Correlation between kidney sodium and potassium handling and the renin-angiotensin-aldosterone system in children with hypertensive disorders

Abstract

Background: Urine sodium and potassium are used as surrogate markers for dietary consumption in adults with hypertension, but their role in youth with hypertension and their association with components of the renin-angiotensin-aldosterone system (RAAS) are incompletely characterized. Some individuals with hypertension may have an abnormal RAAS response to dietary sodium and potassium intake, though this is incompletely described. Our objective was to investigate if plasma renin activity and serum aldosterone are associated with urine sodium and potassium in youth referred for hypertensive disorders.

Methods: This pilot study was a cross-sectional analysis of baseline data from 44 youth evaluated for hypertensive disorders in a Hypertension Clinic. We recorded urine sodium and potassium concentrations normalized to urine creatinine, plasma renin activity, and serum aldosterone and calculated the sodium/potassium (UNaK) and aldosterone/renin ratios. We used multivariable generalized linear models to estimate the associations of renin and aldosterone with urine sodium and potassium.

Results: Our cohort was diverse (37% non-Hispanic Black, 14% Hispanic), 66% were male, and median age was 15.3 years; 77% had obesity and 9% had a secondary etiology. Aldosterone was associated inversely with urine sodium/creatinine (β: -0.34, 95% CI -0.62 to -0.06) and UNaK (β: -0.09, 95% CI -0.16 to -0.03), and adjusted for estimated glomerular filtration rate and serum potassium.

Conclusions: Higher serum aldosterone levels, but not plasma renin activity, were associated with lower urine sodium/creatinine and UNaK at baseline in youth referred for hypertensive disorders. Further characterization of the RAAS could help define hypertension phenotypes and guide management. A higher resolution version of the Graphical abstract is available as supplementary information.

Keywords: Biomarker; Blood pressure; Directed acyclic graph; Natriuresis; Pediatric; UNaK; Youth.

Fig. 1

Directed acyclic graph of the association between aldosterone and the urine sodium/potassium ratio. The causal model is overlaid on a diagram of a nephron and organized in advancing time from left to right. The green node with black arrow denotes the exposure, aldosterone, while the blue node with the black vertical bar denotes the outcome, UNaK. Red nodes denote ancestors of the exposure and the outcome (i.e., potentially confounding factors); blue nodes denote ancestors of the outcome; and light grey nodes denote unobserved (latent) variables. Green arrows denote causal paths while pink arrows denote non-causal (biasing) pathways. The causal model assumes aldosterone is the predominant, day-to-day RAAS downstream regulator of sodium and potassium tubular secretion. We omitted additional RAAS components (including intrarenal/urinary RAAS), hormonal systems, and specific tubular transporters for clarity. AngII, angiotensin II; BAC, Biomarker Analytical Core; BMI_Z, body mass index z-score; eGFR, estimated glomerular filtration rate; HTN, hypertension; K, potassium; Na, sodium; UKCr, urine potassium/creatinine; UNaCr, urine sodium/creatinine; UNaK, urine sodium/potassium ratio. Figure created using DAGitty (code available in Online Resource 1), Adobe Illustrator, and Adobe Photoshop.

Fig. 2a

Association between plasma renin activity and urine sodium/potassium ratio. Regression line (solid red) with 95% confidence limits of the mean predicted values shown in shaded red; red circles indicate individual data points. PRA, plasma renin activity; NaK/, sodium/potassium ratio.

Fig. 2b

Association between serum aldosterone and urine sodium/potassium ratio. Regression line (solid red) with 95% confidence limits of the mean predicted values shown in shaded red; red circles indicate individual data points; p < 0.05 by unadjusted and adjusted generalized linear regression. Na/K, sodium/potassium ratio.

Fig. 2c

Association between aldosterone/renin ratio and urine sodium/potassium ratio. Regression line (solid red) with 95% confidence limits of the mean predicted values shown in shaded red; red circles indicate individual data points. Na/K, sodium/potassium ratio.