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Abstract: FR-PO704

Transcriptomics of Human Arteriovenous Fistula Failure Uncovers an Unexpected Source of Inflammation

Session Information

Category: Dialysis

  • 704 Dialysis: Vascular Access

Authors

  • Martinez, Laisel, University of Miami, Miller School of Medicine, Miami, Florida, United States
  • Tabbara, Marwan, University of Miami, Miller School of Medicine, Miami, Florida, United States
  • Duque Ballesteros, Juan Camilo, University of Miami, Miller School of Medicine, Miami, Florida, United States
  • Selman, Guillermo, Albany Medical College, Albany, New York, United States
  • Paez, Angela, University of Miami, Miller School of Medicine, Miami, Florida, United States
  • Salman, Loay H., Albany Medical College, Albany, New York, United States
  • Vazquez-Padron, Roberto I., University of Miami, Miller School of Medicine, Miami, Florida, United States
Background

Improving arteriovenous fistula (AVF) outcomes requires a better understanding of the biology underlying maturation or failure. Unfortunately, our current knowledge of the biological processes associated with maturation relies on assumptions and extrapolation from other vascular pathologies, which overlooks the uniqueness of AVF remodeling.

Methods

In this study, we used an unbiased “omics” approach based on high-throughput RNA sequencing of human pre-access veins and fistulas to uncover novel molecular targets associated with nonmaturation. We obtained native vein and juxta-anastomotic AVF tissues from patients undergoing two-stage upper arm AVF surgeries at a single center. Paired venous samples from both stages were used to study the vein to AVF transformation at the transcriptomics level.

Results

We discovered a unique molecular signature of pro-inflammatory genes (CSF3R, FPR1, S100A8, S100A9, and VNN2) that was upregulated in native veins that failed vs. matured (FDR<0.05), and whose expression co-localized to smooth muscle cells in the media. Furthermore, expression of S100A8 and S100A9 was significantly associated with postoperative intimal hyperplasia (IH) and the product of medial fibrosis x IH (R2 0.10-0.15, P<0.05). We revealed the drastic vascular transformation that occurs during early remodeling at the molecular level, with >9,500 genes differentially expressed between native veins and AVFs in paired tissue samples.

Conclusion

In conclusion, this work demonstrates the importance of the subclinical inflammatory status of the pre-access vein in AVF nonmaturation, and identifies calprotectin (S100A8/A9) as a potential therapeutic target to prevent this complication. Our transcriptomics data underscores the complexity and uniqueness of vascular remodeling after fistula creation.

Funding

  • NIDDK Support