Circadian changes in urinary Na⁺/K⁺ ratio in humans: is there a role for aldosterone?

Abstract

Background: There are indications that the renal excretion of Na⁺ and K⁺ is affected by the body's circadian rhythm. Aldosterone is known to be the major determinant of urinary Na⁺/K⁺ ratio. However, recent reports suggest that the circadian rhythm of K⁺ excretion does not depend on endogenous aldosterone. We therefore aimed to investigate the diurnal and nocturnal changes in urinary Na⁺/K⁺ ratio, and to test if aldosterone plays a key role.

Methods: We investigated the Na⁺/K⁺ ratios and aldosterone excretion in 12h-day and night urine. Ethical approval was obtained for 24 healthy male subjects, aged 20-30 years, who were included in this study. 12h-day and 12h-night urine samples were collected. Urine concentrations of Na⁺ and K⁺ were analysed using flame photometry and the amount in mmol of these electrolytes was calculated. Urine aldosterone concentrations were analysed using the enzyme immunoassay method. Urinary Na⁺/K⁺ ratios were calculated by dividing the amount of Na⁺ by that of K⁺, both in mmol/12h. Results are presented as mean ± SEM, and analysed using unpaired Student’s t-test.

Results: While a significantly higher Na⁺/K⁺ ratio was observed in the 12h-night urine compared with the 12h-day urine (4.22 ± 0.18 vs 2.91± 0.18, p<0.001, n=24), aldosterone excretion (μg/12h) was similar in both the day and night urine.The significantly increased Na⁺/K⁺ ratio in the nighttime urine observed in this study was shown to be as a result of a significant decrease (p<0.001) in K⁺ excretion at night. Correlation analysis revealed no significant relationships between aldosterone and the Na⁺/K⁺ ratio in both the day and night urine.

Conclusion: Our results suggest that an aldosterone independent mechanism may be responsible for the night time dip in the renal excretion of K⁺. Understanding this mechanism will provide more insights into how this pathway may be targeted in hypertension caused by non-dipping night time renal K⁺ excretion.

Keywords: Na⁺, K⁺, Na⁺/K⁺ ratio, aldosterone, 12h-day, 12h-night, urine