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Recently there has been a renewed interest in the possibility that lipoprotein(a)--Lp(a)--may be important in the pathogenesis of thrombosis-related disease. In nephrotic syndrome, hyperlipidemia is a common finding, and thrombosis is a major complication. With this regard, if Lp(a) levels increase concomitantly with low-density lipoprotein and/or very-low-density lipoprotein levels in nephrotic syndrome, this may be considered a thrombogenic factor. To probe this possibility and to corroborate the relationship between Lp(a) and fibrinolytic profiles, we measured the Lp(a) levels in patients with nephrotic syndrome (n = 43), in patients with chronic glomerulonephritis with less proteinuria than in nephrotic syndrome (n = 28), and in healthy controls (n = 50) and observed the relation between Lp(a) levels and tissue-type plasminogen activator (t-PA) activity, euglobulin fibrinolytic activity, and t-PA antigen. The Lp(a) levels were significantly higher in the patients with nephrotic syndrome as compared with both patients with chronic glomerulonephritis and healthy controls (p < 0.001). There was a direct correlation with serum cholesterol level (r = 0.780; p = 0.0001), triglyceride level (r = 0.445; p = 0.0001), and urine protein level (r = 0.675; p = 0.0001) and a reverse correlation with serum albumin levels (r = 0.566; p = 0.0001). The Lp(a) levels showed a reverse correlation with t-pA activity (r = 0.627; p = 0.0001), total fibrinolytic activity in euglobulin fraction (r = 0.458; p = 0.0001), and t-PA activity divided by the t-PA antigen (r = 0.567; p = 0.0001), but no correlation with t-PA antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Recently, we described that in the physiologic state, urokinase concentration is higher in the renal vein than in the renal artery which suggests that the kidney is the essential organ providing urokinase to the systemic circulation. In end-stage renal disease (ESRD) patients, urokinase provided by the kidney may be decreased, and this might be the cause of decreased systemic fibrinolytic activity seen in ESRD. To study this possibility, we measured fibrinolytic profiles including urokinase, tissue plasminogen activator (t-PA) and fibrinolytic activity in the euglobulin fraction of ESRD patients and compared the results with those of two control groups consisting of renal transplantation patients and age- and sex-matched healthy controls. The euglobulin fibrinolytic activity was 92.2 +/- 14.8 BAU in the ESRD group, 108.7 +/- 13.5 BAU in the kidney transplantation (KT) group and 101.5 +/- 8.0 BAU in the healthy control group. Although it was lower in the ESRD than in the KT (p0.005) and the healthy control group (p0.005), there was no difference between the KT and the healthy control group. t-PA antigen was 1.2 +/- 1.3 ng/ml in the ESRD group, 3.5 +/- 1.7 ng/ml in the KT group and 3.1 +/- 2.1 ng/ml in the healthy control group. It was lower in the ESRD compared to the KT (p0.001) and the healthy control group (p0.001) but there was no difference between the KT and the healthy control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Considering that PAI-1 is an important factor modulating the systemic fibrinolytic activity, the abnormal insulin metabolism frequently seen in end-stage renal disease (ESRD) may cause decreased fibrinolytic activity in concert with PAI-1. To study this possibility, we measured insulin levels and compared it with the fibrinolytic profiles in ESRD patients. Fasting blood sugar, insulin, and C peptide levels were higher in ESRD patients than in the control group. In the ESRD patients, the insulin levels showed a positive correlation with C peptide (r = 0.612, p = 0.0001), fasting blood sugar (r = 0.334, p = 0.044), and PAI-1 antigen (r = 0.474, p = 0.0001) and a reverse correlation with euglobulin fibrinolytic activity (r = 0.5, p = 0.005), but no correlation with t-PA antigen. The euglobulin fibrinolytic activity showed a reverse correlation with PAI-1 antigen (r = 0.289, p = 0.0144), but no correlation with t-PA antigen. Our results suggest that abnormal insulin metabolism and/or insulin resistance, which occur frequently in ESRD, may play an important role in the decrease in systemic fibrinolytic activity by the regulation of the PAI-1 concentration.

To compare the fibrinolytic activity between the renal artery and vein and the systemic circulation, we measured tissue-type plasminogen activator (t-PA), urokinase and total fibrinolytic activity in the blood samples from both the left and right renal artery and vein and the anterior cubital vein of 7 kidney donors. Englobulin fibrinolytic activity was significantly higher in the renal vein [106.6 +/- 5.6 blood activator units (BAU)] than in the renal artery (90.6 +/- 4.1 BAU; p less than 0.001) and cubital vein (94.3 +/- 6.3 BAU, p less than 0.005), but there was no difference between renal artery and cubital vein. t-PA Ag was 2.9 +/- 1.1 ng/ml in the renal vein, 2.6 +/- 1.0 ng/ml in the renal artery and 2.6 +/- 1.1 ng/ml in the cubital vein. There was no difference between renal artery, renal vein and cubital vein. Urokinase was significantly higher in the renal vein (3.3 +/- 0.4 ng/ml) than in the renal artery (2.4 +/- 0.4 ng/ml; p less than 0.001) and cubital vein (2.6 +/- 0.4; p less than 0.005), but there was no difference between the renal artery and cubital vein. In all cases, there was no difference in the fibrin(ogen) degradation product concentration between the renal artery and vein and the cubital vein. These findings suggest that the kidney may be an essential organ for providing urokinase to the systemic circulation.