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Abstract: TH-PO0007

High-Oxalate Diets Alter Monocyte Transcriptomic and Metabolic Responses in Calcium-Oxalate Kidney Stone Formers

Session Information

Category: Bone and Mineral Metabolism

  • 501 Bone and Mineral Metabolism: Basic

Authors

  • Doamekpor, Mary Abla Eyram Megumi, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Verma, Vivek, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Crossman, David K., University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Rosenberg, Alex, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Assimos, Dean G., University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Mitchell, Tanecia, University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Kidney stone (KS) disease affects approximately 10% of the United States population. A risk factor for KS is dietary oxalate, which is known to increase urinary oxalate levels. When urine becomes supersaturated, calcium oxalate (CaOx) crystals can form and stimulate inflammation. We previously reported that dietary oxalate impairs monocyte mitochondrial metabolism and inflammatory signaling in healthy subjects (HS) after an acute dietary oxalate load. The objective of this study was to evaluate the effect of dietary oxalate on monocyte transcriptomics and bioenergetics in HS and CaOx stone formers (SF).

Methods

HS (n=20) and CaOx SF (n=14) were randomly placed on controlled low oxalate (50 mg/day) or moderately high oxalate (250 mg/day) diets for 4 days, followed by a 10-day washout period. Participants were subsequently crossed over to the opposite diet for 4 days. Twenty-four hour urine and blood samples were collected at the end of each dietary phase. Urinary oxalate was measured using ion chromatography-mass spectrometry (IC-MS). RNA from circulating blood monocytes was isolated and sequenced using bulk RNA sequencing (RNA-seq). Monocyte metabolism was assessed using the Seahorse XF Analyzer.

Results

Participants on a moderately high oxalate diet had increased higher oxalate excretion as compared to the low oxalate diet. RNA-seq analysis showed differential gene expression between HS and CaOx SF during moderately high oxalate intake. Ingenuity pathway analysis revealed that CaOx SF had upregulation of key genes associated with inflammation, mitochondrial metabolism, and complement pathways compared to HS during moderately high oxalate intake. In addition, CaOx SF exhibited increased ATP levels in response to higher oxalate intake, whereas HS did not show a similar increase.

Conclusion

These data suggest that higher dietary oxalate alters monocyte transcriptomic profiles, with more pronounced activation of inflammatory and metabolic pathways in CaOx SF compared to HS. Collectively, these findings support a role for diet induced immune dysregulation in KS disease that may contribute to stone risk.

Funding

  • NIDDK Support