Increased expression of hypoxia-inducible factor-1 alpha in venous stenosis of arteriovenous polytetrafluoroethylene grafts in a chronic renal insufficiency porcine model.

PURPOSE: To create a more clinically relevant model of hemodialysis graft failure in pigs by creating chronic renal insufficiency before polytetrafluoroethylene (PTFE) hemodialysis graft placement and to determine the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) at the vein-to-graft anastomosis (VGA).

MATERIALS AND

METHODS

Chronic renal insufficiency was created in 14 castrated juvenile male pigs with complete embolization of the left renal artery and the partial embolization of the right renal artery by infusing 150-250-mum polyvinyl acrylide spherical particles. The efficacy of the embolization was assessed by determining the amount of polyvinyl acrylide particles used per kidney, the weight of the kidneys at sacrifice, and kidney function (blood urea nitrogen [BUN] and creatinine levels). Twenty-eight days after embolization, PTFE grafts were placed from the carotid artery to the ipsilateral jugular vein and removed 3, 7, and 14 days after graft placement. Western blot for HIF-1 alpha was performed in the VGA and control vessel.

RESULTS

The left kidney required two times the polyvinyl acrylide particles than did the right kidney (P < .05). The right kidney weighed nearly three times more than the left (P < .05). The BUN and creatinine levels at graft placement were significantly higher than those at baseline (P < .05). Four grafts were patent at day 3, four at day 7, and four at day 14. By day 7, the mean HIF-1 alpha at the VGA had increased significantly when compared with that of control vessels (P < .05).

CONCLUSIONS

A more clinically relevant porcine model of hemodialysis graft failure was created, and there was significantly increased expression of HIF-1 alpha by day 7 at the VGA.