Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

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 ionization-time 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

Development of a new bioluminescent mutagenicity assay based on the Ames test

5 páginasy 5 figurasA newly developed rapid mutagenicíty assay based on the adenosine triphosphate (ATP)-bioluminescence techníque and the Ames test is described. Salmonella typhimurium strains TA98 and TA100 were exposed in an appropriate liquid medium to the direct mutagens 4-nitroquinoline-N-oxide and methyl methanesulphonate, respectively, and to the indirect mutagen 2-aminoanthracene. Both euxotrophic and prototrophic growth were monitored throughout the incubation period as variations in the intracellular ATP levels by means of the luciferin-luciferase assay. Ater 9-12 h of incubation a dose-response increase in the levels of ATP was readily detected. In order to demonstrate that this increase was due to the growth of revertant bacteria, aliquots from each culture were plated un minimal agar plates. A very good correlation berween the changes in ATP Ievels and the appearance of revertant colonies on the plates was found . Given the rapidity of this method as compared with conventional mutagenicity assays, ít has potential for industrial and environmental applications.Other potential applications are also díscussed.Peer reviewe

Developing Eco-Driving Strategies Considering City Characteristics

One of the challenges of the developed societies is to foster low carbon mobility models, looking at social equity and fair distribution of wealth criteria. It is, in short, the challenge of sustainability. For this reason, sustainable mobility means ensuring that our transport systems respond to economic, social and environmental needs, minimizing their negative repercussions (Government of Spain, 2010). In 2017, the transport sector contribution to EU-28 greenhouse gas emissions was 28.5 % of total. Emissions from transport in 2016 were 26 % above 1990 levels despite a decline between 2008 and 2013 (EEA, 2018a). Emissions need to fall by around two thirds by 2050, compared with 1990 levels, in order to meet the long-term 60 % greenhouse gas emission reduction target as set out in the 2011 Transport White Paper (EC, 2011). Achieving the 2030 targets will require new and expanded policies and approaches to energy efficiency in the Member States that can keep their energy consumption in check (EEA, 2018b)

Producing urban aerobiological risk map for cupressaceae family in the SW iberian peninsula from LiDAR technology.

Given the rise in the global population and the consequently high levels of pollution, urban green areas, such as those that include plants in the Cupressaceae family, are suitable to reduce the pollution levels, improving the air quality. However, some species with ornamental value are also very allergenic species whose planting should be regulated and their pollen production reduced by suitable pruning. The Aerobiological Index to create Risk maps for Ornamental Trees (AIROT), in its previous version, already included parameters that other indexes did not consider, such as the width of the streets, the height of buildings and the geographical characteristics of cities. It can be considered by working with LiDAR (Light Detection and Ranging) data from five urban areas, which were used to create the DEM and DSM (digital elevation and surface models) needed to create one of the parameters. Pollen production is proposed as a parameter (alpha) based on characteristics and uses in the forms of hedges or trees that will be incorporated into the index. It will allow the comparison of different species for the evaluation of the pruning effect when aerobiological risks are established. The maps for some species of Cupressaceae (Cupressus arizonica, Cupressus macrocarpa, Cupressus sempervirens, Cupressocyparis leylandii and Platycladus orientalis) generated in a GIS (geographic information system) from the study of several functions of Kriging, have been used in cities to identify aerobiological risks in areas of tourist and gastronomic interest. Thus, allergy patients can make decisions about the places to visit depending on the levels of risk near those areas. The AIROT index provides valuable information for allergy patients, tourists, urban planning councillors and restaurant owners in order to structure the vegetation, as well as planning tourism according to the surrounding environmental risks and reducing the aerobiological risk of certain areas

Baseline description of patients with obstructive sleep apnea who have suffered a coronary syndrome: save and ISAACC studies

S. Bertran, A. Sánchez-de-la-Torre, K. Loffler, J. Abad, J. Duran-Cantolla, V. Cabriada ... et al

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome.

Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS. Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO <sub>2</sub> ), average duration of events and percentage of time with SaO <sub>2</sub> < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components. From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO <sub>2</sub> and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO <sub>2</sub> and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events. A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society