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SIR 2026

Traditional Poster

Dialysis Interventions

Session: Traditional Poster Presentations

516 - Senolytic Changes in Murine Arteriovenous Fistulas with Chronic Kidney Disease

Monday, April 13, 2026
12:10 PM - 1:10 PM ET
Purpose: Hemodialysis therapy for end-stage kidney disease (ESKD) patients requires suitable vascular access which is most commonly the arteriovenous fistula (AVF). Approximately forty percent of AVFs fail within one year via unclear mechanisms and current therapies are wholly inadequate. Cellular senescence disproportionately affects ESKD patients and may be essential in AVF failure. ESKD itself may also be responsible for an increasing senescent burden and predisposition to deleterious vascular responses. Senescence follows AVF placement in mice and rats with normal kidney function, but the temporal changes and specific localization of senescent cells in uremic conditions remain unknown. Therefore, this study aims to characterize AVF changes in uremic mice over time and versus control vessels.

Materials and Methods: Six- to eight-week-old male C57BL6/J mice received a 5/6 nephrectomy. Twenty-eight days later an AVF was created via a cuff anastomosis connecting the right carotid artery to the right jugular vein. Transcriptomic analysis was performed on the AVF seven days post-AVF, and further samples were collected at fourteen and twenty-eight days post-AVF creation for histological analysis.

Results: Firstly, the morphometry of the AVF outflow vein was assessed and showed reduced neointimal cell density. A whole transcriptomic analysis of the outflow veins at seven days post-AVF placement revealed 1187 upregulated and 3256 downregulated genes as compared to control veins. The differentially expressed genes were significantly enriched in established senescent (SenMayo) and fibrotic (SenSig) gene sets. These were confirmed to also change histologically between 14 and 28 days in the AVF with markers such as p16, p21, and pp53 increasing.

Conclusion: These data support established biomarkers of AVF failure like matrix-metalloproteinases and monocyte chemokines and lend credence to potential novel modulators of AVF survival. In summary, this study reveals for the first time the chronological progression of senescence in the AVF of uremic mice.