Quincy-sous-Sénart, France
Quincy-sous-Sénart, France

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Rostoker G.,Hopital Prive Claude Galien | Rostoker G.,Service Route | Vaziri N.D.,University of California at Irvine
Drugs | Year: 2016

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients. © 2016 The Author(s).


PubMed | Hopital Prive Claude Galien and University of California at Irvine
Type: Journal Article | Journal: Drugs | Year: 2016

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a second hit on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.


Rostoker G.,Hopital Prive Claude Galien | Griuncelli M.,Hopital Prive Claude Galien | Loridon C.,Hopital Prive Claude Galien | Magna T.,Hopital Prive Claude Galien | And 4 more authors.
PLoS ONE | Year: 2014

Background and Objectives: Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients. Design, Setting, Participants and Measurements: We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2∗ contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID) analysis. Results: The CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%). The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex) and the hepcidin level also influenced liver iron content on MRI. Conclusions: The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products. © 2014 Rostoker et al.


Rostoker G.,Nephrology and Dialysis Unit | Cohen Y.,Hopital Prive Claude Galien
Journal of Computer Assisted Tomography | Year: 2014

During the past 2 decades, routine use of recombinant erythropoiesis-stimulating agents (ESAs) has enabled anemia to be corrected in dialysis patients, thereby improving their quality of life and permitting better outcomes. As successful use of ESA requires sufficient available iron, almost all end-stage renal disease patients on ESA now receive concomitant parenteral iron therapy. Radiologists must be aware that iron overload among dialysis patients is now an increasingly recognized clinical situation in the ESA era yet was previously considered rare. The KDIGO Controversies Conference on Iron Management in Chronic Kidney Disease, which took place in San Francisco on March 27 to 30, 2014, recognized the entity of iron overload in hemodialysis patients and called for an agenda of research on this topic, especially by means of magnetic resonance imaging (MRI). It is therefore very likely that radiologists will be heavily solicited in the future by nephrology teams requesting quantitative hepatic MRI in dialysis patients, both for research purposes and for diagnosis and follow-up of iron overload. Radiologists should be aware of the marked differences in the pharmacological properties of available intravenous iron products and their potential interference with MRI. Specific MRI protocols need to be established in radiology divisions for each pharmaceutical iron product, especially for treated dialysis patients. © 2014 Lippincott Williams & Wilkins.


Salvatella N.,Institute Hospitalier Jacques Cartier | Morice M.-C.,Institute Hospitalier Jacques Cartier | Darremont O.,Clinique Saint Augustin | Tafflet M.,French Institute of Health and Medical Research | And 9 more authors.
EuroIntervention | Year: 2011

Aims: We sought to assess the efficacy and safety of everolimus-eluting stents for unprotected left main disease. Methods and results: A total of 173 consecutive patients with de novo significant unprotected left main stenosis received an everolimus-eluting stent in four French centres. Among them, 140 (81%) had involvement of the distal portion of left main, and 129/140 (92%) were treated with provisional side branch T-stenting, with a side branch stenting rate of 20%. Angiographic success was achieved in all cases. At 12 months, the cumulative rate of major adverse cardiac or cerebrovascular events (MACCE) was 26/173 (15%) including death from any cause (N=5, 2.9%), stroke (N=4, 2.3%), Q-wave myocardial infarction (MI) (N=2, 1.2%), non-Q-wave MI (N=6, 3.5%) and any repeat revascularisation (N=16, 9.3%). At one year, the rate of targetlesion revascularisation (TLR) was 5/173 (2.9%), target-vessel revascularisation was 12/173 (7%) and the rate of definite or probable left main stent thrombosis 1/173 (0.6%). Conclusions: Unprotected left main stenting using everolimus-eluting stents and a strategy of provisional side branch T-stenting for distal lesions, is safe and effective in the midterm, with a relatively low rate of events and reintervention at one year. © Europa Edition 2011. All rights reserved.


Bronchial carcinoma may involve the phrenic nerve, confronting the surgeon with a difficult choice. In 10 patients undergoing surgery for bronchial carcinoma without previous diaphragmatic palsy, extension to the nerve was discovered during the thoracotomy, leading to a choice between radical surgery involving resection of the nerve, with subsequent diaphragmatic palsy, or incomplete conservative resection preserving the lung function. Conservative surgery was chosen. The subsequent evolution validated this choice. However, the paucity of papers on such cases, although they are not outstandingly unusual, should be noted. © 2009 Elsevier Masson SAS.


Rostoker G.,Hopital Prive Claude Galien | Griuncelli M.,Hopital Prive Claude Galien | Loridon C.,Hopital Prive Claude Galien | Couprie R.,Hopital Prive Claude Galien | And 8 more authors.
American Journal of Medicine | Year: 2012

Background: Most dialysis patients receiving erythropoesis-stimulating agents (ESA) also receive parenteral iron supplementation. There are few data on the risk of hemosiderosis in this setting. Methods: We prospectively measured liver iron concentration by means of T1 and T2 (*) contrast magnetic resonance imaging (MRI) without gadolinium, in a cohort of 119 fit hemodialysis patients receiving both parenteral iron and ESA, in keeping with current guidelines. Results: Mild to severe hepatic iron overload was observed in 100 patients (84%; confidence interval, [CI] 76%-90%), of whom 36% (CI, 27%-46%) had severe hepatic iron overload (liver iron concentration >201 μmol/g of dry weight). In the cross-sectional study, infused iron, hepcidin, and C-reactive protein values correlated with hepatic iron stores in both univariate analysis (P <.05, Spearman test) and binary logistic regression (P <.05). In 11 patients who were monitored closely during parenteral iron therapy, the iron dose infused per month correlated strongly with both the overall increase and the monthly increase in liver iron concentration (respectively, rho = 0.66, P =.0306 and rho = 0.85, P = 0.0015, Spearman test). In the 33 patients with iron overload, iron stores fell significantly after iron withdrawal or after a major reduction in the iron dose (first MRI: 220 μmol/g (range: 60-340); last MRI: 50 μmol/g (range: 5-210); P <.0001, Wilcoxon's paired test). Conclusions: Most hemodialysis patients receiving ESA and intravenous iron supplementation have hepatic iron overload on MRI. These findings call for a revision of guidelines on iron therapy in this setting, especially regarding the amount of iron infused and noninvasive methods for monitoring iron stores. © 2012 Elsevier Inc. All rights reserved.


PubMed | Hopital Prive Claude Galien
Type: Clinical Trial | Journal: The American journal of medicine | Year: 2012

Most dialysis patients receiving erythropoesis-stimulating agents (ESA) also receive parenteral iron supplementation. There are few data on the risk of hemosiderosis in this setting.We prospectively measured liver iron concentration by means of T1 and T2* contrast magnetic resonance imaging (MRI) without gadolinium, in a cohort of 119 fit hemodialysis patients receiving both parenteral iron and ESA, in keeping with current guidelines.Mild to severe hepatic iron overload was observed in 100 patients (84%; confidence interval, [CI] 76%-90%), of whom 36% (CI, 27%-46%) had severe hepatic iron overload (liver iron concentration >201 mol/g of dry weight). In the cross-sectional study, infused iron, hepcidin, and C-reactive protein values correlated with hepatic iron stores in both univariate analysis (P<.05, Spearman test) and binary logistic regression (P <.05). In 11 patients who were monitored closely during parenteral iron therapy, the iron dose infused per month correlated strongly with both the overall increase and the monthly increase in liver iron concentration (respectively, rho=0.66, P=.0306 and rho=0.85, P=0.0015, Spearman test). In the 33 patients with iron overload, iron stores fell significantly after iron withdrawal or after a major reduction in the iron dose (first MRI: 220 mol/g (range: 60-340); last MRI: 50 mol/g (range: 5-210); P <.0001, Wilcoxons paired test).Most hemodialysis patients receiving ESA and intravenous iron supplementation have hepatic iron overload on MRI. These findings call for a revision of guidelines on iron therapy in this setting, especially regarding the amount of iron infused and noninvasive methods for monitoring iron stores.


PubMed | Hopital Prive Claude Galien
Type: Journal Article | Journal: PloS one | Year: 2014

Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients.We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2* contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID) analysis.The CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%). The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex) and the hepcidin level also influenced liver iron content on MRI.The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products.

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