Tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1) in patients treated with continuous ambulatory...

To establish whether the values of two key enzymes of fibrinolysis, tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1), differ between patients treated with continuous ambulatory peritoneal dialysis (CAPD) and healthy volunteers and whether plasma and dialysate tPA and PAI-1 values vary during one exchange of dialysis solution.

A total of 11 patients with chronic renal failure, treated with CAPD during the peritoneal equilibration test (in addition with blood sampling at time 0), and a control group of 11 healthy volunteers were examined. To identify the factors involved in the changes in tPA and PAI-1, 9 CAPD patients were subsequently monitored, in a crossover manner, during dialysis with solutions of 1.36 and 3.86% dextrose and off dialysis.

Compared with healthy individuals, CAPD-treated patients showed a significantly lower tPA activity (0.39 vs. 0.81 IU/ml, p < 0.05). Changes in plasma fibrinolysis during one exchange of dialysis solution were characterized mainly by a decrease in PAI-1 concentrations and activities caused by the circadian rhythm of fibrinolysis. To explain, in the crossover part of the study, the values of plasma PAI-1 antigen at time 0 (07.00 h) and at time 2 (09.00 h) were 9.4 versus 6.5 ng/ml with the 1.36% solution (p < 0.05), 8.2 versus 4.9 with the 3.86% solution (p < 0.05), and 14.1 versus 9.1 ng/ml off dialysis (p < 0.01). Compared to baseline (0 ng/ml with 1.36 as well as 3.86% solutions), the levels of PAI-1 antigen in dialysis solution rose, apparently due to local production in the peritoneal cavity, to 0.5 ng/ml (p < 0.05) with the 1.36% solution, to 0.7 (p < 0.05) with the 3.86% solution after a 2-hour dwell time, and to 1.6 (p < 0.05) and 1.3 ng/ml (p < 0.05) after a 4-hour dwell time, respectively. Hence, the different dextrose levels in the dialysis solutions had no effect on the monitored parameters of fibrinolysis.

The lower activity of plasma tPA, and the increase in PAI-1 levels in dialysis solutions may contribute to the development of thromboses in CAPD patients and to fibrin formation on the peritoneal surface with consequences such as peritoneal fibrosis.