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

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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.

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Availability of data and material

The datasets generated from this study are available from the corresponding author upon reasonable request.

Code availability

The code used to analyze the data from this study is available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank Victoria Giammattei, BA, Weston Colbaugh, BS, Lauren Valloy, and the rest of the hypertension registry study team for their assistance with data collection, and Caroline Lucas, BA, for managing the study.

Funding

This study was funded by the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases T35 DK007400 to EP; National Heart, Lung, and Blood Institute K23 HL148394, L40 HL148910, and R01 HL146818 to AMS; National Center for Advancing Translational Sciences UL1 TR001420 to the Wake Forest Clinical and Translational Science Award); the Wake Forest Maya Angelou Center for Health Equity; and the Wake Forest School of Medicine Department of Pediatrics.

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Authors and Affiliations

  1. Wake Forest School of Medicine, Winston Salem, NC, USA

    Ella C Perrin

  2. Department of Pediatrics, Section of Nephrology, Brenner Children’s Hospital, Wake Forest School of Medicine, One Medical Center Boulevard, Winston Salem, NC, 27157, USA

    Andrew M South

  3. Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, NC, USA

    Andrew M South

  4. Department of Surgery-Hypertension and Vascular Research, Wake Forest School of Medicine, Winston Salem, NC, USA

    Andrew M South

  5. Center for Biomedical Informatics, Wake Forest School of Medicine, Winston Salem, NC, USA

    Andrew M South

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  1. Ella C Perrin
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Contributions

Ms. Perrin conceptualized the research question, collected the data, visualized the data and assisted with data interpretation, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. South conceptualized and designed the study, supervised data collection, analyzed and interpreted the data, created the figures, at all times had full access to and takes full responsibility for the data, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable fully for all aspects of the work.

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Correspondence to Andrew M South.

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Ethics approval

The Wake Forest School of Medicine Institutional Review Board approved this study (IRB00046001).

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Written informed consent was obtained from parents/guardians and written assent from participants aged 7 years and older in the prospective cohort; the retrospective cohort was deemed exempt from requiring informed consent/assent by the IRB.

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The authors declare no competing interests.

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Perrin, E.C., South, A.M. Correlation between kidney sodium and potassium handling and the renin-angiotensin-aldosterone system in children with hypertensive disorders. Pediatr Nephrol 37, 633–641 (2022). https://doi.org/10.1007/s00467-021-05204-7

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  • DOI: https://doi.org/10.1007/s00467-021-05204-7

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