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Abstract: SA-PO1139

GLP-1 Receptor Agonists and Inflammatory Protein Profiles in Advanced CKD: Insights from Two Cohort Studies

Session Information

Category: CKD (Non-Dialysis)

  • 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Alzyood, Laith, Montefiore Einstein Medical Center, Bronx, New York, United States
  • Paredes, William, Albert Einstein College of Medicine, Bronx, New York, United States
  • Duran, Sally, Albert Einstein College of Medicine, Bronx, New York, United States
  • Islam, Saisha, Albert Einstein College of Medicine, Bronx, New York, United States
  • Abramowitz, Matthew K., Montefiore Einstein Medical Center, Bronx, New York, United States
Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in CKD. Beyond their metabolic effects, GLP-1RAs also exhibit anti-inflammatory properties by modulating cytokine production, oxidative stress, and NF-κB signaling. Inflammation is a key driver of poor outcomes in advanced CKD, yet the impact of GLP-1RA use on systemic inflammation in this population remains unclear. Understanding the proteomic signatures associated with GLP-1RA exposure may clarify underlying mechanisms and inform personalized treatment strategies in CKD stages 4 and 5.

Methods

We measured 250 inflammation and immune response plasma proteins using Nucleic acid Linked Immuno-Sandwich Assay (NULISA™, Alamar Biosciences) in a subset of participants from two prospective cohorts of adults with CKD stages 4–5 and a history of diabetes mellitus. Participants were grouped by GLP-1RA use (n=15) vs. non-use (n=18). Logistic regression adjusted for age and sex was used to assess associations between protein levels and GLP-1RA use. A nominal p-value <0.05 was used for exploratory analyses.

Results

Among the 250 proteins profiled, 9 were significantly associated with GLP-1RA use (p<0.05). These included Angiopoietin-2, CEA-related cell adhesion molecule 5, IL-17A, IL-5 receptor subunit alpha, MHC class II DR alpha, Mucin-16, Progranulin, TNF receptor superfamily member 18, and VEGF-A. Notably, MHC class II DR alpha, IL-17A, and Progranulin were positively associated with GLP-1RA use, suggesting potential immune-modulatory effects of GLP-1RAs in advanced CKD.

Conclusion

In this exploratory analysis, high-sensitivity NULISA™ technology revealed potential inflammatory modulation linked to GLP-1RA use in advanced CKD. While preliminary, these findings offer mechanistic insights that merit further investigation and may ultimately guide biomarker discovery and personalized anti-inflammatory strategies in this high-risk population.

Boxplots of Plasma Protein Levels by GLP-1RA Use in Advanced CKD

Funding

  • NIDDK Support

Digital Object Identifier (DOI)