Kidney Week

Abstract: FR-OR42

Dietary Anion Controls Potassium Excretion: It’s More Than a Poorly Absorbable Anion Effect

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders Research
  November 04, 2022 | Location: W308, Orange County Convention Center‚ West Building
  Abstract Time: 04:39 PM - 04:48 PM

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

• 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic

Authors

• Al-Qusairi, Lama, Johns Hopkins Medicine, Baltimore, Maryland, United States

Lama Al-Qusairi, PhD

• Grimm, Rick, Johns Hopkins Medicine, Baltimore, Maryland, United States

Rick Grimm,

• Zapf, Ava M., Johns Hopkins Medicine, Baltimore, Maryland, United States

Ava M. Zapf,

• Tahaei, Seyedmohammadebrahim, Johns Hopkins Medicine, Baltimore, Maryland, United States

Seyedmohammadebrahim Tahaei,

• Abood, Delaney C., Emory University, Atlanta, Georgia, United States

Delaney C. Abood,

• Wall, Susan M., Emory University, Atlanta, Georgia, United States

Susan M. Wall,

• Welling, Paul A., Johns Hopkins Medicine, Baltimore, Maryland, United States

Paul A. Welling,

Background

Aldosterone-dependent and -independent mechanisms are known to orchestrate potassium excretion in the distal nephron (DN). In the latter, potassium secretion, mediated by ROMK and BK channels, is dependent on lumen-negative transepithelial potential established by ENaC. Poorly absorbable anions, including HCO₃^-, are thought to increase K⁺secretion by hyperpolarizing the membrane potential, but accumulating data indicate luminal anions may also directly influence the expression of the potassium secretory machinery.

Methods

Here we characterize the anion effect in wild-type mice randomized to control, or high KCl or high KHCO₃ diets, and explore mechanisms in knockout mice, lacking aldosterone synthase (AS-KO) or the chloride-bicarbonate exchanger, pendrin (Pds-KO).

Results

Consumption of the high KHCO₃ diet increased urinary potassium K⁺ excretion and the trans-tubular K⁺ gradient (TTKG) significantly more than high KCl diet. Although both diets increased ENaC expression and proteolytic activation and increased ROMK protein abundance and apical membrane expression in the early connecting tubule (CNT), the responses were significantly more pronounced with consumption of the high KHCO₃ diet, despite elevating aldosterone to similar levels. Compared to the more restricted response in the early CNT with the high KCl diet, the high KHCO₃ diet increased apical membrane ROMK along the entire CNT. In addition, the high KHCO₃ diet uniquely increased the abundance of the BK potassium channel b4 subunit, which stabilizes BKa channel membrane localization. Studies in AS-KO mice revealed the stimulatory effects of high KHCO₃ diet on ROMK are not dependent on aldosterone. The KHCO₃diet also uniquely upregulated the Cl^-/HCO₃^- exchanger, pendrin, and studies in pendrin KO mice revealed that pendrin deletion blunted the increase in the TTKG specific to the KHCO3 condition.

Conclusion

In summary, bicarbonate stimulates potassium excretion beyond a non-absorbable anion effect, increasing ENaC cleavage, and apical membrane expression of ROMK and pendrin. The latter plays a significant role in K⁺ secretion by providing the luminal HCO₃^-. The response provides an adaptive mechanism to prevent hyperkalemia and alkalosis while consuming alkaline-ash rich diets.

Funding

• NIDDK Support