1. Investigación

La enfermedad renal crónica (ERC) es un importante problema de salud pública a nivel mun-dial afectando a más del 10% de la población espa˜nola. Se asocia a elevada comorbilidad,mal pronóstico, así como a un gran consumo de recursos en el sistema sanitario. Desde lapublicación del último documento de consenso sobre ERC publicado hace siete a˜nos, hansido escasas las evidencias y los ensayos clínicos que hayan mostrado nuevas estrategiasen el diagnóstico y tratamiento de la ERC, con excepción de los nuevos ensayos en la enfer-medad renal diabética. Esta situación ha condicionado que no se hayan actualizado lasguías internacionales específicas de ERC. Esta rigidez y actitud conservadora de las guíasno debe impedir la publicación de actualizaciones en el conocimiento en algunos aspectos, que pueden ser clave en la detección y manejo del paciente con ERC. En este documento, elaborado en conjunto por diez sociedades científicas, se muestra una actualización sobre conceptos, aclaraciones, criterios diagnósticos, estrategias de remisión y nuevas opciones terapéuticas. Se han revisado las evidencias y los principales estudios publicados en estos aspectos de la ERC, considerándose más bien un documento de información sobre esta patología. El documento incluye una actualización sobre la detección de la ERC, factores de riesgo, cribado, definición de progresión renal, actualización en los criterios de remisión con nuevas sugerencias en la población anciana, monitorización y estrategias de prevención de la ERC, manejo de comorbilidades asociadas, especialmente en diabetes mellitus, funciones del médico de Atención Primaria en el manejo de la ERC y qué no hacer en Nefrología. El objetivo del documento es que sirva de ayuda en el manejo multidisciplinar del paciente con ERC basado en las recomendaciones y conocimientos actuales.

There is growing interest in the potential health-related effects of moderate alcohol consumption and, specifically, of beer. This review provides an assessment of beer-associated effects on cardiovascular and metabolic risk factors to identify a consumption level that can be considered “moderate”. We identified all prospective clinical studies and systematic reviews that evaluated the health effects of beer published between January 2007 and April 2020. Five of six selected studies found a protective effect of moderate alcohol drinking on cardiovascular disease (beer up to 385 g/week) vs. abstainers or occasional drinkers. Four out of five papers showed an association between moderate alcohol consumption (beer intake of 84 g alcohol/week) and decreased mortality risk. We concluded that moderate beer consumption of up to 16 g alcohol/day (1 drink/day) for women and 28 g/day (1–2 drinks/day) for men is associated with decreased incidence of cardiovascular disease and overall mortality, among other metabolic health benefits.

Carotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness, predicting cardiovascular disease. We hypothesized that the amount of physical activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic (T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV values in subjects with impaired glucose metabolism (IGM) and T2D were higher than in normal glycemic subjects (P < 0.001). PA, fasting and 2 h glucose and HbA1c correlated significantly with (cf)PWV, but HDL or LDL cholesterol did not. The 2 h glucose, heart rate and alcohol consumption in T2D subjects had independent effects on (cf)PWV in multiple regression analysis. T2D and IGM were significantly associated to (cf)PWV. Interestingly, lipids did not have an additional effect on (cf)PWV. Subjects walking more than 10 000 steps/day had 0.2 m/s lower (cf)PWV than those walking less than 6000 steps/day. Presence of T2D, elevated heart rate and alcohol consumption in males were associated with increased aortic stiffening in elderly subjects.

Increased caloric intake associated with decreased physical activity and the presence of thrifty genes that are theoretically adapted to enhance the energy storage efficiency, cause metabolic changes that result in diet-related diseases or disorders. Such phenotypes are prevalent in populations of developed countries and their incidence is continuing to rise. Therefore, early diagnosis of diet-related diseases is an exciting field of research. The application of ‘omics’ technology, particularly metabolomics, has revealed the metabolic changes associated to diet-related diseases and also consequences of diet intervention in a global un-targeted way. The on-going development of dietary ideal models could elucidate the sequence of events, starting with the interaction between dietary habits and genetic adaptations that cause the metabolic changes induced as well as auxiliary symptoms and associated diseases. In this review, a range of mass spectrometry techniques applied to metabolomics of diet related diseases is discussed, including the combination of metabolomics with other studies to reveal systems properties of the diseases. Since it is difficult to set up a clinical study based on the probability of finding exploratory biomarkers to be applied in wide-population screening, many metabolomics studies have revealed biomarkers of 31 the complications of the disease, which could have power as prognostic biomarkers.

To study the effect of prolonged diabetes on protein synthesis and on the activities of initiation factors elF-2 and elF-2B in the liver, female rats were treated with streptozotocin. Some animals were mated and studied on day 20 of pregnancy, whereas others were kept virgin and studied in parallel. The protein synthesis rate was measured with an 'in vitro' cellfree system, and was lower in diabetic pregnant and virgin animals than in pregnant and virgin controls (30-60%). The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they always showed a higher protein synthesis rate than their mothers or virgin rats. Protein synthesis rate, RNA concentration, and initiation factor 2 activity were higher in pregnant than in virgin rats. Both activity and level of elF-2 factor changed in parallel to the protein synthesis rate, although no differences could be detected between control and diabetic animals. The eIF-2B activity in tissue extracts from diabetic virgin rats and fetuses was lower than in extracts from their controls, whereas no differences could be detected between pregnant and virgin control rats nor between pregnant control and pregnant diabetic animals. The percentage of the phosphorylated form of eIF-2 factor, eIF-2(uP), was slightly lower in virgin than in pregnant rats but was unaffected by the diabetic condition, while in diabetic fetuses this parameter was lower than in their corresponding controls. The cyclic adenosine monophosphate dependent protein kinase level was lower in diabetic rats than in controls, whereas no changes in the activity of casein kinase II were found. The isoelectric forms of the 13 subunit of eIF-2 factor, eIF-213, were different in the diabetic and the control animals, indicating that insulin deficiency modifies the phosphorylation of specific substrates. Since no differences were detected in RNA or eIF-2 content between control and diabetic rats, translation may, at least partly, be inhibited in the liver by an impairment of peptide chain initiation caused by the decreased eIF-2B activity which nevertheless is independent of eIF2u phosphorylation.

Para estudiar el efecto de la gestación y la diabetes sobre la actividad y la expresión (ARNm) de la lipoproteína lipasa (LPL) y de la lipasa sensible a las hormonas (HSL) en tejidos, las ratas recibieron 40 mg de estreptozotocina/kg y se sacrificaron al día 20 de gestación. En el tejido adiposo blanco {T AB), la actividad y el ARNm de la LPL eran más bajos en las ratas preñadas controles (PC) que en las vírgenes controles (VC), siendo también inferior la actividad en las diabéticas (D) que en las controles(C), tanto vírgenes (V) como preñadas (P). En la glándula mamaria (GM), la actividad y el ARNm de la LPL estaban más altos en las PC que en las VC, y disminuyeron en las PD y VD respecto de las C. En el T AB, la actividad HSL estaba más alta en las P que en las V y era similar en las PC y PD, sin cambios en los niveles de ARNm. En la GM, la actividad y el ARNm de la HSL estaban más bajos en las P que en las V y eran menores en las D que en las C. Estos resultados permiten concluir que los mecanismos de regulación de la actividad y de la expresión molecular (ARNm) de la LPL y de la HSL durante la gestación y la diabetes son específicos de cada tejido. El paralelismo en los cambios de la actividad y el nivel de ARNm de la LPL en el T AB y GM, así como entre la actividad y el ARNm de la HSL en la GM, indican que la regulación a nivel transcripcional de la expresión de estos genes es un mecanismo importante para la captación y movilización de los TO en estos tejidos.

Nuestros resultados permiten sugerir que la administración de antioxidantes capaces de reducir la producción de radicales libres, podrían desempeñar un importante papel en la prevención de los efectos teratogénicos asociados a la diabetes. Tal vez lo más relevante es que los antioxidantes actuarían independientemente del grado de control metabólico alcanzado, por lo que sus efectos podrían añadirse a los conseguidos al obtener un mejor control metabólico.