Abstract: SA-PO0284
Toward Better Understanding of Uremic Vasculopathy
Session Information
- Bone and Mineral Metabolism: Basic Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- Gaweda, Adam E., University of Louisville, Louisville, Kentucky, United States
- Lederer, Eleanor D., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Vu, Christine, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Alvarez, Carlos A., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Treatment of uremic vasculopathy, a significant contributor to the accelerated mortality of Chronic Kidney Disease (CKD), is hampered by the lack of targetable biomarkers in the early stages. We hypothesize that the contributors to uremic vasculopathy vary by CKD stage.
Methods
We abstracted 98 standard and experimental biomarkers from the Chronic Renal Insufficiency Cohort (CRIC) dataset representing mineral and lipid metabolism, inflammatory status, and endothelial damage. To address the complex relationships between these biomarkers and to discover the patterns of GFR-associated change in Cardiac Artery Calcification (CAC) scores, we performed fuzzy C-means clustering of GFR levels and CAC scores. We then compared changes in central tendency measures for these biomarkers as GFR declines.
Results
Figure 1 shows cluster heatmap for GFR 0–80 and CAC 0–400. Cluster 1 represents high CAC (>100) and low GFR (<40 mL/min), and cluster 2 represents low CAC and high GFR. Interleukin 10, renin, and lipocalin-2 are the strongest upregulated markers (FC > 4, p < 0.001), whereas interleukin 1 receptor, xanthosine, 24h urine calcium, interleukin 1B, and 24h urine p-cresol sulfate are the strongest downregulated markers (FC < 0.6, p < 0.001) as GFR level decreases (cluster 2 to cluster 1).
Conclusion
The differences in biomarkers between early and late CKD suggest evolving mechanisms for progression of uremic vasculopathy. Inflammatory processes may play a central role in the pathophysiology of this condition across the spectrum of CKD. Markers of kidney metabolism play a stronger role in late CKD.
Acknowledgment: CRIC data were provided by NIDDK Central Repository, a program of the National Institute of Diabetes and Digestive and Kidney Diseases
Cluster distribution heatmap representing GFR-associated change in CAC score.
Funding
- Veterans Affairs Support