Pendrin regulation is prioritized by anion in high-potassium diets

Ebrahim Tahaei, Truyen D. Pham, Lama Al-Qusairi, Rick Grimm, Susan M. Wall, Paul A. Welling

Research output: Contribution to journalArticlepeer-review


The CI-/HCO3 exchanger pendrin in the kidney maintains acid-base balance and intravascular volume Pendrin is upregulated in models associated with high circulating aldosterone concentration, such as dietary NaCI restriction or an aldosterone infusion However, it has not been established if pendrin is similarly regulated by aldosterone with a high-K4 diet because the effects of accompanying anions have not been considered. Here, we explored how pendrin is modulated by different dietary potassium salts. Wild-type (WT) and aldosterone synthase (AS) knockout (KO) mice were randomized to control high KHCO3 or high KCI diets. Dietary KCI and KHCO3 loading increased aldosterone in WT mice to the same extent but had opposite effects on pendrin abundance. KHCO3 loading increased pendrin protein and transcript abundance. Conversely high-KCI diet feeding caused pen-drin to decrease within 8 h of switching from the high-KHCO3 diet, coincident with an increase in plasma CI- and a decrease in HCO3. In contrast, switching the high-KCI diet to the high-KHCO3 diet caused pendrin to increase in WT mice Experiments in AS KO mice revealed that aldosterone is necessary to optimally upregulate pendrin protein in response to the high KHCO3 diet but not to increase pendrin mRNA. We conclude that pendrin is differentially regulated by different dietary potassium salts and that its regulation is prioritized by the dietary anion, providing a mechanism to prevent metabolic alkalosis with high K4 base diets and safeguard against hyperchloremic acidosis with consumption of high-KCI diets.

Original languageEnglish (US)
Pages (from-to)F256-F266
JournalAmerican Journal of Physiology - Renal Physiology
Issue number3
StatePublished - Mar 2023


  • acid-base
  • aldosterone
  • dietary anion
  • pendrin
  • potassium

ASJC Scopus subject areas

  • Urology
  • Physiology


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