Kidney Week

Abstract: SA-PO835

Impact of Sodium Bicarbonate (NaHCO₃) on Systemic and Urine Metabolites in Patients with and Without CKD

Session Information

• Health Maintenance, Nutrition, Metabolism - II
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1300 Health Maintenance, Nutrition, and Metabolism

Authors

• Scialla, Julia J., Duke University, Durham, North Carolina, United States

Julia J. Scialla,

• Modliszewski, Jennifer L., Duke University, Durham, North Carolina, United States

Jennifer L. Modliszewski,

• Bain, James R., Duke University, Durham, North Carolina, United States

James R. Bain,

• Muehlbauer, Michael, Duke University, Durham, North Carolina, United States

Michael Muehlbauer,

• Ilkayeva, Olga, Duke University, Durham, North Carolina, United States

Olga Ilkayeva,

• Pourafshar, Shirin, University of Virginia, Charlottesville, Virginia, United States

Shirin Pourafshar,

• Tyson, Crystal C., Duke University, Durham, North Carolina, United States

Crystal C. Tyson,

• Svetkey, Laura P., Duke University, Durham, North Carolina, United States

Laura P. Svetkey,

• Corcoran, David L., Duke University, Durham, North Carolina, United States

David L. Corcoran,

• Lin, Pao-Hwa, Duke University, Durham, North Carolina, United States

Pao-Hwa Lin,

Background

Net acid excretion (NAE) falls in early stages of CKD, yet systemic metabolic acidosis (MA) occurs in late CKD. Homeostasis may be maintained by compensatory decrease in acid production. As conjugate bases of endogenously produced acids, organic anions (OAs) lost in the urine are markers of acid production. Modulation of OA excretion may defend against MA and alkalosis. Here we explore changes in urine OAs and potential consequences for systemic metabolism after alkali in a cross-over trial.

Methods

The Acid-Base Compensation in CKD Study was a cross-over trial evaluating 7-days of NaHCO₃ vs. 7-days of NaCl supplementation in the setting of fixed diet in adult, non-diabetic patients with (n=8) and without CKD (n=6). 24h urine, and fasting and 90-minute postprandial plasma were collected at the end of each period. We used nontargeted GC/MS metabolomics to explore the excretion of urine OAs and systemic metabolism in plasma. Linear mixed-effects models and discriminant analyses (sparse PLS-DA) were used to identify metabolites that vary with NaHCO₃ treatment independently in CKD and non-CKD subjects and overall.

Results

We found 15 urine metabolites higher with NaHCO₃ at a nominal p-value <0.05 in CKD participants and 13 lowered in non-CKD. Rise in 3-indoleacetic acid, citric acid/isocitric acid, and glutaric acid in CKD participants were the only significant changes after false discovery rate (FDR) correction (each p=0.01). These changes were not detected in those without CKD. There were no changes in plasma metabolites overall or in any group after FDR correction. A primary component including higher fatty acids and lower leucine, asparagine, serine and lysine, among others, was identified by sparse PLS-DA in fasting plasma samples from the CKD group after NaHCO₃. A component loading directly on fructose, phosphate, urea, valine, leucine and aminomalonic acid, among others, was higher in post-prandial samples overall after NaHCO₃.

Conclusion

Several urine OAs were increased by alkali in CKD suggesting possible increased acid production. Changes in sugars, mineral ions, and protein metabolites in the fed state suggest concurrent changes in nutrient metabolism which could represent an additional response to acid-base manipulation.

Funding

• NIDDK Support