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Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population‐based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10‐year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c‐index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow‐up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population‐based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology “supportive review.”

Background: Experimental studies support a role of complement activation in diabetic nephropathy (DN), yet few clinical correlates exist. We evaluated urinary levels of sC5b-9 membrane attack complex (MAC) in patients with overt DN, and examined its association with the glomerular filtration rate (GFR) decline, proteinuria, and inflammatory biomarkers. We explored different complement pathways and compared our findings to autoimmune glomerulonephritis. Methods: We prospectively followed 83 patients with DN and obtained repeated measurements of proteinuria, complement fragments (sC5b-9, C4a, C1q, mannose-binding lectin–associated serine protease [MASP]-1, and factor Bb), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor (TGF)-β1. We assessed independence and interactions using general linear models and repeated measures analyses and compared levels with subjects with active focal and segmental glomerulosclerosis, ANCA-associated vasculitis, and membranous and IgA nephropathies (n = 63). Results: The diabetic cohort had an initial GFR of 25 ± 9 ml/min per 1.73 m2 and a renal function decline of 2.9 ± 3.0 ml/min per 1.73 m2 per year. All complement biomarkers were strongly intercorrelated and associated with biomarker inflammation and fibrosis, proteinuria, and the rate of renal function decline. There was a significant interaction (P = 0.03) between the level of proteinuria and urinary sC5b-9: in individuals with higher levels of urinary MAC, the relationship between proteinuria and the rate of renal function decline was more pronounced than in those with low urinary MAC. Finally, patients with DN had levels of urinary sC5b-9 comparable to autoimmune glomerulonephritis, when stratified by the level of proteinuria. Conclusion: Urinary MAC is present in patients with overt DN at levels comparable to autoimmune glomerulonephritis and correlates with the GFR decline, supporting that complement activation and its measurement are clinically relevant in DN. Keywords: complement activation, diabetic nephropathy, fibrosis, inflammation, proteinuria, glomerulonephritis

Background: The range of central blood pressure (BP) found in individuals with high-normal brachial BP overlaps the one found in hypertension (HTN) and normotension. As central BP is possibly a better predictor of cardiovascular (CV) disease, the aim of this study was to determine the risk associated with different central/brachial BP patterns. Methods: 13,759 participants from a populational cohort with central BP and prospective data from governmental databases who were not treated for HTN were selected. Major adverse CV events (MACE) comprised myocardial infarction, stroke, heart failure and CV death. Thresholds for brachial and central HTN were identified as 135 and 125 mmHg respectively. Individuals were separated into 4 BP patterns: normal BP; isolated brachial HTN; isolated central HTN; concordant brachial and central HTN. CV risk for each pattern was compared to normal BP with a Cox proportional hazard model adjusted for multiple covariables. Results: 688 MACE occurred over a median follow-up of 70.0 months. Characteristics of individuals in each BP phenotype are presented in Table 1. Only the concordant brachial and central HTN pattern had higher risk of MACE [HR 1.37 95% CI (1.15–1.64), p = 0.001] compared to normal BP. Sensitivity analyses with different definitions of central HTN and after stratification for sex yielded similar results. Demographic characteristics Normal BP (n = 10,611) Isolated brachial HTN (n = 394) Isolated central HTN (n = 496) Concordant HTN (n = 2,258) n 10,611 394 496 2,258 Age 51 (46–57) 53 (47–60) 54 (49–62) 56 (51–63) Male sex 43% 88% 38% 58% Caucasian race 89% 88% 91% 89% Cardiovascular disease 2% 2% 4% 2% Diabetes 4% 8% 3% 6% Active smoking 19% 22% 16% 21% BMI (kg/m2) 26 ± 5 28 ± 3 28 ± 5 28 ± 5 eGFR (ml/min/1.73 m2) 90 ± 14 87 ± 15 89 ± 14 88 ± 14 10-year Framingham risk score (%) 8 ± 7 17 ± 10 11 ± 7 18 ± 12 LDL-c (mmol/L) 3.1 ± 0.8 3.1 ± 0.9 3.3 ± 0.9 3.3 ± 0.9 Heart rate (bpm) 70 ± 10 77 ± 11 65 ± 9 71 ± 11 Aspirin 6% 8% 11% 9% Statin 10% 16% 16% 13% Conclusions: In untreated individuals, both central and brachial BP need to be elevated to increase CV risk. These findings provide support for the utility of routine central BP measurements in clinical practice.

Abstract Background Missing preadmission serum creatinine (SCr) values are a common obstacle to assess acute kidney injury (AKI) diagnosis and outcomes. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines suggest using a SCr computed from the Modification of Diet in Renal Disease (MDRD) with an estimated glomerular filtration rate of 75 ml/min/1.73 m2. We aimed to identify the best surrogate method for baseline SCr to assess AKI diagnosis and outcomes. Methods We compared the use of 1) first SCr at hospital admission 2) minimal SCr over 2 weeks after intensive care unit admission 3) MDRD computed SCr and 4) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) computed SCr to assess AKI diagnosis and outcomes. We then performed multilinear regression models to predict preadmission SCr and imputation strategies to assess AKI diagnosis. Results Our one-year retrospective cohort study included 1001 critically ill adults; 498 of them had preadmission SCr values. In these patients, AKI incidence was 25.1% using preadmission SCr. First SCr had the best agreement for AKI diagnosis (22.5%; kappa = 0.90) and staging (kappa = 0.81). MDRD, CKD-EPI and minimal SCr overestimated AKI diagnosis (26.7%, 27.1% and 43.2%;kappa = 0.86, 0.86 and 0.60, respectively). However, MDRD and CKD-EPI computed SCr had a better sensitivity than first SCr for AKI (93% and 94% vs. 87%). Eighty-eight percent of patients experienced renal recovery at least 3 months after hospital discharge. All methods except the first SCr significantly underestimated the percentage of renal recovery. In a multivariate model, age, male gender, hypertension, heart failure, undergoing surgery and log first SCr best predicted preadmission SCr (adjusted R2 = 0.56). Imputation methods with first SCr increased AKI incidence to 23.9% (kappa = 0.92) but not with MDRD computed SCr (26.7%;kappa = 0.89). Conclusion In our cohort, first SCr performed better for AKI diagnosis and staging, as well as for renal recovery after hospital discharge than MDRD, CKD-EPI or minimal SCr. However, MDRD SCr and CKD-EPI SCr improved AKI diagnosis sensitivity. Imputation methods minimally increased agreement for AKI diagnosis.

Background: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice. Objective: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week. Design: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016. Setting: Ten sites in Canada. Patients: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week. Measurements: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation. Methods: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits. Results: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation. Limitations: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin

Background: Predicting the clinical trajectories of chronic kidney disease (CKD) to discern personalized care remains a complex challenge in nephrology. Understanding the appropriate risk thresholds and time frame associated with predicting risks of key outcomes (kidney failure, cardiovascular (CV) events, and death) is critical in facilitating decision-making. As part of an exploratory research and practice support needs assessment, we aimed to determine the importance of the time frames for predicting key outcomes, and to assess the perceived demand for risk prediction tools among Canadian nephrologists. Methods: A web-based survey was developed by a pan-Canadian expert panel of practitioners. Upon pre-test for clarity and ease of completion, the final survey was nationally deployed to Canadian nephrologists. Anonymous responses were gathered over a 4-month period. The results were analyzed using descriptive statistics. Results: One hundred eleven nephrologists responded to our survey. The majority of the respondents described prediction of events over time frames of 1–5 years as being “extremely important” or “very important” to decision-making on a 5-point Likert scale. To plan for arteriovenous fistula referral, the respondents deemed thresholds which would predict probability of kidney failure between >30 and >50 % at 1 year, as useful, while many commented that the rate of progression should be included for decision-making. Over 80 % of the respondents were not satisfied with their current ability to predict the progression to kidney failure, CV events, and death. Most of them indicated that they would value and use validated risk scores for decision-making. Conclusions: Our national survey of nephrologists shows that the risk prediction for major adverse clinical outcomes is valuable in CKD at multiple time frames and risk thresholds. Further research is required in developing relevant and meaningful risk prediction models for clinical decision-making in patient-centered CKD care.

Knowledge generation through randomized controlled trials (RCTs) is critical to advance the medical evidence base, inform decision-making, and improve care and outcomes. Unfortunately, nephrology has typically lagged behind other medical specialties in this regard. The establishment of formal clinical trial networks can facilitate the successful conduct of RCTs and has significantly increased the number of RCTs performed worldwide in other medical specialties. No such formal network of nephrology trialists exists in Canada. On April 24, 2014, the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) Clinical Trials Committee held a stakeholder engagement meeting to address this gap and improve the nephrology clinical trial landscape in Canada. The meeting was held in Vancouver in association with the 2014 Canadian Society of Nephrology Annual General Meeting and was co-sponsored by the Kidney Foundation of Canada and CANN-NET. Attendees included nephrologists from university- and non-university-affiliated nephrology practices, administrators, and representatives from the Kidney Foundation of Canada. Through structured presentations and facilitated group discussions, the group explored the extent to which nephrology trials are currently happening in Canada, barriers to leading or participating in larger investigator-initiated trials, and strategies to improve clinical trial output in nephrology in Canada. The themes and action items arising from this meeting are discussed.

Running has been developing rapidly in France for several decades, and this practice is accompanied by an increase in the number of sporting events in many areas. However, the geographical logics behind the spatial diffusion of the phenomenon have never been analyzed. This article therefore begins by reviewing the reasons for the development of this phenomenon, before presenting the method used to build the first geographic database of running events in France, which then allows us to draw the characteristic features of this geography on the scale of the French territory. A multiple linear regression shows that the most rural departments tend to have a higher density of running, particularly those located in the southern half of the hexagon, which is also more mountainous, and thus not unrelated to the much more pronounced growth of nature trails than road races. Finally, if this regression model only explains a little more than half of the variance, it is perhaps because the ubiquity of the running phenomenon is such that it results in a very wide spatial coverage, albeit unequal in terms of density, so much so that running has become an event of territorial animation, including in many small towns.

Within the field of urban studies, quantitative research on the assessment of social and urban segregation mainly focuses on the Paris case. Research is also characterised by little historical depth, due in particular to the methodological difficulties corresponding to such an approach. This paper presents a diachronic analysis of the social segregation of the Nantes metropolitan area over forty years (1975-2015). It adopts a quantitative approach combining tools and processes that are often addressed separately. The first part of the paper uses segregation and dissimilarity indexes to measure the evolution of segregation between social groups; it demonstrates the decline in these indexes since the 1970s. The second part uses a combination of multivariate statistical methods (Principal component analysis, Hierarchical classification analysis, Sequence analysis) in order to provide a spatial typology of the successive patterns of urban segregation. These analyses bring evidence of the gentrification dynamics, which concern some central areas in the Nantes metropolitan area. Besides, they highlight the social mix configurations that prevail in most neighbourhoods and municipalities of the metropolitan area. While the urban spatial fragmentations are often mentioned without being empirically grounded, this paper brings a series of quantitative evidences concerning current crucial French political issues and debates.

Background. Uraemia is associated with endothelial dysfunction, but the effect of uraemic plasma on the gene expression pattern of human coronary arterial endothelial cells (HCAEC) has never been defined.Methods. HCAECs were exposed for 48 h to a culture medium supplemented with 20% uraemic vs normal plasma. We extracted mRNA and hybridized it onto Affymetrix HG-U133 Plus2 microarrays. We validated our findings for five genes of interest by real-time PCR and performed evaluations of cell proliferation and apoptosis in HCAECs exposed to uraemic vs normal plasma.Results. Six genes involved in the regulation of cell-cycle progression (CDK-1, topoisomerase II, PDZ-binding kinase, CDCA1, protein SDP35, E2F transcription factor 8) and two genes of the cholesterol efflux system (ABCA1 and ABCG1) were down-regulated in HCAECs exposed to uraemic plasma (>1.75-fold change vs normal). Real-time PCR confirmed the down-regulation observed in the microarray experiment. Cell proliferation was significantly decreased in HCAECs exposed to uraemic vs normal plasma for 48 h (86 vs 95% of serum-starved control, P = 0.006). Exposure to uraemic plasma for 48 h was associated with increased apoptosis of HCAEC as compared with normal plasma (7.7 vs 2.8%, P < 0.001), a phenomenon that was further enhanced when oxidized LDLs (150 µg protein/ml) were added to the medium containing uraemic plasma (16.9 vs 7.7%, P < 0.001).Conclusions. The down-regulation of genes involved in cell-cycle progression and cholesterol efflux from HCAECs exposed to uraemic conditions could contribute to enhancing endothelial dysfunction and atherosclerosis in patients with chronic renal failure. [ABSTRACT FROM AUTHOR]

Background: Central blood pressure (CBP) is a better predictor of cardiovascular burden than peripheral blood pressure (BP). While studies have suggested a reduction in peripheral BP with statins, it remains uncertain to what extent statins reduce CBP and whether this reduction is mediated through a decrease in LDL-cholesterol (LDL). Methods: Of the 20,004 CARTaGENE participants, 17,011 had CBP and LDL measurements (n = 13,439 without, n = 3,133 with statins). Linear and logistic regression analyses were used to evaluate the association between CBP, LDL and statin use (after stratification for treatment indication for the latter). The impact of LDL on the association between statin use and CBP was determined by mediation analyses. All analyses were adjusted for age, sex, diabetes, cardiovascular disease, smoking, eGFR, BMI, uric acid, heart rate, anti-hypertensive agents and aspirin. Results: Lower levels of LDL were associated with lower systolic and diastolic CBP in participants treated with (b = 0.098 and 0.125; p < 0.001) and without statins (b = 0.089 and 0.105; p < 0.001). Statin use as primary prevention (per ACC/AHA guidelines; n = 8,865) was also associated with lower systolic CBP, diastolic CBP and central pulse pressure (b = −0.091, −0.073 and −0.055; p < 0,001). Mediation analyses demonstrated that 15%, 46% and -22% of these effects were achieved through the concomitant changes in LDL (Table 1). In secondary prevention (n = 995), statins use was not associated with lower CBP, although the small sample size may lack power. Conclusion: In this populational cohort, statin use as primary prevention is associated with lower CBP. These changes are mediated directly by statins but also indirectly through effects on LDL.

The progressive evolution of the meaning of residential enclosure in a country such as France is the central assumption of our research: it’s no more a representation of a strong property ownership but a strengthening movement of private appropriation of the residential (new condominiums or single housing master plan community) collective spaces. What methodology and data are likely to display this ? To understand this phenomenon, this paper will show a study based on the analysis of the representation of residential enclosure in the selling of new real estate programmes. Two ways will be explored. First of all, we have made an inventory of all the residential programmes in the first six-month period of 2002. In second time, we have made a semantic analysis of real estate selling brochures ; this last approach will be applied to discussions conducted with ten real estate developers who have intentionally integrated residential enclosure at different levels in their programmes.

Patients with chronic kidney disease (CKD) do not always receive care consistent with guidelines, in part due to complexities in CKD management, lack of randomized trial data to inform care, and a failure to disseminate best practice. At a 2007 conference of key Canadian stakeholders in kidney disease, attendees noted that the impact of Canadian Society of Nephrology (CSN) guidelines was attenuated given limited formal linkages between the CSN Clinical Practice Guidelines Group, kidney researchers, decision makers and knowledge users, and that further knowledge was required to guide care in patients with kidney disease. The idea for the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) developed from this meeting. CANN-NET is a pan-Canadian network established in partnership with CSN, the Kidney Foundation of Canada and other professional societies to improve the care and outcomes of patients with and at risk for kidney disease. The initial priority areas for knowledge translation include improving optimal timing of dialysis initiation, and increasing the appropriate use of home dialysis. Given the urgent need for new knowledge, CANN-NET has also brought together a national group of experienced Canadian researchers to address knowledge gaps by encouraging and supporting multicentre randomized trials in priority areas, including management of cardiovascular disease in patients with kidney failure.

In France, the identification - in promoters’ web-sites - of the real estate programs currently on the market which can be considered as gated and (associated) with control of the access draws a geography marked by ubiquity and territorial discrimination (with a higher concentration in the south of France). The security logics take part of the selling arguments legitimating the multiplication of fencing and protection devices in residential areas across France. This security evidence in the property developers’ arguments symbolizes the rise of a security order that prints a growing brand in territorial management, residential or not.

Depuis les années 2000 en France, un nouveau type d’environnement résidentiel sécurisé (et souvent fermé mais pas de façon systématique) se développe, incarné par les multiples figures du village senior. Ce phénomène soulève l’hypothèse d’une transposition d’un modèle d’entre-soi générationnel des États-Unis, où, dès les années 1950, des retirement communities ou active adults communities sont apparues, qui ont depuis proliféré vers la France. Il pose aussi la question de la construction d’un entre-soi et de sa confrontation à la mixité mais aussi à l’altérité. C’est cette interrogation qui sous-tend cet article. Celui-ci observe les modes d’habiter dans une résidence construite à l’origine exclusivement pour les seniors mais ouverte depuis à des ménages plus jeunes pour combattre la vacance d’une partie des logements. Il s’agit de la Villa Vermeil de Biscarrosse (Landes), complexe résidentiel fermé avec contrôle des accès, composé d’une résidence locative de 108 maisons gérée par le groupe Omnium Finance. Des entretiens longs et semi-directifs ont été conduits en 2008 auprès de résidants de cet ensemble d’habitat et du gestionnaire du club Villa Vermeil. Cette méthode permet de faire émerger les discours d’existence, donnant accès aux images et aux représentations des habitants dans la construction de leur rapport à l’habiter. L’intérêt de cette approche monographique est de bien illustrer la façon dont peut se construire ou non l’entre-soi générationnel et le rapport aux autres classes d’âge, dans un contexte où la mixité intergénérationnelle, étrangère à la conception du projet, a été imposée « après coup », ce qui n’est pas toujours bien perçu par les seniors, loin s’en faut, certains vivant cette mixité imposée comme une trahison et en décalage avec ce qu’ils étaient venus chercher en s’installant dans ce lieu. Since the years 2000 in France, a new type of protected residential environment (often fenced, but not always) develops, embodied by the multiple facets of the “retirement community.” This phenomenon raises the hypothesis of the transposition of a model of generation communities (retirement communities or active adults communities) from the Usa , where this type of communities appeared in the 1950s, and has since proliferated towards France. It begs also the question of community building confronted with diversity and otherness. This question underlies this paper, which observes the residential ways of living in a retirement community that has been opened to younger households in order to mitigate the effects of partial vacancy. The focus is the Villa Vermeil of Biscarrosse (Landes, France), a set of 108 rental houses managed by the Omnium Finance group. In-depth interviews were carried out with the inhabitants and the local administrator of this fenced and protected residence. The dwellers’ discourses on their state of living emerge clearly through this method, giving access to their representation and use of the residential space. This monographic approach illustrates how different generations may or may not find their way to cohabitate in the context of an intergenerational mix that was imposed “after the fact.” Some senior people perceive and resent this diversity as treason and in disharmony with what they were seeking in the first place when moving there.

This article studies the geographic spread of cohousing in the United States. As no exhaustive census of intentional communities has yet to be completed, we will discuss the principles underlying the constitution of an original database and then analyze the spatial diffusion of the phenomenon. This statistically marginal habitat has mostly developed in three areas: The West Coast, the Northeast, Colorado and New Mexico. This geography seems to correlate with territories that generally voted for the Democratic candidate in the 2016 presidential election.