Kidney Week

Abstract: TH-PO0048

NaDC1 KO Mice Are Predisposed to Metabolic Acidosis Due to a Defect in Renal Citrate Reabsorption

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

• Erspamer, Kayla J., Lucile Salter Packard Children's Hospital at Stanford, Palo Alto, California, United States

Kayla J. Erspamer, MD

• Lo, Robin H., Stanford University School of Medicine, Stanford, California, United States

Robin H. Lo, MD

• Newberry, Katherine P., Stanford University School of Medicine, Stanford, California, United States

Katherine P. Newberry

• Moe, Orson W., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Orson W. Moe, MD

• Hering-Smith, Kathleen S., Tulane University School of Medicine, New Orleans, Louisiana, United States

Kathleen S. Hering-Smith, MS, PhD, FASN

• Pao, Alan C., Stanford University School of Medicine, Stanford, California, United States

Alan C. Pao, MD

Background

The apically-located sodium dicarboxylate co-transporter 1 (NaDC1) mediates luminal entry of citrate into the proximal tubule and deletion of NaDC1 in mice increases urinary citrate excretion, a key inhibitor of calcium crystallization. Yet the contribution of NaDC1 to citrate or acid-base physiology is not clear.

Methods

NaDC1 knockout (KO) or wild type (WT) mice (9-15 weeks, male & female) were fed a standard gel diet or a gel diet with 0.1 M HCl (~0.05 mEq H⁺/gram body weight) for 2, 4, or 7 days. Urine was collected in metabolic cages for 24 hours. Urine pH was measured with pH electrode. Urinary citrate and ammonia were measured with enzymatic assays and blood chemistries with iSTAT. Data was analyzed by two-way ANOVA.

Results

NaDC1 KO mice excreted more urinary citrate compared with WT mice on a standard or acid diet. Both KO and WT mice responded with hypocitraturia when challenged with an acid diet, but KO mice still excreted more urinary citrate (Fig 1A). Urine pH was lower in KO mice compared with WT mice on a standard diet. With acid challenge, urine pH decreased in WT mice, but urine pH was not different in KO mice (Fig 1B). Urinary ammonia (NH₄⁺/NH₃) excretion was higher in WT mice, but not in KO mice, after 4 days of an acid load. WT and KO mice had similar blood pH, HCO₃^- and pCO₂ on a standard diet, whereas KO mice trended towards metabolic acidosis when fed an acid diet (Fig 2).

Conclusion

NaDC1 KO mice excrete more urinary citrate, more acidic urine, and more urinary ammonia at baseline, predisposing them to metabolic acidosis due to a defect in renal reabsorption of citrate. This study highlights the importance of urinary citrate reabsorption by NaDC1 in acid-base homeostasis.

Acknowledgment

This work was supported by the Stanford Maternal and Child Health Research Institute. The presenting author is named the Tashia and John Morgridge Endowed Postdoctoral Fellow. This work was also supported by the Stanford Transplant and Tissue Engineering Center of Excellence Fellowship Grant.
We'd like to thank Chao Li for primer design.

Figure 1. Twenty-four-hour urinary citrate (A) or urine pH (B) in WT or NaDC1 KO mice fed a standard or acid diet for 2, 4 or 7 days (n=6-15 per group) **p < 0.002, ***p < 0.001.

Figure 2. Arterial blood chemistries in WT or NaDC1 KO mice fed a standard or acid diet after four days. All data are presented as mean ± SEM. Blood HCO₃^- did not reach statistical significance with preliminary data.