -e176.
AMA StyleMarion Sallée, Stéphane Burtey. Myeloma cast nephropathy: the dusk of high cutoff haemodialysis. The Lancet Haematology. 2019; 6 (4):e174-e176.
Chicago/Turabian StyleMarion Sallée; Stéphane Burtey. 2019. "Myeloma cast nephropathy: the dusk of high cutoff haemodialysis." The Lancet Haematology 6, no. 4: e174-e176.
A 60-year-old man with alteration of consciousness was admitted to the intensive care unit for rhabdomyolysis and aspiration pneumonitis. During hospitalization, the patient was diagnosed with septic shock, edema, ascites, and acute kidney injury (AKI). AKI was attributed to prostatic obstruction and required urethral catheterization. In addition, 12 days after admission, a suprapubic cystostomy was performed because of unsuccessful …
Julien Fromonot; Marion Marlinge; Camille Petit; Stephane Burtey; Regis Guieu. Sudden Onset Nephrotic-Range Proteinuria. Clinical Chemistry 2019, 65, 600 -601.
AMA StyleJulien Fromonot, Marion Marlinge, Camille Petit, Stephane Burtey, Regis Guieu. Sudden Onset Nephrotic-Range Proteinuria. Clinical Chemistry. 2019; 65 (4):600-601.
Chicago/Turabian StyleJulien Fromonot; Marion Marlinge; Camille Petit; Stephane Burtey; Regis Guieu. 2019. "Sudden Onset Nephrotic-Range Proteinuria." Clinical Chemistry 65, no. 4: 600-601.
Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy – CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs’ seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels.
Ophélie Fourdinier; on behalf of the European Uremic Toxin Work Group-EUTox; Eva Schepers; Valérie Metzinger-Le Meuth; Griet Glorieux; Sophie Liabeuf; Francis Verbeke; Raymond Vanholder; Benjamin Brigant; Anneleen Pletinck; Momar Diouf; Stéphane Burtey; Gabriel Choukroun; Ziad A. Massy; Laurent Metzinger. Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients. Scientific Reports 2019, 9, 1 -12.
AMA StyleOphélie Fourdinier, on behalf of the European Uremic Toxin Work Group-EUTox, Eva Schepers, Valérie Metzinger-Le Meuth, Griet Glorieux, Sophie Liabeuf, Francis Verbeke, Raymond Vanholder, Benjamin Brigant, Anneleen Pletinck, Momar Diouf, Stéphane Burtey, Gabriel Choukroun, Ziad A. Massy, Laurent Metzinger. Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients. Scientific Reports. 2019; 9 (1):1-12.
Chicago/Turabian StyleOphélie Fourdinier; on behalf of the European Uremic Toxin Work Group-EUTox; Eva Schepers; Valérie Metzinger-Le Meuth; Griet Glorieux; Sophie Liabeuf; Francis Verbeke; Raymond Vanholder; Benjamin Brigant; Anneleen Pletinck; Momar Diouf; Stéphane Burtey; Gabriel Choukroun; Ziad A. Massy; Laurent Metzinger. 2019. "Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients." Scientific Reports 9, no. 1: 1-12.
The kidney harbours different types of endothelia, each with specific structural and functional characteristics. The glomerular endothelium, which is highly fenestrated and covered by a rich glycocalyx, participates in the sieving properties of the glomerular filtration barrier and in the maintenance of podocyte structure. The microvascular endothelium in peritubular capillaries, which is also fenestrated, transports reabsorbed components and participates in epithelial cell function. The endothelium of large and small vessels supports the renal vasculature. These renal endothelia are protected by regulators of thrombosis, inflammation and complement, but endothelial injury (for example, induced by toxins, antibodies, immune cells or inflammatory cytokines) or defects in factors that provide endothelial protection (for example, regulators of complement or angiogenesis) can lead to acute or chronic renal injury. Moreover, renal endothelial cells can transition towards a mesenchymal phenotype, favouring renal fibrosis and the development of chronic kidney disease. Thus, the renal endothelium is both a target and a driver of kidney and systemic cardiovascular complications. Emerging therapeutic strategies that target the renal endothelium may lead to improved outcomes for both rare and common renal diseases.
Noemie Jourde-Chiche; Fadi Fakhouri; Laetitia Dou; Jeremy Bellien; Stephane Burtey; Marie Frimat; Pierre-André Jarrot; Gilles Kaplanski; Moglie Le Quintrec; Vincent Pernin; Claire Rigothier; Marion Sallée; Veronique Fremeaux-Bacchi; Dominique Guerrot; Lubka T. Roumenina. Endothelium structure and function in kidney health and disease. Nature Reviews Nephrology 2019, 15, 87 -108.
AMA StyleNoemie Jourde-Chiche, Fadi Fakhouri, Laetitia Dou, Jeremy Bellien, Stephane Burtey, Marie Frimat, Pierre-André Jarrot, Gilles Kaplanski, Moglie Le Quintrec, Vincent Pernin, Claire Rigothier, Marion Sallée, Veronique Fremeaux-Bacchi, Dominique Guerrot, Lubka T. Roumenina. Endothelium structure and function in kidney health and disease. Nature Reviews Nephrology. 2019; 15 (2):87-108.
Chicago/Turabian StyleNoemie Jourde-Chiche; Fadi Fakhouri; Laetitia Dou; Jeremy Bellien; Stephane Burtey; Marie Frimat; Pierre-André Jarrot; Gilles Kaplanski; Moglie Le Quintrec; Vincent Pernin; Claire Rigothier; Marion Sallée; Veronique Fremeaux-Bacchi; Dominique Guerrot; Lubka T. Roumenina. 2019. "Endothelium structure and function in kidney health and disease." Nature Reviews Nephrology 15, no. 2: 87-108.
Aims Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine‐associated TMA (G‐TMA). Methods From 1998 to 2015, all cases of G‐TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results G‐TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m–2. Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new‐onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion This large cohort confirms the severity of G‐TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
Florence Daviet; Franck Rouby; Pascale Poullin; Julie Moussi‐Francès; Marion Sallée; Stephane Burtey; Julien Mancini; Florence Duffaud; Renaud Sabatier; Bertrand Pourroy; Aurélie Grandvuillemin; Steven Grange; Véronique Frémeaux‐Bacchi; Paul Coppo; Joëlle Micallef; Noémie Jourde‐Chiche. Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort. British Journal of Clinical Pharmacology 2018, 85, 403 -412.
AMA StyleFlorence Daviet, Franck Rouby, Pascale Poullin, Julie Moussi‐Francès, Marion Sallée, Stephane Burtey, Julien Mancini, Florence Duffaud, Renaud Sabatier, Bertrand Pourroy, Aurélie Grandvuillemin, Steven Grange, Véronique Frémeaux‐Bacchi, Paul Coppo, Joëlle Micallef, Noémie Jourde‐Chiche. Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort. British Journal of Clinical Pharmacology. 2018; 85 (2):403-412.
Chicago/Turabian StyleFlorence Daviet; Franck Rouby; Pascale Poullin; Julie Moussi‐Francès; Marion Sallée; Stephane Burtey; Julien Mancini; Florence Duffaud; Renaud Sabatier; Bertrand Pourroy; Aurélie Grandvuillemin; Steven Grange; Véronique Frémeaux‐Bacchi; Paul Coppo; Joëlle Micallef; Noémie Jourde‐Chiche. 2018. "Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort." British Journal of Clinical Pharmacology 85, no. 2: 403-412.
Thomas Chevalier; Stéphane Burtey; Fabrice Barlesi. Specialists to the Rescue of Oncologists for the Management of Toxicity Occurring Under Combination of Anticancer Therapies. Journal of Thoracic Oncology 2018, 13, e231 -e232.
AMA StyleThomas Chevalier, Stéphane Burtey, Fabrice Barlesi. Specialists to the Rescue of Oncologists for the Management of Toxicity Occurring Under Combination of Anticancer Therapies. Journal of Thoracic Oncology. 2018; 13 (11):e231-e232.
Chicago/Turabian StyleThomas Chevalier; Stéphane Burtey; Fabrice Barlesi. 2018. "Specialists to the Rescue of Oncologists for the Management of Toxicity Occurring Under Combination of Anticancer Therapies." Journal of Thoracic Oncology 13, no. 11: e231-e232.
Vascular access infection is a frequent complication in hemodialysis patients. We report the second case worldwide of a prosthetic hemodialysis vascular graft infection by Coxiella burnetii, with intense hypermetabolism on PET-CT, Q fever serology consistent with persistent infection, and positive C. burnetii DNA in the blood and removed vascular graft.
Vincent Ernest; Serge Cammilleri; Philippe Amabile; Mathilde Fedi; Stephane Burtey; Clarissa Von Kotze; Marion Pelletier; Valérie Moal; Eric Guedj; Cindy Perron; Raafat Boustani; Yvon Berland; Philippe Brunet; Didier Raoult; Pierre-Edouard Fournier; Noémie Jourde-Chiche. Hemodialysis vascular graft as a focus of persistent Q fever. Infection 2018, 46, 881 -884.
AMA StyleVincent Ernest, Serge Cammilleri, Philippe Amabile, Mathilde Fedi, Stephane Burtey, Clarissa Von Kotze, Marion Pelletier, Valérie Moal, Eric Guedj, Cindy Perron, Raafat Boustani, Yvon Berland, Philippe Brunet, Didier Raoult, Pierre-Edouard Fournier, Noémie Jourde-Chiche. Hemodialysis vascular graft as a focus of persistent Q fever. Infection. 2018; 46 (6):881-884.
Chicago/Turabian StyleVincent Ernest; Serge Cammilleri; Philippe Amabile; Mathilde Fedi; Stephane Burtey; Clarissa Von Kotze; Marion Pelletier; Valérie Moal; Eric Guedj; Cindy Perron; Raafat Boustani; Yvon Berland; Philippe Brunet; Didier Raoult; Pierre-Edouard Fournier; Noémie Jourde-Chiche. 2018. "Hemodialysis vascular graft as a focus of persistent Q fever." Infection 46, no. 6: 881-884.
Chronic kidney disease (CKD) is associated with high risk of thrombosis. Indole-3 acetic acid (IAA), an indolic uremic toxin, induces the expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVEC) via the transcription factor aryl hydrocarbon receptor (AhR). This study aimed to understand the signaling pathways involved in AhR-mediated TF induction by IAA. We incubated human endothelial cells with IAA at 50 µM, the maximal concentration found in patients with CKD. IAA induced TF expression in different types of human endothelial cells: umbilical vein (HUVEC), aortic (HAoEC), and cardiac-derived microvascular (HMVEC-C). Using AhR inhibition and chromatin immunoprecipitation experiments, we showed that TF induction by IAA in HUVEC was controlled by AhR and that AhR did not bind to the TF promoter. The analysis of TF promoter activity using luciferase reporter plasmids showed that the NF-κB site was essential in TF induction by IAA. In addition, TF induction by IAA was drastically decreased by an inhibitor of the NF-κB pathway. IAA induced the nuclear translocation of NF-κB p50 subunit, which was decreased by AhR and p38MAPK inhibition. Finally, in a cohort of 92 CKD patients on hemodialysis, circulating TF was independently related to serum IAA in multivariate analysis. In conclusion, TF up-regulation by IAA in human endothelial cells involves a non-genomic AhR/p38 MAPK/NF-κB pathway. The understanding of signal transduction pathways related to AhR thrombotic/inflammatory pathway is of interest to find therapeutic targets to reduce TF expression and thrombotic risk in patients with CKD.
Tawfik Addi; Stéphane Poitevin; Nathalie McKay; Kamel Eddine El Mecherfi; Omar Kheroua; Noémie Jourde-Chiche; Alix De Macedo; Bertrand Gondouin; Claire Cerini; Philippe Brunet; Françoise Dignat-George; Stephane Burtey; Laetitia Dou. Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells. Archives of Toxicology 2018, 93, 121 -136.
AMA StyleTawfik Addi, Stéphane Poitevin, Nathalie McKay, Kamel Eddine El Mecherfi, Omar Kheroua, Noémie Jourde-Chiche, Alix De Macedo, Bertrand Gondouin, Claire Cerini, Philippe Brunet, Françoise Dignat-George, Stephane Burtey, Laetitia Dou. Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells. Archives of Toxicology. 2018; 93 (1):121-136.
Chicago/Turabian StyleTawfik Addi; Stéphane Poitevin; Nathalie McKay; Kamel Eddine El Mecherfi; Omar Kheroua; Noémie Jourde-Chiche; Alix De Macedo; Bertrand Gondouin; Claire Cerini; Philippe Brunet; Françoise Dignat-George; Stephane Burtey; Laetitia Dou. 2018. "Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells." Archives of Toxicology 93, no. 1: 121-136.