Endothelial cell injury markers in chronic renal failure on conservative treatment and continuous ambulatory peritoneal dialysis.
OBJECTIVE
In chronic renal failure in dialyzed patients vascular damage is frequently observed and it is probable that disturbances in fibrinolytic activity and endothelial dysfunction may play a role in vascular complications such as stroke or ischemic heart disease. There have been a few data concerning hemostasis in chronic renal failure. Since hemostatic disturbances in nephrotic syndrome mimick those observed in patients maintained on chronic ambulatory peritoneal dialyses (CAPD), the aim of the study was to assess adhesion molecules (P-selectin, E-selectin, ICAM, VCAM and markers of endothelial cell injury), von Willebrand factor, thrombomodulin, and TFPI (tissue factor pathway inhibitor) in CAPD patients as well as in subjects with chronic renal failure (CRF) treated conservatively.


METHODS
The studies were performed on 23 CAPD patients, 24 patients with nephrotic syndrome and 24 sex- and age-matched healthy volunteers. TFPI total, full length, truncated, von Willebrand factor, trombomodulin, P-selectin, E-selectin, ICAM, VCAM and vascular endothelial growth factor (VEGF) and its receptor sFlt3 were assayed using commercially available kits. We evaluated also thrombin activity (thrombin-antithrombin complexes (TAT), prothrombin fragments 1 and 2) and the degree of plasmin generation.


RESULTS
In CAPD and CRF patients, concentrations of the adhesion molecules P-selectin, E-selectin, ICAM and VCAM were significantly higher when compared to the control group. Concentrations of total, free and truncated TFPI were significantly higher in CAPD and CRF patients when compared to the healthy volunteers. Concentrations of 'classical' markers of endothelial cell injury, von Willebrand factor and thrombomodulin, were significantly higher in CAPD and CRF patients when compared to the control group. In CAPD patients, VCAM and thrombomodulin were significantly elevated when compared to the CRF patients.


CONCLUSIONS
The elevated levels of adhesion molecules in CAPD patients probably reflect inadequate clearance as well as enhanced synthesis/release. They may also indicate endothelial cell injury as well as elevated levels of von Willebrand factor and trombomodulin and increased ICAM and VCAM in CAPD patients. Our studies indicate that in renal failure patients, particularly on CAPD, there is evidence of endothelial cell injury and a high degree of hypercoagulation relative to healthy subjects. It may lead to fibrin deposition in the vascular wall, thrombus formation, and development and progression of atherosclerosis with its complications.
Małyszko
Jolanta
J
Department of Nephrology and Transplantology, Medical University, Białystok, Poland. jolmal@poczta.onet.pl
Małyszko
Jacek S
JS
Myśliwiec
Michał
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D001792:Blood Platelets; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000293:injuries* / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010979:Platelet Function Tests
D015415:Biomarkers