Evidence for a gastrointestinal-renal kaliuretic signaling axis in humans
Open accessAbstract
A gastrointestinal-renal kaliuretic signaling axis has been proposed to regulate potassium excretion in response to acute potassium ingestion independent of the extracellular potassium concentration and aldosterone. Here we studied this presumed axis in 32 individuals in our clinical pharmacology unit while on a 20 mmol sodium and 60 mmol potassium diet. The serum potassium concentration, potassium excretion, aldosterone, and insulin were measured following either a 35 mmol oral potassium load, a potassium- and sodium-deficient complex meal, or a potassium-deficient complex meal plus 35 mmol potassium. This design allowed determination of the component effects on potassium handling of the meal and potassium load separately. The meal plus potassium test was repeated following aldosterone blockade with eplerenone to specifically evaluate the role of aldosterone. In response to the potassium-deficient meal plus 35 mmol potassium, the serum potassium did not increase but the hourly mean potassium excretion increased sharply. This kaliuresis persisted following aldosterone blockade with eplerenone, further suggesting independence from aldosterone. Thus, a gastrointestinal-renal kaliuretic signaling axis exists in humans mediating potassium excretion independent of changes in the serum potassium concentration and aldosterone. The implication of this mechanism is yet to be determined but may account for a significant component of potassium excretion following a complex potassium-rich meal.
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K+ intake activates a feedforward control in which distal tubule K+ secretion is stimulated before changes in plasma K+ concentration or aldosterone concentration can be observed.
“K+ intake has been shown to activate a feedforward control in which distal tubule K+ secretion is stimulated before changes in plasma K+ concentration or ALD concentration can be observed [1, 15–18].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [17]
Predicted urine K+ excretion captures the observed trend of a decrease in urine K+ excretion [17].
“the predicted urine K+ excretion (Fig 5D) captures the observed trend of a decrease in urine K+ excretion [17].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [17]
The predicted trend in plasma K+ concentration is consistent with data reported by Preston et al. [17].
“The predicted trend in plasma K+ concentration is consistent with data reported by Preston et al. [17] (Fig 4F).”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [17]
Predicted plasma K+ concentration and urine K+ excretion match observed trends [17].
“The predicted plasma K+ concentration and urine K+ excretion (Figs 4F and 5D) match the observed trends [17].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [17]
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A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls
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“[17] that was used to fit the baseline model parameters.”
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- Authors
- Preston, R. A., Afshartous, D., Rodco, R., Alonso, A. B., & Garg, D.
- Affiliations
- University of Miami (US)
- Corresponding author
- Preston, Richard A.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 88
- Issue
- 6
- Pages
- 1383-1391
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W1172355299
- Cited by
- 57
- References
- 43
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 1
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- potassium excretion, eplerenone, aldosterone blockade, serum potassium, insulin, potassium homeostasis
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