K⁺ balance in mammals relies on regulated renal K⁺ excretion matching unregulated fluctuating K⁺ intake. Upon a K⁺ rich meal, rapid and powerful K⁺ excretion is needed. Renal K⁺ secretion is stimulated by the increased tubular flow. We speculated that high K⁺ intake acutely increases urinary flow to stimulate K⁺ excretion.

Mice were K⁺ challenged through diets or gavage. Post K⁺ loading urinary output, osmolarity, [K⁺]_u, [Na⁺]_u, plasma osmolarity, [copeptin]_p, [K⁺]_p, and [Na⁺]_p were measured. To locate the mechanism of K⁺‐induced diuresis in the glomerular/tubular system we measured creatinine excretion and assessed functional transport in isolated perfused TALs and CDs during an acute [K⁺]_bl switch from 3.6 to 6.5 mM. Molecular adaptations of transport proteins involved in water reabsorption were investigated by immunoblotting.

(1) Mice switched from a 1% to 2% K⁺ diet increased diuresis within 12 hours and reciprocally reduced diuresis when switched from 1% to 0.01% K⁺ diet. (2) A single K⁺ gavage load, corresponding to 25%‐50% of daily K⁺ intake, induced 100% increase in diuresis within 30 minutes. This occurred despite augmented plasma osmolarity and AVP synthesis. (3) K⁺ gavage did not change GFR. (4) In isolated perfused TALs, shifting [K⁺]_bl from 3.6 to 6.5 mM did not affect AVP‐induced NaCl transport. (5) In sharp contrast, in isolated perfused CDs, shifting [K⁺]_bl from 3.6 to 6.5 mM markedly reduced CD AVP sensitivity, ie inhibited water absorption.

Dietary K⁺ loading induces a rapidly on‐setting diuresis. The mechanism of K⁺‐induced diuresis involves desensitization of the CD to AVP.