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

ABSTRACT

INTRODUCTION: Chronic insufficiency alters homeostasis, in part due to endothelial inflammation. Plasminogen 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 fistulae (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 distribution 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.