The fibrinolytic system in chronic renal failure

Background: Patients with chronic renal failure (CRF) face a high risk of c ardiovascular morbidity and mortality. Impaired fibrinolysis has recently b een acknowledged to function as a risk factor for cardiovascular ischemic c omplications. Whether changes in fibrinolytic function contribute to the in creased 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 i n 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) (g roup 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. Howev er, 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 markedl y disturbed in ESRD due to a decreased availability of t-PA. Thus, it may b e speculated that the development of atherothrombotic events in hemodialysi s patients is, at least in part, due to an impaired fibrinolysis.