Evidence for a gastrointestinal-renal kaliuretic signaling axis in humans

Richard A. Preston, David Afshartous, Rolando Rodco, Alberto B. Alonso, Dyal Garg

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1383-1391
Number of pages9
JournalKidney international
Issue number6
StatePublished - Dec 1 2015


  • Distal tubule
  • Potassium channels
  • Signaling

ASJC Scopus subject areas

  • Nephrology


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