Measurement Of Urinary Sodium Excretion Research Articles

EXAMINATION OF THE EFFECT OF LIRAGLUTIDE ON BLOOD PRESSURE AND URINARY SODIUM EXCRETION

Objective: GLP-1 analog is suitable for use in obese diabetic patients as a drug having an effect of improving postprandial blood glucose and suppressing weight loss. Recently, it has been reported that the use of this drug causes hypotension, and its mechanism is to act on the GLP-1 receptor of the proximal tubule to promote sodium excretion and increase NO production of vascular endothelium. However, few clinical reports have examined the antihypertensive effects of GLP-1 analogs. We investigated the effects of liraglutide on blood pressure and urinary sodium excretion. Design and method: The subjects were ten patients with type 2 diabetes who admitted to our department for the adjustment of the antidiabetic treatment regimen (age 66.9 ± 11.7 years, male 40%). Before introduction of liraglutide and before discharge, various tests including blood pressure and blood glucose control index and measurement of urinary sodium excretion. The dose of liraglutide was 0.3 mg/day for the first week, then increased to 0.6 mg/day, up to a maximum of 0.9 mg/day. Results: Both BMI and HbA1c (NGSP) decreased with the administration of liraglutide (BMI from 28.1 ± 3.8 to 27.0 ± 3.7, p < 0.001, HbA1c from 8.7 ± 1.5% to 7.5 ± 1.1%, p < 0.001). Urinary Na excretion increased with administration of liraglutide (frome 135.7 ± 13.71 mEq/day to 155.2 ± 30.7 mEq/day, p < 0.05). Systolic blood pressure tended to decrease in patients with hypertension (from 130.9 ± 15.0 mmHg to 124.0 ± 11.5 mmHg, p = 0.06). Conclusions: Liraglutide, a GLP-1 analog, showed an improvement in glycemic control and a weight loss effect, as well as a decrease in urinary Na excretion. The drug was considered to exhibit antihypertensive effects, particularly in cases of hypertensive complications.

Effects of within-person variability in spot urinary sodium measurements on the associations with blood pressure and risk of cardiovascular disease in 0.5 Million adults in UK Biobank

Abstract Background Randomised control trials have demonstrated direct positive and causal associations of 24-hr measurements of urinary sodium excretion on blood pressure. However, prospective studies, which often used spot (not 24-hr) measurements of urinary sodium, have reported J-shaped associations with higher risks of cardiovascular disease (CVD) at sodium intake <4 g/day. The reasons for the discrepant results are not fully understood, but have prompted some to question the World Health Organisation's recommendations to restrict sodium intake to <2.3g/day. Purpose We examined the effects of within-person variability in spot urinary sodium (UNa) measurements on immediate and delayed associations of UNa with blood pressure at baseline and at resurvey, and with incident cardiovascular disease in the UK Biobank (UKB). Methods Baseline spot urine samples were measured in 502,619 adults at baseline and in 20,346 participants who were resurveyed at 4 years after baseline. Linear regression was used to assess associations of baseline UNa measurements with systolic blood pressure (SBP; mmHg) at baseline and at resurvey. Cox regression was used estimate the associations between baseline measures of UNa with incident CVD events (recorded from linkage with hospital records). All analyses were adjusted for confounders and corrected for regression dilution bias. Results After excluding participants with prevalent diseases, the primary analyses involved 386,060 adults who were followed-up for a median of 7.8 years, during which ∼13,000 CVD events occurred. Estimated mean (SD) urinary sodium excretion was 77.4 mmol/L (SD 44.4, IQR = 42.8–103.7 mmol/L), and mean SBP/DBP were 137.5/82.3 (SD 18.5/10.1) mmHg, respectively. Within-person variability in UNa was high, with a self-correlation of 0.35 at 4 years between measurements. After adjustment for confounders and correction for regression dilution bias, a 100 mmol/L higher UNa was associated with an immediate 3.2 mmHg higher SBP (95% confidence interval [CI]: 2.8–3.6) in cross-sectional analyses (Figure 1). However, the corresponding associations of baseline UNa with SBP at resurvey was completely attenuated (p=0.20). The predicted risk of CVD was 1.06 (95% CI 1.06–1.07, p<0.001) for a 3.2 mmHg higher SBP, but the observed risk for a 100 mmol/L higher UNa was 0.95 (95% CI 0.82–1.10, p=0.47) (Figure 1). Conclusions While spot measurements of UNa were strongly associated with immediate effects on SBP, the magnitude of within-person variability in UNa precluded detection of associations with SBP several years after baseline or with risk of CVD. The extreme within-person variability in spot UNa may explain the discrepant results of the trials and observational studies of sodium and blood pressure. Figure 1. Spot UNa with SBP and CVD in UK Biobank Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Core funding from the Medical Research Council-Population Health Research Unit, British Heart Foundation

Intrarenal signaling mediated by CCK plays a role in salt intake-induced natriuresis.

The natriuretic hormone CCK exhibits its gene transcripts in total kidney extracts. To test the possibility of CCK acting as an intrarenal mediator of sodium excretion, we examined mouse kidneys by 1) an in situ hybridization technique for CCK mRNA in animals fed a normal- or a high-sodium diet; 2) immuno-electron microscopy for the CCK peptide, 3) an in situ hybridization method and immunohistochemistry for the CCK-specific receptor CCKAR; 4) confocal image analysis of receptor-mediated Ca2+ responses in isolated renal tubules; and 5) metabolic cage experiments for the measurement of urinary sodium excretion in high-salt-fed mice either treated or untreated with the CCKAR antagonist lorglumide. Results showed the CCK gene to be expressed intensely in the inner medulla and moderately in the inner stripe of the outer medulla, with the expression in the latter being enhanced by high sodium intake. Immunoreactivity for the CCK peptide was localized to the rough endoplasmic reticulum of the medullary interstitial cells in corresponding renal regions, confirming it to be a secretory protein. Gene transcripts, protein products, and the functional activity for CCKAR were consistently localized to the late proximal tubule segments (S2 and S3) in the medullary rays, and the outer stripe of the outer medulla. Lorglumide significantly diminished natriuretic responses of mice to a dietary sodium load without altering the glomerular filtration rate. These findings suggest that the medullary interstitial cells respond to body fluid expansion by CCK release for feedback regulation of the late proximal tubular reabsorption.

For Patients with Kidney Disease, Very High Salt Intake Increases Cardiovascular Risk

In a recent, large, international study, high sodium intake was associated with increased risk for cardiovascular disease (CVD; NEJM JW Cardiol Aug 2016 and Lancet 2016 May 20; [e-pub]). The current investigators studied this association in 3757 people with chronic kidney disease at seven U.S. locations (mean age, 58; 45% women). Every participant had at least one measurement of urinary sodium excretion. At follow-up …

Iodine status in preschool children and evaluation of major dietary iodine sources: a German experience

Even mild iodine deficiency may negatively affect cognitive performance, especially at a young age. Our aim was to investigate iodine status in very young children and to assess the importance of iodized salt in processed foods of which the use has decreased during the last years in Germany. Twenty-four hours urinary iodine excretion (UIE) as a marker of iodine intake was measured in 378 24 h urine samples collected 2003-2010 by 221 3 to <6 years old participants of the DONALD Study. Parallel 3-d weighed dietary records and measurements of urinary sodium excretion provided data on the daily consumption of the most important iodine sources in the children's diet (iodized salt, milk, fish, meat and eggs). Time trends of UIE (2003-2010) and contributions of the different food groups were analyzed by using linear mixed-effects regression models. Median UIE of 71 μg/d in boys and 65 μg/d in girls (P = 0.03), corresponding to an iodine intake of 82 and 75 μg/d, respectively (assumption: 15% non-renal iodine losses), was below the recommended dietary allowance (RDA) of 90 μg/d. Milk, salt and egg intake were significant predictors of UIE; milk and salt together accounted for >80% of iodine supply. Between 2003 and 2010, UIE decreased significantly by approximately 1 μg/d per year. The contribution of salt intake to UIE decreased from 2003-2006 to 2007-2010. In countries where salt is a major iodine source, already modest decreases in the iodized proportion of salt used in processed foods may relevantly impair iodine status even in preschool children.

1046 Iodine Status in Preschool Children and Evaluation of Major Dietary Iodine Sources: A German Experience

PurposeEven mild iodine deficiency may negatively affect cognitive performance, especially at a young age. Our aim was to investigate iodine status in very young children and to assess the importance...

Abnormal Circadian Rhythm of Diuresis or Nocturnal Polyuria in a Subgroup of Children With Enuresis and Hypercalciuria is Related to Increased Sodium Retention During Daytime

In a subgroup of children with enuresis an increase in nighttime water and solute excretion has been documented. To investigate if modifications in renal function are involved in nocturnal enuresis, we assessed circadian variation in natriuresis and tubular sodium handling in polyuric hypercalciuric children. A total of 10 children with proved hypercalciuria and nocturnal polyuria and 10 age matched controls were included in the study. A 24-hour urine collection was performed in 8 sampling periods for measurement of urinary sodium excretion. Segmental tubular sodium transport was investigated during a daytime oral water load test and calculated according to standardized clearance methodology. The children with enuresis showed a marked increase in the fractional excretion of sodium during the night (0.93% +/- 0.36%), while daytime sodium excretion was decreased (0.84% +/- 0.23%). Analysis of segmental tubular sodium transport revealed decreased delivery of sodium to distal tubule (C(H2O) + C(Na) = 10.7 ml/100 ml glomerular filtration rate), indicating increased proximal tubular sodium reabsorption but also stimulation of distal sodium reabsorption as demonstrated by increased fractional distal sodium reabsorption (92.9% +/- 2.2%, controls 90.5% +/- 2.9%). Increased distal reabsorption was associated with increased fractional potassium excretion (17.5% +/- 2.7%, controls 13.6% +/- 6.4%), indicating increased distal tubular sodium/potassium exchange. No intrinsic defect in renal tubular sodium transport was found, but during the day increased sodium reabsorption in proximal and distal tubules was observed, suggesting extrarenal factors to be involved in altered circadian variation in solute and water excretion by the kidney.

Mineralocorticoid activity of 18-OH-DOC and DOCA in dogs with an aortic-caval fistula.

The mineralocorticoid activity of 18-hydroxydeoxycorticosterone (18-OH-DOC) was measured during chronic electrolyte balance studies or during the postprandial increase in electrolyte excretion in conscious dogs with an aortic-caval fistula. In the chronic balance study, daily doses of DOCA and 18-OH-DOC ranging from 1 to 25 mg were administered intramuscularly for 3 consecutive days each, 6 h prior to feeding. For the postprandial study, 2-10 mg of DOCA and 18-OH-DOC were administered at feeding and postprandial electrolyte excretion was measured hourly for 6 h. Sodium and fluid retention in the dogs with an aortic-caval fistula was related to the dose of mineralocorticoid administered and equivalent sodium-retaining responses were achieved with 6-10 times more 18-OH-DOC than DOCA. Rapid absorption of both steroids was suggested from the postprandial measurements of urinary sodium excretion. Slight potassium retention occurred during the chronic administration of large doses of DOCA but the postprandial potassium responses produced by the steroids were variable and suggested a slight kaliuresis. The data also emphasize the importance of mineralocorticoids in sodium retention and ascites formation in this experimental model of high-output heart failure.

SOME BIOLOGICAL ACTIVITIES OF CERTAIN PROGESTOGENS: I. 17?-HYDROXYPROGESTERONE 17-n-CAPROATE

Immature virgin female rabbits were injected for 6 days with 5 mcg of estradiol and then treated with 4 daily doses of progesterone 17alpha-hydroxyprogesterone caproate (HPC) or 17alpha-hydroxyprogesterone (17alpha-OHP). Segments of uteri were taken on the fifth day for histological evaluation. The decrease in progestational efficacy of progesterone following 17alpha-hydroxylation was completely reversed by subsequent esterification with caproic acid which led to a potentiation of progesterone. 17alpha-OHP HPC and testosterone were administered subcutaneously daily for 20 days to immature castrated male rats. The animals were autopsied on Day 21 and organ weights were recorded. High doses of testosterone (1 mg) proved thymolytic but neither 17alpha-OHP nor HPC showed such activity. In contrast both 17alpha OHP and HPC tended to increase adrenal weights. Prostatic hypertrophy was evident following 17alpha-OHP but no androgenic activity was noted with comparable doses of HPC. Measurements of urinary sodium excretion were made in intact and adrenalectomized male rats. Animals treated with .3 mg progesterone daily for 3 days excreted more sodium than did rats given comparable doses of HPC. Pretreatment with progesteone for 3 days or 1 hour prior to the sodium load resulted in sodium retention in adrenalectomized rats. combinations of estradiol with progesterone 9alpha-fluoro-11beta-hydroxyprogesterone (FHP) 17alpha-OHP or HPC were administered to immature female mice daily for 3 days. FHP was the most potent antagonist of estradiol. Antiuterotrophic and progestational activities were virtually abolished when progesterone was hydroxylated in the 17alpha position.

SOME BIOLOGICAL ACTIVITIES OF CERTAIN PROGESTOGENS: I. 17?-HYDROXYPROGESTERONE 17-n-CAPROATE

Immature virgin female rabbits were injected for 6 days with 5 mcg of estradiol and then treated with 4 daily doses of progesterone 17alpha-hydroxyprogesterone caproate (HPC) or 17alpha-hydroxyprogesterone (17alpha-OHP). Segments of uteri were taken on the fifth day for histological evaluation. The decrease in progestational efficacy of progesterone following 17alpha-hydroxylation was completely reversed by subsequent esterification with caproic acid which led to a potentiation of progesterone. 17alpha-OHP HPC and testosterone were administered subcutaneously daily for 20 days to immature castrated male rats. The animals were autopsied on Day 21 and organ weights were recorded. High doses of testosterone (1 mg) proved thymolytic but neither 17alpha-OHP nor HPC showed such activity. In contrast both 17alpha OHP and HPC tended to increase adrenal weights. Prostatic hypertrophy was evident following 17alpha-OHP but no androgenic activity was noted with comparable doses of HPC. Measurements of urinary sodium excretion were made in intact and adrenalectomized male rats. Animals treated with .3 mg progesterone daily for 3 days excreted more sodium than did rats given comparable doses of HPC. Pretreatment with progesteone for 3 days or 1 hour prior to the sodium load resulted in sodium retention in adrenalectomized rats. combinations of estradiol with progesterone 9alpha-fluoro-11beta-hydroxyprogesterone (FHP) 17alpha-OHP or HPC were administered to immature female mice daily for 3 days. FHP was the most potent antagonist of estradiol. Antiuterotrophic and progestational activities were virtually abolished when progesterone was hydroxylated in the 17alpha position.