The role of hypoxia in venous neointimal hyperplasia in hemodialysis grafts

PROJECT SUMMARY In 2020, nearly 808,000 U.S. patients had end-stage kidney disease (ESKD) and the majority underwent hemodialysis (HD) using arteriovenous fistulas (AVFs). AVFs have ~62% 1-year patency due to venous neointimal hyperplasia (VNH) and venous stenosis (VS). The molecular mechanisms of VS/VNH after AVF are not understood. We completed a randomized, blinded phase 1 clinical trial where 21 patients (5 females, average 65 yo) underwent periadventitial delivery of autologous adipose derived mesenchymal stem cells (MSC, n=10) or placebo to the outflow vein at new upper extremity AVF creation. The primary endpoint was time to AVF maturation. It was significantly decreased in MSC treated patients versus controls (1.5 vs 2.5 m respectively, Log Rank: P