Bénédicte Stengel

Université Paris-Sud 11, Orsay, Île-de-France, France

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Publications (111)483.48 Total impact

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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;
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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 : JASN. 10/2014;
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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; · 35.21 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.
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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.
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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.
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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; · 29.98 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; · 0.50 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). · 6.49 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; · 8.52 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. 01/2014;
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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 01/2014; 9(2):e84144. · 3.53 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 01/2014; 9(6):e99781. · 3.53 Impact Factor
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    ABSTRACT: 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.
    PLoS ONE 01/2014; 9(11):e111949. · 3.53 Impact Factor
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    ABSTRACT: Nephrogenic systemic fibrosis (NSF) has been related to the use of gadolinium-based contrast agents (GBCAs) in patients undergoing dialysis. The Prospective Fibrose Nephrogénique Systémique study, a French prospective study supported by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament) and the French Societies of Nephrology, Dermatology, and Radiology, aimed at determining the incidence of NSF in patients undergoing long-term dialysis. Adult patients undergoing long-term dialysis receiving a magnetic resonance imaging (MRI) examination prescribed between January 15, 2009 and May 31, 2011, with or without GBCA were included. The methodology was based on a patient form intended to detect any dermatological event (DE) that may occur within 4 months after the examination. Further investigations were planned with their physicians if a DE was reported. A total of 571 patients were included. A total of 50.3% received GBCA. Among them, 93.4% received a macrocyclic GBCA, usually gadoteric acid (88.9%). All in all, 22 patients (3.9%) reported a DE. Dermatological diagnoses did not reveal any evidence of NSF. The incidence of NSF after a single dose of a macrocyclic GBCA is null in our sample of 268 patients undergoing dialysis (hemodialysis and peritoneal dialysis). This incidence is just lower than 0.5%. When contrast-enhanced MRI can be essential, or even decisive, to the diagnosis, these results are important and reassuring if physicians need to perform contrast-enhanced MRI in patients undergoing dialysis.
    Investigative radiology 10/2013; · 4.85 Impact Factor
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    ABSTRACT: While much has been learned about the epidemiology and treatment of end-stage renal disease (ESRD) in the last 30 years, chronic kidney disease (CKD) before the end-stage has been less investigated. Not enough is known about factors associated with CKD progression and complications, as well as its transition to ESRD. We designed the CKD-renal epidemiology and information network (REIN) cohort to provide a research platform to address these key questions and to assess clinical practices and costs in patients with moderate or advanced CKD. A total of 46 clinic sites and 4 renal care networks participate in the cohort. A stratified selection of clinic sites yields a sample that represents a diversity of settings, e.g. geographic region, and public versus for-profit and non-for-profit private clinics. In each site, 60-90 patients with CKD are enrolled at a routine clinic visit during a 12-month enrolment phase: 3600 total, including 1800 with Stage 3 and 1800 with Stage 4 CKD. Follow-up will continue for 5 years, including after initiation of renal replacement therapy. Data will be collected from medical records at inclusion and at yearly intervals, as well as from self-administered patient questionnaires and provider-level questionnaires. Patients will also be interviewed at baseline, and at 1, 3 and 5 years. Healthcare costs will also be determined. Blood and urine samples will be collected and stored for future studies on all patients at enrolment and at study end, and at 1 and 3 years in a subsample of 1200. The CKD-REIN cohort will serve to improve our understanding of the biological, clinical and healthcare system determinants associated with CKD progression and adverse outcomes as well as of international variations in collaboration with the CKD Outcome and Practice Pattern Study (CKDopps). It will foster CKD epidemiology and outcomes research and provide evidence to improve the health and quality of life of patients with CKD and the performances of the healthcare system in this field.
    Nephrology Dialysis Transplantation 09/2013; · 3.37 Impact Factor
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    ABSTRACT: Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
    Journal of the American Society of Nephrology 09/2013; · 8.99 Impact Factor
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    ABSTRACT: Background. Incidence rates of renal replacement therapy (RRT) for end-stage renal disease vary consider-ably worldwide. This study examines the independent association between the general population, health care system and renal service characteristics and RRT inci-dence rates. Methods. RRT incidence data (2003–2005) were obtained from renal registries; general population age and health and macroeconomic indices were collected from secondary sources. Renal service organization and resource data were obtained through interviews and questionnaires. Linear regression models were built to establish the factors inde-pendently associated with RRT incidence, stratified by the Human Development Index where required. False discovery rate (FDR) correction was adjusted for multiple testing. Results. Across the 46 countries (population 1.25 billion), RRT incidence rates ranged from 12 to 455 (median 130) per million population. Gross domestic product (GDP) per cap-ita [incidence rate ratio (IRR): 1.02 per $1000 increase, P FDR ¼ 0.047], percentage of GDP spent on health care (IRR: 1.11 per % increase, P FDR ¼ 0.006) and dialysis facility reimbursement rate relative to GDP (IRR: 0.76 per GDP per capita-sized increase in reimbursement rate, P FDR ¼ 0.007) were independently associated with RRT incidence. In more developed countries, the private for-profit share of haemodialysis facilities was also associated with higher incidence (IRR: 1.009 per % increase, P FDR ¼ 0.003). Conclusions. Macroeconomic and renal service factors are more often associated with RRT incidence rates than measured demographic or general population health status factors.
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    ABSTRACT: This chapter provides a set of indicators on incident patients with renal replacement therapy. In 2011, in 25 French regions (99% population), 9 248 patients started a treatment by dialysis (incidence of dialysis: 149 per million inhabitants) and 334 patients with a pre-emptive graft without previous dialysis (incidence of pre-emptive graft: 5 per million inhabitants). One patient among two are over 70 years old at renal replacement therapy initiation. As in 2010, incidence rate seems to stabilize.
    Néphrologie & Thérapeutique 09/2013; 9S1:S19-S37. · 0.50 Impact Factor
  • American Journal of Kidney Diseases 07/2013; 62(1):182–184. · 5.29 Impact Factor

Publication Stats

2k Citations
483.48 Total Impact Points

Institutions

  • 2008–2014
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2013
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France
  • 1990–2012
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2011
    • University of Bristol
      Bristol, England, United Kingdom
  • 1998–2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • INRS
      Lutetia Parisorum, Île-de-France, France
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Medical Informatics
      Amsterdam, North Holland, Netherlands