Kidney Week

Abstract: TH-PO0049

AE4 Sustains β-Intercalated Cell-Mediated Bicarbonate Excretion During Respiratory Alkalosis

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  October 22, 2026 | Location: Exhibit Hall A, 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

• Skjoldborg, Benedikte S. R., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Benedikte S. R. Skjoldborg

• Trans, Laura Woidemann, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Laura Woidemann Trans, MS

• Leipziger, Jens G., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Jens G. Leipziger, MD, DrMed

• Berg, Peder, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Peder Berg, MD, PhD

• Vitzthum, Helga, Universitatsklinikum Hamburg-Eppendorf Zentrum fur Experimentelle Medizin, Hamburg, HH, Germany

Helga Vitzthum, PhD

Background

Hyperventilation lowers arterial pCO₂, causing respiratory alkalosis and triggering renal bicarbonate excretion to restore blood pH. Unpublished own data show that this renal response is fast (onsetting after ~10 min) and mediated by β-intercalated cells (β-IC) via pendrin-dependent apical Cl^-/HCO₃^- exchange. Sustained secretion requires base uptake for substrate availability. The basolateral anion exchanger 4 (AE4) is highly and specifically expressed in β-IC and a proposed mediator of this flux. However, AE4’s functional contribution to renal base excretion during respiratory alkalosis remains unknown. Defining its role is essential for understanding how the kidney sustains bicarbonate excretion to support systemic pH recovery during acute hypocapnia.

Methods

AE4 function was examined in anesthetized (ketamine 100 mg/kg and xylazine 10 mg/kg, i.p.), mechanically ventilated C57BL/6 AE4 WT and KO mice. After 30 minutes of normoventilation (end-tidal CO₂ ~3,78%), respiratory alkalosis was induced by controlled hyperventilation (end-tidal CO₂ <2% for 60 minutes). Arterial blood gas analysis confirmed pCO₂levels ~20 mmHg. Urinary pH was continuously monitored via micro pH electrodes in a bladder catheter and urine was collected every 5 minutes for further analysis.

Results

After correction for genotype-matched time-control drift, WT mice showed a hyperventilation-induced ΔpH of 0.257 ± 0.076, whereas AE4 KO mice showed a smaller response of 0.076 ± 0.150 (mean ± SEM, n=3 hyperventilated mice per genotype), corresponding to a 0.181 pH unit difference and approximately 3.4-fold larger response in WT mice.

Conclusion

These preliminary data suggest that AE4 contributes to the rapid urinary alkalinization response during acute respiratory alkalosis, with additional experiments ongoing to increase group sizes. The impaired response in AE4 KO mice supports a role for AE4-mediated basolateral bicarbonate uptake in sustaining pendrin-dependent β-IC bicarbonate secretion, thereby enabling effective urinary alkalinization and systemic pH recovery.