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)

Using a complex stimulating mixture containing ADP, epinephrine and collagen, a significantly (p less than 0.002) enhanced platelet aggregability, expressed as platelet sensitivity factor (PSF) was noted in platelet rich plasma of patients with proteinuria (PSF = 472 +/- 125), as against normal weight normolipidemic control subjects (PSF = 32.76 +/- 2.67). A significantly negative correlation (r. -0.579; p less than 0.001) was found between serum albumin concentration and the logarithmic values of platelet sensitivity factor. Plasma von Willebrand factor activity expressed as a percentage of normal was also significantly (p less than 0.001) higher in proteinuric patients (287% +/- 25.8) than in control subjects (99% +/- 5.02), but this hemostatic variable did not correlate with the logarithm of platelet sensitivity factor. Platelet aggregability was higher in hyperlipidemic nephrotic patients than in proteinuric patients with normal serum lipids, while renal failure led to a decrease of platelet function. The raised plasma levels of von Willebrand factor noted in proteinuric patients were not influenced by either hyperlipidemia or by chronic renal failure. It is concluded that changes affecting platelet function in the nephrotic syndrome are produced by other mechanisms than these leading to an increase of endothelia-derived von Willebrand factor. Both changes may, however, contribute to the thrombotic tendency of nephrotic patients.
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PMID:Plasma von Willebrand factor antigen and activity and platelet aggregability in patients with proteinuria. 261 81

In the acute serum sickness model in rabbits, we investigated platelet release of 5-HT, platelet surface immunoglobulins, and platelet aggregation in response to ADP, together with the effect of dipyridamole and the Clr antagonist FUT-175. The immune release of 5-HT from platelets occurred between 4 and 6 days after injection of bovine serum albumin (BSA), before immune elimination and proteinuria, but coincident with the appearance of immune complexed BSA in the circulation. Nevertheless, platelet turnovers were not detectably accelerated. Treatment with dipyridamole 50 mg/kg/24 h prevented the release of 5-HT and inhibited proteinuria, glomerular hypercellularity and immune complexes in the glomeruli. Using the Clr antagonist FUT-175, similar abrogation of the disease was obtained. We conclude that in the nephritis of acute serum sickness in rabbits, some of the immune release from platelets may be the result of immune complex binding to the platelet, perhaps through the receptor for C3b.
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PMID:Platelet involvement in the nephritis of acute serum sickness in rabbits: protection by dipyridamole and FUT-175. 404 28

It has been reported that agents which block the prostaglandin system inhibit the development of glomerulonephritis. However, the mechanisms of these effects are not clear. We studied the effect of a selective thromboxane A2 (TxA2) synthetase inhibitor, 1-benzylimidazole (BIm), on the immune complex glomerulonephritis produced by bovine serum albumin (BSA) in New Zealand white rabbits. As the BSA nephritis developed, there was no change of creatinine (Cr), serum urea nitrogen (SUN), or creatinine clearance (Ccr), but urinary protein excretion increased almost 3-fold. Coagulation and fibrinolytic studies suggested a hypercoagulable state and increased fibrinolytic activity. Platelet aggregation showed the reduction of maximum aggregation induced by ADP and collagen. Histological examination by light microscopy, immunofluorescence, and electron microscopy revealed glomerular polymorphonuclear leukocyte (PMN) infiltration, mononuclear cell (MON) proliferation, and fibrin deposition. In 70% of the rabbits, IgG and C3 deposits were seen by immunofluorescence mainly in mesangial areas. The administration of BIm to BSA nephritis had no effects on Cr, SUN or Ccr, but it significantly lessened the proteinuria. The study of coagulation and fibrinolytic activity suggested a less hypercoagulable state, and more efficient fibrinolysis occurred than in the group without BIm. BIm tended to normalize platelet aggregation. It also lessened the histological PMN infiltration (p less than 0.05), MON proliferation (p less than 0.01), and fibrin deposition (p less than 0.05). These data suggest that TxA2 may play an important pathogenetic role in the development and progression of glomerulonephritis.
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PMID:Effects of a selective thromboxane A2 synthetase inhibitor on immune complex glomerulonephritis. 622 42

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.
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PMID:Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate. 673 1

Disturbances in serum lipids, hemostasis and platelet functions are frequent features in some kidney diseases and may contribute to the progression of atherosclerosis with its complications. Recently, an attention has been paid on beneficial effects of fish oil on serum lipids and hemostasis, and proteinuria. The purpose of this work was to assess platelet functions, some hemostatic parameters and serum lipids in patients with chronic glomerulonephritis treated with Trienyl. The study was performed on 7 patients with glomerulonephritis, before, 3 and 6 months following fish oil treatment. A small and nonsignificant rise in cholesterol, HDL and LDL was found, whereas triglycerides level fell significantly following 3 and 6 months of therapy Fibrinogen concentration was lowered significantly 6 months following fish oil administration. Platelet aggregation in platelet-rich plasma remained unaltered during therapy, whereas platelet responses to ADP and arachidonic acid in the whole blood were inhibited after 6 months of the therapy. Unsaturated omega 3 fatty acids in Trienyl alter lipid metabolism, platelet/vessel wall interactions and proteinuria and therefore might be beneficial in therapy of glomerulonephritis, particularly in combination treatment.
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PMID:[Effect of treating glomerulonephritis with omega 3 fatty acids for selected parameters of hemostasis, blood platelet function and lipid metabolism]. 899 60

Patients with diabetes mellitus have a variety of platelet and coagulation system dysfunctions. At least theoretically, these can contribute to microvascular complications. Intensive glycemic control has been demonstrated to decrease microvascular complications in type 1 diabetics. We studied 16 patients with type 1 diabetes mellitus (11 men and five women; mean age, 39 years) with albuminuria greater than 0.1 g/d and/or proteinuria greater than 0.3 g/d and a creatinine clearance rate higher than 30 mL/min. They received a regimen including three to four injections of insulin per day with or without a weekly infusion of intravenous insulin, and were evaluated for 6 months. We compared the plasma level of von Willebrand factor, platelet aggregation responses to adenosine diphosphate (ADP), epinephrine, and collagen, and platelet adhesion at the beginning of the study and at follow-up intervals. Glycemic control improved significantly. There were no significant differences in the platelet aggregation responses to ADP (1.59 +/- 0.34 v 1.88 +/- 0.23 mmol/L, P = .3; normal, 4.6 +/- 0.2), epinephrine (0.50 +/- 0.20 v 1.11 +/- 0.31 mmol/L, P = .06; normal, 7.6 +/- 1.5), or collagen (92.4 +/- 6.61 v 82.60 +/- 3.78 seconds, P = .6; normal, 79.1 +/- 3.1) or in platelet adhesion (126.31 +/- 16.95 v 195.08 +/- 30.2 platelets, P = .34; normal, 68.6 +/- 1.4). Baseline von Willebrand factor increased, but not significantly (166.38% +/- 10.6% v 142.72% +/- 14.73%, P = .21; normal, 102.0% +/- 6.0%). In type 1 diabetic patients with established microvascular complications of nephropathy, a statistically significant improvement in glycemic control did not improve the in vitro platelet function abnormalities. Improved glycemic control delays the progression of microvascular disease through mechanisms not measured by tests of platelet function.
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PMID:Improved glycemic control and platelet function abnormalities in diabetic patients with microvascular disease. 1064 69

Proton NMR spectroscopy of urine has previously been used to gain insight into the site and mechanism of toxic injury to the kidney. d-Serine injures the rat kidney, causing selective necrosis of the proximal straight tubules. Damage is accompanied by proteinuria, glucosuria, and amino aciduria, the latter preceding the onset of necrosis. This study has employed (1)H NMR spectroscopy of urine and (1)H NMR and (31)P NMR spectroscopy of kidney extracts to examine the nephrotoxic action of d-serine. Urine was collected 0-8 h (all doses) and 8-24, 24-48, 48-72, 72-96, and 96-120 h (500 mg/kg only) postdosing from Alderley Park rats given d-serine (62.5, 125, 250, and 500 mg/kg ip). (1)H NMR spectra were monitored for markers of tubular damage. Additionally, ATP and ADP were quantitated in kidney perchloric acid extracts, prepared after 0.5, 1, 2, 4, and 8 h (500 mg/kg) to assess energy status; serine was also measured in these samples. At 500 mg/kg, glucosuria, amino aciduria, and reduced citrate, alpha-ketoglutarate, and succinate were observed in urine at 0-8 h. Furthermore, serine and pyruvate levels were elevated at this time. After 8-24 h, similar changes were observed; however, they were more severe reflecting the development of the lesion prior to recovery. These perturbations were dose-related, in particular, for serine and pyruvate, with no alterations seen at 62.5 mg/kg. Kidney serine concentration rapidly increased, where it was maximal after 30 min and cleared by 8 h. A decline in ATP, to approximately 60-70% of control, was observed within the kidney at 2-4 h postdosing, when necrosis first becomes evident suggesting that mitochondrial function might be impaired in the early stages of d-serine-induced nephrotoxicity. The use of NMR spectroscopy has given a comprehensive overview of the effects of d-serine in vivo. Information on the excretion of serine and its effect on renal energy metabolism provides insight into the possible mechanism of renal tubule injury.
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PMID:1H NMR pattern recognition and 31P NMR studies with d-Serine in rat urine and kidney, time- and dose-related metabolic effects. 1456 62

The pathogenesis of glomerular alterations and proteinuria in corticosteroid-responsive nephrotic syndrome (CRNS) is unknown. As an isoform of plasma hemopexin (Hx) with protease activity may be implicated in this disease, we have studied the inhibition of Hx by ADP and reactivation to its active form by endothelial or mesangial cells in vitro. We hypothesized that these cells might potentially be able to convert the inactivated form of Hx (Hxi) to active Hx (Hxa) in vitro, mediated by cellular ecto-ADPase. Since ecto-ADPase (CD39) is upregulated after stimulation of these cells with lipopolysaccharide (LPS) or certain cytokines, we postulated that this conversion might occur specifically after inflammatory stimulation of these cells. Human endothelial or mesangial cell cultures were incubated overnight with or without LPS (10.0 ng/ml) or TNFalpha (10.0 ng/ml), washed and subsequently incubated with Hxi (1.5 mg/ml) in serum-free conditions (Hxi was prepared by treatment of Hxa with ADP or ADP-beta-S). After 60 min, supernatants were tested for their capacity to alter glomerular extracellular matrix molecules (i.e. ecto-apyrase) in vitro using standard methods, and compared with Hxi that had not been incubated with cells. Supernatants containing Hxa (1.5 mg/ml) served as positive control. The results show significant activity in supernatants with Hxi (prepared using native ADP). However, Hxi inactivated by ADP-beta-S (which is non-hydrolyzable) could not be reactivated after contact with LPS-stimulated or unstimulated cells in vitro. As ecto-ADPase of these cells is upregulated by LPS, we believe that reactivation of Hxi to Hxa is mediated by cellular ecto-ADPase. Although the relevance of this inflammation-mediated activation mechanism of Hx in patients with CRNS requires further experimentation, our preliminary observations suggesting that this mechanism is corticosteroid dependent may support a potential role of Hxa in CRNS.
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PMID:Regulation of plasma hemopexin activity by stimulated endothelial or mesangial cells. 1475 38

It is believed that platelets play a key role in the production of pre-eclamptic toxaemia and toxaemia of pregnancy. Toxaemia of pregnancy is described as a condition of chronic DIC where there is thrombocytopenia as well as raised fibrin degradation products. Since fibrinogen receptors are involved in the final stage of the platelet aggregation reaction, we wanted to investigate the platelet receptors for fibrinogen in normal and abnormal pregnancy. Thirty-six normal pregnant women (12 in their 2nd trimester, 24 in their 3rd trimester), 24 pregnant pre-eclamptic toxaemia cases and 16 non-pregnant controls were included in the present study. All patients with pre-eclamptic toxaemia had oedema, proteinuria and hypertension. Flow cytometric study of platelets was undertaken utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated (final concentration 0.02 M) platelets. The intensity of platelet fluorescence was classified into three groups and expressed in arbitrary units. The results indicate that there are a higher number of stimulated platelets expressing fibrinogen receptors in the circulation of patients with pre-eclampsia. Thus, it is possible to hypothesize that platelets showing increased fibrinogen receptors aggregate and form microthrombi in smaller vessels in women with pre-eclamptic toxaemia.
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PMID:Functional and fibrinogen receptor studies in platelets in pre-eclamptic toxaemia of pregnancy. 1680 Oct 92

Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) (also known as CD39) is the dominant vascular ectonucleotidase. By hydrolyzing ATP and ADP to AMP, ENTPD1 regulates ligand availability to a large family of P2 (purinergic) receptors. Modulation of extracellular nucleotide metabolism is an important factor in several acute and subacute models of vascular injury. We hypothesized that aberrant nucleotide signaling would promote chronic glomerular injury in diabetic nephropathy. Inducing diabetes in ENTPD1-null mice with streptozotocin resulted in increased proteinuria and more severe glomerular sclerosis compared with matched diabetic wild-type mice. Diabetic ENTPD1-null mice also had more glomerular fibrin deposition and glomerular plasminogen activator inhibitor-1 (PAI-1) staining than wild-type controls. In addition, ENTPD1-null mice showed increased glomerular inflammation, in association with higher levels of monocyte chemoattractant protein-1 (MCP-1) expression. Mesangial cell PAI-1 and MCP-1 mRNA expression were upregulated by ATP and UTP but not ADP or adenosine in vitro. The stable nucleotide analog ATPgammaS stimulated sustained expression of PAI-1 and MCP-1 in vitro, whereas the stable adenosine analog NECA [5'-(N-ethylcarboxamido)adenosine] downregulated expression of both genes. Extracellular nucleotide-stimulated upregulation of MCP-1 is, at least in part, protein kinase C dependent. We conclude that ENTPD1 is a vascular protective factor in diabetic nephropathy that modulates glomerular inflammation and thromboregulation.
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PMID:The vascular ectonucleotidase ENTPD1 is a novel renoprotective factor in diabetic nephropathy. 1747 21


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