Plasminogen activator inhibitor-1 activity and 4G/5G polymorphism in hemodialysis

Introduction: Chronic insufficiency alters homeostasis, in part due to endothelial inflammation. Plasmi- nogen activator inhibitor-1 (PAI-1) is increased in renal disease, contributing to vascular damage. We assessed PAI- 1 activity and PAI-1 4G/5G polymorphism in hemodialysis (HD) subjects and any association between thrombotic vascular access (VA) events and PAI-1 polymorphism. Methods: Prospective, observational study in 36 HD patients: mean age: 66.6 ± 12.5 yr, males n=26 (72%), time on HD: 28.71 ± 22.45 months. Vascular accesses: 10 polytetrafluoroethylene grafts (PTFEG), 22 arteriovenous fistu- lae (AVF), four dual lumen catheters (CAT). Control group (CG): 40 subjects; mean age: 60.0 ± 15 yrs, males n=30 (75%). Group A (GA): thrombotic events (n=12), and group B (GB): No events (n=24). Groups were no different according to age (69.2 ± 9.12 vs. 65.3 ± 14.5 yrs), gender (males: 7; 58.3% vs. 18; 81.8%), time on HD (26.1 ± 14.7 vs. 30.1 ± 38.7 months), causes of renal failure. Time to follow-up for access thrombosis: 12 months. Results: PAI-1 levels in HD: 7.21 ± 2.13 vs. CG: 0.42 ± 0.27 U/ml (p<0.0001). PAI-1 4G/5G polymorphic variant di- stribution in HD: 5G/5G: 6 (17%), 4G/5G: 23 (64%); 4G/4G: 7 (19%) and in CG: 5G/5G: 14 (35%); 4G/5G: 18 (45%); 4G/4G: 8 (20%). C-reactive protein (CRP) in HD: 24.5 ± 15.2 mg/L vs. in CG 2.3 ± 0.2 mg/L (p<0.0001). PAI-1 4G/5G variants: GA: 5G/5G: 3; 4G/5G: 8; 4G/4G: 1; GB: 5G/5G: 3; 4G/5G: 15; 4G/4G: 6. Thrombosis occurred in 8/10 patients (80%) with PTFEG, 3/22 (9%) in AVF, and 1/4 (25%) in CAT. Among the eight PTFEG patients with thrombosis, seven were PAI 4G/5G. Conclusions: PAI-1 levels were elevated in HD patients, independent of their polymorphic variants, 4G/5G being the most prevalent variant. Our data suggest that in patients with PTFEG the 4G/5G variant might be associated with an increased thrombosis risk. (J Vasc Access 2008; 9: 142-7)