Kidney Week

Abstract: FR-PO581

Compensatory Upregulation of Renal H+/K+- ATPase Function in Pendrin-Null Mice Serving K+ Preservation

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Ayasse, Niklas, Universitatsklinikum Mannheim, Mannheim, Baden-Württemberg, Germany

Niklas Ayasse, MD

• Berg, Peder, Aarhus Universitet Institut for Biomedicin, Aarhus, Midtjylland, Denmark

Peder Berg, MD

• Sorensen, Mads Vaarby, Aarhus Universitet Institut for Biomedicin, Aarhus, Midtjylland, Denmark

Mads Vaarby Sorensen, PhD

• Leipziger, Jens G., Aarhus Universitet Institut for Biomedicin, Aarhus, Midtjylland, Denmark

Jens G. Leipziger, MD, DrMed

Background

The renal Cl^-/HCO₃^- exchanger pendrin (SLC26A4) contributes to the maintenance of acid/base and intravascular volume homeostasis. Several studies have also suggested a possible role of pendrin in K⁺homeostasis. The aim of this study was to identify possible compensatory K⁺ retaining mechanisms in pendrin null mice. Since K⁺ deficiency potently stimulates the activation of renal H⁺/K⁺-ATPases (HKA), we hypothesized that functional HKA activity is increased in pendrin null mice, thus allowing the preservation of K⁺homeostasis. We recently suggested that benzamil can block the renal HKAs and thus may serve to functionally test its activity in vivo.

Methods

The acute effect of benzamil on urinary pH was investigated in bladder-catheterized pendrin^+/+ and pendrin^-/-mice. The magnitude of benzamil-induced urinary alkalization was used as a surrogate for the functional activity of the renal HKA. The effect was investigated under control and low K⁺ diet conditions to increase HKA activity.

Results

Under control diet conditions, baseline urinary pH was lower in pendrin^-/- mice as compared to pendrin^+/+mice. This may be caused by reduced pendrin-dependent HCO₃^- secretion or activation of an unknown tubular H⁺ secretory mechanism or both. Interestingly, the magnitude of benzamil-induced urinary alkalization was greater in the pendrin^-/- mice. Under low K⁺ diet conditions, baseline urinary pH was not different between the pendrin^+/+ and the pendrin^-/- group. Benzamil-induced urinary alkalization was larger in WTs during K⁺-depletion, but not different between K⁺ depleted ^+/+ and ^-/- mice.

Conclusion

We propose that benzamil may function to indicate the HKA activity. Its greater effect in pendrin^-/- mice under control diet indicates an increased baseline activity of the renal HKAs, likely caused by hypokalemia in these mice. The marked augmentation of benzamil-induced urine alkalization during low K+ conditions was confirmed in this study. The absence of dietary potassium depletion-induced increase of HKA activity in pendrin ^-/- mice could indicate a ceiling effect of the activated renal HKA. We suggest that renal HKA might indeed contribute to K⁺ preservation in the absence of pendrin. This might indicate a hierarchical relationship where the need to preserve K⁺ occurs at the expense of H⁺ loss despite higher plasma HCO₃^- levels.