Explore the vast range of titles available.

Intradialytic hypotension (IDH) is a frequent and serious complication of chronic haemodialysis, linked to adverse long-term outcomes including increased cardiovascular and all-cause mortality. IDH is the end result of the interaction between ultrafiltration rate (UFR), cardiac output and arteriolar tone. Thus excessive ultrafiltration may decrease the cardiac output, especially when compensatory mechanisms (heart rate, myocardial contractility, vascular tone and splanchnic flow shifts) fail to be optimally recruited. The repeated disruption of end-organ perfusion in IDH may lead to various adverse clinical outcomes affecting the heart, central nervous system, kidney and gastrointestinal system. Potential interventions to decrease the incidence or severity of IDH include optimization of the dialysis prescription (cool dialysate, UFR, sodium profiling and high-flux haemofiltration), interventions during the dialysis session (midodrine, mannitol, food intake, intradialytic exercise and intermittent pneumatic compression of the lower limbs) and interventions in the interdialysis period (lower interdialytic weight gain and blood pressure–lowering drugs). However, the evidence base for many of these interventions is thin and optimal prevention and management of IDH awaits further clinical investigation. Developing a consensus definition of IDH will facilitate clinical research. We review the most recent findings on risk factors, pathophysiology and management of IDH and, based on this, we call for a new consensus definition of IDH based on clinical outcomes and define a roadmap for IDH research.

Background: The consumption of sweetened beverages is associated with increased risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus. Objective: We hypothesized that the metabolic effects of fructose in sugary beverages might be modulated by the speed of ingestion in addition to the overall amount. Design: Thirty healthy subjects free of any disease and medication were recruited into two groups. After overnight fasting, subjects in group 1 drank 500 mL of apple juice over an hour by drinking 125 mL every 15 min, while subjects in group 2 drank 500 mL of apple juice over 5 min. Blood samples were collected at time zero and 15, 30, 60, and 120 min after ingestion to be analyzed for serum glucose, insulin, homeostatic model assessment (HOMA-IR) score, fibroblast growth factor 21, copeptin, osmolarity, sodium, blood urea nitrogen (BUN), lactate, uric acid, and phosphate levels. Results: Serum glucose, insulin, HOMA-IR, fibroblast growth factor 21, copeptin, osmolarity, sodium, BUN, and lactate levels increased following apple juice ingestion. The increases were greater in the fast-drinking group, which were more significant after 15 min and 30 min compared to baseline. The changes in uric acid were not statistically different between the groups. Phosphate levels significantly increased only in the fast-drinking group. Conclusion: Fast ingestion of 100% apple juice causes a significantly greater metabolic response, which may be associated with negative long-term outcomes. Our findings suggest that the rate of ingestion must be considered when evaluating the metabolic impacts of sweetened beverage consumption.

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. While the δ subunit is poorly expressed in the human kidney, we recently found that its gene variants are associated with blood pressure and kidney function. The δ subunit is expressed in the human vasculature where it may influence vascular function. Moreover, we recently found that the δ subunit is also expressed human antigen presenting cells (APCs). Our studies indicate that extracellular Na + enters APCs via ENaC leading to inflammation and salt-induced hypertension. In this review, we highlight recent findings on the role of extra-renal ENaC in inflammation, vascular dysfunction, and blood pressure modulation. Targeting extra-renal ENaC may provide new drug therapies for salt-induced hypertension.

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. IMAT was measured via calf muscle MRI, and body composition (BMI, fat mass index), metabolic markers (hs‐CRP, TNF‐α, IL‐6, insulin resistance), and circulating cell‐free mitochondrial DNA (ccf‐mtDNA) were assessed. Muscle function was evaluated with handgrip strength. IMAT differences between groups were tested using inverse propensity weighting. We analyzed 25 MHD patients and 23 controls. Median age was 53 years, BMI 30.4 kg/m2, 83% were male, and 56% were African American. Baseline characteristics were similar between groups, except for race. MHD patients had higher IMAT (p < 0.01) and elevated TNF‐α, IL‐6, and hs‐CRP (p < 0.01). IMAT was positively correlated with IL‐6 in MHD patients and with TNF‐α in controls. Handgrip strength was inversely correlated with IMAT in the full cohort (p < 0.01). Our findings highlight the role of IMAT in inflammation and functional decline in CKD, suggesting its potential as a therapeutic target.

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. Changes in serum inflammatory markers and insulin‐mediated protein synthesis, breakdown and net balance in the whole‐body and skeletal muscle compartments were assessed using hyperinsulinaemic–hyperaminoacidemic clamp technique at baseline and Week 12. Results Among 24 patients, median (interquartile range) age was 51 (40, 61), 79% were African American and 21% had diabetes mellitus. All patients initiated on intervention completed the study, and no serious adverse events were observed. There was a statistically significant decrease in serum high‐sensitivity C‐reactive protein in the pioglitazone group compared with placebo, but not in the IL‐1ra group. No significant differences in the changes of whole‐body or skeletal muscle protein synthesis, breakdown and net balance were found between the groups. Conclusions In this pilot study, there were no statistically significant effects of 12 weeks of IL‐1ra or pioglitazone on protein metabolism in patients on MHD. Clinicaltrials.gov registration: NCT02278562.

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. CV and renal diseases increase with age, and there are sex differences evident in both the prevalence and progression of CV and renal disease. These age and sex differences seen in cardio-renal health implicate sex hormones as potentially important regulators to be studied. One such regulator is G protein-coupled estrogen receptor 1 (GPER1). GPER1 has been implicated in estrogen signaling and is expressed in a variety of tissues including the heart, vasculature, and kidney. GPER1 has been shown to be protective against CV and renal diseases in different experimental animal models. GPER1 actions involve multiple signaling pathways: interaction with aldosterone and endothelin-1 signaling, stimulation of the release of nitric oxide, and reduction in oxidative stress, inflammation, and immune infiltration. This review will discuss the current literature regarding GPER1 and cardio-renal health, particularly in the context of aging. Improving our understanding of GPER1-evoked mechanisms may reveal novel therapeutics aimed at improving cardio-renal health and clinical outcomes in the elderly.

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. Hence, the aim of this review was to describe linkages between the composition of the microbiota and CVD, CVD risk factors such as hypertension, diet, ageing, and sex differences. We have also highlighted potential therapies for improving the composition of the gut microbiota, which may result in better cardiovascular health.

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 (23Na‐MRI) and proton (1H‐MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic‐euglycemic clamp. Results Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high‐sensitivity C‐reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high‐sensitivity C‐reactive protein and interleukin‐6 (p for interaction = 0.022 and 0.006, respectively). Conclusions Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation. Intermuscular adipose tissue and tissue sodium in healthy individuals.

Background To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. Methods Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. Results IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group ( p  > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). Conclusion RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC’s renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

Background and objectivesContrast-induced nephropathy (CIN) is a relatively common complication following primary coronary angiography (CAG) or percutaneous coronary intervention (PCI), especially in at-risk patients. The goal of this study is to evaluate the role of pre-procedural serum osmolarity as a risk factor for CIN in patients undergoing elective CAG for stable coronary artery disease (CAD).Materials and methodsA total of 356 stable CAD patients scheduled to undergo CAG or PCI were included in this two-center study. Serum osmolarity was calculated on admission. CIN was defined according to the KDIGO criteria.ResultsThere were 45 (12.6%) patients who developed CIN 48–72 h after CAG or PCI. CIN patients had a higher prevalence of diabetes (51.1% in those with CIN vs 24.4% in those without CIN, p < 0.001), higher serum glucose (129 mg/dL in those with CIN vs 108 mg/dL in those without CIN, p < 0.001), blood urea nitrogen (22.4 mg/dL in those with CIN vs 19.0 mg/dL in those without CIN, p = 0.01) and serum osmolarity (294.2 mOsm in those with CIN vs 290.1 mOsm in those without CIN, p < 0.001) levels, had received a higher dose of contrast (250 mL in those with CIN vs 200 mL in those without CIN, p = 0.03) but had lower hemoglobin (12.9 g/dL in those with CIN vs 13.6 g/dL in those without CIN, p = 0.04) level. In multivariate analysis, serum osmolarity [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.04–1.18 for each mOsm/L increase; p = 0.001], diabetes (OR 2.43, 95% CI 1.26–4.71; p = 0.01), C-reactive protein (OR 1.04, 95% CI 1.01–1.08 for each mg/dL increase; p = 0.02) and contrast volume (OR 34.66, 95% CI 1.25–962.22 for each L increase; p = 0.04) remained as independent predictors of CIN. Serum sodium, glucose and blood urea nitrogen contributed to the excess serum osmolarity of CIN patients.ConclusionSerum osmolarity is a cheap and widely available marker that can reliably predict CIN after CAG or PCI. Future research should focus on determining a clinically optimal cutoff for serum osmolarity that would warrant preventive interventions. Furthermore, later research may investigate the role of serum osmolarity not only as a risk factor but also as a pathogenetic mechanism underlying CIN.