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Abstract: FR-PO703

Preexisting venous Medial Matrix Metalloproteinase (MMP)-2 and Arteriovenous Fistula (AVF) Maturation: Findings from the Hemodialysis Fistula Maturation (HFM) Consortium Study

Session Information

Category: Dialysis

  • 704 Dialysis: Vascular Access

Authors

  • Shiu, Yan-Ting, University of Utah, SALT LAKE CITY, Utah, United States
  • Le, Ha Do, University of Utah, SALT LAKE CITY, Utah, United States
  • Allon, Michael, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Robbin, Michelle L., University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Hudkins, Kelly L., University of WA, Seattle, Washington, United States
  • Alpers, Charles E., University of WA, Seattle, Washington, United States
  • Greene, Tom, University of Utah, SALT LAKE CITY, Utah, United States
  • Cheung, Alfred K., University of Utah, SALT LAKE CITY, Utah, United States
Background

AVF maturation requires adequate outward remodeling (luminal expansion) and limited inward remodeling (neointimal hyperplasia) to facilitate increases in AVF diameter and blood flow. MMP-2 and MMP-9 are critical for vascular remodeling in other settings. Inhibition of MMP-2 and MMP-9 reduces neointimal hyperplasia following vascular injury or graft implantation in animals with normal renal function. However, the clinical relevance of MMP-2 and MMP-9 in AVF diameter (a net result of luminal expansion and neointimal hyperplasia) and blood flow remains unclear.

Methods

We prepared histological slides of venous samples from 100 randomly selected patients at the time of AVF creation in the HFM Study. The protein expression levels of MMP-2 and MMP-9 were quantified by immunohistochemistry and ImageJ, and reported as a percentage of the total medial area. We then investigated the statistical associations of MMP-2 or MMP-9 levels with AVF diameter and blood flow assessed using duplex ultrasound at 6 weeks after AVF creation.

Results

Venous medial MMP-2 (Fig. 1) and MMP-9 expression varied widely among patients. We found a negative association of venous medial MMP-2 with the 6-week AVF diameter (Δ diameter = –0.23 mm; 95% CI, –0.44 to –0.02; p=0.029) and a trend for AVF blood flow (Δ flow = –39 ml/min; 95% CI, –106 to –29; p=0.26), per 10% increase in MMP-2. No association was found between MMP-9 and the 6-week AVF diameter or blood flow.

Conclusion

Preexisting venous medial MMP-2 expression was associated with impaired AVF maturation in this subset of HFM patients. More rigorous validation of this observation using a larger cohort is necessary.

Funding

  • NIDDK Support