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Introduction: Klotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated. Methods: We conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR=60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry. Results: APatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p<0.001), mRNA expression in blood circulating cells and carotid artery wall (2.92 [2.06-4.8] vs. 3.69 [2.42-7.13] log.a.u., p=0.015; 0.41 [0.16-0.59] vs. 0.79 [0.37-1.4] log.a.u., p=0.013, respectively) and immunoreactivity in the intimal-medial area of the carotids (4.23 [4.15-4.27] vs. 4.49 [4.28-4.63] log µm2 p=0.008). CIMT was inversely related with Klotho levels in serum (r= -0.717, p<0.001), blood mRNA expression (r=-0.426, p=0.011), and with carotid artery mRNA and immunoreactivity levels (r= -0.45, p=0.07; r= -0.455, p= 0.006, respectively). Multivariate analysis showed that serum Klotho, together with the gene expression levels of tumor necrosis factor TNFa in blood circulating cells, were independent determinants of CIMT values (adjusted R2 = 0.593, p<0.001). Discussion: The results of this study in subjects with eGFR=60mL/min/1.73m2 show that patients with carotid artery atherosclerosis and higher values of CIMT present reduced soluble Klotho levels, as well as decreased KL mRNA expression in peripheral blood circulating cells and Klotho protein levels in the intima-media of the carotid artery wall. [ABSTRACT FROM AUTHOR]

Klotho protein has been associated with beneficial effects that contribute to the maintenance of cardiovascular health. Diverse studies suggest that alterations in the levels of this molecule may be associated with pathophysiological abnormalities that result in increased cardiovascular risk. The primary aim of this proof-of-concept study was to analyse the existence of a potential link between Klotho gene polymorphisms and the expression level of this gene in the vascular wall, and additionally with the incidence of cardiovascular disease and cardiovascular risk factors. Our results indicate that the variant G-395A, located in the promoter region, influences Klotho gene vascular expression and is associated with the incidence of diabetes. Similarly, the exonic variant KL-VS was associated with the incidence of atherosclerotic vascular disease and coronary artery disease. Moreover, vascular expression levels of Klotho were related with the incidence of diabetes mellitus and coronary artery disease. These findings, which need to be confirmed in larger studies, suggest a potential role of Klotho in the pathogenesis of vascular damage. [ABSTRACT FROM AUTHOR]

Introduction: the preliminary nutritional screening tool CIPA (food intake, proteins, anthropometry) is positive when it fulfills one of the following: control food intake (CI) 48-72 h < 50%, albumin < 3 g/dl, total protein < 5 g/dl, body mass index (BMI) < 18,5 kg/m2 or mid-upper arm circumference (MUAC) ≤ 22,5 cm. The use of two protein parameters increases costs and difficulty; one of them can be suppressed without affecting validity.Objectives: to evaluate the effectiveness of screening CIPA after exclusion of total protein.Method: prospective study of hospitalized patients; prevalence or risk of malnutrition was evaluated through CIPA and Subjective Global Assessment (SGA). Hospital malnutrition according to complete CIPA screening (with total proteins and albumin, [CIPAc] and without total proteins [CIPAw/p]) and concordance between both methods were analyzed, as well as the association of the positive screening result with clinical outcomes.Results: three hundred and forty-three patients were analyzed. The prevalence or risk of malnutrition identified by complete CIPA (c) was 38.19% (33.02-43.36); by CIPA without protein (w/p), 37.32% (32.17-42.46); and SGA was 29.15% (24.32-33.99). Kappa index: 0.981 between both CIPAs, p < 0.001. Both CIPA and SGA detect patients with higher mortality in hospital and one month after discharge. Early readmission was higher in positive CIPA, statistical significantly in CIPAw/p (screening with positive results 21.88% vs screening with negative results 13.49%, p = 0.044), SGA 20.01% vs 15.23%, p = 0.28. Length of stay was higher in patients with positive screening in CIPAc, CIPAw/p and SGA.Conclusions: CIPAw/p is equally or more effective than the previously validated full CIPA; therefore, it could replace the latter saving costs. The prevalence of malnutrition is high in both variants and they are able to predict which patient has worse clinical prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Klotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated., Methods: We conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR≥60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry., Results: APatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p<0.001), mRNA expression in blood circulating cells and carotid artery wall (2.92 [2.06-4.8] vs. 3.69 [2.42-7.13] log.a.u., p=0.015; 0.41 [0.16-0.59] vs. 0.79 [0.37-1.4] log.a.u., p=0.013, respectively) and immunoreactivity in the intimal-medial area of the carotids (4.23 [4.15-4.27] vs. 4.49 [4.28-4.63] log µm2 p=0.008). CIMT was inversely related with Klotho levels in serum (r= -0.717, p<0.001), blood mRNA expression (r=-0.426, p=0.011), and with carotid artery mRNA and immunoreactivity levels (r= -0.45, p=0.07; r= -0.455, p= 0.006, respectively). Multivariate analysis showed that serum Klotho, together with the gene expression levels of tumor necrosis factor TNFa in blood circulating cells, were independent determinants of CIMT values (adjusted R2 = 0.593, p<0.001)., Discussion: The results of this study in subjects with eGFR≥60mL/min/1.73m2 show that patients with carotid artery atherosclerosis and higher values of CIMT present reduced soluble Klotho levels, as well as decreased KL mRNA expression in peripheral blood circulating cells and Klotho protein levels in the intima-media of the carotid artery wall., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Donate-Correa, Martín-Núñez, Martin-Olivera, Mora-Fernández, Tagua, Ferri, López-Castillo, Delgado-Molinos, López-Tarruella, Arévalo-Gómez, Pérez-Delgado, González-Luis and Navarro-González.)

Introduction: the preliminary nutritional screening tool CIPA (food intake, proteins, anthropometry) is positive when it fulfills one of the following: control food intake (CI) 48-72 h < 50%, albumin < 3 g/dl, total protein < 5 g/dl, body mass index (BMI) < 18,5 kg/m2 or mid-upper arm circumference (MUAC) ≤ 22,5 cm. The use of two protein parameters increases costs and difficulty; one of them can be suppressed without affecting validity., Objectives: to evaluate the effectiveness of screening CIPA after exclusion of total protein., Method: prospective study of hospitalized patients; prevalence or risk of malnutrition was evaluated through CIPA and Subjective Global Assessment (SGA). Hospital malnutrition according to complete CIPA screening (with total proteins and albumin, [CIPAc] and without total proteins [CIPAw/p]) and concordance between both methods were analyzed, as well as the association of the positive screening result with clinical outcomes., Results: three hundred and forty-three patients were analyzed. The prevalence or risk of malnutrition identified by complete CIPA (c) was 38.19% (33.02-43.36); by CIPA without protein (w/p), 37.32% (32.17-42.46); and SGA was 29.15% (24.32-33.99). Kappa index: 0.981 between both CIPAs, p < 0.001. Both CIPA and SGA detect patients with higher mortality in hospital and one month after discharge. Early readmission was higher in positive CIPA, statistical significantly in CIPAw/p (screening with positive results 21.88% vs screening with negative results 13.49%, p = 0.044), SGA 20.01% vs 15.23%, p = 0.28. Length of stay was higher in patients with positive screening in CIPAc, CIPAw/p and SGA., Conclusions: CIPAw/p is equally or more effective than the previously validated full CIPA; therefore, it could replace the latter saving costs. The prevalence of malnutrition is high in both variants and they are able to predict which patient has worse clinical prognosis.

Background and Objectives: Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients., Methods: Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1μg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study., Results: Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction., Conclusions: Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Protein Klotho, beyond its role as a regulator of the phosphatemia, is also involved in the maintaining of the cardiovascular health, being associated its alterations with the development of cardiovascular damage and increased morbi-mortality. For all this, nowadays Klotho is the subject of a thorough research which is focused on uncover its intimate mechanisms of action, and in analyzing the utility of its modulation as a potential strategy with clinical applicability. Molecular mechanisms of Klotho are not well understood but an emerging research area links Klotho deficiency with vascular pathology. Changes in this protein have been associated with cardiovascular-related complications like inflammation, vascular calcification, and endothelial dysfunction. All this is particularly relevant if considering the recent discovery of Klotho expression in vascular tissue.