Plasminogen activator inhibitor-1 activity and 4G/5G polymorphism in hemodialysis.
BACKGROUND
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.
Trimarchi
H
H
Nephrology Unit, British Hospital of Buenos Aires, Argentina. htrimarchi@hotmail.com
Duboscq
C
C
Genoud
V
V
Lombi
F
F
Muryan
A
A
Young
P
P
Schwab
M
M
Castanon
M
M
Rodriguez-Reimundes
E
E
Forrester
M
M
Pereyra
H
H
Campolo-Girard
V
V
Seminario
O
O
Alonso
M
M
Kordich
L
L
D000368:Aged; D001166:Arteriovenous Shunt, Surgical; D001807:Blood Vessel Prosthesis; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D005260:Female; D006083:Graft Occlusion, Vascular / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011138:Polytetrafluoroethylene; D011446:Prospective Studies; D006435:Renal Dialysis; D018709:Statistics, Nonparametric; D013927:Thrombosis / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; D011138:Polytetrafluoroethylene; D002097:C-Reactive Protein