Kidney Week

Abstract: FR-OR096

Systemic Antifibrotic Therapy Improves Arteriovenous Fistula Remodeling in Experimental Models

Session Information

• Vascular Access: Featured Research
  October 23, 2026 | Location: Room 603, Convention Center
  Abstract Time: 05:10 PM - 05:20 PM

Category: Dialysis

• 803 Dialysis: Vascular Access

Authors

• Arroliga Mejia, Pablo A., University of Miami Miller School of Medicine, Miami, Florida, United States

Pablo A. Arroliga Mejia

• Wei, Yuntao, University of Miami Miller School of Medicine, Miami, Florida, United States

Yuntao Wei, MD

• Sussman, Matthew Steven, University of Miami Miller School of Medicine, Miami, Florida, United States

Matthew Steven Sussman, MD

• Tabbara, Marwan, University of Miami Miller School of Medicine, Miami, Florida, United States

Marwan Tabbara, MD

• Duque, Juan, University of Miami Miller School of Medicine, Miami, Florida, United States

Juan Duque, MD

• Vazquez-Padron, Roberto I., University of Miami Miller School of Medicine, Miami, Florida, United States

Roberto I. Vazquez-Padron, PhD

• Martinez, Laisel, University of Miami Miller School of Medicine, Miami, Florida, United States

Laisel Martinez, PharmD, MS

Background

Postoperative vascular fibrosis is one of the most important determinants of arteriovenous fistula (AVF) maturation failure. It affects venous compliance, limits expansive remodeling, and prevents the vessel from maintaining an adequate luminal diameter in the presence of thrombi or intimal hyperplasia. Therefore, systemic anti-fibrotic treatments may represent a viable strategy to improve AVF maturation.

Methods

In this study, carotid-jugular AVFs were created in 17 nephrectomized mice that were randomly allocated to receive daily intraperitoneal injections of pirfenidone (200 mg/kg/day) or vehicle for 21 days starting on the day of AVF creation. Vessel remodeling was assessed using blood flow measurements and histologic analyses. We also evaluated the transcriptional effects of pirfenidone on primary human myofibroblasts in vitro.

Results

Fistulas from pirfenidone-treated mice exhibited higher blood flows compared with vehicle-treated controls. Pirfenidone also decreased postoperative fibrosis and increased luminal area in mouse AVFs, while preventing the postoperative accumulation of COL8A1, an inflammatory collagen associated with human AVF failure. In vitro, pirfenidone inhibited myofibroblast activation in response to both pro-fibrotic and inflammatory stimuli (TGFβ and IL1β).

Conclusion

Systemic anti-fibrotic treatments exert beneficial effects on experimental AVFs, possibly by regulating both pro-fibrotic and anti-inflammatory myofibroblast activation mechanisms.

Acknowledgment

This research was funded by the National Institutes of Health (grant numbers R01-DK132888, R01-DK121227, R01-DK136297, R21-DK138390); the Florida Department of Health (grant number 22K07); the Veterans Affairs (grant numbers IK6-BX006823, I01-BX006080)

Funding

• NIDDK Support