fibrinopeptide-a and Nephrotic-Syndrome

Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by radioimmunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated in the majority of nephrotics (P < 0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis "in vivo." A positive correlation was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64, P < 0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics, caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis.

Topics: Adolescent; Adult; Aged; Enzyme-Linked Immunosorbent Assay; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Nephrotic Syndrome

Quantitative changes of hemostatic molecular markers were studied in patients with nephrotic syndrome. The plasma levels of fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), products of thrombin activation, and fragment F1 + 2 (F1 + 2), a product of prothrombin activation, were measured by enzyme immunoassay in 21 patients with nephrotic syndrome and in 16 normal controls. The mean value of FPA was 17.5 +/- 7.5 ng/ml (mean +/- SD) in nephrotic patients and 4.5 +/- 0.3 ng/ml in normal controls (P < 0.02); F1 + 2 concentration was 1.4 +/- 0.3 ng/ml in nephrotic patients and 0.5 +/- 0.1 ng/ml in normal controls (P < 0.001); TAT level was 1.0 +/- 0.3 microgram/l in nephrotic patients and 0.2 +/- 0.1 microgram/l in normal controls (P < 0.05). These data indicated intravascular hemostasis activation. Based on these results, we propose that low antithrombin III level in nephrotic patients may be due to both urinary loss and intravascular consumption.

Topics: Adult; Aged; Antithrombin III; Biomarkers; Female; Fibrinopeptide A; Hemostasis; Humans; Immunoenzyme Techniques; Male; Middle Aged; Nephrotic Syndrome; Peptide Hydrolases; Reference Values

Fibrinopeptide A (FPA), a sensitive index of in vivo thrombin activity, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), specific markers of platelet intravascular activation, have been measured in plasma by radioimmunoassays in 23 patients with nephrotic syndrome and in 32 normal subjects. FPA concentration was 2.40 +/- 1.42 ng/ml (mean +/- SD) in nephrotic patients and 1.16 +/- 0.58 ng/ml in normal controls (p less than 0.001); beta TG concentration was 57.9 +/- 33.2 ng/ml in nephrotic patients and 25.7 +/- 7.4 ng/ml in controls (p less than 0.001); PF4 level was not different from controls. These data indicate in vivo blood hypercoagulability and platelet hyperfunction in nephrotic syndrome. Moreover, we have documented a slow in vitro FPA generation pattern (delta FPA): 0.97 +/- 0.51 ng/ml/10 min; this suggests that thrombin activity is predominantly local.

Topics: Adolescent; Adult; Aged; beta-Thromboglobulin; Biomarkers; Creatine; Female; Fibrinopeptide A; Hemostasis; Humans; Male; Middle Aged; Nephrotic Syndrome; Osmolar Concentration; Platelet Factor 4

Plasma fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 concentrations were determined by radioimmunoassay in 46 patients with glomerulonephritis and the nephrotic syndrome. An increase in plasma FPA and B beta 15-42 levels was noted in these patients; this increase was marked in the nephrotic patients. There was a positive correlation in these patients between plasma FPA and B beta 15-42 levels. The B beta 15-42/FPA ratio was significantly higher in nonnephrotic patients compared with controls. Intravascular coagulation with subsequent fibrinolysis to regulate fibrin formation may occur in patients. A positive correlation was found between plasma B beta 15-42 level and serum urea nitrogen or serum creatinine concentration, suggesting that plasma B beta 15-42 level is influenced not only by plasmin action, but also by renal dysfunction.

Topics: Adolescent; Adult; Blood Coagulation; Blood Urea Nitrogen; Cholesterol; Creatinine; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Glomerulonephritis; Humans; Middle Aged; Nephrotic Syndrome; Peptide Fragments; Radioimmunoassay; Serum Albumin