Abstract 280: Are There Sex-specific Differences in Arteriovenous Fistula Maturation?

Abstract

The arteriovenous fistula (AVF) is the preferred method of dialysis access due to its proven superior long term outcomes. However, women have lower rates of AVF maturation than men (38% vs. 60%), preventing optimal AVF use. Using a novel mouse AVF model that recapitulates human AVF maturation, we tested the hypothesis that there is a difference in male and female AVF maturation. Aortocaval fistulae were created in male and female C57BL/6 mice (9-10wk). At days 0, 3, 7, 14 and 21, aortic and IVC diameters and flow velocity were monitored by Doppler ultrasound. We then calculated shear stress. Using qPCR, we measured messenger RNA (mRNA). AVF were examined at day 21 and AVF wall thickness was measured by computer morphometry. Female mice weighed less preoperatively and at day 21 (p<0.05). They also had larger suprarenal aortic diameter (p=0.002) but smaller infrarenal IVC diameter (p<0.05) at baseline. After AVF creation, there was similar dilation of the infrarenal aorta and IVC in both male and female mice (p>0.05). Infrarenal IVC mean velocity was decreased in female mice at baseline and at day 3, 14 and 21 (p<0.05). Similarly, mean laminar shear stress magnitude in the infrarenal IVC was decreased in female mice at day 7 (p=0.03), 14 (p=0.04) and 21 (p=0.01). There was no difference in the infrarenal aorta shear stress magnitude (p=0.80). mRNA of KLF2, a marker of laminar shear stress, was decreased in the venous limb of female AVF on day 21 (p=0.048). Preoperatively, female mice had thinner venous walls (p=0.035). However, at day 21, AVF wall thickness was similar (p=0.18). AVF in female mice have lower magnitudes of laminar shear stress, lower expression of KLF2 mRNA and a higher percent increase in wall thickness. These findings suggest a mechanism underlying the diminished rates of AVF maturation in women.