Kidney Week

Abstract: SA-PO0479

Molecular Mechanism of Augmented Renal Bicarbonate (HCO3-) Excretion During Respiratory Alkalosis

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  November 08, 2025 | 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

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

Laura Woidemann Trans, MS

• Malte, Hans, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Hans Malte

• Damsgaard, Christian, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Christian Damsgaard, MSc, PhD

• Andersen, Jesper Frank, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Jesper Frank Andersen, MD

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

Jens G. Leipziger, DrMed, MD

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

Peder Berg, MD, PhD

Background

During respiratory alkalosis, the kidneys increase urinary HCO₃^- excretion to regulate blood pH, as well demonstrated under high-altitude conditions. The molecular mechanism underlying this renal response remains unknown, but augmentation of renal HCO₃^- excretion during metabolic alkalosis was recently shown to depend on pendrin and CFTR in the collecting duct β-intercalated cells (β-ICs). Furthermore, secretin was shown to activate β-ICs. We hypothesized that β-IC pendrin is necessary for renal compensation of respiratory alkalosis.

Methods

Under anesthesia, bladder-catheterized pendrin wildtype (WT) and knockout (KO) mice were mechanically ventilated to assess the renal response to hyperventilation-induced respiratory alkalosis. Additionally, intermittently-closed-flow respirometry was performed to quantify the ventilatory response of pendrin WT and KO mice to hypoxia.

Results

A sharp increase in urine pH occurred shortly (i.e., 10-15 minutes) after initiation of hyperventilation in WT mice. This effect was completely absent in KO mice. Arterial blood gas analyses confirmed respiratory alkalosis during hyperventilation in both genotypes. Furthermore, KO mice displayed a reduced hyperventilatory response and larger body temperature decreases during hypoxia in intermittently-closed-flow respirometry.

Conclusion

Our results demonstrate that β-IC pendrin function is necessary for the ability to increase urinary HCO₃^- excretion during respiratory alkalosis and that renal compensation initiates immediately. They also reveal that compromised β-IC function impairs ventilatory compensation to hypoxia, resulting in decreased metabolism. Hence, this study provides novel insights into the molecular mechanisms of renal compensation of respiratory alkalosis and their importance during hypoxia.

End-tidal CO₂ and urine pH in pendrin WT and KO mice during hyperventilation

Funding

• Private Foundation Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025ky37e9r5