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Abstract: PO1015

Gender-Specific Risk Genes in Arteriovenous Fistula Failure

Session Information

Category: Dialysis

  • 703 Dialysis: Vascular Access

Authors

  • Vazquez-Padron, Roberto I., University of Miami School of Medicine, Miami, Florida, United States
  • Tabbara, Marwan, University of Miami School of Medicine, Miami, Florida, United States
  • Rojas, Miguel G., University of Miami School of Medicine, Miami, Florida, United States
  • Challa, Akshara Sree, University of Miami School of Medicine, Miami, Florida, United States
  • Duque, Juan Camilo, University of Miami School of Medicine, Miami, Florida, United States
  • Salman, Loay H., University of Miami School of Medicine, Miami, Florida, United States
  • Martinez, Laisel, University of Miami School of Medicine, Miami, Florida, United States
Background

Gender is known to play a role in arteriovenous fistula remodeling and risk of failure. However, the clinical and molecular mechanisms behind this phenomenon have not been elucidated.

Methods

To address this question, 48 pre-access veins obtained at the time of two-stage AVF creation (24 matured and 24 failed postoperatively) and 40 postoperative transposition samples (20 matured and 20 failed) were randomly selected from the University of Miami Vascular Biorepository and submitted for bulk RNA sequencing. Females and males were equally represented in both outcome groups and were similar in demographics and baseline characteristics. We searched for common and sex-specific differentially expressed genes (DEG) in pre-access veins and postoperative samples in association with failure.

Results

In the pre-access vein, we found 28 DEG between veins that matured or failed postoperatively (log2FoldChange>1, FDR<0.05) and in common between both sexes. In male veins, 1180 transcripts were differentially expressed between both outcomes, whereas no female-specific DEG were detected in the same number of individuals. Principal component analyses demonstrated more transcriptional variability in both outcome groups in females, decreasing our power to identify female-specific genes in the vein. In postoperative samples, we found 156 DEG between fistulas that matured or failed and in common between both sexes. In addition, 143 female-specific and 153 male-specific genes were differentially expressed between outcomes, indicating gender relevant processes of postoperative remodeling. Both sexes showed a downregulation of genes related to responses to external stimuli and stress. However, gene set enrichment analysis (GSEA) revealed a suppression of cell-surface receptor signaling and cell adhesion mechanisms in males but not in females, suggesting a sex-specific effect in cell migration.

Conclusion

In conclusions, these analyses uncover potential differences in postoperative remodeling between females and males in relation to AVF failure. They also indicate a more complex transcriptional landscape in female tissues which may affect our ability to predict remodeling in this group of patients. These data may open the door to personalized medicine in preventing or treating vascular access complications.

Funding

  • NIDDK Support