Kidney Week

Abstract: FR-PO605

The Renal AE4 Transporter (Slc4a9) Prevents Life-Threatening Hypochloremic Metabolic Alkalosis During NaCl Restriction and Base Loading

Session Information

• Fluid and Electrolytes: Basic - I
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Vitzthum, Helga, University Medical Centre Hamburg-Eppendorf , Hamburg, Germany

Helga Vitzthum,

• Koch, Mirijam, University Medical Centre Hamburg-Eppendorf , Hamburg, Germany

Mirijam Koch,

• Hübner, Christian A., University Hospital Jena, Jena, Germany

Christian A. Hübner,

• Ehmke, Heimo, University Medical Centre Hamburg-Eppendorf , Hamburg, Germany

Heimo Ehmke,

Background

The renal transporter AE4 (Slc4a9) is localized to the basolateral membrane of type B intercalated cells (β-ICs) in the collecting duct. Recently, it has been shown that β-ICs contribute to renal sodium (Na⁺) reabsorption during dietary salt restriction. Currently it is generally assumed that AE4 constitutes the primary basolateral Na⁺ extrusion pathway in β-ICs, but there is still no direct evidence of such a role.

Methods

We subjected AE4 knockout mice and their wildtype littermates (WT) to either a salt (NaCl) deficient diet alone (10 days) or a salt deficient diet combined with an additional base load (230 mM NaHCO₃, 7 days). We analyzed the effects of each diet on plasma volume, renal Na⁺ and Cl^- handling, renal protein expression levels of NHE3, NCC, ENaC and pendrin, plasma renin and aldosterone levels, and acid-base homeostasis.

Results

Surprisingly, AE4 knockout mice did not show any signs of Na⁺ loss or volume contraction or compensatory activation of other renal Na⁺ reabsorption pathways under salt deficient diet. However, we observed that AE4 knockout mice developed a mild hypochloremic metabolic alkalosis under these conditions, which severely aggravated when the animals were additionally subjected to a base load (NaHC0₃). In contrast, WT littermates maintained normal Na⁺ and acid-base balance under both diet regimes. While WT mice markedly increased pendrin expression during the base load, this response was completely absent in AE knockout animals.

Conclusion

The findings show that the renal transporter AE4 (Slc4a9) is dispensable for Na⁺ homeostasis during salt restriction, but is essential for the stimulatory effect of alkalosis on the upregulation of the apical Cl^-/HCO₃^- exchanger pendrin. Insufficient function of AE4 can cause life threatening hypochloremic metabolic alkalosis during base loading conditions (e.g. vomiting).