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Abstract: PO0567

CKD Is Associated with Attenuated Plasma Metabolome Response to Oral Glucose Tolerance Testing

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Ahmadi, Armin, Department of Medicine, Division of Nephrology. University of California Davis, Davis, California, United States
  • Bennett, Brian J., Department of Medicine, Division of Nephrology. University of California Davis, Davis, California, United States
  • Gamboa, Jorge, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • Zelnick, Leila R., Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, United States
  • Raftery, Daniel, Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • Roshanravan, Baback, Department of Medicine, Division of Nephrology. University of California Davis, Davis, California, United States
Background

Chronic kidney disease (CKD) is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of the response to oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruption in incretin response.

Methods

Using targeted metabolic profiling, we examined the plasma metabolome in 58 moderate to severe non-diabetic CKD patients with estimated glomerular filtration rate (eGFR)<60ml/min per 1.73m2 and 37 healthy controls with normal eGFR before and after 2h of 75g oral glucose challenge. We used linear mixed effect models adjusting for potential confounders of age, sex, race, and body weight to determine the interaction of eGFR and change in metabolites in response to OGTT by CKD status. Pathway analyses were performed using Metaboanalyst.

Results

CKD patients had lower eGFR compared to healthy control (37.3 ± 12.5 Vs. 89.3 ± 17.1 ml/min per 1.73m2). Oral glucose challenge was associated with a marked reduction in a wide array of metabolites, predominantly amino acids, TCA cycle intermediates, and bile acids. CKD status was associated with attenuated OGTT induced prominent changes in pathways of taurine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, nicotinamide metabolism, and TCA cycle (Figure 1).

Conclusion

Targeted plasma metabolic profiling in response to OGTT suggests a broad disruption of amino acid and mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into the incretin response in patients with CKD and the impact of incretin mimetics such as GLP-1 receptor agonist.

Figure 1: Pathway analysis of OGTT challenege in CKD vs control subjects.

Funding

  • NIDDK Support