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)

In order to ascertain whether ciclosporin (Cs) has an inhibitory effect on the vascular permeability factor (VPF) production, various quantities of Cs were added to T lymphocyte cultures from 8 children with minimal change nephrotic syndrome (MCNS) and the VPF activity of culture supernatants was assayed. As a result of the addition of Cs, a dose-dependent inhibition of VPF production was seen. VPF production was inhibited by a level of between 100 and 250 ng/ml of Cs in vitro. The reduction of proteinuria by Cs in MCNS might be due to the inhibition of VPF production.
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PMID:Inhibition of vascular permeability factor production by ciclosporin in minimal change nephrotic syndrome. 143 87

A 59-year-old man developed a nephrotic syndrome and mild renal failure after treatment with phenylbutazone. Light microscope examination of a renal biopsy specimen showed minimal glomerular alterations, and electron microscopy showed diffuse fusion of epithelial cell foot processes without immune deposits. The interstitium revealed focal lymphocyte infiltrates identified as activated T-cells by immune histologic differentiation. The unusual combination of nephrotic syndrome with acute interstitial nephritis is a rare adverse reaction of nonsteroidal antiinflammatory drugs (NSAID). A disordered cell-mediated immunity could lead to interstitial infiltration of T-lymphocytes which, releasing lymphokines and a vascular permeability factor, cause the glomerular proteinuria. In addition, NSAID inhibition of prostaglandin synthesis may enhance production of these lymphocyte-derived substances. Since the nephrotic syndrome persisted 5 months after withdrawal of phenylbutazone, steroid therapy was initiated and 2 months later the renal insufficiency and proteinuria were resolved.
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PMID:[Nephrotic syndrome and acute interstitial nephritis after phenylbutazone]. 293 8

Idiopathic nephrotic syndrome (INS) is associated with a disorder of T-lymphocyte function, and an enhanced production of a vasoactive lymphokine, the vascular permeability factor (VPF). In an attempt to evaluate lymphocyte activation in various phases of INS, we measured beta 2-microglobulin (beta 2m) levels in lymphocyte culture supernatants (LCS). In 23 cases of untreated active INS, beta 2m levels in unstimulated LCS were significantly increased in comparison with those of 13 cases of untreated INS in complete remission (p less than 0.001), of 17 cases of active membranous nephropathy (p less than 0.01) and of 14 controls (p less than 0.001). In 13 patients treated with cyclosporine (Cs) (3-4.5 mg/kg/d) during 3 months, beta 2m levels were within the normal range. Although the beta 2m of 7 Cs patients without proteinuria was lower than 5 Cs patients with residual proteinuria, the difference was not statistically significant. In 15 prednisone(Pr)-treated INS patients, beta 2m levels were normalized. However their beta 2m levels were lower in 8 cases of complete remission than in 7 cases of persistent proteinuria (p less than 0.05). Concanavalin-A stimulation increased beta 2m amounts in all groups with a similar magnitude. In vitro addition of Cs (100 ng/ml) inhibited both beta 2m and VPF elevations observed in active INS. beta 2m level and VPF activity were significantly correlated (r = 0.54, p less than 0.01). High levels of beta 2m in LCS from INS are the consequence of an enhanced cellular synthesis and they are inhibited by Pr and Cs. Thus beta 2m increase in INS indeed reflects lymphocyte activation.
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PMID:Enhanced beta 2-microglobulin levels in lymphocyte culture supernatants from patients with idiopathic nephrotic syndrome: inhibition of lymphocyte activation by cyclosporine. 306 18

Vascular permeability factor (VPF) is the most potent known mediator of vessel wall permeability. In the kidney, it is expressed preferentially in the glomerular visceral epithelial cells. The present study was designed to clarify the proposed role of VPF in diseases with increased glomerular permeability as here exemplified by the congenital nephrotic syndrome of the Finnish type (CNF). For this, we studied the expression levels and the sites of synthesis of VPF and its kinase-insert domain receptor (KDR) in kidneys of patients with CNF using Northern and in situ hybridization techniques and immunohistologic staining with anti-VPF antibody. In addition, we extended the study to include analysis of fetal kidney tissue and cultured glomerular cells of normal and CNF kidneys. In CNF and in normal kidneys VPF was localized in the visceral epithelial aspect of the glomeruli and in the collecting ducts, as also earlier described. A new finding was its localization also in the juxtaglomerular area. The VPF receptor KDR was found in glomeruli in the endothelial cells, but it was not detected in the peritubular capillaries. no consistent differences in the levels of VPF or KDR mRNAs or in their sites of production were seen in CNF and control samples. Also the distribution of VPF antigen in the CNF kidneys and normal kidneys was similar. Thus, we propose that VPF and KDR are not directly involved in the pathogenesis of the proteinuria in CNF.
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PMID:Mechanisms of proteinuria: vascular permeability factor in congenital nephrotic syndrome of the Finnish type. 891 Sep 28

Idiopathic nephrotic syndrome of childhood is thought to be associated with T lymphocyte dysfunction often triggered by viral infections, with the production of circulating factor(s) resulting in proteinuria. In view of the conflicting evidence of T cell activation and Th1 or Th2 pattern of cytokine synthesis in this disease, this study examined the mRNA expression of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL-13 from CD4+ and CD8+ T cells in steroid-responsive nephrotic patients in relapse and remission. Fifty-five children with steroid-responsive nephrotic syndrome were included in this study, together with 34 normal controls and 24 patient controls with viral infections. RNA was isolated from purified CD4+ or CD8+ cells from peripheral blood and subjected to reverse transcription-PCR. Cytokine mRNA expression was measured semiquantitatively, and a cytokine index was derived from densitometric readings, with cyclophilin as the housekeeping gene. Both cross-sectional and paired data showed an increased CD4+ and CD8+ IL-13 mRNA expression in patients with nephrotic relapse as compared to remission, normal, and patient controls (P < 0.008). This was also associated with increased cytoplasmic IL-13 expression in phorbol myristate acetate/ionomycin-activated CD3+ cells (6.66+/-3.39%) from patients with nephrotic relapse compared to remission (2.59+/-1.35%) (P < 0.0001). However, there was no significant difference in CD4+ or CD8+ IL-2, interferon-gamma and IL-4 mRNA expression. IL-13 is an important T cell cytokine with anti-inflammatory and immunomodulatory functions on B cells and monocytes. It is conceivable that IL-13 may act on monocytes to produce vascular permeability factor(s) involved in the pathogenesis of proteinuria in patients with relapse nephrotic syndrome.
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PMID:Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. 1007 3

The antiproteinuric effect of angiotensin-converting enzyme inhibitors underscores the importance of a hemodynamic injury and the renin-angiotensin system in the proteinuria of various glomerular diseases. Vascular endothelial growth factor (VEGF), a potent promoter of vascular permeability, is induced in mesangial cells by both mechanical stretch and TGF-beta1. This study investigates the effect of TGF-beta blockade, angiotensin II (AngII), and the interaction between AngII and stretch on human mesangial cell VEGF production. Exposure to AngII (1 microM) induced a significant increase in VEGF mRNA and protein levels (1.5+/-0.1 and 1.7+/-0.3, respectively, fold increase over control, P<0.05). The AngII receptor (AT1) antagonist Losartan (10 microM) prevented AngII-induced, but not stretch-induced, VEGF protein secretion (AngII 1.7+/-0.3, AngII + Losartan 1.0+/-0.1, P<0.05; stretch 2.4+/-0.4, stretch + Losartan 2.6+/-0.5). Stretch-induced VEGF production was also unaffected by the addition of an anti-TGF-beta neutralizing antibody (stretch 2.85+/-0.82 versus stretch + anti-TGF-beta 2.84+/-0.01, fold increase over control). Simultaneous exposure to both AngII and stretch for 12 h had an additive effect on VEGF production (AngII 1.6+/-0.1, stretch 2.6+/-0.27, AngII + stretch 3.1+/-0.35). Conversely, preexposure to stretch magnified AngII-induced VEGF protein secretion (unstretched + AngII 1.3+/-0.0, stretched + AngII 1.9+/-0.1, P<0.01) with a parallel 1.5-fold increase in AT1 receptor levels. AngII and stretch can both independently induce VEGF production; in addition, mechanical stretch upregulates the AT1 receptor, enhancing the cellular response to AngII.
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PMID:Interaction of angiotensin II and mechanical stretch on vascular endothelial growth factor production by human mesangial cells. 1020 56

Vascular endothelial growth factor (VEGF) mediates increased vascular permeability and endothelial mitogenesis, and may orchestrate normal glomerular permselectivity and proteinuria. Distinct isoforms result from differential gene splicing. VEGF binds to two cell surface tyrosine-kinase receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase-1). The latter also exists in a soluble form (sFlt), which is inhibitory. We have studied patterns of VEGF-isoform and VEGF-receptor expression in isolated single normal human glomeruli. mRNA from 190 glomeruli (from 20 individuals) was harvested on to magnetic beads, and nested reverse transcription-PCR was performed using primers for the VEGF isoforms and VEGF receptors. Simultaneous nested reverse transcription-PCR for CD45 was conducted in order to exclude leucocyte contamination. Unexpected products were isolated, cloned and sequenced. Multiple patterns of glomerular VEGF mRNA isoform expression were identified. Most frequently (58%), all three common forms were expressed. VEGF(189) (i.e. 189-amino-acid form of VEGF) was expressed in 63%, VEGF(165) in 85% and VEGF(121) in 84% of glomeruli. Two unexpected PCR products were also identified: 18% of glomeruli expressed VEGF(145), and 27% of glomeruli expressed a new truncated VEGF splice variant, VEGF(148), lacking exon 6, the terminal part of exon 7 and exon 8. Multiple patterns of VEGF-receptor expression were also identified, the most common being expression of all three isoforms (28%). Overall, KDR was seen in 59% of glomeruli, Flt-1 in 45% and sFlt in 57%. Thus the expression of VEGF within normal glomeruli is complex and variable, with inter- and intra-individual variation. Furthermore, sFlt appears to be the co-dominant form of VEGF receptor expressed within glomeruli, suggesting that, in healthy individuals, a degree of VEGF autoregulation is the norm. The physiological importance of VEGF(148) remains to be confirmed.
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PMID:Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. 1046 55

Dysregulation of Flt-1, a major receptor for vascular permeability factor (VPF), may provide a mechanism for the development of proteinuria in minimal change nephropathy (MCN). The gene for Flt-1 has a polymorphic dinucleotide repeat. We have demonstrated an 88% predominance of one allele and an 80% rate of homozygosity for this polymorphism with no association with MCN.
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PMID:Dinucleotide repeat polymorphisms within the Flt-1 gene in minimal change nephropathy. 1055 96

The concept that some forms of proteinuria may be induced by the action of circulating systemic permeability factors on the glomerular capillary wall is intriguing. First proposed in the 1970s in the context of steroid-sensitive nephrotic syndrome, the immune system was proposed as a source of such a vascular permeability factor (VPF). More recently, some forms of focal segmental glomerular sclerosis appear to be associated with another type of systemic factor. This paper reviews the evidence for such factors and compares the properties of a number of candidate VPFs.
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PMID:Vascular permeability factors in steroid-sensitive nephrotic syndrome and focal segmental glomerulosclerosis. 1295 37

Male gender is associated with a more rapid progression of renal disease independent of blood pressure, dietary protein intake, or serum lipid levels. Recently, we reported a key role for the intrarenal vasculature in progressive renal disease (Kang D-H, Kanellis J, Hugo C, Truong L, Anderson S, Kerjaschki D, Schreiner GF, Johnson RJ: Role of endothelium in progressive renal disease. J Am Soc Nephrol 2002, 13:806-816). We hypothesized that estrogen-mediated preservation of the renal vasculature could account for the better renal outcome in female rats. We analyzed micro- and macrovascular changes in the 5/6 remnant kidney (RK) models both in male (n = 24) and female (n = 24) Sprague-Dawley rats up to 12 weeks after renal mass reduction. At 12 weeks, male and female RK rats had equivalent blood pressure, glomerular tuft area, and RK/body weight, but male rats showed worse renal function, proteinuria, glomerulosclerosis (%), and tubulointerstitial fibrosis. At 12 weeks peritubular capillary (PTC) EC proliferation and PTC density were higher in female RK rats whereas macrovascular changes in preglomerular vessels (smooth muscle cell proliferation, medial wall thickening, and adventitial fibrosis) were less prominent. The expression of vascular endothelial growth factor (VEGF) and VEGF type 2 receptor (flk-1) in renal cortex assessed by immunostaining were higher in female RK rats. To dissect the mechanism of sex hormone-induced vascular remodeling and VEGF regulation, we investigated the in vitro effect of 17 beta-estradiol (17 beta E, 10 nmol/L) on proliferation and VEGF expression of renal tubular cells (rat proximal tubular cells), vascular smooth muscle cells (VSMCs), and human umbilical vein endothelial cells (HUVECs). 17 beta E directly stimulated the proliferation of HUVECs, whereas it inhibited serum-induced proliferation of VSMCs. 17 beta E stimulated VEGF mRNA expression both in renal tubular cells and VSMCs. However, when cells were pretreated with a nitric oxide donor to simulate the in vivo condition, 17 beta E inhibited VEGF mRNA expression and protein release in VSMCs. In conclusion, female RK rats developed less glomerulosclerosis and renal failure compared to male RK rats in association with greater preservation of PTC and less preglomerular arteriopathy. Estrogen stimulated basal VEGF expression in renal tubular cells. We propose that estrogen may protect female rats in progressive renal disease by stimulating VEGF expression and maintaining a healthy intrarenal vasculature.
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PMID:The impact of gender on progression of renal disease: potential role of estrogen-mediated vascular endothelial growth factor regulation and vascular protection. 1474 71


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