Dataset Information

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

ABSTRACT:

Aim

To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo.

Methods

In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fluid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with (51)Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-ANG II) and aldosterone (p-Aldo) were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fluid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman's two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.

Results

At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang II and p-Aldo were increased during active treatments (P < 0.001). After hypertonic saline, u-NKCC2 increased during amiloride (6% ± 34%; P = 0.081) and increased significantly during placebo (17% ± 24%; P = 0.010). U-AQP2 increased significantly during amiloride (31% ± 22%; P < 0.001) and placebo (34% ± 27%; P < 0.001), while u-NKCC2 and u-AQP2 did not change significantly during BFTZ (-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261). U- ENaCγ increased in all three groups (P < 0.050). PRC, AngII and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ (P = 0.048). cDBP decreased significantly during BFTZ (P < 0.001), but not during amiloride or placebo. There were no significant differences in body fluid volumes.

Conclusion

After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.

SUBMITTER: Jensen JM

PROVIDER: S-EPMC4491934 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

Jensen Janni M JM Mose Frank H FH Kulik Anna-Ewa O AE Bech Jesper N JN Fenton Robert A RA Pedersen Erling B EB

World journal of nephrology 20150701 3

<h4>Aim</h4>To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo.<h4>Methods</h4>In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fluid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo tw ...[more]

PMID: 26167467

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Project description:BackgroundThe relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method.MethodsWe included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis.ResultsAmong 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94).ConclusionsHigher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).

Project description:ImportanceIn 2010, the Institute of Medicine (now the National Academy of Medicine) recommended collecting 24-hour urine to estimate US sodium intake because previous studies indicated 90% of sodium consumed was excreted in urine.ObjectiveTo estimate mean population sodium intake and describe urinary potassium excretion among US adults.Design, setting, and participantsIn a nationally representative cross-sectional survey of the US noninstitutionalized population, 827 of 1103 (75%) randomly selected, nonpregnant participants aged 20 to 69 years in the examination component of the National Health and Nutrition Examination Survey (NHANES) collected at least one 24-hour urine specimen in 2014. The overall survey response rate for the 24-hour urine collection was approximately 50% (75% [24-hour urine component response rate] × 66% [examination component response rate]).Exposures24-hour collection of urine.Main outcomes and measuresMean 24-hour urinary sodium and potassium excretion. Weighted national estimates of demographic and health characteristics and mean electrolyte excretion accounting for the complex survey design, selection probabilities, and nonresponse.ResultsThe study sample (n = 827) represented a population of whom 48.8% were men; 63.7% were non-Hispanic white, 15.8% Hispanic, 11.9% non-Hispanic black, and 5.6% non-Hispanic Asian; 43.5% had hypertension (according to 2017 hypertension guidelines); and 10.0% reported a diagnosis of diabetes. Overall mean 24-hour urinary sodium excretion was 3608 mg (95% CI, 3414-3803). The overall median was 3320 mg (interquartile range, 2308-4524). In secondary analyses by sex, mean sodium excretion was 4205 mg (95% CI, 3959-4452) in men (n = 421) and 3039 mg (95% CI, 2844-3234) in women (n = 406). By age group, mean sodium excretion was 3699 mg (95% CI, 3449-3949) in adults aged 20 to 44 years (n = 432) and 3507 mg (95% CI, 3266-3748) in adults aged 45 to 69 years (n = 395). Overall mean 24-hour urinary potassium excretion was 2155 mg (95% CI, 2030-2280); by sex, 2399 mg (95% CI, 2253-2545) in men and 1922 mg (95% CI, 1757-2086) in women; and by age, 1986 mg (95% CI, 1878-2094) in adults aged 20 to 44 years and 2343 mg (95% CI, 2151-2534) in adults aged 45 to 69 years.Conclusions and relevanceIn cross-sectional data from a 2014 sample of US adults, estimated mean sodium intake was 3608 mg per day. The findings provide a benchmark for future studies.

Dataset Information

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

Aim

Methods

Results

Conclusion

Publications

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

Similar Datasets

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