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Abstract: PO1091

Non-Reabsorbable Anions Enhance Potassium Excretion by Multiple Mechanisms

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Al-Qusairi, Lama, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Grimm, Rick, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Pham, Truyen D, Emory University School of Medicine, Atlanta, Georgia, United States
  • Zapf, Ava, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Abood, Delaney C., Emory University School of Medicine, Atlanta, Georgia, United States
  • Wall, Susan M., Emory University School of Medicine, Atlanta, Georgia, United States
  • Welling, Paul A., Johns Hopkins Medicine, Baltimore, Maryland, United States
Background

Potassium (K+) secretion in the distal nephron (DN) is governed, in part, by the lumen-negative transepithelial potential (Vte), created by ENaC-mediated sodium reabsorption, and partially attenuated by paracellular chloride (Cl-) reabsorption. K+ secretion increases when nonreabsorbable anions (NRA), such as HCO3- or beta-hydroxybutyrate, replace luminal Cl-. Although this allows an appropriate response to alkaline-ash rich diets, it can drive exaggerated K+secretion in alkalosis. According to textbook views, NRA facilitates K+ secretion solely by increasing the lumen-negative Vte. However, the effects of NRA on the potassium secretory machinery have not been determined.

Methods

Wild-type C57BL6J mice were randomized to control (1%K+), potassium chloride (KCl:5%K+) or potassium bicarbonate (KHCO3:5%K+) diets for 10 days. Physiological, molecular and imaging analysis were performed. Pendrin-KO mice were examined to assess the specific role of pendrin in NRA-mediated potassium excretion.

Results

Consumption of the high KHCO3 diet increased urinary potassium K+ excretion and the trans-tubular K+ gradient (TTKG) significantly more than with the high KCl diet, consistent with an NRA response. Both diets increased aldosterone to the same extent, correlating with similar increases in ENaC expression and proteolytic activation. Surprisingly, the high KHCO3 diet significantly enhanced ROMK protein expression and apical localization in the late distal convoluted tubule and CNT more than the high KCl diet. The diets also induced opposite changes in Pendrin protein and apical membrane localization; Pendrin decreased with the high KCl diet but increased in the high HKCO3 diet. The high KHCO3 diet also uniquely induced a remodeling of the intercalated cells in the late DCT and CNT, whereby the number of pendrin-positive cells increased without change in principal cells. Pendrin-KO mice excrete the high dietary KHCO3 load to the same extent as WT mice but develop metabolic alkalosis.

Conclusion

In summary, NRA stimulates potassium excretion beyond a Vte effect. By increasing apical membrane ROMK and Pendrin expression, and remodeling the DN, mice increase the capacity to adapt to alkaline-ash rich diets, preventing hyperkalemia and alkalosis.

Funding

  • NIDDK Support