Kidney Week

Abstract: TH-PO0051

V-ATPase B1 Knockout Mice Develop Metabolic Acidosis and Increased Kidney Bacterial Burden After Long-Term Uropathogenic Escherichia coli Challenge

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

• Saxena, Vijay, Indiana University School of Medicine, Indianapolis, Indiana, United States

Vijay Saxena, PhD

• Hains, David S., Indiana University School of Medicine, Indianapolis, Indiana, United States

David S. Hains, MD, MBA

• Arregui, Samuel, Indiana University School of Medicine, Indianapolis, Indiana, United States

Samuel Arregui

• Schwaderer, Andrew L., Indiana University School of Medicine, Indianapolis, Indiana, United States

Andrew L. Schwaderer, MD

Background

The multisubunit vacuolar-type H+ATPases (V-ATPases) mediate organelle acidification and extracellular pH regulation. Renal collecting duct intercalated cells (ICs) are the major cell types involved in physiological urine acidification and recovery from acidosis and alkalosis and protect against ascending uropathogen invasion. It has been shown that mutation is B1 subunit of V-ATPase (B1 KO) causes renal tubular acidosis in humans and B1 KO mice challenged with oral acid load display metabolic acidosis and alkaline urine (Finberg KE et al, PNAS, 2005). We challenged B1 KO mice with UPEC strain CFT073 to uncover if V-ATPase B1 subunit is also an important regulator of urinary tract infection (UTI) susceptibility

Methods

B1 KO were obtained from Jackson labs and bred as homozygous mating pairs. UTI was induced in female mice by transurethral UPEC (CFT073) challenge for single, double dose for short term (24 hour) and long term (4 week) follow up. Kidney and bladder burdens were measured by culturing tissue lysates. Urine and blood pH were measured using iSTAT system and EG7+ cartridges. Flowcytometry was performed on kidney single cell suspension to access innate immune cell phenotypes.

Results

UPEC challenge of 2 doses at 3–4-hour interval to wild type B6 and B1 KO mice led to decreased blood pH and significantly increased urine pH together with increased blood sodium in B1 KO mice indicating severe metabolic acidosis and reduced kidney function. Bladder bacterial burden showed increasing trend, but surprisingly kidney bacterial burdens were tending lower in both one and two UPEC doses while after long term (4 wk) UPEC exposure, kidney burdens were significantly higher. Kidney histology showed large number of darkly stained infiltrating cells and tubular damage. Flowcytometry of kidney innate immune cells revealed increased M2 macrophages (CD11b⁺CD206⁺F4/80⁺) population at indicative of anti-inflammatory, profibrotic response upon UPEC challenge

Conclusion

V-ATPase B1 deficiency predisposes to metabolic acidosis in short term and UTI susceptibility in long term follow up with M2 macrophage expansion in kidney suggestive of profibrotic, anti-inflammatory signaling

Acknowledgment

supported by NIDDK R01DK132366

Funding

• NIDDK Support