Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome.
Nephrotic syndrome is associated with numerous blood coagulation abnormalities and a marked propensity to thromboembolism. The present study was undertaken to examine the status of the fibrinolytic system in this hypercoagulable state. We measured the antigen concentrations or activities of plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), alpha 2-antiplasmin, alpha 1-antitrypsin, and alpha 2-macroglobulin as well as total antiplasmin activity and D-dimer concentration in the plasma of 39 patients with nephrotic syndrome and 32 normal controls subjects. In addition, antigen concentrations of plasminogen, alpha 2-antiplasmin, alpha 1-antitrypsin, and alpha 2-macroglobulin were measured in the urine of the study populations. The nephrotic group showed marked elevations of plasma t-PA, plasminogen, alpha 2-macroglobulin, and D-dimer and a significant reduction of plasma alpha 2-antiplasmin and alpha 1-antitrypsin as compared with the normal control group. Plasma alpha 2-macroglobulin was directly related to 24-hour urinary protein excretion and inversely related to serum albumin concentration. None of the proteins measured were detectable in the urine of normal controls. However, substantial amounts of plasminogen, alpha 2-antiplasmin, and alpha 1-antitrypsin and small amounts of alpha 2-macroglobulin were recovered in the urine of patients with nephrotic syndrome. Despite the lack of clinically demonstrable thrombosis, plasma D-dimer was markedly elevated in the nephrotic group, suggesting concurrent activation of coagulation and fibrinolytic pathways. In addition, the study revealed multiple abnormalities of the plasma fibrinolytic proteins and documented their urinary excretion in patients with nephrotic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Vaziri
N D
ND
Department of Medicine, University of California, Irvine.
Gonzales
E C
EC
Shayestehfar
B
B
Barton
C H
CH
D000293:Adolescent; D000328:Adult; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood* / Q000652:urine*; D015849:Plasminogen Inactivators / Q000378:metabolism; D011480:Protease Inhibitors / Q000097:blood* / Q000652:urine*; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin