Relationship between Sodium Intake and Water Intake: The False and the True.

BACKGROUND: Generally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial. The purpose of this review is to provide examples of how the kidney handles water in relation to salt intake/output. It is based on re-analysis of previously published studies in which salt intake was adjusted to several different levels in the same subjects, and in databases of epidemiologic studies in populations on an ad libitum diet. Summary and Key Messages: These re-analyses allow us to draw the following conclusions: (1) In a steady state situation, the urine volume (and thus the fluid intake) remains unchanged over a large range of sodium intakes. The adaptation to a higher sodium excretion rests only on changes in urinary sodium concentration. However, above a certain limit, this concentration cannot increase further and the urine volume may then increase. (2) In population studies, it is not legitimate to assume that sodium is responsible for changes in urine volume, since people who eat more sodium also eat more of other nutrients leading to an increase in the excretion of potassium, urea and other solutes, besides sodium. (3) After an abrupt increase in sodium intake, fluid intake is increased in the first few days, but urine volume does not change. The extra fluid drunk is responsible for an increase in body weight.

Reduced insulin secretion and nocturnal dipping of blood pressure are associated with a disturbed circadian pattern of urine excretion in metabolic syndrome.

INTRODUCTION: An impaired Na and water excretion rate during daytime is associated with increased cardiovascular risk factors. Recent findings suggest that disturbed circadian rhythms may play an important role in salt-sensitive hypertension and reduced ß-cell function. METHODS: This study investigated clinical implications of the circadian pattern of urine excretion [evaluated as the day to night ratio of urine flow rate (D/N of V)] in 76 patients with metabolic syndrome (MS) not taking diuretics. We analyzed 24-h urinary excretion and blood pressure (BP) during separate day and night periods. In addition nondiabetic patients (n = 46 of 76) underwent an oral glucose tolerance test. RESULTS: The D/N of V varied largely among subjects (tertile 1 = 1.95 ± 0.40, tertile 3 = 0.67 ± 0.14). In the patients with low D/N of V, systolic BP dipped less at night, independently of age and creatinine clearance (P < 0.01). During the first 60 min of the oral glucose tolerance test, the rise in plasma insulin and the insulinogenic index were positively correlated with the D/N of V, even after adjustment for age, waist circumference, 24-h urine volume, and BP (P < 0.001 for both), suggesting inadequate insulin secretion in poor daytime excretors. CONCLUSION: In patients with MS, a disturbed circadian pattern of urine excretion is associated with a reduced nocturnal dipping of systolic BP and a reduced glucose-induced insulin secretion. These results underline the clinical importance of impaired circadian rhythms in MS and prompt further studies to evaluate the potential of the D/N of V as a prognostic marker in MS patients.

Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists.

The mechanisms by which arginine vasopressin (AVP) exerts its antidiuretic and pressor effects, via activation of V2 and V1a receptors, respectively, are relatively well understood, but the possible associated effects on sodium handling are a matter of controversy. In this study, normal conscious Wistar rats were acutely administered various doses of AVP, dDAVP (V2 agonist), furosemide, or the following selective non-peptide receptor antagonists SR121463A (V2 antagonist) or SR49059 (V1a antagonist). Urine flow and sodium excretion rates in the next 6 h were compared with basal values obtained on the previous day, after vehicle treatment, using each rat as its own control. The rate of sodium excretion decreased with V2 agonism and increased with V2 antagonism in a dose-dependent manner. However,for comparable increases in urine flow rate, the V2 antagonist induced a natriuresis 7-fold smaller than did furosemide. Vasopressin reduced sodium excretion at 1 mug/kg but increased it at doses >5 umg/kg,an effect that was abolished by the V1a antagonist. Combined V2 and V1a effects of endogenous vasopressin can be predicted to vary largely according to the respective levels of vasopressin in plasma,renal medulla (acting on interstitial cells), and urine (acting on V1a luminal receptors). In the usual range of regulation, antidiuretic effects of vasopressin may be associated with variable sodium retention. Although V2 antagonists are predominantly aquaretic, their possible effects on sodium excretion should not be neglected. In view of their proposed use in several human disorders, the respective influence of selective (V2) or mixed (V1a/V2) receptor antagonists on sodium handling in humans needs reevaluation.

[Difference in urine concentration according to gender and ethnicity: possible involvement in the different susceptibility to various renal and cardiovascular diseases]. / Différence de concentration urinaire selon le sexe ou l'origine ethnique: implications possibles dans la susceptibilité variable à différentes pathologies rénales et cardiovasculaires.

Men and African-Americans are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women and Caucasians. Previous studies suggest that the antidiuretic effects of vasopressin and/or a greater urine concentration are associated with the rate of progression of these diseases. The present review addresses possible sex and ethnic-related differences in urine volume and osmolality which could participate in this male and black higher predominance. We reanalyzed 24h-urine data collected previously by different investigators for other purposes. In studies concerning healthy subjects (six studies) or patients with chronic kidney disease or Diabetes mellitus (three studies), men excreted a larger osmolar load than women, with a 15 to 30% higher urinary osmolality (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) and a similar 24h urine volume than in women. In two American studies, African-Americans showed a significantly higher urinary concentration than Caucasians and a lower 24h-urine volume. Sex and ethnic differences in thirst threshold, vasopressin level, or other regulatory mediators may contribute to the higher urinary concentration of men and of African Americans. These differences could play a role in the greater susceptibility of these subjects to these pathologies. New prospective studies should take into account the antidiuretic effects of vasopressin as a potential risk factor in the initiation and progression of cardiovascular and renal diseases.

Ethnic differences in urine concentration: possible relationship to blood pressure.

The mechanisms that account for the susceptibility of black individuals to hypertension and their reduced ability to excrete sodium are poorly understood. Vasopressin administration has been shown in healthy humans to delay sodium excretion along with its antidiuretic action. Black individuals have been reported to have higher vasopressin levels than white individuals. Therefore, this study investigated retrospectively 24-h urine volume (V) and urine concentration index (urine-to-plasma ratio of creatinine concentration), as well as their possible relationships with BP, in a cohort of 141 healthy young black and white individuals (18 to 40 y). Black individuals were found to have a significantly lower V and higher urine concentration than white individuals, especially during daytime. In addition, they exhibited a blunted nocturnal fall in fluid and electrolyte excretion and a higher pulse pressure than white individuals. Higher urine concentration and lower V were associated significantly with higher PP (but not with systolic or diastolic BP) in men. These relations remained significant after adjustment for age, body mass index, and sodium and potassium excretion. These results suggest that an enhanced tendency to concentrate urine may delay the excretion of the daily ingested fluid and sodium and may increase pulse pressure in young normotensive individuals. The higher urine concentration that is observed in black individuals (which could represent an adaptation to better water conservation) may participate in their enhanced susceptibility to hypertension. If these results are confirmed in further studies, then vasopressin V2 receptor antagonists might offer a novel antihypertensive strategy, especially in the black population.

Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease.

Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of progression of chronic kidney disease (CKD), increased urinary albumin excretion, and delayed renal sodium excretion. The present review addresses possible sex-related differences in urine volume and osmolality (U(osm)) that could participate in this male risk predominance. Because of the scarcity of information, we reanalyzed 24-h urine data collected previously by different investigators for other purposes. In nine studies concerning healthy subjects (6 studies) or patients with CKD or diabetes mellitus, U(osm) (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) was 21-39% higher (i.e., about a 150 mosm/kgH2O difference) in men than in women. Urine volume was not statistically different. Thus, the larger osmolar load of men (related to their higher food intake) is excreted in a more concentrated urine with no difference in urine volume. This sex difference was not influenced by the level of sodium excretion and was still present in CKD patients. Sex differences in thirst threshold, AVP level, and other regulatory mediators may all contribute to the higher male U(osm). Because of the previously demonstrated adverse effects of vasopressin and/or high urine concentrating activity, the greater tendency of men to concentrate urine could participate in their greater susceptibility to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.