Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Prevalence of vitamin D deficiency in rheumatoid arthritis (RA): data from the Comedra cohort

National audienc

Comparison of front-of-pack labeling to clarify german consumers about the nutritional value of food color coded labels improve on all other systems

International audienc

Unsaturated fatty acid intakes during midlife are positively associated with later cognitive function in older adults with modulating effects of antioxidant supplementation

Background: Given the drastic demographic changes characterized as "population aging," the disease burden related to dementia is a major public health problem. The scientific literature documenting the link between mono-and polyunsaturated fatty acids (MUFAs, PUFAs) and cognitive function during aging is plentiful, but findings are inconsistent. Objectives: We aimed to evaluate the association between intakes of unsaturated fatty acids at midlife and cognitive performance 13 y later in French adults, and to test for a modulating effect of antioxidant supplementation. Methods: Fatty acid intakes were estimated with the use of repeated 24-h records (1994-1996) among 3362 subjects (mean +/- SD age: 65.5 +/- 4.6 y) of the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study, including an intervention phase (1994-2002) during which participants were randomly assigned to an "antioxidant supplementation" or placebo group. Cognitive performance was assessed at follow-up only (in 2007-2009) via a battery of 6 standardized neuropsychological tests. A global cognitive score was calculated as the sum of T-scores of the 6 tests. Multivariable-adjusted regression analyses were performed to provide regression coefficients and 95% CIs. Results: In multivariable models, total MUFAs, total PUFAs, and n-6 PUFAs (omega-6 PUFAs) were positively associated with overall cognitive functioning. n-3 PUFA (omega-3 PUFA) intakes showed positive associations among supplemented participants only (mean difference (Tertile3 versus Tertile1): 1.40; 95% CI: 0.30, 2.51; P-trend = 0.01, P-interaction = 0.01). A detrimental role of arachidonic acid for cognitive functioning was only detected in the placebo group (mean difference (Tertile3 versus Tertile1): -1.38; 95% CI: -2.57, -0.18; P-trend = 0.02, P-interaction = 0.07). Conclusion: Whereas higher total MUFA and n-6 PUFA intakes may be generally beneficial for maintaining cognitive health during aging, a higher consumption of n-3 fatty acids may only be beneficial among individuals with an adequate antioxidant status. These findings underline the importance of not only focusing on specific nutrients for dementia prevention, but also considering the complex interaction between consumed nutrients

Comparison of front-of-pack labeling to clarify german consumers about the nutritional value of food color coded labels improve on all other systems

International audienc

Mindfulness Is Associated with the Metabolic Syndrome among Individuals with a Depressive Symptomatology

International audienceThe Metabolic Syndrome (MetS) is a major public health burden. Dispositional mindfulness has recently been associated with eating disorders, being overweight, and could therefore be associated with the MetS. We aimed to examine in a cross-sectional design the relationship between mindfulness, the MetS, and its risk factors in a large sample of the adult general population and the influence of depressive symptomatology on this association. Adults participating in the NutriNet-Sante study who had completed the Five Facets Mindfulness Questionnaire and attended a clinical and biological examination were available for inclusion. Multivariable logistic regression models adjusted for socio-demographic and lifestyle factors were performed. A total of 17,490 individuals were included. Among individuals with a depressive symptomatology, those with higher mindfulness were less likely to have a MetS (OR: 0.73, 95% CI: 0.57-0.93), a high waist circumference, a low HDL-cholesterol level and an elevated fasting blood glucose level (all p<0.05). In those without depressive symptomatology, individuals with higher mindfulness were less likely to have a high waist circumference (p<0.01). In conclusion, higher mindfulness was associated with lower odds of developing a MetS only among individuals with a depressive symptomatology

Prospective association between adherence to the MIND diet and subjective memory complaints in the French NutriNet-Sante cohort

ObjectivesOur objective was to examine whether adherence to the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) was associated with SMC (as measured by the cognitive difficulties scale; CDS) in the NutriNet-Sante cohort.MethodsThe study sample consisted of 6011 participants aged60years at baseline, without SMC at the beginning. SMC were defined by a CDS score43 (corresponding to the 4th CDS quartile) and SMC cases were participants with SMC at least once during follow-up. The MIND diet score (0-15 points) is a hybrid of the Mediterranean Diet and the Dietary Approaches to Stop Hypertension (DASH) scores, which includes ten brain healthy food groups and five unhealthy food groups. We used Cox proportional hazards models to estimate Hazard Ratios (HR) and 95% confidence intervals (95% CI).ResultsOver a mean follow-up of 6 years, approximately 15% and 30% cases of SMC were identified among participants aged 60-69 and 70 years, respectively. The MIND diet score was not significantly associated with SMC in the full sample and among participants aged 60-69years. Among participants aged70 years, a significant inverse association was observed between adherence to the MIND diet and SMC (HRtertile 3 vs tertile 1=0.69, 95% CI=0.47-0.99). This relationship was strengthened after exclusion of participants with depressive symptoms (HRtertile 2 vs tertile 1=0.69, 95% CI=0.49-0.97; HRtertile 3 vs tertile 1=0.62, 95% CI=0.41-0.93).ConclusionsThese findings suggest that the MIND diet could help to prevent or delay SMC among older adults without depressive symptoms