Background:
AVFs are the lifeline of dialysis patients, but can often occlude. The most common cause of AVF failure is inflammation-driven neointimal hyperplasia and thrombosis. Here, we investigated whether statin therapy with well-recognized anti-inflammatory properties can improve murine AVF patency, and further assessed the anti-inflammatory effects.
Methods:
One week prior to AVF creation, mice were randomized to oral atorvastatin 1.14mg/kg/day or control 100ul PBS (both n=10), administered by daily gavage. AVF were created using an end-to-side internal jugular vein and carotid artery anastomosis. AVF blood flow was measured (Transonic blood flow probe) at day 0 and weekly thereafter until occlusion (blood flow < 0.1ml/min). On day 6, CLIO-VT680, an inflammatory cell-targeted fluorescent nanoparticle, was injected intravenously (10mg/kg). 24 hours later, in vivo survival epifluorescence molecular imaging was performed to visualize inflammatory cell in the AVF venous outflow limb. Histopathological assessment of AVF was performed in on day 7 and 14 mice (6 statin each, 6 control each) to assess venous outflow area, AVF scarring via collagen, and adventitial macrophage content.
Results:
At day 7, the in vivo venous outflow cellular inflammation signal (CLIO-VT680 TBR) was significantly lower in statin-treated mice (3.5±0.16 vs 4.5±0.5 PBS, p=0.02). Adventitial macrophage content was significantly lower in statin group at day 14 (p=0.01). Positive AVF remodeling, a desirable feature for clinical AVF patency, was higher in the statin group as compared to the PBS group (p=0.02 at week 1, p=0.002 at week 2). In vivo, statin-treated animals exhibited greater AVF blood flow (BF) preservation from day 7 to day 14 (ΔAVF BF +0.14±0.2 ml/min vs. -0.79±0.32 ml/min PBS, p=0.02). The ΔAVF BF from day 7 to day 14 correlated inversely and significantly with the day 7 CLIO-VT680 cellular inflammation (r=-0.56, p=0.02), indicating that baseline inflammation may predict AVF failure. Kaplan Meier survival analysis showed median AVF patency in mice treated with statin was 28 days compared to 14 days in PBS treated group (p<0.05).
Conclusion:
Statin therapy prolongs AVF patency and preserves AVF blood flow in association with diminished AVF cellular inflammation.
A circularly polarised antenna for a wireless blood-flow sensor
