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Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role. Resumen: Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43- en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea, manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43- sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43− no sólo en la fisiopatología del HPTS sino también en su papel patogénico sistémico.

Resumen: Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43− en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea (manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de la fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43− sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43−, no solo en la fisiopatología del hiperparatiroidismo secundario sino también en su papel patogénico sistémico. Abstract: Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43− on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of secondary hyperparathyroidism but also of its systemic pathogenic role.

BackgroundAlthough European guidelines recommend vascular ultrasound for the assessment of cardiovascular risk in low-to-moderate risk individuals, no algorithm properly identifies patients who could benefit from it. The aim of this study is to develop a sex-specific algorithm to identify those patients, especially women who are usually underdiagnosed.MethodsClinical, anthropometrical, and biochemical data were combined with a 12-territory vascular ultrasound to predict severe atheromatosis (SA: ≥ 3 territories with plaque). A Personalized Algorithm for Severe Atheromatosis Prediction (PASAP-ILERVAS) was obtained by machine learning. Models were trained in the ILERVAS cohort (n = 8,330; 51% women) and validated in the control subpopulation of the NEFRONA cohort (n = 559; 47% women). Performance was compared to the Systematic COronary Risk Evaluation (SCORE) model.ResultsThe PASAP-ILERVAS is a sex-specific, easy-to-interpret predictive model that stratifies individuals according to their risk of SA in low, intermediate, or high risk. New clinical predictors beyond traditional factors were uncovered. In low- and high-risk (L&H-risk) men, the net reclassification index (NRI) was 0.044 (95% CI: 0.020–0.068), and the integrated discrimination index (IDI) was 0.038 (95% CI: 0.029–0.048) compared to the SCORE. In L&H-risk women, PASAP-ILERVAS showed a significant increase in the area under the curve (AUC, 0.074 (95% CI: 0.062–0.087), p-value: < 0.001), an NRI of 0.193 (95% CI: 0.162–0.224), and an IDI of 0.119 (95% CI: 0.109–0.129).ConclusionThe PASAP-ILERVAS improves SA prediction, especially in women. Thus, it could reduce the number of unnecessary complementary explorations selecting patients for a further imaging study within the intermediate risk group, increasing cost-effectiveness and optimizing health resources.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT03228459].

Resumen: Introducción: Los pacientes con enfermedad renal crónica (ERC) tiene alto riesgo de morbimortalidad cardiovascular. Las alteraciones estructurales cardiacas subclínicas tienen valor pronóstico en estos pacientes. El objetivo fue estudiar la calcificación valvular, su evolución y relación con diferentes factores de riesgo. Material y métodos: Se seleccionó aleatoriamente parte de la muestra del estudio NEFRONA analizando la calcificación valvular aórtica y mitral en ecocardiogramas de la visita basal y a los 24 meses. Resultados: Se estudiaron 397 pacientes con filtrado glomerular estimado (FGE) basal de 33 ml/min/1.73 m2 con disminución significativa hasta 30.9 ml/min/1.73 m2 Se produjo aumento del área de placa carotidea y femoral, así como aumento de los pacientes con calcificación valvular a los 24 meses. Se observó asociación positiva de la calcificación mitral a 24 meses con la edad, el índice tobillo brazo (ITB) y el producto calcio fósforo (CaxP) basal, sin asociación con el FGE. La calcificación aórtica a los 24 meses presentó asociación positiva con el área total de placa carotidea, el fósforo y la edad basal, sin relación con el FGE. Conclusiones: Se objetivó en pacientes con ERC, sin enfermedad cardiovascular conocida progresión de la calcificación valvular a dos años independientemente del FGE. Presentaron mayor calcificación valvular mitral aquellos de mayor edad, mayor ITB y producto CaxP. Presentaron mayor calcificación valvular aórtica aquellos de mayor edad, mayores niveles de fósforo y mayor área total de placa carotidea. La identificación de estos pacientes con mayor riesgo, podría ayudar a evitar eventos cardiovasculares futuros intensificando el seguimiento. Abstract: Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methods: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. Results: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. Conclusions: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methods: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. Results: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. Conclusions: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups. Resumen: Introducción: Los pacientes con enfermedad renal crónica (ERC) tiene alto riesgo de morbimortalidad cardiovascular. Las alteraciones estructurales cardiacas subclínicas tienen valor pronóstico en estos pacientes. El objetivo fue estudiar la calcificación valvular, su evolución y relación con diferentes factores de riesgo. Material y métodos: Se seleccionó aleatoriamente parte de la muestra del estudio NEFRONA analizando la calcificación valvular aórtica y mitral en ecocardiogramas de la visita basal y a los 24 meses. Resultados: Se estudiaron 397 pacientes con filtrado glomerular estimado (FGE) basal de 33 ml/min/1.73 m2 con disminución significativa hasta 30.9 ml/min/1.73 m2 Se produjo aumento del área de placa carotidea y femoral, así como aumento de los pacientes con calcificación valvular a los 24 meses. Se observó asociación positiva de la calcificación mitral a 24 meses con la edad, el índice tobillo brazo (ITB) y el producto calcio fósforo (CaxP) basal, sin asociación con el FGE. La calcificación aórtica a los 24 meses presentó asociación positiva con el área total de placa carotidea, el fósforo y la edad basal, sin relación con el FGE. Conclusiones: Se objetivó en pacientes con ERC, sin enfermedad cardiovascular conocida progresión de la calcificación valvular a dos años independientemente del FGE. Presentaron mayor calcificación valvular mitral aquellos de mayor edad, mayor ITB y producto CaxP. Presentaron mayor calcificación valvular aórtica aquellos de mayor edad, mayores niveles de fósforo y mayor área total de placa carotidea. La identificación de estos pacientes con mayor riesgo, podría ayudar a evitar eventos cardiovasculares futuros intensificando el seguimiento.

Background and objective: The hypertriglyceridaemic waist (HTW) phenotype is defined for the general population. Chronic kidney disease (CKD) tends to bring on changes in body composition, is associated with higher comorbidity than the general population and, furthermore, shows reverse epidemiology with related prognostic variables like cholesterol and body mass index. Our objective was to identify cut-off points in the population with CKD and to analyse its relationship with cardiovascular risk (CVR). Methods: We included 2,271 CKD patients from the NEFRONA cohort. Triglyceride and waist cut-off points were selected through quintiles analysis and receiver operating characteristic (ROC) curves evaluation, using the presence of moderate to severe atherosclerosis score (AS 2-3) as outcome variable. Then, we analysed HTW prevalence and its association with other cardiovascular risk factors, and we measured the magnitude of its effect on AS 2-3 and cardiovascular event or death (CVEoD) by multivariate regression analysis. Results: We selected the cut-off points: triglyceride concentrations ≥143 mg/dl with waist circumference values >102 cm in men and 94 cm in women (sensitivity 26%; specificity 87%). Specific HTW prevalence was 22.4%, without significative differences between CKD stages. The multivariate regression analysis shows specific HTW as an independent AS 2-3 (OR 1.61; 95% CI: 1.12-2.32, p = 0.011) and CVEoD (HR 3.08; 95% CI: 1.66-5.72, p = 0.000) risk factor. An interaction between phosphorus level and specific HTW was identified. Conclusions: Adapting the HTW definition might improve specificity to assess cardiovascular risk in the population with CKD. It identifies an additional CVR in a population in which other screening methods have not proven to be useful, and it is easily clinically accessible. Its interaction with phosphorus levels suggests an association between HTW and bone-mineral metabolism regulation. Resumen: Antecedentes y objetivo: El fenotipo de cintura hipertrigliceridémica (FCH) se define para población general. La Enfermedad Renal Crónica (ERC) asocia cambios en la composición corporal, elevada comorbilidad y una epidemiología reversa en relación con el colesterol y el índice de masa corporal. Nuestro objetivo fue identificar los puntos de corte en población con ERC y analizar su relación con el riesgo cardiovascular (RCV). Métodos: Incluimos 2271 enfermos renales de la cohorte NEFRONA. Seleccionamos los puntos de corte de triglicéridos y cintura mediante análisis de quintiles y curvas ROC, utilizando presencia de enfermedad ateroesclerótica moderada-severa (EA2-3) como variable resultado. Analizamos la prevalencia del mismo y su asociación con otros factores de riesgo cardiovascular, incluimos análisis de regresión multivariable para medir la magnitud de su efecto frente a las variables EA2-3 y evento o muerte cardiovascular (EoMCV). Resultados: Seleccionamos los puntos de corte: Triglicéridos ≥ 143 mg/dl con cintura > 102 cm en varones o 94 cm en mujeres (Sensibilidad 26%; Especificidad 87%). La prevalencia del FCH específico fue 22.4%, sin diferencias entre estadios de ERC. Asoció aumento de riesgo independiente frente a EA2-3 (OR 1.61; IC 95%: 1.12-2.32, p = 0.011) y EoMCV (HR 3.08; IC 95%: 1.66-5.72, p = 0.000). Identificamos una interacción entre FCH y fósforo. Conclusiones: Adaptar la definición del FCH en la población con ERC mejora su rendimiento diagnóstico. Identifica un RCV adicional en una población donde otros métodos de cribado no han mostrado utilidad, siendo de fácil acceso clínico. Su interacción con los niveles de fósforo podría reflejar un papel en la regulación del metabolismo óseo-mineral.

Resumen: Antecedentes y objetivo: El fenotipo de cintura hipertrigliceridémica (FCH) se define para población general. La Enfermedad Renal Crónica (ERC) asocia cambios en la composición corporal, elevada comorbilidad y una epidemiología reversa en relación con el colesterol y el índice de masa corporal. Nuestro objetivo fue identificar los puntos de corte en población con ERC y analizar su relación con el riesgo cardiovascular (RCV). Métodos: Incluimos 2271 enfermos renales de la cohorte NEFRONA. Seleccionamos los puntos de corte de triglicéridos y cintura mediante análisis de quintiles y curvas ROC, utilizando presencia de enfermedad ateroesclerótica moderada-severa (EA2-3) como variable resultado. Analizamos la prevalencia del mismo y su asociación con otros factores de riesgo cardiovascular, incluimos análisis de regresión multivariable para medir la magnitud de su efecto frente a las variables EA2-3 y evento o muerte cardiovascular (EoMCV). Resultados: Seleccionamos los puntos de corte: Triglicéridos ≥ 143 mg/dl con cintura > 102 cm en varones o 94 cm en mujeres (Sensibilidad 26%; Especificidad 87%). La prevalencia del FCH específico fue 22.4%, sin diferencias entre estadios de ERC. Asoció aumento de riesgo independiente frente a EA2-3 (OR 1.61; IC 95%: 1.12-2.32, p = 0.011) y EoMCV (HR 3.08; IC 95%: 1.66-5.72, p = 0.000). Identificamos una interacción entre FCH y fósforo. Conclusiones: Adaptar la definición del FCH en la población con ERC mejora su rendimiento diagnóstico. Identifica un RCV adicional en una población donde otros métodos de cribado no han mostrado utilidad, siendo de fácil acceso clínico. Su interacción con los niveles de fósforo podría reflejar un papel en la regulación del metabolismo óseo-mineral. Abstract: Background and objective: The hypertriglyceridaemic waist (HTW) phenotype is defined for the general population. Chronic kidney disease (CKD) tends to bring on changes in body composition, is associated with higher comorbidity than the general population and, furthermore, shows reverse epidemiology with related prognostic variables like cholesterol and body mass index. Our objective was to identify cut-off points in the population with CKD and to analyse its relationship with cardiovascular risk (CVR). Methods: We included 2271 CKD patients from the NEFRONA cohort. Triglyceride and waist cut-off points were selected through quintiles analysis and receiver operating characteristic (ROC) curves evaluation, using the presence of moderate to severe atherosclerosis score (AS 2-3) as outcome variable. Then, we analysed HTW prevalence and its association with other cardiovascular risk factors, and we measured the magnitude of its effect on AS 2-3 and cardiovascular event or death (CVEoD) by multivariate regression analysis. Results: We selected the cut-off points: triglyceride concentrations ≥143 mg/dl with waist circumference values >102 cm in men and 94 cm in women (sensitivity 26%; specificity 87%). Specific HTW prevalence was 22.4%, without significative differences between CKD stages. The multivariate regression analysis shows specific HTW as an independent AS 2-3 (OR 1.61; 95% CI: 1.12-2.32, p = 0.011) and CVEoD (HR 3.08; 95% CI: 1.66-5.72, p = 0.000) risk factor. An interaction between phosphorus level and specific HTW was identified. Conclusions: Adapting the HTW definition might improve specificity to assess cardiovascular risk in the population with CKD. It identifies an additional CVR in a population in which other screening methods have not proven to be useful, and it is easily clinically accessible. Its interaction with phosphorus levels suggests an association between HTW and bone-mineral metabolism regulation.

Renal fibrosis is a deleterious process and a final manifestation of chronic kidney disease. Here, the authors demonstrate a role of alpha-synuclein in the maintenance of the epithelial phenotype of renal proximal tubular epithelial cells and in protecting kidney parenchyma against injury.

Objective: There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. Methods: A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53–63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clínica Universidad de Navarra – Body Adiposity Estimator [CUN-BAE], and Deurenberg’s formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora’s equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. ­Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p ≤ 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p ≤ 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. Conclusion: Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.

Background: Little is known about the prevalence of cerebral microangiopathy (CM), which is related to cognitive impairment, in an asymptomatic population. Pulsatility index (PI) is an easily measurable parameter of cerebral vascular resistance in transcranial duplex of the middle cerebral artery (MCA) study. We aimed to determine the prevalence of CM measured by PI of MCA in low to moderate vascular risk subjects.Methods: We included 3,721 subjects between 45 and 70 years without previous history of vascular disease or diabetes mellitus and with at least one other vascular risk factor from the cross-sectional study ILERVAS (Lleida, Spain). Patients underwent transcranial duplex to determine MCA-PI. Possible CM was defined by MCA-PI >1.1. Carotid and femoral arteries ultrasound registration was done to determine the presence, the number, and the area of atheromatous plaques. Body mass index (BMI), pulse pressure (PP) and laboratory data were also recorded.Results: 439 (11.8%) subjects were excluded due to the low quality of transcranial duplex images. Median age was 57 [IQR 52, 62] years. Possible CM was found in 424 (12.9%) subjects. CM patients had higher prevalence of plaques than non-CM (77.4 vs. 66.4%, p < 0.001). PI showed a positive linear correlation with the number of territories with plaques (r = 0.130, p < 0.001), and the total plaque area (r = 0.082, p < 0.001). The predictors of possible CM were the age, male gender, and PP.Conclusions: In low-to-moderate vascular risk asymptomatic population, the proportion of abnormal brain microvascular bed determined by MCA-PI is not negligible. The planned 10-year follow-up will describe the clinical relevance of these findings.

There is controversial information about the accumulation of advanced glycation end-products (AGEs) in obesity. We assessed the impact of total and abdominal adiposity on AGE levels via a cross-sectional investigation with 4254 middle-aged subjects from the ILERVAS project. Skin autofluorescence (SAF), a non-invasive assessment of subcutaneous AGEs, was measured. Total adiposity indices (BMI and Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE)) and abdominal adiposity (waist circumference and body roundness index (BRI)) were assessed. Lean mass was estimated using the Hume index. The area under the receiver operating characteristic (ROC) curve was evaluated for each index. Different cardiovascular risk factors (smoking, prediabetes, hypertension and dyslipidemia) were evaluated. In the study population, 26.2% showed elevated SAF values. No differences in total body fat, visceral adiposity and lean body mass were detected between patients with normal and high SAF values. SAF levels showed a very slight but positive correlation with total body fat percentage (estimated by the CUN-BAE formula) and abdominal adiposity (estimated by the BRI). However, none of them had sufficient power to identify patients with high SAF levels (area under the ROC curve

Abstract Background Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. Methods Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. Results Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c

Abstract Background Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes. Methods We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine–Gray competing risk models were used to perform the statistical analysis. Results During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7. Conclusions The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.

This study explores those skills associated with modeling that preservice primary and secondary teachers develop when working with measure. The sample was made up of a total of 12 master's degree students and 13 primary school teacher students, who worked in groups to solve a task, which was specically designed to develop skills associated with measure through modeling. The analysis of the models produced by the prospective teachers revealed a great wealth of ideas and evidence of the dependence on formulae for the calculation and estimation of areas. Results also indicate relationship between the model's closeness to the real situation and the tendency of participants to validate it, as well as the importance of the layout of the task on the produced models.

The Global Burden of Disease (GBD) study measures the health of populations worldwide and by country on an annual basis and aims at helping guide public policy on health issues. The GBD estimates for Spain in 2016 and recent trends in mortality and morbidity from 2006 to 2016 were recently published. According to these estimates, chronic kidney disease was the 8th cause of death in Spain in 2016. Among the top ten causes of death, chronic kidney disease was the fastest growing from 2006 to 2016, after Alzheimer disease. At the current pace of growth, chronic kidney disease is set to become the second cause of death in Spain, after Alzheimer disease, by 2100. Additionally, among major causes of death, chronic kidney disease also ranked second only to Alzheimer as the fastest growing cause of Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). Public resources devoted to prevention, care and research on kidney disease should be in line with both its current and future burden. Resumen: El estudio Global Burden of Disease (GBD) mide la salud de las poblaciones en todo el mundo y en cada país de forma annual, y tiene como objetivo ayudar a orientar las políticas públicas sobre cuestiones de salud. Recientemente se publicaron las estimaciones GBD 2016 para España y las tendencias recientes en mortalidad y morbilidad de 2006 a 2016. Según estas estimaciones, la enfermedad renal crónica fue la octava causa de muerte en España en 2016. Entre las 10 principales causas de muerte, la enfermedad renal crónica fue la que más creció entre 2006 y 2016, después de la enfermedad de Alzheimer. Al ritmo actual de crecimiento, la enfermedad renal crónica se convertirá en la segunda causa de muerte en España, después del Alzheimer, hacia el 2100. Además, entre las principales causas de muerte, la enfermedad renal crónica también ocupa el segundo lugar después del Alzheimer como la que más creció en años vividos con discapacidad (AVD) y en años de vida ajustados por discapacidad (AVAD). Los recursos públicos dedicados a la prevención, atención e investigación de la enfermedad renal deberían estar en línea con su carga actual y futura. Keywords: Chronic kidney disease, Mortality, Research funding, Ranking, Public health, Palabras clave: Enfermedad renal crónica, Mortalidad, Financiación de la investigación, Clasificación, Salud pública

This study presents an experience that combines problem-posing and Math Trails in the context of future teachers’ instruction. Pre-service teachers in the third year of their studies were faced with the design of tasks to be included in Math Trails for primary school students. The study analyzes, from a quantitative approach, 117 tasks contained in 11 Math Trails. The analysis was performed on the basis of classification variables (grade, mathematical content and object or real element involved in every task) and research variables which provide information about the nature of the tasks (procedural vs. problem-solving, level of cognitive demand, degree of contextualization, openness and creativity). Additionally, relationships between the different categories of analysis have been studied. The results reveal certain biases in the tasks in relation to the contents addressed (an abundance of tasks with a geometric component and a scarcity of tasks involving algebra or probability concepts). Most of the tasks are presented in a real context. However, a higher percentage of procedural tasks than problem-solving tasks is observed, with a predominance of low openness, creativity and cognitive demand. These results provide useful lines of work to address difficulties faced by future teachers in the STEAM field.

The aim of this study was to develop and validate a methodology to carry out olive grove inventories based on open data sources and automatic photogrammetric and satellite image analysis techniques. To do so, tools and protocols have been developed that have made it possible to automate the capture of images of different characteristics and origins, enable the use of open data sources, as well as integrating and metadating them. They can then be used for the development and validation of algorithms that allow for improving the characterization of olive grove surfaces at the plot and cadastral polygon scales. With the proposed system, an inventory of the Andalusian olive grove has been automatically carried out at the level of cadastral polygons and provinces, which has accounted for a total of 1,519,438 hectares and 171,980,593 olive trees. These data have been contrasted with various official statistical sources, thus ensuring their reliability and even identifying some inconsistencies or errors of some sources. Likewise, the capacity of the Sentinel 2 satellite images to estimate the FCC at the cadastral polygon, parcel and 10 × 10 m pixel level has been demonstrated and quantified, as well as the opportunity to carry out inventories with temporal resolutions of approximately up to 5 days.

The dehesa is an anthropic complex ecosystem typical of some areas of Spain and Portugal, with a key role in soil and biodiversity conservation and in the search for a balance between production, conservation and ecosystem services. For this reason, it is essential to have tools that allow its characterization, as well as to monitor and support decision-making to improve its sustainability. A multipurpose and scalable tool has been developed and validated, which combines several low-cost technologies, computer vision methods and RGB aerial orthophotographs using open data sources and which allows for automated agroforestry inventories, identifying and quantifying units with important ecological significance such as: trees, groups of trees, ecosystem corridors, regenerated areas and sheets of water. The development has been carried out from images of the national aerial photogrammetry plan of Spain belonging to 32 dehesa farms, representative of the existing variability in terms of density of trees, shrub species and the presence of other ecological elements. First, the process of obtaining and identifying areas of interest was automated using WMS services and shapefile metadata. Then, image analysis techniques were used to detect the different ecological units. Finally, a classification was developed according to the OBIA approach, which stores the results in standardized files for Geographic Information Systems. The results show that a stable solution has been achieved for the automatic and accurate identification of ecological units in dehesa territories. The scalability and generalization to all the dehesa territories, as well as the possibility of segmenting the area occupied by trees and other ecological units opens up a great opportunity to improve the construction of models for interpreting satellite images.

A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m2, and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population.

Abstract Background Cardiovascular (CV) disease due to atherosclerosis is a major cause of morbidity and mortality in adult patients with diabetes, either type 1 or type 2 diabetes. The aim of the study was to assess the association of the frequency and the burden of subclinical carotid atherosclerotic disease in patients with type 1 diabetes according to the presence and severity of diabetic retinopathy (DR). Methods A cross-sectional study was conducted in 340 patients with type 1 diabetes (41.5% with DR), and in 304 non-diabetic individuals. All participants were free from previous CV disease and chronic kidney disease (CKD). B-mode carotid ultrasound imaging was performed in all the study subjects. Patients with type 1 diabetes underwent a full eye examination, and DR patients were divided into two groups: mild disease and advanced disease. Results In the group of patients with type 1 diabetes, the percentage of patients with carotid plaques was higher in those with DR compared with those without DR (44.7% vs. 24.1%, p

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.

A concern in Mathematics Education is the professional development of the teacher and to promote effective training programs. The literature provides principles guiding the design of such programs, which were considered for an instruction intended to strengthen the teacher’s practice in relation to the development of mathematical skills. The objective of this work was to study if the designed program was effective, in relation to the impact on the teacher’s teaching. A case study on a group of in-service teachers focused on the ability of mathematical modeling (MM) and their perspectives of this skill was carried out. This was divided into three moments: before, during, and after the program. The findings show that, before the program, teachers conceived modeling from epistemological, pragmatic and conceptual perspectives; during the program, they focused on the pragmatic and educational perspectives; and at the end of the program, the group was stripped of the pragmatic, epistemological and conceptual perspectives to move towards the educational and socio-critical. They were also able to justify the choice or disassociation of one or more of them. The study advances towards the concretion of more specific and robust professional development programs for mathematics teachers.

This paper shows a tool for the analysis of written productions that allows for the characterization of the mathematical models that students develop when solving modeling tasks. For this purpose, different conceptualizations of mathematical models in education are discussed, paying special attention to the evidence that characterizes a school model. The discussion leads to the consideration of three components, which constitute the main categories of the proposed tool: the real system to be modeled, its mathematization and the representations used to express both. These categories and the corresponding analysis procedure are explained and illustrated through two working examples, which expose the value of the tool in establishing the foci of analysis when investigating school models, and thus, suggest modeling skills. The connection of this tool with other approaches to educational research on mathematical modeling is also discussed.

Llama fibre has the potential to become the most valuable textile resource in the Puna region of Argentina. In this study near infrared reflectance spectroscopy was evaluated to predict the mean fibre diameter in llama fleeces. Analyses between sets of carded and non-carded samples in combination with spectral preprocessing techniques were carried out and a total of 169 spectral signatures of llama samples in Vis and NIR ranges (400–2500 nm) were obtained. Spectral preprocessing consisted in wavelength selection (Vis–NIR, NIR and discrete ranges) and multiplicative and derivative pretreatments; spectra without pretreatments were also included, while modified partial least squares (M-PLS) regression was used to develop prediction models. Predictability was evaluated through R2: standard cross validation error (SECV), external validation error (SEV) and residual predictive value (RPD). A total of 54 calibration models were developed in which the best model (R2 = 0.67; SECV = 1.965; SEV = 2.235 and RPD = 1.91) was obtained in the Vis–NIR range applying the first derivative pretreatment. ANOVA analysis showed differences between carded and non-carded sets and the models obtained could be used in screening programs and contribute to valorisation of llama fibre and sustainable development of textile industry in the Puna territory of Catamarca. The data presented in this paper are a contribution to enhance the scarce information on this subject.

Abstract Background LADA is probably the most prevalent form of autoimmune diabetes. Nevertheless, there are few data about cardiovascular disease in this group of patients. The aim of this study was to investigate the frequency of carotid atherosclerotic plaques in patients with LADA as compared with patients with classic type 1 diabetes and type 2 diabetes. Methods Patients with LADA were matched for age and gender in different proportions to patients with type 2 diabetes, and classic type 1 diabetes. None of the patients had clinical cardiovascular disease. All subjects underwent B-mode carotid ultrasound to detect atheroma plaques. Demographics were obtained from all subjects. Results We included 71 patients with LADA, 191 patients with type 2 diabetes and 116 patients with type 1 diabetes. Carotid atherosclerosis was more frequent in patients with LADA compared with type 2 diabetes (73.2% vs. 56.9%, P = 0.0018) and classic type 1 diabetes (57.1%, P = 0.026); these changes occurred despite healthier macrovascular risk profiles in the former. Age (P

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.

Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.

Carotid intima media thickness (cIMT) displays prognostic value as a marker of cardiovascular risk in dialysis patients. However, few data are available regarding the impact of dialysis modality on cIMT. The aim of this study is to determine whether the modality of dialysis influences cIMT values. We compared 237 peritoneal dialysis (PD) and 451 hemodialysis (HD) patients without previous cardiovascular disease included in NEFRONA, a prospective, observational and multicenter study. This cross sectional study included the determination of cIMT in 6 carotid territories by arterial ultrasound. cIMT was determined in territories without atheroma plaque and averaged. A second analysis was performed using all territories, giving a truncated cIMT value of 1,5 mm to territories presenting with atheroma plaque. Age and plaque presence at baseline were the clinical variables more closely associated to cIMT in dialysis patients. The evaluation of the impact of the modality of dialysis on cIMT showed that PD patients had lower cIMT than HD patients, both in territories with no plaques and when using truncated cIMT values. No differences were found between right and left sides, neither in cIMT or truncated cIMT values. Lineal multivariate analysis adjusted by several clinical variables showed a statistically significant association of PD with a lower cIMT (slope -0.036; SD 0.010). These results were also confirmed when truncated cIMT values were used. We conclude that the modality of dialysis has an impact on cITM. HD patients have greater global cIMT than PD patients, and PD is and independent factor associated with a lower cIMT.

Traditionally, the teaching and learning of algebra has been addressed at the beginning of secondary education with a methodological approach that broke traumatically into a mathematical universe until now represented by numbers, with bad consequences. It is important, then, to find methodological alternatives that allow the parallel development of arithmetical and algebraic thinking from the first years of learning. This article begins with a review of a series of theoretical foundations that support a methodological proposal based on the use of specific manipulative materials that foster a deep knowledge of the decimal number system, while verbalizing and representing quantitative situations that underline numerical relationships and properties and patterns of numbers. Developing and illustrating this approach is the main purpose of this paper. The proposal has been implemented in a group of 25 pupils in the first year of primary school. Some observed milestones are presented and analyzed. In the light of the results, this well-planned early intervention contains key elements to initiate algebraic thinking through the development of number sense, naturally enhancing the translation of purely arithmetical situations into the symbolic language characteristic of algebraic thinking.

Prediabetes is closely related to excess body weight and adipose distribution. For this reason, we aimed to assess and compare the diagnostic usefulness of ten anthropometric adiposity indices to predict prediabetes. Cross-sectional study with 8188 overweight subjects free of type 2 diabetes from the ILERVAS project (NCT03228459). Prediabetes was diagnosed by levels of glycated hemoglobin (HbA1c). Total body adiposity indices [BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) and Deurenberg’s formula] and abdominal adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora’s equation, A body shape index, and body roundness index) were calculated. The area under the receiver-operating characteristic (ROC) curve, the best cutoff and the prevalence of prediabetes around this value were calculated for every anthropometric index. All anthropometric indices other than the A body adiposity were higher in men and women with prediabetes compared with controls (p < 0.001 for all). In addition, a slightly positive correlation was found between indices and HbA1c in both sexes (r ≤ 0.182 and p ≤ 0.026 for all). None of the measures achieved acceptable levels of discrimination in ROC analysis (area under the ROC ≤ 0.63 for all). Assessing BMI, the prevalence of prediabetes among men increased from 20.4% to 36.2% around the cutoff of 28.2 kg/m2, with similar data among women (from 29.3 to 44.8% with a cutoff of 28.6 kg/m2). No lonely obesity index appears to be the perfect biomarker to use in clinical practice to detect individuals with prediabetes.

Background and objectives: Chronic kidney disease (CKD) and atherosclerosis are 2 interrelated diseases that increase the risk of cardiovascular morbidity and mortality. The objectives of the ILERVAS project are: (1) to determine the prevalence of subclinical arterial disease and hidden kidney disease; (2) to assess the impact of early diagnosis of both diseases on cardiovascular morbidity and mortality and also on the progression of CKD; (3) to have a platform of data and biological samples. Methods: Randomised intervention study. From 2015 to 2017, 19,800 people (9900 in the intervention group and 9900 in the control group) aged between 45 and 70 years without previous history of cardiovascular disease and with at least one cardiovascular risk factor will be randomly selected from the primary health care centres across the province of Lleida. A team of experts will travel around in a mobile unit to carry out the following baseline tests on the intervention group: Artery ultrasound, (carotid, femoral, transcranial and abdominal aorta), ankle-brachial index, spirometry, determination of advanced glycation end products, dried blood spot and urine spot tests. Additionally, blood and urine samples will be collected and stored in the biobank to identify new biomarkers using omics studies. Participants will be followed up until 2025 for identification of cardiovascular events, treatment changes and changes in lifestyle. Conclusions: The ILERVAS project will reveal the prevalence of subclinical vascular disease and hidden kidney disease, determine whether or not their early diagnosis brings health benefits and will also allow investigation of new risk factors.

Antecedentes y objetivos: La enfermedad renal crónica (ERC) y la ateromatosis son 2 enfermedades interrelacionadas que aumentan el riesgo de morbimortalidad cardiovascular. Los objetivos del proyecto ILERVAS son: 1) conocer la prevalencia de enfermedad ateromatosa subclínica y de enfermedad renal oculta; 2) valorar el impacto de su diagnóstico precoz sobre la morbimortalidad cardiovascular y la progresión de la ERC; 3) disponer de una plataforma de datos y muestras biológicas. Métodos: Estudio de intervención aleatorizado. Entre 2015 y 2017 se incluirá a 19.800 personas (9.900 en el grupo de intervención y 9.900 en el grupo control) entre 45 y 70 años, sin antecedentes de enfermedad cardiovascular y que presenten al menos un factor de riesgo cardiovascular, seleccionadas aleatoriamente de los centros de atención primaria (AP) de la provincia de Lérida. Un equipo técnico experto se desplazará con una unidad móvil para realizar las exploraciones basales al grupo de intervención: ecografía arterial (carótida, femoral, transcraneal y aorta abdominal), medición del índice tobillo-brazo, espirometría, detección de los productos de glicación avanzada y analítica seca de sangre y orina. Adicionalmente, se recogerán muestras de sangre y orina que serán almacenadas en el biobanco para identificar nuevos biomarcadores con biología de sistemas. Los participantes serán seguidos hasta 2025 para la identificación de eventos cardiovasculares, cambios de tratamiento y modificación de estilos de vida. Conclusiones: El proyecto ILERVAS permitirá conocer la prevalencia de enfermedad vascular y de enfermedad renal subclínicas, evaluar si su diagnóstico precoz tiene un beneficio en la salud e investigar factores de riesgo emergentes.

Introduction: Initiation of peritoneal dialysis (PD) with 3 exchanges has become common practice in recent years, despite the lack of published clinical data. Objective: To describe experience with incremental peritoneal dialysis (IPD) at a single site. Material and methods: A total of 46 IPD patients undergoing 2-year clinical, laboratory, treatment and progression follow-up. Results: To 25% of patients were transplanted on IPD. Mean time on IPD before transfer to conventional PD of 24 months, half of the patients because of fluid balance. Good clinical and biochemical results with a peritonitis rate of one episode per 99 months. There was an improvement in the loss of residual kidney function compared to the pre-dialysis period (−7.06 vs. −1.58 ml/min/year; P = .0001). Conclusions: IPD with 3 peritoneal exchanges offers good results. Most patients remain stable during the first 2 years and there is an improvement in the loss of residual kidney function compared to the pre-dialysis period.

Introducción: En los últimos años el inicio de diálisis peritoneal (DP) con 3 recambios se ha convertido en una práctica habitual, aunque se dispone de pocos resultados clínicos publicados. Objetivo: Descripción de la experiencia de inicio con DP incremental (DPI) en un centro. Material y métodos: A 46 pacientes en DPI se les realizó seguimiento clínico, analítico y tratamiento, y se estudió su evolución a 2 años. Resultados: A un 25% de los pacientes se les trasplanta en DPI. Tiempo medio de transferencia a DP convencional de 24 meses. La mitad de los pacientes son transferidos por manejo de líquidos. Buena estabilidad clínica y analítica con tasa de peritonitis de un episodio cada 99 meses. Enlentecimiento de la pérdida de función renal residual respecto al período prediálisis (−7,06 vs. −1,58 ml/min/año; p = 0,0001). Conclusiones: La experiencia en DPI con 3 recambios de inicio es positiva. La mayoría de los pacientes se mantienen estables durante los 2 primeros años, con un enlentecimiento de la pérdida de función renal residual respecto el período prediálisis.

El hiperparatiroidismo secundario (HPTS) es una complicación habitual en pacientes con enfermedad renal crónica que se caracteriza por unos niveles elevados de hormona paratiroidea (PTH) y una serie de anomalías en el metabolismo mineral-óseo. En pacientes con HPTS, el tratamiento con paricalcitol, un activador selectivo de los receptores de la vitamina D, ha demostrado reducir los niveles de PTH con mínimas variaciones del calcio y del fósforo séricos. El efecto clásico de paricalcitol es el de mediador en la homeostasis mineral y ósea. Sin embargo, estudios recientes han indicado que los beneficios del tratamiento con paricalcitol van más allá de la reducción de PTH, por ejemplo, ocasionando efectos positivos en la enfermedad cardiovascular y en la supervivencia. El objetivo del presente trabajo es revisar los estudios más significativos sobre los llamados efectos pleiotrópicos del tratamiento con paricalcitol en pacientes con ERC.

Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD.

The control of refrigeration in the food chain is fundamental at all stages, with special emphasis on the retail stage. The implementation of information and communication technologies (IoT, open-source hardware and software, cloud computing, etc.) is representing a revolution in the operational paradigm of food control. This paper presents a low-cost IoT solution, based on free hardware and software, for monitoring the temperature in refrigerated retail cabinets. Specifically, the use of the ESP-8266-Wi-Fi microcontroller with DS18B20 temperature sensors is proposed. The ThingSpeak IoT platform is used to store and process data in the cloud. The solution presented is robust, affordable, and flexible, allowing to extend the scope of supervising other relevant parameters in the operating process (light control, energy efficiency, consumer presence, etc.).

[This corrects the article DOI: 10.1371/journal.pone.0186921.].

BACKGROUND:Chronic kidney disease (CKD) patients experience a high risk of cardiovascular disease (CV); however, the factors involved in CV-related morbidity and mortality in these patients have not been fully defined. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine, which exhibits pleiotropic activities on endothelial, vascular smooth muscle and inflammatory cells, with relevant effects on atheromatous plaque formation. On this basis, the present study aims to investigate the role of TRAIL in atheromatosis progression in CKD patients. METHODS:Circulating TRAIL levels were measured in 378 CKD patients belonging to the Spanish National Observatory of Atherosclerosis in Nephrology (NEFRONA) study. All patients were free of previous CV events. Carotid and femoral B-mode ultrasound was performed to detect the presence of plaque at baseline and after 24 months of follow-up. RESULTS:The lowest levels of TRAIL at baseline were significantly (p

Chronic kidney disease (CKD) patients, characterized by traditional and nontraditional risk factors, are prone to develop atheromatosis and thus cardiovascular events and mortality. The angiogenesis of the adventitial vasa vasorum (aVV) surrounding the carotid has been described as the atheromatosis initiator. Therefore, the aim of the study was to (1) evaluate if the carotid aVV in CKD patients increases in comparison to its physiological value of healthy patients; (2) explore which traditional or nontraditional risk factor including inflammation, bone and mineral metabolism, and anemia could be related to the aVV angiogenesis. CKD patients without previous cardiovascular events (44, stages 3-4; 37, stage 5D) and 65 healthy subjects were compared. The carotid aVV and the intima-media thickness (cIMT) were evaluated by ultrasound. CKD patients at stages 3-4 showed higher aVV of the right carotid artery even after adjusting for age. Importantly, a multiple linear regression model showed hemoglobin levels > 12.5 g/dL as the factor for an estimated higher aVV of the right carotid artery. In conclusion, the association of hemoglobin with higher aVV could suggest the role of high hemoglobin in the higher incidence of adverse cardiovascular outcomes in CKD patients.

Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, p2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4-6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, p

There is limited and inconclusive information regarding the influence of the modality of renal replacement therapy on the atherosclerotic burden of patients on dialysis. The aim of this study was to compare the prevalence of asymptomatic atheromatous carotid disease, as also its rate of progression and cardiovascular outcomes, in two matched populations of patients treated with hemodialysis (HD) and peritoneal dialysis (PD).Following a prospective, observational and multicenter design, we compared 237 PD and 237 HD patients without previous cardiovascular disease, included in the NEFRONA study, and matched for age, sex, diabetes and time on dialysis. Carotid ultrasound study was performed at baseline and after two years of follow-up in 6 carotid territories. Atheromatous vascular disease (AVD) progression was defined as any increase in the number of territories with plaques after 2 years. Fatal and non fatal cardiovascular events were also recorded during 36-month of follow-up.At baseline, PD patients presented a worse general cardiovascular risk profile than HD patients. On the contrary, some markers of prevalent atherosclerotic disease (common carotid intima-media thickness and ankle-brachial index) were more favorable in PD patients. During follow-up, we observed no differences either in the rate of progression of atheromatous vascular disease (OR 1.78, 95% CI 0.80-4.06, p = 0.161) or in the incidence of cardiovascular events (OR 1.51, 95% CI 0.85-2.66, p = 0.159), according to the modality of dialysis.Dialysis modality did not impact on atherosclerotic carotid disease progression or cardiovascular outcomes, in two groups of patients treated with PD or HD.

Aims. To assess whether circulating 25-hydroxyvitamin D3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease. Methods. We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. Results. We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg2/dL2) product was positively associated with the presence of carotid plaques (ORadj = 1.078; 95% CI: 1.017–1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus

Abstract The author found errors in Table 1 after publication of the original article [1].

There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants’ adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg’s formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora’s equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables. ClinTrials.gov Identifier: NCT03228459.

A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87⁻109) vs. 94 (82⁻105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89⁻112) vs. 93 (80⁻107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88⁻107) vs. 94 (83⁻105) % of predicted, p = 0.027) and FEV1 (100 (89⁻110) vs. 95 (84⁻108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.