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)

The effects of a 14-day course of ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with glomerulonephritis. Patients were divided into two groups. In the first, the level of fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of fibrin degradation products and fibrinogen, suggesting that fibrin degradation products derived from ancrod-cleaved-fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in fibrinogen, a disproportionate increase in levels of fibrin degradation products suggested that a significant amount derived from sources other than plasmin digested ancrod-cleaved-fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in proteinuria. Microvascular thrombosis decreased significantly, indicating effective removal of fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with lupus nephritis. With ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs, gamma globulin and anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that ancrod had favorable effects on immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of fibrin degradation products; fibrosclerosis index and glomerular sclerosis increased in patients with initial low levels of fibrin degradation products. Fibrinolysis expressed as the 48 h (fibrin degradation products/fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular sclerosis in the whole group, and especially in those with initial high levels of fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fibrinolysis in glomerulonephritis treated with ancrod: renal functional, immunologic and histopathologic effects. 327 33

Increased plasma activity of plasminogen activator inhibitor 1 (PAI-1) is considered as a risk factor for thrombosis associated with atherosclerosis by reduction of fibrinolysis. Since nephropathic patients with non-insulin-dependent diabetes mellitus (NIDDM) are a cardiovascular high-risk group, which has yielded only controversial results as to the regulation of PAI-1, we compared 19 overt nephropathic NIDDM patients (mean age 63 years, serum creatinine 1.9 mg/dl, proteinuria 4.2 g/day) to 17 nondiabetic nephropathic patients with various causes of renal insufficiency (mean age 63 years, serum creatinine 2.8 mg/dl, proteinuria 3.9 g/day). We found normal PAI-1 levels for patients with diabetic nephropathy and significantly elevated PAI-1 levels within the upper normal range for nondiabetic nephropathic patients. Common risk factors in both groups were very high levels of fibrinogen, lipoprotein(a), serum cholesterol, and LDL cholesterol.
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PMID:Plasminogen activator inhibitor 1 activity and lipoprotein(a) in nephropathic patients with non-insulin-dependent diabetes mellitus versus patients with nondiabetic nephropathy. 795 56

From the clinical point of view proteinuric hypertension or preeclampsia is the most important form of hypertension in pregnancy and carries the greatest risks for mother and foetus. The syndrome 'preeclampsia' differs from other types of hypertension and its effects on mother and foetus are not clearly benefited by lowering the blood pressure with drugs. The characteristic morphological changes and altered vascular reactivity which develop in preeclampsia commence at about 14 weeks gestation, long before hypertension or proteinuria appear. Many abnormalities in coagulation mechanisms appear in preeclampsia and some may play an important part in pathogenesis. Increased plasminogen activator inhibitor may play a key role. Antihypertensive drugs used during pregnancy may reduce foetal mortality and the incidence of preeclampsia. Calcium supplementation and aspirin may reduce the incidence of preeclampsia in high risk subjects. Heparin and dipyridamole may reduce the risk of preeclampsia in high risk patients with renal disease.
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PMID:Hypertension in pregnancy. 819 15

Fibrin is an important mediator of injury in severe proliferative forms of glomerulonephritis (GN). Normal glomeruli express fibrinolytic activity, which may protect against the injurious effects of fibrin deposition. Changes in glomerular fibrinolytic activity (GFA) may play an important role in modulating fibrin accumulation in GN. To study the changes in GFA associated with fibrin deposition in GN, autologous phase anti-glomerular basement antibody initiated GN (anti-GBM GN) was studied in rabbits. Net GFA was significantly reduced in association with glomerular fibrin deposition (1.3 +/- 0.8 ng fibrin lysed/10(3) glomeruli/2 hr, normal 57.1 +/- 25.4 ng fibrin lysed/10(3) glomeruli/2 hr, P < 0.02). Reduced GFA in fibrin associated GN was associated with decreased expression of tissue type plasminogen activator (tPA) and increased expression of plasminogen activator inhibitor type-1 (PAI-1) and glomerular macrophage infiltration. In a fibrin independent model of anti-GBM induced GN (heterologous phase), with equivalent injury (proteinuria), net GFA was increased (174 +/- 64 ng fibrin lysed/10(3) glomeruli/2 hr). This was associated with increased tPA and uPA, and decreased PAI-1 in the absence of significant macrophage infiltration. These studies demonstrate that fibrin deposition in GN is associated with a net reduction of GFA, attributable to reduced expression of plasminogen activators and augmentation of PAI-1. Reduction of GFA may potentiate glomerular fibrin deposition and consequent glomerular injury. The association between glomerular macrophage influx and reduction in GFA suggests that this change may be directed by macrophages.
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PMID:Glomerular fibrinolytic activity in anti-GBM glomerulonephritis in rabbits. 823 Oct 28

Twenty-three insulin-dependent diabetics with proteinuria (3.3 g/day: range 0.3 to 8.9) and azotemia (creatinine clearance: 58 mL/min, range 30 to 112) were tested for 24-h mean arterial blood pressure; instantaneous heart rate variations to a computerized protocol involving timed ventilation, assumption of upright posture, and Valsalva maneuver; plasma fibrinogen, viscosity, fibrinolytic activity, and plasminogen activator inhibitor. These were to test the hypothesis that autonomic dysfunction is associated with altered concentrations of plasma fibrinogen, fibrinolytic activity, viscosity, and plasminogen activator inhibitor. We have previously shown the absence of a correlation between level of blood pressure, clinical and standard laboratory testing, and the results of the autonomic function testing protocol used in this study. In this group of patients, plasma fibrinogen concentration was correlated (positively) with mean arterial pressure and (negatively) with heart rate variation in response to the Valsalva maneuver. The greater the mean arterial pressure or the worse the Valsalva results, the higher the plasma fibrinogen concentration. In addition, patients with one or no abnormal autonomic function tests had a mean fibrinogen of less than 400 mg/dL compared to the group of patients with two or more abnormal tests who had a mean fibrinogen of 500 mg/dL. In patients with demonstrated parasympathetic abnormalities, postural heart rate variation testing also discerned a differential in plasma fibrinogen. Lower concentration of plasminogen activator inhibitor throughout the day, and greater fibrinolytic activity in the morning were also noted to be present in patients with abnormal heart rate response to the Valsalva maneuver. We conclude that there are relationships between high blood pressure, autonomic function, and hemostatic factors favoring thrombogenesis that may be related by common mechanisms and treatments in the diabetic with kidney disease.
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PMID:Relationship between autonomic function and plasma fibrinogen, viscosity, and elements of fibrinolytic activity in diabetic nephropathy. 912 13

BACKGROUND: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether angiotensin inhibition influences the onset of NIDDM and brings about a regression of renal injury in diabetes mellitus. METHODS AND RESULTS: Six-week-old OLETF rats were treated with the angiotensin-converting enzyme (ACE) inhibitors imidapril or enalapril for 16 weeks. Systolic blood pressure is increased in an age-dependent manner in OLETF rats. In this study, the elevation in systolic blood pressure was dose-dependently reduced by ACE inhibitor treatment. In OLETF rats, plasma concentrations of insulin and glucose increased and the glucosuria occurred at the age of 22 weeks. Simultaneously, OLETF rats exhibited proteinuria and nodular lesions in glomeruli. The ACE inhibitor treatment almost completely reduced glucosuria, and also decreased plasma concentrations of insulin and glucose in OLETF rats. ACE inhibitor treatment lessened the proteinuria and attenuated morphologically the severity of nodular lesions in OLETF rats. Moreover, increases in plasminogen activator inhibitor 1 (PAI-1) in OLETF rats were reduced by the ACE inhibitor treatment, and the improvement of glomerular lesions was related to decreases of PAI-1 and angiotensin II levels in plasma but not to improvement of glucose metabolism. CONCLUSIONS: ACE inhibitors delay onset of NIDDM with attenuation of kidney injury. The regression of kidney lesions is probably due to angiotensin reductions but not to glucose metabolism per se. ACE inhibitor drug therapy may be useful in preventing NIDDM and the subsequent renal injury in patients with NIDDM.
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PMID:Angiotensin-Converting Enzyme Inhibition Delays Onset of Glucosuria With Regression of Renal Injuries in Genetic Rat Model of Non-Insulin-Dependent Diabetes Mellitus. 1068 15

Both basic and experimental data indicate that the renin-angiotensin system through angiotensin II mediates its classic hemodynamic role, but also has a significant deleterious role in a number of cardiac, vascular, and renal disorders. Indeed, evidence indicates that angiotensin II negatively impacts endothelial function, cardiac remodeling, vessel wall hypertrophy, atherosclerosis, and progressive renal disease. Newer data point to a significant role for angiotensin II in inflammation and in inducing plasminogen activator inhibitor. This widespread negative effect can be countered by newer antihypertensive drugs, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers. Both small and large clinical trials suggest a large benefit of such drugs on not only organ-specific endpoints such as renal disease or proteinuria, but on global cardiovascular events. It does appear that when blood pressure is significantly elevated, lowering blood pressure does indeed provide protection for larger endpoints such as stroke. However, at lower blood pressure levels, a hemodynamically independent effect is likely to be contributing to the positive effects. We should embrace these effects and champion them for our patients.
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PMID:Are clinical endpoint benefits of angiotensin converting enzyme inhibitors independent of their blood pressure effects? 1211 56

Moderate alcohol consumption has shown beneficial effects in experimental and human cardiovascular disease. With the use of rat models of acute and chronic progressive anti-thy1 glomerulonephritis (GN), we tested the hypothesis that moderate alcohol intake is protective in renal fibrotic disease. In acute anti-thy1 GN, untreated nephritic rats showed marked mesangial cell lysis and induced nitric oxide production at day 1 and high proteinuria, glomerular matrix accumulation, and transforming growth factor (TGF)-beta(1), fibronectin, and plasminogen activator inhibitor (PAI)-1 expression at day 7 after disease induction, respectively. In animals 15 wk after induction of chronic progressive anti-thy1 GN, disease was characterized by significantly reduced renal function, persisting albuminuria as well as increased glomerular and tubulointerstitial matrix expansion, TGF-beta(1), fibronectin, and PAI-1 protein expression. In both anti-thy1 GN models, an ethanol intake of approximately 2 ml per day and animal was achieved, however, disease severity was not significantly altered by moderate alcohol consumption in any of the protocols. In conclusion, moderate alcohol intake does not influence renal matrix protein production and accumulation in acute and chronic progressive anti-thy1 glomerulofibrosis. The study suggests that, in contrast to cardiovascular disorders, moderate alcohol consumption might not provide specific protection in renal fibrotic disease.
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PMID:Moderate alcohol intake has no impact on acute and chronic progressive anti-thy1 glomerulonephritis. 1267 38

A 1-year-old boy with hemophagocytic lymphohistiocytosis exhibited proteinuria 1 month after unrelated cord blood cell transplantation, which persisted without hematuria. Laboratory study showed an increase of factor VIII-related antigen and total plasminogen activator inhibitor, suggesting endothelial injury. Histological examination of autopsy materials showed increased mesangial matrices and double-contoured basement membranes, and ultrastructurally, swelling of the endothelial cells and widening of the subendothelial space with mesangial interposition. Thrombosis was not observed at any of the sites. This case may be vasculopathy distinct from thrombotic microangiopathy (TMA) or a variant form of TMA following blood stem cell transplantation (BSCT). This vasculopathy should be considered in the differential diagnosis of proteinuria in the early stages after BSCT.
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PMID:Glomerular vasculopathy after unrelated cord blood transplantation. 1270 Sep 71

In fibrotic renal disease, elevated TGF-beta and angiotensin II lead to increased plasminogen activator inhibitor type 1 (PAI-1). PAI-1 appears to reduce glomerular mesangial matrix turnover by inhibiting plasminogen activators, thereby decreasing plasmin generation and plasmin-mediated matrix degradation. We hypothesized that therapy with a mutant human PAI-1 (PAI-1R) that binds to matrix vitronectin but does not inhibit plasminogen activators, would enhance plasmin generation, increase matrix turnover, and decrease matrix accumulation in experimental glomerulonephritis. Three experimental groups included normal, untreated disease control, and PAI-1R-treated nephritic rats. Plasmin generation by isolated day 3 glomeruli was dramatically decreased by 69%, a decrease that was reversed 43% (P < 0.02) by in vivo PAI-1R treatment. At day 6, animals treated with PAI-1R showed significant reductions in proteinuria (48%, P < 0.02), glomerular staining for periodic acid-Schiff positive material (33%, P < 0.02), collagen I (28%, P < 0.01), collagen III (34%, P < 0.01), fibronectin (48%, P < 0.01), and laminin (41%, P < 0.01), and in collagen I (P < 0.01) and fibronectin mRNA levels (P < 0.02). Treatment did not alter overexpression of TGF-beta1 and PAI-1 mRNAs, although TGF-beta1 protein was significantly reduced. These observations strongly support our hypothesis that PAI-1R reduces glomerulosclerosis by competing with endogenous PAI-1, restoring plasmin generation, inhibiting inflammatory cell infiltration, decreasing local TGF-beta1 concentration, and reducing matrix accumulation.
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PMID:A mutant, noninhibitory plasminogen activator inhibitor type 1 decreases matrix accumulation in experimental glomerulonephritis. 1289


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