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)

We have measured the level of vascular endothelial growth factor (VEGF) in maternal plasma during normotensive pregnancy and in pregnancies complicated by pre-eclampsia. VEGF was measured using a competitive enzyme immunoassay. Plasma VEGF was significantly elevated (P < 0.0001) in the pre-eclamptic group (median value 32.7 ng mL-1, range 10.3-64.0), compared with the normotensive group (median value 11.7 ng mL-1, range 6.3-24.3). VEGF is a potent regulator of endothelial cell function. The increased level found in women with pre-eclampsia indicates that VEGF may be involved in the maternal endothelial cell dysfunction associated with this condition. An increase in VEGF, a potent regulator of microvascular permeability, may also contribute to the extravasation of plasma proteins and the subsequent development of proteinuria, both characteristic features of pre-eclampsia.
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PMID:Maternal plasma levels of vascular endothelial growth factor in normotensive pregnancies and in pregnancies complicated by pre-eclampsia. 901 97

The zucker diabetic fatty (ZDF-fa/fa) rat is one of the attractive models for type II diabetes based on impaired glucose tolerance caused by the inherited insulin-resistance gene fa. Characterization of nephropathy in this model may provide useful insights into the mechanism of the progression of diabetic nephropathy. The present study analyzed the pathophysiology of diabetes and nephropathy, including the process of glomerulosclerosis in this model by biochemical and morphometric analyses. In addition, we conducted studies in podocytes in culture to examine the direct effects of high glucose on podocytes. ZDF-fa/fa rats showed overt diabetes despite hyperinsulinemia as early as 3 months of age. Blood glucose levels increased further with a considerable decrease of insulin levels at 5 months. Glomerular filtration rate (GFR) was significantly elevated until 3 months, but fell to the level seen in lean rats by 7 months. Proteinuria started to rise during the period of increased GFR, and increased further after GFR had fallen to within the normal range. Renal fibronectin, collagen iv, and vascular endothelial growth factor mRNA levels were increased at 7 months. Glomerulosclerosis commenced as early as 5 months of age, and was associated with glomerular hypertrophy and mild mesangial expansion with evidence of accentuated podocyte injury, as revealed by increased expression of desmin. Electron microscopy suggested that degeneration of podocytes and the development of tuft adhesions were responsible for the glomerular sclerosis in this model. In addition, glomeruli from the diabetic rats showed up-regulation of the cyclin kinase inhibitors, p21 and p27. Further studies suggested that the increase in p27 expression was predominantly caused by podocytes, because predominant immunolocalization of p27 in podocytes in diabetic rats and high glucose medium induced cell hypertrophy accompanied by p27 up-regulation in differentiated podocyte cell lines. In conclusion, progressive diabetic nephropathy in ZDF-fa/fa rats is associated with evidence of podocyte injury. High concentrations of ambient glucose induced podocyte hypertrophy and stress in vitro, suggesting that the podocyte is a likely target of the diabetic milieu.
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PMID:Podocyte injury promotes progressive nephropathy in zucker diabetic fatty rats. 1179 23

The role of the vascular endothelium in progressive renal disease is not well understood. This review presents evidence that progressive renal disease is characterized by a progressive loss of the microvasculature. The loss of the microvasculature correlates directly with the development of glomerular and tubulointerstitial scarring. The mechanism is mediated in part by a reduction in the endothelial proliferative response, and this impairment in capillary repair is mediated by alteration in the local expression of both angiogenic (vascular endothelial growth factor) and antiangiogenic (thrombospondin 1) factors in the kidney. The alteration in balance of angiogenic growth factors is mediated by both macrophage-associated cytokines (interleukin-1beta) and vasoactive mediators. Finally, there is intriguing evidence that stimulation of angiogenesis and/or capillary repair may stabilize renal function and slow progression and that this benefit occurs independently of effects on BP or proteinuria. Therefore, angiogenic agents may represent a novel therapeutic approach for slowing the progression of renal disease.
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PMID:Role of the microvascular endothelium in progressive renal disease. 1185 89

Diabetic renal disease is associated with lipid deposits in the kidney. The purpose of our study was to determine whether there is altered regulation of the sterol regulatory element-binding proteins (SREBPs) in the diabetic kidney and whether SREBPs mediate the abnormal renal lipid metabolism and diabetic renal disease. In streptozotocin-induced diabetes in the rat, there were marked increases in SREBP-1 and fatty acid synthase (FAS) expression, resulting in increased triglyceride (TG) accumulation. Treatment of diabetic rats with insulin prevented the increased renal expression of SREBP-1 and the accumulation of TG. The role of hyperglycemia in the up-regulation of SREBP-1 was confirmed in renal cells cultured in a high glucose media. High glucose induced increased expression of SREBP-1a and -1c mRNA, SREBP-1 protein, and FAS, resulting in increased TG content. To determine a direct role for SREBP in mediating the increase in renal lipids and glomerulosclerosis, we studied SREBP-1a transgenic mice with increased renal expression of SREBP-1. The increase in SREBP-1 was associated with increased expression of FAS and acetyl CoA carboxylase, resulting in increased TG content, increased expression of transforming growth factor beta1 and vascular endothelial growth factor, mesangial expansion, glomerulosclerosis, and proteinuria. Our study therefore indicates that renal SREBP-1 expression is increased in diabetes and that SREBP-1 plays an important role in the increased lipid synthesis, TG accumulation, mesangial expansion, glomerulosclerosis, and proteinuria by increasing the expression of transforming growth factor beta and vascular endothelial growth factor.
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PMID:Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus. 1187 60

Glucocorticoids are widely prescribed for renal diseases. It is believed that glucocorticoids attenuate immune-mediated renal diseases by suppressing the cell-mediated immune system. However, there is evidence that glucocorticoids influence the expression of such growth factors as vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and connective tissue growth factor (CTGF), which are known to influence the development or progression of renal diseases. Therefore, we undertook this study to determine whether glucocorticoids regulate proteinuria or extracellular matrix (ECM) production by altering these growth factors. Mesangial proliferative glomerulonephritis was induced in rats by intravenous injection of monoclonal antibody (OX-7), and dexamethasone (20 mg/kg) was administered intraperitoneally from the third to seventh disease day. Glomerular expression of VEGF, TGF-beta1, and CTGF, the amount of urinary protein, and glomerular ECM were measured on the seventh disease day. The nephritic group showed proteinuria and greater VEGF, TGF-beta1, and ECM production. Dexamethasone aggravated proteinuria (protein, 0.4 +/- 0.1 mg/mg creatinine in the NC group, 6.3 +/- 2.0 mg/mg creatinine in the DC group, and 21.1 +/- 1.9 mg/mg creatinine in the D-Dex group; P < 0.05) and diminished VEGF release (22 +/- 3 pg/mg total protein in the NC group, 292 +/- 26 pg/mg total protein in the DC group, and 198 +/- 23 pg/mg total protein in the D-Dex group; P < 0.05). Expression of TGF-beta1, CTGF, and ECM was not altered significantly by dexamethasone treatment. We found that glucocorticoid diminishes VEGF release and at the same time exacerbates proteinuria in rats with this type of glomerulonephritis.
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PMID:Glucocorticoid diminishes vascular endothelial growth factor and exacerbates proteinuria in rats with mesangial proliferative glomerulonephritis. 1197 43

A loss of the microvascular endothelium occurs in the remnant kidney model of renal disease and may play an important role in progression (Kang et al, J Am Soc Nephrol, 12:1434, 2001). Given that nitric oxide (NO) is a potent endothelial cell survival factor, we hypothesized that stimulating (with L-arginine) or blocking (with nitro-L-arginine methyl ester, (L-NAME)) NO synthesis could modulate the integrity of the microvasculature and hence affect progression of renal disease. Rats underwent 5/6 nephrectomy (RK) and then were randomized at 4 weeks to receive vehicle, L-NAME, or L-arginine for 4 weeks. Systolic blood pressure and renal function was measured, and tissues were collected at 8 weeks for histological and molecular analyses. The effect of modulation of NO on vascular endothelial growth factor (VEGF) expression in rat aortic vascular smooth muscle cells (SMC) and mouse medullary thick ascending limb tubular epithelial cells (mTAL) was also studied. Inhibition of NO with L-NAME was associated with more rapid progression compared to RK alone, with worse blood pressure, proteinuria, renal function, glomerulosclerosis, and tubulointerstitial fibrosis. The injury was also associated with more glomerular and peritubular capillary endothelial cell loss in association with an impaired endothelial proliferative response. Interestingly, the preglomerular endothelium remained intact or was occasionally hyperplastic, and this was associated with a pronounced proliferation of the vascular SMCs with de novo expression of VEGF. Cell culture studies confirmed a divergent effect of NO inhibition on VEGF expression, with inhibition of VEGF synthesis in mTAL cells and stimulation of VEGF in vascular SMC. In contrast to the effects of NO inhibition, stimulation of NO with L-arginine had minimal effects in this rat model of progressive renal disease. These studies confirm that blockade of NO synthesis accelerates progression of renal disease in the remnant kidney model, and support the hypothesis that one of the pathogenic mechanisms may involve accelerated capillary loss and impaired angiogenesis of the renal microvasculature. Interestingly, inhibition of NO synthesis did not lead to a loss of the preglomerular endothelium, which may relate to the effect of NO blockade to stimulate VEGF synthesis in the adjacent vascular smooth muscle cell.
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PMID:Nitric oxide modulates vascular disease in the remnant kidney model. 1210 8

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

Proteinuria occurs in all degrees of radiation nephropathy and can be present without other symptoms. In this study, radiation-induced proteinuria in C3H mice demonstrated a clear dose-response relationship and was apparent before the onset of significant structural vascular changes and decreases in renal function. This suggests that proteinuria is not a secondary event due to loss of the vascular structure. In an attempt to ameliorate radiation-induced proteinuria and progressive renal failure, two factors were studied. The influence of reactive oxygen species (ROS), which are generated by infiltrating neutrophils and mediate proteinuria in models of acute glomerular injury, was the first to be investigated. Short-term administration of the reactive oxygen scavengers superoxide dismutase (SOD) and catalase did not reverse an established radiation-induced proteinuria. Continuous administration of the antioxidant N-acetylcysteine (NAC) also failed to inhibit this proteinuria. However, since no direct assessment of the impact of these interventions on renal redox status was made, the putative role of ROS in radiation-induced proteinuria and nephropathy remains undefined. The second factor studied was vascular endothelial growth factor (Vegf), which is suggested to be involved in glomerular vessel permeability and the development of proteinuria in some models of renal disease. Northern blot analysis of mRNA from whole kidneys did not demonstrate any increased expression of Vegf after irradiation. There was also no change in the ratio of the different Vegf isoforms (PCR analysis), either in the whole kidney or in isolated glomeruli. No significant role for Vegf was identified for radiation-induced vascular changes or proteinuria, although post-transcriptional changes cannot be excluded.
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PMID:Proteinuria and vascular changes after renal irradiation: the role of reactive oxygen species (ROS) and vascular endothelial growth factor (Vegf). 1253 22

There are about 2.5 million glomeruli in the kidneys each consisting of a barrel of glomerular basement membrane surrounded by glomerular endothelial cells on the inside and glomerular epithelial cells with established foot processes (podocytes) on the outside. Defects in this filtration apparatus lead to glomerular vascular leak or proteinuria. The role of vascular endothelial growth factor (VEGF) in the regulation of glomerular vascular permeability is still unclear. Recent studies indicate that patients receiving anti-VEGF antibody therapy may have an increased incidence of proteinuria. In a different setting, pregnancies complicated by preeclampsia are associated with elevated soluble VEGF receptor 1 protein (sFlt-1), endothelial cell dysfunction and proteinuria. These studies suggest that neutralization of physiologic levels of VEGF, a key endothelial survival factor, may lead to proteinuria. In the present study, we evaluated the potential of anti-VEGF neutralizing antibodies and sFlt-1 in the induction of proteinuria. Our studies demonstrate that anti-VEGF antibodies and sFlt-1 cause rapid glomerular endothelial cell detachment and hypertrophy, in association with down-regulation of nephrin, a key epithelial protein in the glomerular filtration apparatus. These studies suggest that down-regulation or neutralization of circulating VEGF may play an important role in the induction of proteinuria in various kidney diseases, some forms of cancer therapy and also in women with preeclampsia.
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PMID:Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. 1253 98

To study the relationship between serum vascular endothelial growth factor (VEGF) and proteinuria in adriamycin-induced nephrotic rats, a rat model of adriamycin-induced nephrotitis was developed by injection of adriamycin into a tail vein in a rat. At different time points, 24-h urinary protein excretion was measured by using Coomassie brilliant blue method and the serum VEGF levels detected by using ELISA assay. The interventional effect of VEGF on this model was observed. The results showed that: (1) The adriamycin-induced nephrotic syndrome rat model was developed successfully; (2) Serum VEGF levels and proteinuria were significantly increased at 7th day after intravenous injection of adriamycin. There was a positive correlation between serum VEGF levels and 24-h urinary protein excretion (r = 0.67, P < 0.05). (3) The 24-h urinary protein excretion was significantly increased in the rats receiving administration of VEGF (P < 0.05). It was concluded that VEGF might play an important role in the pathogenesis of proteinuria in adriamycin-induced nephrotic rats.
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PMID:The study on the relationship between serum vascular endothelial growth factor and proteinuria in adriamycin-induced nephrotic rats. 1253 53


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