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)

Blood coagulation, fibrinolytic, and inhibitory proteins in end-stage renal disease: effect of hemodialysis.

Patients with end-stage renal disease (ESRD) are at risk of ischemic cardiovascular complications and vascular thrombosis. These observations prompted the present survey of the blood coagulation, fibrinolytic, and inhibitory proteins in a group of 31 ESRD patients and 32 normal controls. Immunologic and functional assays were used to quantitate plasma antigen concentrations and/or functional activities of factors XII, XI, IX, VIII, VII, X, II, and XIII, von Willebrand factor, fibrinogen, fibronectin, high molecular weight kininogen, D-dimer, antithrombin III, protein C, protein S, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor, alpha 2-antiplasmin, alpha 1-antitrypsin, and alpha 2-macroglobulin as well as antiplasmin activity. The coagulant activities of factors XII, IX, X, and II were significantly reduced in ESRD patients despite their normal or increased plasma antigen concentrations. In addition, the ESRD patients showed hyperfibrinogenemia and significant elevations of plasma concentrations of D-dimer, von Willebrand factor, factor VII, and factor XIII antigens. They also exhibited significant reductions of antithrombin III, free protein S, plasminogen, and tissue-type plasminogen activator concentrations. Despite ultrafiltration, plasma factor IX activity and von Willebrand factor and fibrinogen concentrations decreased after hemodialysis with little or slight changes in other measured parameters. The ESRD patients studied here exhibited numerous abnormalities of coagulation, fibrinolytic, and inhibitory proteins at multiple levels. These abnormalities may be involved in the pathogenesis of cardiovascular complications and vascular thrombosis in this population. The precise mechanism(s) and clinical significance of the observed abnormalities are unknown and await further investigation.

Coagulation and inhibitory and fibrinolytic proteins in essential hypertension.

Arterial hypertension (HTN) increases the risk of cerebral coronary, and other vascular complications that frequently involve platelet activation and blood coagulation. Several key proteins in the blood coagulation, fibrinolytic and inhibitory systems were studied in 29 men with HTN (aged 45 +/- 3 yr) and 15 normal men of the same age. Plasma levels of high-molecular-weight kininogen and factors XII, IX, VII, X, II, and XIII, as well as von Willebrand factor (vWF), fibrinogen, fibronectin, alpha 2-antiplasmin, tissue-plasminogen activator, D-dimer, platelet factor-4, and protein C were measured by the use of appropriate functional and immunologic assays before and after a cardiopulmonary exercise stress test. The concentrations of vWF, alpha 2-antiplasmin, and D-dimer were significantly (P < 0.02) higher in the HTN group as compared with the control group. The exercise stress test resulted in significant rises in the plasma vWF, alpha 2-antiplasmin, and tissue-plasminogen activator levels in the two groups. The concentrations of vWF and D-dimer were related to diastolic blood pressure (r = 0.44 and 0.40, respectively; P < 0.02). Levels of vWF also were related to left ventricular mass index and left ventricular posterior wall and septal thickness (r = 0.34, 0.43, and 0.34, respectively; P < 0.05). The constellation of these findings suggests a low-grade fibrin formation and degradation, the magnitude of which is related to the diastolic blood pressure. The observed abnormalities can potentially contribute to the cardiovascular complications of untreated HTN.

Relationship of asymptomatic bacteriuria and renal scarring in children with neuropathic bladders who are practicing clean intermittent catheterization.

OBJECTIVE: To determine whether untreated asymptomatic bacteriuria is associated with renal scarring in children with neuropathic bladders managed with clean intermittent catheterization (CIC). DESIGN: Retrospective study of 207 patients aged 1 to 30 years (mean 11.9 +/- 5.5 years) treated with CIC for a mean duration of 6.6 +/- 3.9 years by the spina bifida program at Children's National Medical Center. All patients were examined for renal scarring with dimercaptosuccinic acid (DMSA) renal scans. Catheterized urine cultures were obtained annually, but bacteriuria ( > 10,000 colony-forming units of a single organism per milliliter) was treated only if the patients had symptoms or if vesicoureteral reflux (VUR) was present. RESULTS: Of 207 children, 176 (85%) had one or more episodes of untreated asymptomatic bacteriuria and 72 (35%) had one or more febrile episodes associated with positive urine culture results. Biannual DMSA scans detected 54 new scarring episodes in 42 patients. Of newly recognized scars, 55% were preceded within 1 year by a febrile infection, 26% were detected in patients with VUR and asymptomatic bacteriuria, and 19% were detected in new patients during their initial examination. Univariate analysis revealed that new scarring was present in 35 of 176 patients with asymptomatic bacteriuria compared with 7 of 31 patients without (p = 809). Logistic regression analysis revealed that factors associated with scarring were febrile infections (adjusted odds ratio [OR] = 30.6, 95% confidence interval [CI] = 9.8 to 95.8), age more than 20 years (OR = 4.3, CI = 1.01 to 18.5), the presence of bladder trabeculation (OR = 2.7, CI = 1.0 to 7.6), and VUR (OR = 58.8, CI = 6.3 to 547.3), but asymptomatic bacteriuria was not associated with scarring. CONCLUSION: In the absence of VUR, asymptomatic bacteriuria in patients undergoing CIC is not a significant risk factor for scarring and does not require antibiotic therapy.