Intermuscular adipose tissue and muscle function in patients on maintenance hemodialysis.

Sarcopenia is common in advanced chronic kidney disease (CKD), contributing to poor outcomes. Intermuscular adipose tissue (IMAT) may worsen muscle function through metabolic and inflammatory pathways. We conducted a cross-sectional study comparing maintenance hemodialysis (MHD) patients and controls to assess IMAT and its associations.

Salt sensitivity of blood pressure: mechanisms and sex-specific differences.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease in individuals with or without hypertension. However, the mechanisms and management of SSBP remain unclear, mainly because the diagnosis of this condition relies on salt loading-depletion protocols that are not feasible in the clinic. The prevalence of hypertension is lower in premenopausal women than in men, but this sex-specific difference is reversed after menopause.

INTERMUSCULAR ADIPOSE TISSUE AND MUSCLE FUNCTION IN PATIENTS ON MAINTENANCE HEMODIALYSIS.

Background And Aims: Sarcopenia, defined as a loss in muscle mass and strength, is common in patients with advanced chronic kidney disease (CKD), leading to poor outcomes. Intermuscular adipose tissue (IMAT) accumulation is associated with metabolic and functional abnormalities in chronic disease conditions. This study assesses IMAT in maintenance hemodialysis (MHD) patients and its association with metabolic markers and physical performance.

Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals.

Background And Aims: High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower-extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association.

Methods: Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (Na-MRI) and proton (1H-MRI) imaging of the calf.

Myeloid Cell Glucocorticoid, Not Mineralocorticoid Receptor Signaling, Contributes to Salt-Sensitive Hypertension in Humans via Cortisol.

Background: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality, yet the etiology is poorly understood. We previously found that serum/glucocorticoid-regulated kinase 1 (SGK1) and epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel (ENaC)-dependent sodium entry into monocyte-derived antigen-presenting cells (APCs) and activation of NADPH oxidase, leading to the formation of isolevuglandins (IsoLGs) in SSBP. Whereas aldosterone via the mineralocorticoid receptor (MR) activates SGK1 leading to hypertension, our past findings indicate that levels of plasma aldosterone do not correlate with SSBP, and there is little to no MR expression in APCs.

A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.

Background: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD.

Methods: Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks.

Eicosanoid-Regulated Myeloid ENaC and Isolevuglandin Formation in Human Salt-Sensitive Hypertension.

Background: The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesized that epithelial sodium channel-dependent isolevuglandin-adduct formation in APCs is regulated by epoxyeicosatrienoic acids (EETs) and leads to salt-sensitive hypertension in humans.

Regulation of human salt-sensitivite hypertension by myeloid cell renin-angiotensin-aldosterone system.

Salt sensitivity of blood pressure is a phenomenon in which blood pressure changes according to dietary sodium intake. Our previous studies found that high salt activates antigen presenting cells, resulting in the development of hypertension. The mechanisms by which salt-induced immune cell activation is regulated in salt sensitivity of blood pressure are unknown.

High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals.

Background And Aims: High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association.

Methods And Results: In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using Na magnetic resonance imaging.

The epithelial sodium channel in inflammation and blood pressure modulation.

A major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models including rat or mouse, and thus remains the least understood of the four subunits.

Inflammation and oxidative stress in salt sensitive hypertension; The role of the NLRP3 inflammasome.

Salt-sensitivity of blood pressure is an independent risk factor for cardiovascular disease and affects approximately half of the hypertensive population. While the precise mechanisms of salt-sensitivity remain unclear, recent findings on body sodium homeostasis and salt-induced immune cell activation provide new insights into the relationship between high salt intake, inflammation, and hypertension. The immune system, specifically antigen-presenting cells (APCs) and T cells, are directly implicated in salt-induced renal and vascular injury and hypertension.

Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney Damage.

Salt-sensitive hypertension is a major risk factor for cardiovascular morbidity and mortality. The pathophysiologic mechanisms leading to different individual BP responses to changes in dietary salt remain elusive. Research in the last two decades revealed that the immune system plays a critical role in the development of hypertension and related end organ damage.

Association of Genetically Predicted Fibroblast Growth Factor-23 with Heart Failure: A Mendelian Randomization Study.

Background And Objectives: Elevated fibroblast growth factor-23 (FGF23) has been consistently associated with heart failure, particularly heart failure with preserved ejection fraction, among patients with CKD and in the general population. FGF23 may directly induce cardiac remodeling and heart failure. However, biases affecting observational studies impede robust causal inferences.

DC ENaC-Dependent Inflammasome Activation Contributes to Salt-Sensitive Hypertension.

Background: Salt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel EnaC (epithelial sodium channel) leads to the formation of IsoLGs (isolevuglandins) and release of proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension.

The Use of Healthy Eating Index 2015 and Healthy Beverage Index for Predicting and Modifying Cardiovascular and Renal Outcomes.

Purpose Of Review: With the wide recognition of the importance of dietary patterns rather than isolated nutrient groups on health outcomes, numerous diet quality indices have been designed to evaluate the overall food intake quality in the last two decades.

Recent Findings: The newest version of the Healthy Eating Index (HEI), HEI-2015, is a diet quality index that measures adherence to the recommendations of the 2015-2020 Dietary Guidelines for Americans. While the key nutrient groups are included in most diet quality indices, differences in other components and the scoring system differentiate HEI.

Recent advances in modulation of cardiovascular diseases by the gut microbiota.

The gut microbiota has recently gained attention due to its association with cardiovascular health, cancers, gastrointestinal disorders, and non-communicable diseases. One critical question is how the composition of the microbiota contributes to cardiovascular diseases (CVDs). Insightful reviews on the gut microbiota, its metabolites and the mechanisms that underlie its contribution to CVD are limited.

Emerging Roles for G Protein-Coupled Estrogen Receptor 1 in Cardio-Renal Health: Implications for Aging.

Cardiovascular (CV) and renal diseases are increasingly prevalent in the United States and globally. CV-related mortality is the leading cause of death in the United States, while renal-related mortality is the 8th. Despite advanced therapeutics, both diseases persist, warranting continued exploration of disease mechanisms to develop novel therapeutics and advance clinical outcomes for cardio-renal health.

Bile acids and salt-sensitive hypertension: a role of the gut-liver axis.

Salt-sensitivity of blood pressure (SSBP) affects 50% of the hypertensive and 25% of the normotensive populations. Importantly, SSBP is associated with increased risk for mortality in both populations independent of blood pressure. Despite its deleterious effects, the pathogenesis of SSBP is not fully understood.

Sox6, A Potential Target for MicroRNAs in Cardiometabolic Disease.

Purpose Of Review: The study aims to review recent advances in knowledge on the interplay between miRNAs and the sex-determining Region Y (SRY)-related high-mobility-group box 6 (Sox6) in physiology and pathophysiology, highlighting an important role in autoimmune and cardiometabolic conditions.

Recent Findings: The transcription factor Sox6 is an important member of the SoxD family and plays an indispensable role in adult tissue homeostasis, regeneration, and physiology. Abnormal expression of the Sox6 gene has been implicated in several disease conditions including diabetes, cardiomyopathy, autoimmune diseases, and hypertension.

Nutrition, Immunology, and Kidney: Looking Beyond the Horizons.

Purpose Of Review: Chronic kidney disease (CKD) is epidemic throughout the word. Despite various novel therapeutic opportunities, CKD is still associated with high morbidity and mortality. In CKD, patient's chronic inflammation is frequent and related with adverse outcomes.

Salt-Sensitivity of Blood Pressure and Insulin Resistance.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation.

Substitution of Sugar-Sweetened Beverages for Other Beverages: Can It Be the Next Step Towards Healthy Aging?

Purpose Of Review: With the prolongation of life expectancy, the gap between lifespan and "health span," the disease-free lifespan, has been widening due to the massive burden of age-related chronic diseases and research on healthy aging has been gaining momentum. A growing body of evidence suggests that diet is a strong determinant of healthy aging and consumption of sugar-sweetened beverages (SSB), a major source of added sugars, predicts poor health outcomes in the aging population, including cardiovascular disease, diabetes, and cancer. Evidence further supports a link between sugar-sweetened beverages-triggered pathological processes and biologic factors of aging, including inflammaging, oxidative stress, and alterations in intestinal microbiota.

Salt Sensitivity of Blood Pressure in Blacks and Women: A Role of Inflammation, Oxidative Stress, and Epithelial Na Channel.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for mortality and morbidity due to cardiovascular disease, and disproportionately affects blacks and women. Several mechanisms have been proposed, including exaggerated activation of sodium transporters in the kidney leading to salt retention and water. Recent studies have found that in addition to the renal epithelium, myeloid immune cells can sense sodium the epithelial Na channel (ENaC), which leads to activation of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex, increased fatty acid oxidation, and production of isolevuglandins (IsoLGs).