Pendrin regulation is prioritized by anion in high-potassium diets

Regulation of the Cl − /[Formula: see text] exchanger pendrin has been suggested to explain the aldosterone paradox. A high-K + diet has been proposed to downregulate a pendrin-mediated K + -sparing NaCl reabsorption pathway to maximize urinary K + excretion. Here, we challenged the hypothesis, revealing that the accompanying anion, not K + , drives pendrin expression. Pendrin is downregulated with a high-KCl diet, preventing acidosis, and upregulated with an alkaline-rich high-K + diet, preventing metabolic alkalosis. Pendrin regulation is prioritized for acid-base balance.