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)

Thrombomodulin is an endothelial cell membrane protein acting as a cofactor for the activation of plasma protein C. Recently, it was found that soluble forms of thrombomodulin exist in plasma. Although the physiological significance of circulating thrombomodulin is presently obscure, it may reflect injury of the endothelial cell. In the present study, we examined plasma thrombomodulin concentrations in 106 Type 2 (non-insulin-dependent) diabetic patients. Plasma thrombomodulin was determined by a sandwich ELISA employing monoclonal anti-thrombomodulin antibodies. The patients with proteinuria had higher plasma thrombomodulin concentrations (61.0 +/- 36.0 ng/ml) compared to the patients without proteinuria (33.6 +/- 9.5 ng/ml, P less than 0.001) and control subjects (32.8 +/- 6.5 ng/ml, P less than 0.001). Plasma thrombomodulin concentrations were positively correlated with the level of serum creatine, blood urea nitrogen, urinary albumin and urinary beta 2-microglobulin (P less than 0.001 for each), but not with fasting plasma glucose, hemoglobin A1c or fructosamine. Elevated plasma thrombomodulin was also observed in the patients with pre-proliferative (63.4 +/- 28.9 ng/ml) or proliferative retinopathy (57.4 +/- 34.7 ng/ml), but not in the patients with non-proliferative retinopathy (33.5 +/- 12.9 ng/ml) or those without retinopathy (32.4 +/- 8.9 ng/ml). Even in the 81 diabetic subjects without proteinuria as determined by a dip and read method, and whose serum creatinine was lower than 1.0 mg/dl, the plasma thrombomodulin concentration was significantly higher in the patients with pre-proliferative (41.5 +/- 4.4 ng/ml) and proliferative retinopathy (41.0 +/- 12.8 ng/ml) compared to the patients without retinopathy (32.2 +/- 8.8 ng/ml) and those with non-proliferative retinopathy (31.9 +/- 7.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma thrombomodulin concentration in diabetes mellitus. 217 97

The intraglomerular presence of thrombomodulin (TM) was examined in 19 patients with lupus glomerulonephritis (GN). TM is a cell surface glycoprotein found on endothelial cells and plays a key role in the protein C anticoagulant pathway. Renal biopsy specimens of patients with lupus GN and several kinds of renal disease other than lupus GN, i.e., membranous GN, IgA GN, minimal change nephrotic syndrome (MCNS) and hemolytic uremic syndrome (HUS) were examined by indirect immunofluorescence, using three kinds of monoclonal antibodies against human TM: KA-2, KA-3 and KA-4. It has been reported that KA-3 and KA-4 bind to enzyme-digested TM as well as intact TM, while KA-2 recognizes intact TM only. In the glomeruli from both normal subjects and patients with MCNS, only very weak staining of TM was found. Patients with HUS showed negative TM staining in the glomeruli. In contrast, positive to strongly positive staining of KA-2 as well as of KA-3 and KA-4 was observed mainly along the capillary wall of glomeruli from patients with lupus GN. Some patients with non-lupus GN showed positive staining of these monoclonal antibodies, but the staining was far more intense in most patients with lupus GN than in the patients with non-lupus GN. Staining of albumin and transferrin by the indirect method was negative in all cases of lupus GN that showed positive staining of TM. There was no relationship between the intensity of TM staining and the degree of proteinuria, creatinine clearance or histologic types of lupus GN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced presence of thrombomodulin in the glomeruli of lupus glomerulonephritis. 802 12

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. 828 43

The object of this study was to investigate the relationship of thrombomodulin (TM) and glycosylated hemoglobin (HbA1C) in pregnant diabetics and to determine clinical correlates. We performed a prospective cohort study of 53 patients: 25 women with insulin-dependent diabetes (group 1) and 28 with gestational diabetes (group 2). Group 1 underwent monthly determinations of HbA1C and TM. Group 2 underwent determination at 36 weeks of gestation. There was a significant difference in HbA1C between groups 1 and 2 (p=0.0005), but there was no difference in TM. There was no correlation between TM and HbA1C. TM levels correlated positively with serum creatinine (r=0.46, p=0.002), proteinuria (r=0.48, p=0.007), and duration of diabetes (r=0.41, p=0.042). TM was significantly higher in diabetics of advanced White Classification (p=0.008). With good control, TM does not appear to be elevated in a diabetic pregnancy. TM may be a marker of endothelial damage that correlates more with duration of diabetes and renal disease than with HbA1C, which reflects short-term control.
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PMID:Circulating thrombomodulin levels and clinical correlates in pregnant diabetics. 960 46

Plasma thrombomodulin (PTM) may be a marker of vascular endothelial damage and is increased in active vasculitis. However, since PTM is a mixture of glycoproteins (MW between 28 to 105 kD), some may be variably excreted by the kidney. PTM level thus may be affected both renal impairment and proteinuria. This study examines patients with varied renal pathology and relates PTM levels to renal function and proteinuria. PTM levels were measured in eighty nine renal patients with varied renal pathology: 23 patients on hemodialysis (HD), 66 with variable renal function (from normal to severe renal impairment), and proteinuria from insignificant to nephrotic range. PTM levels rose as renal function declined and were highest in HD patients. PTM levels also seemed to rise with increasing proteinuria. Indeed, this relationship appeared to be exaggerated in patients with hypertensive and diabetic nephropathy compared to those with primary glomerulonephritis. Measurements of PTM are clearly affected both by renal function and proteinuria. Thus the confidence limits above which an abnormal level is recognised should be increased as renal function declines.
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PMID:Plasma thrombomodulin in renal disease: effects of renal function and proteinuria. 987 5

Thrombomodulin is an endothelial cell membrane glycoprotein and is detected in plasma and serum after endothelial injury. In our study comprising 311 patients with systemic lupus erythematosus (SLE) clinical and laboratory associations of elevated thrombomodulin serum concentrations were examined. Elevated thrombomodulin concentrations were detected in 7.1% of the SLE patients and were associated with nephritis including the laboratory parameters proteinuria and erythrocyte casts, vasculitis and neurological involvement of the central nervous system. These correlations remained significant after consideration of the influence of renal function. In SLE, the serum thrombomodulin concentration may become a marker to monitor damage of endothelial cells and involvement of the central nervous system.
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PMID:Thrombomodulin in systemic lupus erythematosus: association with clinical and laboratory parameters. 1065 Oct 75

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a relatively recently described glycoprotein (MM 55 KDa) that can be converted into its active form by the thrombin/thrombomodulin complex and potentially inhibits fibrinolysis. Since it represents a link between coagulation and fibrinolysis, TAFI can be expected to play a part in various clinical conditions associated with a thrombotic tendency. Preeclampsia (PE) and intrauterine fetal growth retardation (IUFGR) are fairly common complications of pregnancy that are characterized by hemostatic abnormalities. TAFI antigen and its influence on hemostasis was investigated in 46 women with PE and/or IUFGR and in 16 normal pregnancies. We found a significant decrease of TAFI antigen in the patient group. Using the recently described method Overall Hemostatic Potential (OHP) in plasma we measured clot lysis time (CLT) and overall fibrinolytic potential (OFP). We found that CLT is prolonged and OFP decreased in patients with PE and/or IUFGR. Since OFP did not increase after addition of the specific inhibitor of TAFI (potato tuber carboxypeptidase inhibitor), it seems that TAFI does not contribute to the impairment of fibrinolysis in these patients. Since serum albumin was decreased together with presence of proteinuria and aminotransferases were increased in the patients, it seems that one explanation for the decrease in TAFI could be reduced hepatic synthesis and an increased loss in urine. It an be speculated that this mechanism can prevent more serious thrombotic complications in patients with PE and/or IUFGR.
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PMID:Does thrombin activatable fibrinolysis inhibitor (TAFI) contribute to impairment of fibrinolysis in patients with preeclampsia and/or intrauterine fetal growth retardation? 1236 37

Thromboembolic complications are often seen in patients with nephrotic syndrome. Markers of endothelial cell injury [thrombomodulin, intracellular adhesion molecule, vascular cell adhesion molecule, thrombin activatable fibrinolysis inhibitor (TAFI), protein Z, vascular endothelial growth factor, markers of thrombin and plasmin generation] were studied in 22 patients with nephrotic syndrome. All these parameters studied, except protein Z and D-dimers, were significantly higher in patients with nephrotic syndrome, whereas protein Z was significantly lower when compared with the healthy volunteers. None of the endothelial cell markers (thrombomodulin, P-selectin, E-selectin, intracellular adhesion molecule, vascular cell adhesion molecule), thrombin and plasmin generation markers (thrombin-antithrombin complexes, prothrombin fragments 1 + 2, plasmin-antiplasmin complexes, D-dimers), protein C, protein Z, vascular endothelial growth factor, and TAFI concentration and activity were directly correlated with the level of proteinuria, albumin, cholesterol, triglycerides or creatinine, except significant positive correlations between TAFI activity and serum creatinine, E-selectin and albumin as well as negative correlations between plasmin-antiplasmin complexes and proteinuria. In these patients, there is evidence of endothelial cell injury and probably secondary activation of the coagulation cascade. Elevated circulating TAFI antigen and activity might be a new link in the pathogenesis of impaired fibrinolysis and the progression of atherosclerosis in nephrotic syndrome. Protein Z deficiency might also contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome.
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PMID:Markers of endothelial cell injury and thrombin activatable fibrinolysis inhibitor in nephrotic syndrome. 1243 47

Preeclampsia is the most common medical disorder of pregnancy. Early onset preeclampsia is defined as presentation of hypertension and proteinuria before 34 weeks of gestation. Alterations of endothelial cells and fibrin deposition in microvasculature lead to enhanced activation of the coagulation cascade and impaired fibrinolysis associated with multiple organ dysfunctions. Plasma samples were obtained from 50 patients with severe preeclampsia before 34 weeks of gestation and in 61 patients with late preeclampsia. Factor VIIIR:Ag, fibrinogen, D-dimer, and thrombomodulin increased with advanced pregnancy. The platelet count is very important because of the close correlation with the activations parameters of D-dimer and antithrombin. Our results were consistent with activated coagulation and lowering of platelet count in severe cases with early onset preeclampsia. Women who develop early onset preeclampsia characterized a subgroup of patients with more and severe hematologic abnormalities than women with late preeclampsia (after 34 weeks of gestation).
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PMID:Hemostatic abnormalities in patients with severe preeclampsia. 1763 90

Endothelial function impairment may constitute a link between nephrotic syndrome and atherosclerosis. We assessed changes in plasma thrombomodulin, von Willebrand factor and plasminogen activator inhibitor-1 at different stages of idiopathic nephrotic syndrome in children and correlated them with clinical and biochemical parameters. The study group included 132 nephrotic children (aged 2-18 years) divided into four groups, i.e. in acute phase of the disease with proteinuria, during steroid-induced remission, steroid-free remission, and in long-term, steroid-free remission. Forty-one healthy children served as controls. Plasma thrombomodulin, plasminogen activator inhibitor-1 and von Willebrand factor activity were increased in children with early nephrotic relapse. They systematically decreased in later stages of the disease but the increase in von Willebrand factor persisted in drug-free remission. These disturbances were dependent on the degree of proteinuria and serum albumin concentration. The study revealed that nephrotic children show markers of endothelial dysfunction that are dependent on the disease activity. This leads to the hypothesis that children with severe clinical course of nephrotic syndrome may be at high risk of accelerated atherogenesis.
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PMID:Markers of endothelial dysfunction in children with idiopathic nephrotic syndrome. 1796 17


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