Bénédicte Stengel

Université du Droit et de la Santé Lille 2, Lille, Nord-Pas-de-Calais, France

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Publications (121)564.33 Total impact

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    ABSTRACT: Acetate-free dialysis (AFD) improves haemodynamic stability during dialysis, compared with standard haemodialysis (HD) with a small amount of acetic acid. Using the national REIN registry, we classified 15 160 incident patients who started HD from 2008 to 2010 into three exposure categories according to the type of dialysate used in their dialysis unit: standard dialysate only (reference), both standard and AFD (mixed unit) or HCl dialysate only (100% HCl unit). Cox survival analysis was adjusted for 15 baseline comorbidities, laboratory data and haemodiafiltration (HDF). We took patient clustering within units into account, used age as the time scale and treated patient exposure to AFD and to HDF as time-dependent variables. Median age (interquartile range) was 70.5 years (58.1-78.8). Over a median follow-up of 1.8 years (1.2-2.6), 658 patients were dialysed in a 100% HCl unit, 3021 in a mixed unit and 11 481 were never exposed to AFD. The relation between AFD and mortality was not constant with age (Schoenfeld residuals test P = 0.01 for mixed group and P = 0.03 for 100%HCl group). Patients older than 70 years had a significantly lower mortality risk associated with AFD [hazard ratio (HR) = 0.79, 95% confidence interval (CI) = 0.67 to 0.94 for patients exposed in a 100% HCl unit; HR = 0.83, 95% CI = 0.74 to 0.94 for patients exposed in a mixed unit], but no association was found in younger patients. AFD was associated with improved survival independent of comorbidities and HDF in patients aged 70 years and older but not in patient younger than 70 years. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
    Nephrology Dialysis Transplantation 06/2015; DOI:10.1093/ndt/gfv248 · 3.49 Impact Factor
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    ABSTRACT: Glycated hemoglobin (HbA1c) is used to diagnose diabetes mellitus (DM) and guide its management. The association between higher HbA1c and progression to ESRD and mortality has been demonstrated in populations with DM. This study examined the association between HbA1c and these end points in a population with CKD and without DM. In the hospital-based NephroTest cohort study, measured GFR (mGFR) was taken by (51)Cr-EDTA renal clearance and HbA1c in 1165 adults with nondialysis CKD stages 1-5 and without DM between January 2000 and December 2010. The median follow-up was 3.48 years (interquartile range, 1.94-5.82) for the competing events of ESRD and pre-ESRD mortality. Time-fixed and time-dependent Cox models were used to estimate hazard ratios (HRs) for ESRD and mortality according to HbA1c, treated continuously or in tertiles. At inclusion, the mean mGFR was 42.2±19.9 ml/min per 1.73 m(2), and the mean HbA1c value was 5.5%±0.5%. During follow-up, 109 patients died, and 162 patients reached ESRD. Pre-ESRD mortality was significantly associated with HbA1c treated continuously: for every 1% higher HbA1c, the crude HR was 2.16 (95% confidence interval [95% CI], 1.27 to 3.68), and it was 1.85 (95% CI, 1.05 to 3.24) after adjustment for mGFR and other risk factors of death. After excluding incident diabetes over time, the updated mean of HbA1c remained significantly associated with higher mortality risk: adjusted HR for the highest (5.7%-6.4%) versus the lowest tertile (<5.3%) was 2.62 (95% CI, 1.16 to 5.91). There was no association with ESRD risk after adjustment for risk factors of CKD progression. In a CKD cohort, HbA1c values in the prediabetes range are associated with mortality. Such values should be therefore included among the risk factors for negative outcomes in CKD populations. Copyright © 2015 by the American Society of Nephrology.
    Clinical Journal of the American Society of Nephrology 05/2015; 10(6). DOI:10.2215/CJN.08540814 · 5.25 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). Collaborative meta-analysis. 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants). Available eGFR, ACR, and 50 or more AKI events. Age, sex, race, eGFR, urine ACR, and interactions. Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR. Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code. Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 05/2015; DOI:10.1053/j.ajkd.2015.02.337 · 5.76 Impact Factor
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    ABSTRACT: Muscle wasting predicts mortality in patients with end-stage renal disease (ESRD), but its role in the progression of chronic kidney disease (CKD) is uncertain. We studied CKD outcomes associated with low muscle mass, assessed by urinary creatinine excretion (UCr). The NephroTest cohort included 1429 patients with CKD stages 1-4 and both measured glomerular filtration rate (mGFR) (by (51)Cr-EDTA) and estimated glomerular filtration rate (eGFR) (by CKD-Epidemiology Collaboration equation). We used cause-specific Cox models to estimate hazard ratios (HRs) for the competing risks of ESRD and death associated with gender-specific UCr quartiles. UCr was 13.6 ± 3.2 mmol/24 h (0.17 ± 0.05 mmol/kg/24 h) in men and 9.2 ± 2.1 (0.14 ± 0.05) in women. It was positively associated with mGFR, but not with eGFR. Over a median follow-up of 3.6 (2.1-5.8) years, 229 patients developed ESRD and 113 patients died before ESRD. Compared with patients in the highest UCr quartile, those in the lowest quartile had a higher crude HR (95% confidence interval) for pre-ESRD death: 4.3 (2.4-7.7), which was weakened, but remained statistically significant, independent of demographics, mGFR and several other factors: 2.1 (1.04-4.3). Their crude ESRD risk was not higher: HR: 0.95 (0.65-1.4), and even tended to be lower after adjusting for mGFR and log-proteinuria: HR: 0.70 (0.45-1.1). Adjustment for eGFR instead of mGFR reversed this relationship: HR: 1.7 (1.1-2.7). In early stage CKD, low UCr is associated with higher risk for mortality, but not for ESRD. Using creatinine-based equation to adjust for GFR may bias the relationship of UCr with ESRD risk. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
    Nephrology Dialysis Transplantation 03/2015; DOI:10.1093/ndt/gfv047 · 3.49 Impact Factor
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    ABSTRACT: Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1-4. All patients had measured glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m(2). Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06-3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98-3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.Kidney International advance online publication, 11 March 2015; doi:10.1038/ki.2015.52.
    Kidney International 03/2015; DOI:10.1038/ki.2015.52 · 8.52 Impact Factor
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    ABSTRACT: In studies investigating risk factors of chronic kidney disease (CKD) progression, one may be interested in estimating factors effects on both a fall of glomerular filtration rate (GFR) below a specific level (i.e., a CKD stage) and death. Such studies have to account for the fact that GFR is measured at intermittent visit only, which implies that progression to the stage of interest is unknown for patients who die before being observed at that stage. Our objective was to compare the results of an illness-death model that handles this uncertainty, with frequently used survival models. This study included 1,519 patients from the NephroTest cohort with CKD stages 1-4 at baseline (69% males, 59±15 years, median protein/creatinine ratio [PCR] 27.4 mg/mmol) and subsequent annual measures of GFR (follow-up time 4.3±2.7 years). Each model was used to estimate the effects of sex, age, PCR, and GFR at baseline on the hazards of progression to CKD stage 5 (GFR<15 mL/min/1.73 m2, n = 282 observed) and death (n = 168). For progression to stage 5, there were only minor differences between results from the different models. The differences between results were higher for the hazard of death before or after progression. Our results also suggest that previous findings on the effect of age on end-stage renal disease are more likely due to a strong impact of age on death than to an effect on progression. The probabilities of progression were systematically under-estimated with the survival model as compared with the illness-death model. This study illustrates the advantages of the illness-death model for accurately estimating the effects of risk factors on the hazard of progression and death, and probabilities of progression. It avoids the need to choose arbitrary time-to-event and time-to-censoring, while accounting for both interval censoring and competition by death, using a single analytical model.
    PLoS ONE 12/2014; 9(12):e114839. DOI:10.1371/journal.pone.0114839 · 3.53 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.Kidney International advance online publication, 10 December 2014; doi:10.1038/ki.2014.361.
    Kidney International 12/2014; DOI:10.1038/ki.2014.361 · 8.52 Impact Factor
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    ABSTRACT: Background: Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods: We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by Cr-51-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results: Baseline mean urinary creatinine excretion decreased from 15.3 +/- 3.1 to 12.1 +/- 3.3 mmol/24 h (0.20 +/- 0.03 to 0.15 +/- 0.04 mmol/kg/24 h) in men, with mGFR falling from >60 to <15 mL/min/1.73 m(2), and from 9.6 +/- 1.9 to 7.6 +/- 2.5 (0.16 +/- 0.03 to 0.12 +/- 0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53 +/- 0.12 mL/min/1.73 m(2) per year and that of urinary creatinine excretion rate, 0.28 +/- 0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m(2) had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions: Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass.
    PLoS ONE 11/2014; 9(11):e111949. DOI:10.1371/journal.pone.0111949 · 3.53 Impact Factor
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    ABSTRACT: Proteinuria and hyperphosphatemia are cardiovascular risk factors independent of GFR. We hypothesized that proteinuria induces relative phosphate retention via increased proximal tubule phosphate reabsorption. To test the clinical relevance of this hypothesis, we studied phosphate handling in nephrotic children and patients with CKD. Plasma fibroblast growth factor 23 (FGF-23) concentration, plasma phosphate concentration, and tubular reabsorption of phosphate increased during the proteinuric phase compared with the remission phase in nephrotic children. Cross-sectional analysis of a cohort of 1738 patients with CKD showed that albuminuria≥300 mg/24 hours is predictive of higher phosphate levels, independent of GFR and other confounding factors. Albuminuric patients also displayed higher plasma FGF-23 and parathyroid hormone levels. To understand the molecular mechanisms underlying these observations, we induced glomerular proteinuria in two animal models. Rats with puromycin-aminonucleoside-induced nephrotic proteinuria displayed higher renal protein expression of the sodium-phosphate co-transporter NaPi-IIa, lower renal Klotho protein expression, and decreased phosphorylation of FGF receptor substrate 2α, a major FGF-23 receptor substrate. These findings were confirmed in transgenic mice that develop nephrotic-range proteinuria resulting from podocyte depletion. In vitro, albumin did not directly alter phosphate uptake in cultured proximal tubule OK cells. In conclusion, we show that proteinuria increases plasma phosphate concentration independent of GFR. This effect relies on increased proximal tubule NaPi-IIa expression secondary to decreased FGF-23 biologic activity. Proteinuria induces elevation of both plasma phosphate and FGF-23 concentrations, potentially contributing to cardiovascular disease.
    Journal of the American Society of Nephrology 10/2014; DOI:10.1681/ASN.2014010104 · 9.47 Impact Factor
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    ABSTRACT: Abstract We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
    Nature Genetics 10/2014; DOI:10.1038/ng.3118 · 29.65 Impact Factor
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    ABSTRACT: Introduction La perte de masse musculaire prédit la mortalité chez les patients dialysés, mais son rôle dans la progression de la maladie rénale chronique (MRC) est incertain. Nous avons étudié les liens entre la masse musculaire évaluée à partir de la créatininurie des 24 h et le risque de décès et d’insuffisance rénale terminale traitée (IRTT). Patients et méthodes Dans une cohorte prospective de 1429 patients avec une MRC stades 1 à 4, la créatininurie des 24 h et le débit de filtration glomérulaire (DFG) évalué par la clairance du 51Cr-EDTA ont été mesurés à l’inclusion. La créatininurie des 24 h a été étudiée en quartiles avec des seuils spécifiques par sexe : 11,3, 13,3, 15,5 mmol/24 h pour les hommes et 7,5, 9,0, 10,5 pour les femmes. Ses liens avec la mortalité et la survie rénale ont été analysés par modèle de Cox en ajustant sur un ensemble de facteurs de confusion. Résultats La créatininurie moyenne était de 13,6 ± 3,2 mmol/24 h (0,17 ± 0,05 mmol/kg/24 h) chez les hommes et de 9,2 ± 2,1 (0,14 ± 0,05) chez les femmes. Durant un suivi médian de 3,6 ans, 229 patients ont développé une IRTT, et 113 sont décédés avant IRTT. Après ajustement sur les facteurs démographiques, le DFG, la protéinurie, les facteurs de risque cardiovasculaire, les marqueurs nutritionnels et inflammatoires, le hazard ratio (HR) de mortalité était de 2,1 [1,02–4,3] pour le premier quartile de créatininurie comparé au 4e. Aucune association significative entre la créatininurie et le risque d’IRTT n’a été mise en évidence. Discussion et conclusion Chez les patients atteints de MRC, une excrétion urinaire faible de créatinine est associée à un accroissement de la mortalité, mais n’est pas liée à la progression vers l’IRTT.
    Néphrologie & Thérapeutique 09/2014; 10(5):268–269. DOI:10.1016/j.nephro.2014.07.321 · 0.55 Impact Factor
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    ABSTRACT: Objectif Évaluer les apports protéiques dans une cohorte hospitalière multicentrique de patients avec une MRC de stades 1 à 5 non dialysés, et étudier les relations entre ces apports et le risque d’insuffisance rénale terminale traitée (IRTT). Patients et méthodes Les apports en protéines ont été estimés à partir de l’azote uréique urinaire des 24 h (UUN) chez 1594 patients (formule de Maroni), et à partir d’enquêtes alimentaires sur 7 jours dans un sous-groupe de 784 patients. Les risques compétitifs d’IRTT et de mortalité avant dialyse sont étudiés chez 1412 patients avec un DFG mesuré par la clairance rénale du 51Cr-EDTA ≥ 15 mL/min/1,73 m2. Résultats DFG médian (IQR), 38,2 (26,6,53,4) mL/min/1,73 m2, âge moyen ± SD, 59 ± 15 ans et IMC, 26,6 ± 5,2 kg/m2. L’UUN est de 1,09 ± 0,30 g/kg de poids réel/jour sans différence significative par sexe ; dans le sous-groupe, il est de 1,13 ± 0,34 vs 1,12 ± 0,34 par l’enquête alimentaire. L’UUN diminue significativement de 1,18 ± 0,29 à 0,93 ± 0,26 avec la baisse du DFGm ≥ 60–< 15 mL/min/1,73 m2. Vingt pour cent des patients ont des apports protéiques > 1,3 g/kg/j et 14 % < 0,8. Après 3,5 ans de suivi médian, 224 IRTT et 117 décès pré-IRTT sont observés. Les hazard ratios ajustés d’IRTT associés à l’augmentation de 0,1 g/kg/j d’apport protéique sont de 1,08 (IC 95 %, 1,02–1,13) avec UUN et de 1,14 (1,07–1,20) avec l’enquête alimentaire. Il n’y avait pas d’association avec la mortalité pré-IRTT. Discussion et conclusion En dépit d’une nette diminution des apports protéiques avec la baisse du DFG, des consommations excessives restent fréquentes. Dans cette population, plus les apports protéiques sont faibles, plus le risque d’IRTT diminue, suggérant un effet bénéfique sur la progression de la MRC, sans augmentation apparente du risque de mortalité.
    Néphrologie & Thérapeutique 09/2014; 10(5):269. DOI:10.1016/j.nephro.2014.07.322 · 0.55 Impact Factor
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    ABSTRACT: Introduction Lorsque l’on s’intéresse aux facteurs associés au passage du DFG sous un certain seuil, on sait seulement que ce passage s’est produit entre deux mesures consécutives du DFG. Cette incertitude sur le temps de passage complique les analyses statistiques, notamment en présence de risques compétitifs, quand certains patients décèdent ou sont perdus de vue pendant le suivi. Pour ces patients, il peut exister une incertitude sur le fait qu’il y ait eu ou non progression sous le seuil avant ces évènements. Notre objectif était de comparer les résultats d’un modèle statistique illness-death gérant cette incertitude par rapport à des modèles de survie standard habituellement utilisés dans la littérature. Matériels et méthodes Cette étude incluait 1519 patients aux stades 1 à 4 de la MRC (69 % d’hommes, 60 ± 15 ans, médiane du ratio protéinurie/créatininurie (PCR) 27,4 mg/mmol). Les effets du sexe, de l’âge, de la protéinurie, et du DFG mesuré à l’inclusion sur la survenue du stade 5 (DFG < 15 mL/min/1,73 m2 ; n = 282 transitions observées) et du décès (n = 168) ont été estimés avec les différents modèles. Résultats Des différences mineures ont été trouvées sur les estimations des effets des facteurs de risque sur la transition vers le stade 5 de la MRC dans les différents modèles. Les résultats concernant le décès dépendaient de la distinction ou non du passage par le stade 5 avant le décès. On observe par exemple un effet de la protéinurie sur le risque de décéder lorsqu’on ne prend pas en compte la transition vers le stade 5, avec un risque relatif (RR) de 1,3 (IC 95 % 1,1–1,5) pour une augmentation d’une unité du log PCR. Cet effet n’est pas retrouvé dans le modèle illness-death lorsqu’on distingue le décès avant la survenue du stade 5 (RR = 1,1 ; IC 95 % 0,9–1,4) et le décès après la survenue du stade 5 (RR = 1,2 ; IC 95 % 0,9–1,5). Discussion et conclusion Cette étude fournit des résultats rassurants par rapport à l’utilisation des modèles de survie standard lorsqu’on s’intéresse à l’association entre des facteurs de risque et la progression de la MRC, si ces facteurs de risque ne sont pas associés avec la survenue du décès. Elle montre cependant l’importance de distinguer le décès avant et après la transition vers le stade d’intérêt, afin de mieux identifier les facteurs agissant sur les transitions entre les stades de la MRC de ceux ayant un impact sur le décès.
    Néphrologie & Thérapeutique 09/2014; 10(5):267. DOI:10.1016/j.nephro.2014.07.318 · 0.55 Impact Factor
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    ABSTRACT: The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD). We investigated its relation to iron disorders, inflammation and hemoglobin (Hb) level in 199 non-dialyzed, non-transplanted patients with CKD stages 1-5. All had their glomerular filtration rate measured by 51Cr-EDTA renal clearance (mGFR), as well as measurements of iron markers including hepcidin and of erythropoietin (EPO). Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/mL [8.8-28.7] to 36.1 ng/mL [14.1-92.3] when mGFR decreased from ≥60 to <15 mL/min/1.73 m2 (p = 0.02). Patients with absolute iron deficiency (transferrin saturation (TSAT) <20% and ferritin <40 ng/mL) had the lowest hepcidin levels (5.0 ng/mL [0.7-11.7]), and those with a normal iron profile (TSAT ≥20% and ferritin ≥40), the highest (34.5 ng/mL [23.7-51.6]). In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin's negative association with Hb level indicates that it is not down-regulated in CKD anemia.
    PLoS ONE 06/2014; 9(6):e99781. DOI:10.1371/journal.pone.0099781 · 3.53 Impact Factor
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    ABSTRACT: IMPORTANCE The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of -57% or greater) is a late event. OBJECTIVE To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION Individual meta-analysis of 1.7 million participants with 12 344 ESRD events and 223 944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of -57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of -30%. However, changes of -30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of -57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of -57%, was 83% (95% CI, 71%-93%) for estimated GFR change of -40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of -30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
    JAMA The Journal of the American Medical Association 06/2014; 311(24). DOI:10.1001/jama.2014.6634 · 30.39 Impact Factor
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    ABSTRACT: The emergence of new effective therapeutic strategies for the treatment of resistant hypertension such as renal sympathetic denervation technique has lead to a renewed interest in the screening and assessment of prognosis of this specific entity which constitutes a subset of uncontrolled hypertension. Its prevalence is unknown, but estimated between 12 and 15 % among hypertensive subjects from the general population. Several factors have been associated with the development of resistant hypertension, four of which are essential: age, diabetes, chronic kidney disease and vascular structural alteration. Excessive salt intake is also a risk factor for poorly controlled hypertension in patients with salt-dependent hypertension, and may participate to the genesis of resistant hypertension. Because of population ageing and increasing prevalence of diabetes, obesity and chronic kidney disease, the prevalence of resistant hypertension is expected to rise. A better understanding of its determinants and associated risks (such as chronic kidney disease) would identify high-risk groups that may benefit from extensive diagnosis work up and more specific treatments.
    Néphrologie & Thérapeutique 06/2014; DOI:10.1016/j.nephro.2013.12.006 · 0.55 Impact Factor
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    ABSTRACT: The emergence of new effective therapeutic strategies for the treatment of resistant hypertension such as renal sympathetic denervation technique has lead to a renewed interest in the screening and assessment of prognosis of this specific entity which constitutes a subset of uncontrolled hypertension. Its prevalence is unknown, but estimated between 12 and 15 % among hypertensive subjects from the general population. Several factors have been associated with the development of resistant hypertension, four of which are essential: age, diabetes, chronic kidney disease and vascular structural alteration. Excessive salt intake is also a risk factor for poorly controlled hypertension in patients with salt-dependent hypertension, and may participate to the genesis of resistant hypertension. Because of population ageing and increasing prevalence of diabetes, obesity and chronic kidney disease, the prevalence of resistant hypertension is expected to rise. A better understanding of its determinants and associated risks (such as chronic kidney disease) would identify high-risk groups that may benefit from extensive diagnosis work up and more specific treatments.
    Néphrologie & Thérapeutique 04/2014; · 0.55 Impact Factor
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    ABSTRACT: Aims/hypothesis The aim was to study geographic variations and recent trends in the incidence of end-stage renal disease (ESRD) by diabetes status and type, and in patient condition and modalities of care at initiation of renal replacement therapy. Methods Data from the French population-based dialysis and transplantation registry of all ESRD patients were used to study geographic variations in 5,857 patients without diabetes mellitus, 227 with type 1 diabetes mellitus, and 3,410 with type 2. Trends in incidence and patient care from 2007 to 2011 were estimated. Results Age- and sex-adjusted incidence rates were higher in the overseas territories than in continental France for ESRD unrelated to diabetes and related to type 2 diabetes, but quite similar for type 1 diabetes-related ESRD. ESRD incidence decreased significantly over time for patients with type 1 diabetes (−10% annually) and not significantly for non-diabetic patients (0.2%), but increased significantly for patients with type 2 diabetes (+7% annually until 2009 and seemingly stabilised thereafter). In type 2 diabetes, the net change in the absolute number was +21%, of which +3% can be attributed to population ageing, +2% to population growth and +16% to the residual effect of the disease. Patients with type 2 diabetes more often started dialysis as an emergency (32%) than those with type 1 (20%) or no diabetes. Conclusions/interpretation The major impact of diabetes on ESRD incidence is due to type 2 diabetes mellitus. Our data demonstrate the need to reinforce strategies for optimal management of patients with diabetes to improve prevention, or delay the onset, of diabetic nephropathy, ESRD and cardiovascular comorbidities, and to reduce the rate of emergency dialysis.
    Diabetologia 04/2014; 57(4). DOI:10.1007/s00125-014-3160-9 · 6.88 Impact Factor
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    ABSTRACT: Iron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia. We studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (<40 ng/mL), transferrin saturation (TSAT<20%) and total iron binding capacity (TIBC<50 µmol/L) in 1011 outpatients with non-dialysis CKD participating in the Nephrotest study. All had glomerular filtration rates measured (mGFR) by (51)Cr-EDTA renal clearance; 199 also had hepcidin measures. The TSAT-TIBC-ferritin index explained Hb variation better than indexes combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non-inflammatory functional iron deficiency (ID) to be more common than either absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in all abnormal, compared with normal, iron profiles, and decreased more when mGFR was below 30 mL/min/1.73 m(2) (interaction p<0.0001). In patients with mGFR<30 mL/min/1.73 m(2), the Hb decreases associated with hypotransferrinaemia, non-inflammatory functional ID, and absolute ID were 0.83±0.16 g/dL, 0.51±0.18 and 0.89±0.29, respectively. Compared with normal iron profiles, hepcidin was severely depressed in absolute ID but higher in hypotransferrinaemia. The combined TSAT-TIBC-ferritin index identifies hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms of iron disorders in CKD anaemia. Both disorders were associated with a greater decrease in Hb when mGFR was <30 mL/min/1.73 m(2). Taking these iron profiles into account may be useful in stratifying patients in clinical trials of CKD anaemia and might improve the management of iron therapy.
    PLoS ONE 02/2014; 9(2):e84144. DOI:10.1371/journal.pone.0084144 · 3.53 Impact Factor
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    ABSTRACT: Cystic kidney diseases and toxic interstitial nephritis may be complicated by renal tumors. Long-term lithium intake is associated with tubulointerstitial nephritis and renal cysts but to date such an association with tumors has not been determined. We evaluated this in a retrospective study to determine whether lithium-treated patients were at higher risk of renal tumors compared with lithium-free patients with chronic kidney disease (CKD), and to the general population. Over a 16-year period, 14 of 170 lithium-treated patients had renal tumors, including seven malignant and seven benign tumors. The mean duration of lithium exposure at diagnosis was 21.4 years. The renal cancers included three clear-cell and two papillary renal cell carcinomas, one hybrid tumor with chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal tumors, particularly cancers and oncocytomas, was significantly higher in lithium-treated patients compared with 340 gender-, age-, and estimated glomerular filtration rate (eGFR)-matched lithium-free patients. Additionally, the Standardized Incidence Ratio of renal cancer was significantly higher in lithium-treated patients compared with the general population: 7.51 (95% confidence interval (CI) (1.51-21.95)) and 13.69 (95% CI (3.68-35.06)) in men and women, respectively. Thus, there is an increased risk of renal tumors in lithium-treated patients.Kidney International advance online publication, 22 January 2014; doi:10.1038/ki.2014.2.
    Kidney International 01/2014; 86(1). DOI:10.1038/ki.2014.2 · 8.52 Impact Factor

Publication Stats

2k Citations
564.33 Total Impact Points


  • 2014
    • Université du Droit et de la Santé Lille 2
      Lille, Nord-Pas-de-Calais, France
  • 2006–2014
    • Université Paris-Sud 11
      • Faculty of Medicine
      Orsay, Île-de-France, France
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • INRS
      Lutetia Parisorum, Île-de-France, France
  • 1995–2014
    • French Institute of Health and Medical Research
      • Centre de Recherche en Épidémiologie et Santé des Populations CESP U1018
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Intercommunal Creteil
      Créteil, Île-de-France, France
  • 1990–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2013
    • Hôpital Paul-Brousse – Hôpitaux universitaires Paris-Sud
      Villejuif, Île-de-France, France
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France
  • 2012
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2009
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • University of Limoges
      Limages, Limousin, France
  • 2003–2007
    • Leiden University
      Leyden, South Holland, Netherlands