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

• Published in: The journal of vascular access Vol. 9; no. 2; pp. 142 - 147
• Main Authors: Trimarchi, H, Duboscq, C, Genoud, V, Lombi, F, Muryan, A, Young, P, Schwab, M, Castanon, M, Rodriguez-Reimundes, E, Forrester, M, Pereyra, H, Campolo-Girard, V, Seminario, O, Alonso, M, Kordich, L
• Format: Journal Article
• Language: English
• Published: United States 01-04-2008
• Subjects: Aged; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis; C-Reactive Protein - metabolism; Chi-Square Distribution; Female; Graft Occlusion, Vascular - genetics; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; Polymorphism, Genetic; Polytetrafluoroethylene; Prospective Studies; Renal Dialysis; Statistics, Nonparametric; Thrombosis - genetics
• ISSN: 1129-7298; 1724-6032
• DOI: 10.1177/112972980800900212

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.
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.
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.
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.