Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrotic syndrome (NS) is associated with several disorders of hemostasis: thrombocytosis and platelet hyperaggregability; increased plasma levels of factors V and VIII, and of fibrinogen with blood hyperviscosity; decreased plasma levels of natural anticoagulants: free protein S, and antithrombin III compensated by increased levels of alpha 2-macroglobulin; lowered fibrinolytic activity. Intensity of hypercoagulability is related to the degree of hypoalbuminemia; however, the role of hypercoagulability in the increased incidence of thromboembolic events, including renal vein thrombosis, is not proved. Clotting disorders are due to urinary losses of anticoagulants or to increased liver synthesis of procoagulants stimulated by hypoalbuminemia. Moreover, changes in clotting factors levels may be due to intravascular thrombin formation (marked by increased plasma levels of fibrinopeptide A). During active phases of glomerulonephritides (GN) with NS, thrombin formation might in fact arise in glomeruli, following activation of the glomerular hemostasis system. Isolated glomeruli from human crescentic GN, rabbit nephrotoxic GN and rat HgCl2 autoimmune GN produce excessive amounts of procoagulant (tissue factor) activity (PCA). Sequential studies of the self-limited HgCl2 GN showed that glomerular PCA, proteinuria and glomerular fibrin deposits peaked concomitantly at the acme of the disease, suggesting that immunologically mediated glomerular damage had triggered the extrinsic coagulation pathway.
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PMID:Coagulation factors in nephrotic syndrome. 225 77

Proteinuria is characteristic of many glomerular conditions, and often exceeds 2-3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from 'overload' proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinuria leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in hematuric conditions. Therapies designed to reduce proteinuria per se may have a role in the treatment of glomerulopathies.
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PMID:Proteinuria and progression in human glomerular diseases. 225 80

In the experiments on white rats was studied the role of excessive thrombinogenesis in the development of acquired antithrombin III deficiency in the experimental nephrotic syndrome. It was determined that excess thrombin generation induced the marked acceleration of 125I-antithrombin III clearance from blood stream in consequence formation of thrombin antithrombin III complexes with the following limited proteolysis of the inhibitor by enzyme. These results give evidence that apart from proteinuria the excess thrombin generation accompanied by nephrotic syndrome play a part in the development of acquired deficiency of antithrombin III in this experimental pathology.
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PMID:Mechanisms of the development of acquired antithrombin III deficiency in the experimental nephrotic syndromes. 246 24

Twenty cases of primary nephrotic syndrome were treated with urokinase at a dosage of 60,000 units per day for two successive weeks. The results showed that after treatment the concentrations of fibrinogen, urine FDP, alpha 2-plasma inhibitor and plasminogen were significantly decreased (P value less than 0.01, less than 0.01, less than 0.001, less than 0.005 respectively). The concentration of antithrombin III was significantly increased (P less than 0.05). It is suggested that the treatment obviously increased the fibrinolytic activity and improved the hypercoagulated state. The clinical data showed that in addition to decrease of proteinuria and obvious increase of urine volume, the clinical manifestations and laboratory parameters showed no significant difference. Further study on the dosage and indications of urokinase is needed and the activity of coagulation and fibrinolysis in patients with deep vein thrombosis of lower extremities was also discussed.
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PMID:[Primary nephrotic syndrome treated with urokinase--a report of 20 cases]. 258 15

Preeclampsia, a major cause of fetal and maternal morbidity and mortality, may be difficult to distinguish clinically from other hypertensive disorders of pregnancy. Signs helpful in its diagnosis include presentation during late gestation in a nullipara with edema and proteinuria, and one or more of the following: hemoconcentration, hypoalbuminemia, liver function and/or coagulation abnormalities, and increased urate levels. Measures that may prove useful in differentiating preeclampsia from less dangerous forms of hypertension are decreased antithrombin III levels, increments in serum iron and carboxyhemoglobin, and decreases in urinary calcium. Major pathophysiological features of preeclampsia are decreased cardiac output, pulmonary capillary wedge pressure, and plasma volume; and marked increases in peripheral vascular resistance, as well as exaggerated pressor responses to endogenous angiotensin II and catecholamines. Renal hemodynamics decrease, in part as a result of a characteristic morphological lesion in glomeruli ("endotheliosis"), and there may be increased vascular permeability leading to albumin loss from the intravascular space. When gestation is advanced, termination is the treatment of choice; when temporization is required, several antihypertensive medications whose safety and efficacy have been tested in pregnant women are available. Magnesium sulfate remains the drug of choice for impending convulsions (the eclamptic phase of the disease). Finally, the etiology of preeclampsia remains unknown, but a popular theory suggests that alterations in prostaglandin metabolism may be responsible for the hypertension and coagulopathy in this disorder. In this respect, prophylactic treatment with low doses of aspirin, which decrease platelet thromboxane production but spare endothelial prostacyclin release, may decrease the incidence of preeclampsia in "high-risk" populations.
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PMID:Preeclampsia: pathophysiology, diagnosis, and management. 265 50

Preeclampsia is a complication of pregnancy characterized by hypertension, edema and proteinuria, beginning after 20 weeks of gestation. Six percent of the pregnant women in North America develop this disease, which is associated with increased morbidity and mortality for the mother and her baby. The physiopathology remains uncertain despite many research efforts. Actual hypotheses seek to explain the vasospasm that characterizes the disease. Among the many factors influencing vascular reactivity and possibly implicated are: the renin-angiotensin system, prostaglandins, progesterone and its metabolites, calcium, magnesium, digoxin-like immunoreactive substance(s), auricular natriuretic factor, substances secreted by platelets and leukotrienes. Prevention of the disease is limited by the absence of a biological or clinical marker with good sensitivity and appropriate specificity. Many biochemical or hematological parameters have been reported: uric acid, calcium, magnesium, proteinuria, blood iron, hematocrit, platelet count, antithrombin III, estrogen and progesterone. The combination of several tests could be superior to the use of each test individually, providing a better sensitivity and improving the positive predictive value. With early detection, new therapies for the prevention of the disease could be experimented on the higher risk women before the apparition of clinical symptoms or signs. Furthermore, those tests could be used in the study of the pathophysiology and in the choice of the best therapy.
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PMID:[Preeclampsia: physiopathology and prospects for early detection]. 269 75

Plasma levels of antithrombin III were tested during pregnancy in a control group of normal patients and in a study group that included patients with moderate and severe pre-eclampsia and chronic hypertension. The control group showed mean antithrombin III activity of 97.9 +/- 20.9%, the severe pre-eclamptic patients 22.33 +/- 18.22%, the moderate pre-eclamptic patients 56.0 +/- 7.56%, and the chronic hypertensive patients 77.5 +/- 6.69%. The difference between normal pregnancy and moderate pre-eclampsia was significant at P less than 0.002, normal pregnancy and severe pre-eclampsia P less than 0.002, moderate and severe pre-eclampsia P less than 0.002, chronic hypertension and normal pregnancy P less than 0.1, and chronic hypertension and severe pre-eclampsia P less than 0.002. All the severe pre-eclamptic patients and 2 out of 6 of the moderate pre-eclamptic women were below 55.7% (mean - 2S.D.) of normal antithrombin III activity. Patients with heavy proteinuria had depressed antithrombin III activity. However, chronic hypertensive pregnancies, although rather a small group, had almost normal values of plasma antithrombin III activity. The plasma antithrombin III value may thus help to distinguish between chronic hypertension and severe pre-eclamptic disease.
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PMID:Plasma antithrombin III levels in pre-eclampsia and chronic hypertension. 290 94

Plasma protein C (PC) antigen concentration has been shown to be normal or increased in patients with proteinuria. However, the available data concerning PC anticoagulant activity in nephrotic syndrome (NS) are limited. We measured plasma PC antigen concentration. PC anticoagulant activity, total and free protein (PS) concentrations, and antithrombin III (AT-III) antigen concentration in 21 adult patients with NS. The results were compared with those obtained in a control group of normal volunteers. PC antigen concentration and its anticoagulant activity were significantly increased in the NS group when compared with the normal control group. Likewise, plasma total and free PS values were significantly higher in the NS patients than the corresponding values found in the control group. In contrast, plasma AT-III antigen concentration was significantly reduced in patients with NS. A negative correlation was found between plasma PC and AT-III levels. These observations suggest that increased plasma PC concentration and anticoagulant activity in NS may afford some protection against the thrombotic diathesis associated with antithrombin deficiency and other coagulation abnormalities in this otherwise hypercoagulable state.
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PMID:Increased levels of protein C activity, protein C concentration, total and free protein S in nephrotic syndrome. 313 21

We measured the plasma concentrations of the natural anticoagulant protein C and its cofactor protein S in 17 patients with severe proteinuria. In addition, prothrombin and antithrombin III levels were measured in the same group of patients. These results were compared with results obtained in 26 healthy controls and a group of 14 patients with chronic renal insufficiency (CRI) but minimal proteinuria. Protein C, protein S, and prothrombin levels were not significantly different between healthy controls and patients with CRI. However, protein C, protein S, and prothrombin levels were significantly elevated in 71%, 82%, and 76%, respectively, of patients with proteinuria. Antithrombin III levels were decreased in three of these 17 patients with proteinuria. Plasma concentrations of protein C, protein S, and prothrombin correlated significantly with each other and were inversely correlated with serum albumin concentrations. In three patients, high protein C, protein S, and prothrombin levels returned to normal during remission of the proteinuric state. Proteins C and S were not detectable in the urine of two patients with high-grade proteinuria. Thus, the plasma levels of the vitamin K-dependent, natural anticoagulant protein C and its cofactor protein S are increased in patients with proteinuria. The elevated plasma levels of other vitamin K-dependent proteins, such as prothrombin, suggest a generalized elevation in vitamin K-dependent protein synthesis in patients with proteinuria.
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PMID:Plasma concentrations of the natural anticoagulants protein C and protein S in patients with proteinuria. 316 Aug

Six women without hypertension or proteinuria, admitted for severe upper abdominal pain in the third trimester of pregnancy had elevated serum liver enzymes (SGOT, SGPT), markedly increased serum LDH levels, thrombocytopenia and abnormal blood coagulation tests, in particular low antithrombin III levels, indicating disseminated intravascular coagulation (DIC). Liver biopsies showed periportal and/or focal parenchymal lesions with large fibrin deposits, comparable to the liver lesions in eclampsia. Immunofluorescence (IF) showed microthrombi and large fibrin deposits. Three of the six women recovered spontaneously before delivery; in the remaining three all signs and symptoms rapidly disappeared after delivery. Perinatal outcome was poor. Seven women with pregnancy-induced hypertension and elevated serum liver enzymes constituted a reference series. Histopathological examination of liver biopsies in the reference group revealed periportal and/or focal parenchymal lesions in three whereas IF showed fibrin deposition in all seven, but less extensive than in the study group. The present findings indicate that upper abdominal pain in the last trimester of pregnancy can be caused by a syndrome of (pre)-eclamptic liver damage and DIC, even when hypertension and proteinuria are lacking.
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PMID:A syndrome of liver damage and intravascular coagulation in the last trimester of normotensive pregnancy. A clinical and histopathological study. 351 56


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