Kidney Week

Abstract: TH-PO415

Oral NaHCO3 Activates the Splenic Anti-Inflammatory Pathway Promoting M2-Macrophage Polarization

Session Information

• Nutrition, Inflammation, Metabolism: Basic Mechanisms
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Nutrition, Inflammation, and Metabolism

• 1401 Nutrition, Inflammation, Metabolism

Authors

• O'Connor, Paul, Augusta University, Augusta, Georgia, United States

Paul O'Connor,

• Baban, Babak, Augusta University, Augusta, Georgia, United States

Babak Baban,

• Ray, Sarah C, Augusta University, Augusta, Georgia, United States

Sarah C Ray,

• Tucker, Matthew, Augusta University, Augusta, Georgia, United States

Matthew Tucker,

• Harris, Ryan A, Augusta University, Augusta, Georgia, United States

Ryan A Harris,

Background

Oral sodium bicarbonate (NaHCO₃) may slow decline in kidney function in CKD, yet the mechanisms mediating this beneficial effect remain unclear. In the current study we tested the hypothesis that oral NaHCO₃ intake promotes anti-inflammatory-M2 macrophage polarization by activating the splenic anti-inflammatory pathway in both rats and humans.

Methods

8-10 week old male Sprague Dawley rats maintained on a standard pellet diet with water ad libitum were utilized. To determine the effect of oral NaHCO₃ on macrophage polarization, drinking water was replaced with solutions of NaHCO₃ in tap water containing (0, 0.01, 0.05 or 0.1M NaHCO₃; n=3 per treatment group) with all solutions made equimolar (0.1M) with the addition of NaCl. Following 4 days of drinking NaHCO₃, rats were anesthetized, the left kidney and spleen harvested and prepared for flow cytometry analysis.
In a separate study, 7 healthy volunteers were given a single dose of NaHCO₃ following an overnight fast. Venous blood was drawn for flow cytometry analysis, at baseline and 1 and 2 hours following ingestion of 2g of NaHCO₃ in 250 ml of bottled water.

Results

We found that addition of NaHCO₃ to the drinking water of rats resulted in a dose dependent increase in renal macrophage polarization away from an M1 (inflammatory) and toward an M2 (anti-inflammatory) phenotype with as little as 3 days of drinking 0.01M NaHCO₃ solution (P_DOSE=0.02). Most of the polarization effect could be attributed to an increase in renal M2 macrophages, with the % of renal cells identified as M2’s increasing from 2% to 8% at the highest dose of NaHCO₃ (0.1M; P_DOSE=0.006). The effect of 0.1M NaHCO₃ on renal macrophage polarization was confirmed in a separate group of rats (n=5/5; P=0.007) and was abolished with prior splenectomy.
In human blood, T-cells were reduced from 15.6±0.8 at baseline to 13.0±0.8% of all leukocytes at 2 hours post NaHCO₃ ingestion; (P=0.01). Inflammatory cells, M1 macrophages (P=0.054) and Th17+ cells (P=0.06), tended to decrease, whereas, M2 macrophages tended to increase from 48.4±1.2 at baseline to 50.9±0.4% of all macrophages 2 hours post NaHCO₃ (p=0.054).

Conclusion

Our data indicate that oral NaHCO₃ may activate the splenic anti-inflammatory pathway in rats and humans. Activation of these pathways may underlie part of the beneficial effects of NaHCO₃ observed in CKD patients.

Funding

• NIDDK Support