No abstract

A single 24-h urine collection cannot predict sodium, potassium, or chloride intake; thus, multiple collections are necessary. This information is important when assessing electrolyte intake in individuals.

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes ( P <0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events ( P =0.049) and a 21% additional risk reduction for heart failure ( P =0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.

Relative to a single baseline 24-hour sodium measurement, the use of subsequent 24-hour urine samples resulted in different estimations of an individual's sodium intake, whereas population averages remained similar. This finding had significant consequences for the association between sodium intake and long-term cardiovascular and renal outcomes.

The assumption that sodium accumulation in the human body is always accompanied by water retention has been challenged by data showing that sodium can be stored nonosmotically. Here we investigated the contribution of nonosmotic sodium storage to short-term sodium homeostasis after hypertonic saline infusion in healthy individuals on a low-sodium diet. During four hours after infusion, we compared the observed changes in plasma sodium concentration and urinary cation excretion with changes that were calculated with the Adrogue-Madias and Nguyen-Kurtz formula, formulations widely implemented to guide the treatment of dysnatremias. We included 12 healthy non-smoking male individuals with normal blood pressure, body mass index, and kidney function. Right after infusion, the average observed plasma sodium change from baseline (3.5 mmol/L) was similar to the predicted changes by the Adrogue-Madias (3.3 mmol/L) and Nguyen-Kurtz formula (3.1 mmol/L). However, the observed plasma sodium concentration change after four hours (-1.8 mmol/L) was very different from the changes as predicted by the Adrogue-Madias (0.4 mmol/L) and the Nguyen-Kurtz formula (-0.9 mmol/L). Moreover, only 47% and 55%, respectively, of the expected sodium and potassium excretion were retrieved in the urine. Thus, healthy individuals are able to osmotically inactivate significant amounts of sodium after hypertonic saline infusion. Further research is needed to uncover factors that determine nonosmotic sodium storage.

Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume. J Am Soc Nephrol 26: 777-783, 2015. doi: 10.1681 In Western society, average daily intake of salt is 8-12 g, thereby greatly exceeding the recommended amount by the World Health Organization of 5 g daily. 1,2 This recommendation is on the basis of the observation that dietary salt intake exceeding 5 g/d, which is equivalent to 2 g or 85 mmol sodium, is associated with hypertension and increased cardiovascular risk in many cohort studies. 3,4 Other than negative effects on cardiovascular morbidity and mortality, high salt intake has also been related to intermediate end points for kidney damage, such as proteinuria, in both patients with CKD and the general population. 5,6 Dietary salt restriction is, therefore, regarded as an important target for improvement of global health. 4 For example, in the United States, it has been estimated that a reduction of dietary salt intake by 3 g/d would reduce annual health costs by $10-$24 billion. 7 Generally, detrimental effects of excessive sodium intake have been linked to expansion of extracellular volume (ECV) and hypertension, which is evidenced by various observations that low sodium reduces BP in both normotensive individuals and individuals with hypertension. 4,8 The increase in BP after dietary sodium excess is highly variable, with some individuals showing a relatively small increase, whereas large BP increases can be observed in others. 9,10 It is likely that these individual variations in salt sensitivity differentially affect cardiovascular and renal risk and may also explain the inconsistent results from population studies investigating the relation between sodium intake and cardiovascular risk. 11 According to Guyton's pressurenatriuresis curve, the kidney regulates long-term BP by altering renal sodium e...

Globally, average dietary sodium intake is double the recommended amount, whereas potassium is often consumed in suboptimal amounts. High sodium diets are associated with increased cardiovascular and renal disease risk, while potassium may have protective properties. Consequently, patients at risk of cardiovascular and renal disease are urged to follow these recommendations, but dietary adherence is often low due to high sodium and low potassium content in processed foods. Adequate monitoring of intake is essential to guide dietary advice in clinical practice and can be used to investigate the relationship between intake and health outcomes. Daily sodium and potassium intake is often estimated with 24-h sodium and potassium excretion, but long-term balance studies demonstrate that this method lacks accuracy on an individual level. Dietary assessment tools and spot urine collections also exhibit poor performance when estimating individual sodium and potassium intake. Collection of multiple consecutive 24-h urines increases accuracy, but also patient burden. In this narrative review, we discuss current approaches to estimating dietary sodium and potassium intake. Additionally, we explore alternative methods that may improve test accuracy without increasing burden.

Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer’s disease. In animal models of hypertension, many of Alzheimer’s disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain barrier dysfunction. Removal of amyloid β and other waste products depends in part on clearance via the brain interstitial fluid (ISF). Here we studied the impact of hypertension on ISF drainage, using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). At 8 months, high (500 kD) and low (3 kD) fluorescent molecular weight tracers released passively into the hippocampus showed a drastically enhanced spreading in SHR. Tracer spreading was inhomogeneous, with accumulation at ISF-CSF borders, around arteries, and towards the stratum lacunosum moleculare. These locations stained positively for the astrocyte marker GFAP, and aquaporin 4. Despite enhanced dispersion, clearance of tracers was not affected in SHR. In conclusion, these data indicate enhanced bulk flow of ISF in the hippocampus of hypertensive rats. ISF drains along astrocytes towards the cerebrospinal fluid compartment, which leads to sieving of high molecular weight solutes. Sieving may lead to a local increase in the concentration of waste products and potentially promotes the aggregation of amyloid β.