The fibrinolytic system in chronic renal failure.
BACKGROUND
Patients with chronic renal failure (CRF) face a high risk of cardiovascular morbidity and mortality. Impaired fibrinolysis has recently been acknowledged to function as a risk factor for cardiovascular ischemic complications. Whether changes in fibrinolytic function contribute to the increased cardiovascular risk in CRF, however, remains unclear.


METHODS
In the present study, tissue-plasminogen activator (t-PA) and its main antagonist plasminogen activator inhibitor-1 (PAI- 1) were determined in 12 subjects with normal renal function (group A) [serum creatinine (Cr) <1.3 mg/dl], 24 patients with impaired renal function (Cr 1.3-6.5 mg/dl) (group B) and 22 patients with endstage renal disease (ESRD) on hemodialysis (Cr>6.5 mg/dl) (group C).


RESULTS
Plasma concentrations of PAI-1 and t-PA antigen as well as the PAI-1:t-PA molar ratio were unchanged in group B as compared to group A. However, in ESRD patients (group C), t-PA concentrations markedly decreased [13.7 +/- 2.9 ng/ml vs. 32.8 +/- 4.7 ng/ml (group B, p <0.01) and 35.4 +/- 8.4 ng/ml (group A, p <0.01)] while PAI-1 antigen concentrations remained in the control range. Thus, the PAI-1:t-PA molar ratio significantly increased in group C patients [12.4 +/- 4. 0 vs. 6.0 +/- 2.5 (group B; p<0.01) and 4.5 +/- 1.7 (group A; p<0.01].


CONCLUSIONS
From our data it may be suggested that fibrinolysis is markedly disturbed in ESRD due to a decreased availability of t-PA. Thus, it may be speculated that the development of atherothrombotic events in hemodialysis patients is, at least in part, due to an impaired fibrinolysis.
Lottermoser
K
K
Medizinische Universitäts-Poliklinik, Bonn, Germany.
Petras
S
S
Pöge
U
U
Fimmers
R
R
Hertfelder
H J
HJ
Schiermeyer
B
B
Vetter
H
H
Düsing
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D010959:Tissue Plasminogen Activator