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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular adenine nucleotides are considered mediators of inflammation because they modulate functions of neutrophils and platelets. Until now, this role for adenine nucleotides has not been studied in vivo. In particular in the rat kidney, where ATP- and ADPase activity is present in the glomerular basement membrane, studies about the role of nucleotides may increase our understanding of the dynamics of glomerulonephritis (GN). Therefore, we examined effects of adenine derivatives ATP gamma S, ADP beta S and 2chloro-adenosine (2chloro-ADO) in vitro and during anti-Thy1 GN. The in vitro results show that ADP beta S and ATP gamma S are not degraded by glomerular nucleotidases but, on the other hand do stimulate O2- production of peritoneal exudate cells (PEC). In contrast, 2chloro-ADO significantly inhibits O2- production of peritoneal exudate cells. For in vivo studies rats were rendered nephritic by intravenous injection of monoclonal anti-Thy1 IgG (5 mg/kg body weight). Subsequently, rats were treated with saline (group 1, N = 10), 2chloro-ADO (group 2, N = 10), ADP beta S (group 3, N = 10) or ATP gamma S (group 4, N = 10). All analogs (10 mg/kg body weight) were administered both at t = 0 and t = 12 hour. After 24 hours, rats were sacrificed and kidneys were examined histochemically. In an additional group of nephritic rats (N = 5) proteinuria was studied after 2-chloro-ADO treatment. Results show increased intraglomerular platelet aggregation in nephritic rats treated with ADP beta S, whereas 2chloro-ADO inhibits aggregation significantly as compared with nephritic rats receiving saline. The percentage of granulocytes producing O2- is significantly increased in glomeruli after treatment of nephritic rats with ATP gamma S, whereas cell influx itself is not changed. In contrast, 2chloro-ADO inhibits intraglomerular O2- production, which is associated with the complete inhibition of proteinuria in the early phase of anti-Thy1 GN. These data demonstrate significant pro-inflammatory activities of extracellular adenine nucleotides during anti-Thy1 GN suggesting an anti-inflammatory role for glomerular ATP/ADPase, which in concert with 5' nucleotidase converts ATP and ADP to antiinflammatory ADO.
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PMID:Modulation of anti-Thy1 nephritis in the rat by adenine nucleotides. Evidence for an anti-inflammatory role for nucleotidases. 153 30

Although both ecto-ADPase and prostacyclin (PGI2) inhibit platelets and neutrophils, their action in acute glomerulonephritis is unknown. We tested the PGI2 analog Iloprost and 2chloroadenosine (2Cl-ADO), an analog of adenosine, the end product of nucleotidase activities, during anti-Thy1 nephritis. Rats received anti-Thy1 immunoglobulin G (5 mg/kg body weight, intravenously) and subsequently one subcutaneous injection of either 2Cl-ADO (10 mg/kg body weight; (n = 6) or Iloprost (1 mg/kg body weight; n = 6). Control rats received anti-Thy1 immunoglobulin G with saline (n = 6) or saline alone (n = 6). After 24 hours, kidneys were processed for light-microscopical evaluation. Proteinuria was studied in additional rats. Results showed that both drugs inhibited intraglomerular platelet activation (P < 0.005). 2Cl-ADO also reduced intraglomerular O2- production of neutrophils (P < 0.05), in contrast to Iloprost. Intraglomerular immunoglobulin G deposition, complement activation, neutrophil influx, and myeloperoxidase release were not affected by 2Cl-ADO or Iloprost. However, proteinuria was completely prevented by both drugs. It is concluded that PGI2 and nucleotidases are potentially able to attenuate this form of nephritis by inhibiting platelet activity, whereas nucleotidases also inhibit neutrophil activity in vivo.
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PMID:Attenuation of anti-Thy1 glomerulonephritis in the rat by anti-inflammatory platelet-inhibiting agents. 767 50

An acute model for IgA-mediated glomerular inflammation in rats was induced by the in situ deposition of IgA directly into the glomerular mesangium. F(ab')2 anti-Thy1 MoAb was used to anchor an antigen, DNP (2,4-dinitrophenol), in the glomeruli of rats. Subsequent infusion of rat polymeric (p-) or monomeric (m-) IgA MoAb with specificity for DNP resulted in mesangial deposition of IgA in both groups of rats. However, acute proteinuria was observed only in p-IgA-treated rats and not in PBS- or m-IgA-treated rats. Immunofluorescence analysis revealed deposition of C3 in an identical pattern to that of IgA in the glomeruli of p-IgA-treated rats. No mesangial deposits of C4 or C1q were seen in these animals. Rats receiving m-IgA or PBS displayed no detectable C3, C4 or C1q deposition. The amount of proteinuria in p-IgA-treated rats was related to the amount of deposited C3. The presence of intraglomerular monocytes was only observed 2 days after p-IgA injection. By light microscopy, aneurysm formation, mesangial hypercellularity and matrix expansion were seen only in p-IgA-treated rats. However, by 37 days post-injection complete resolution of the lesions was observed. No histological renal changes were observed in PBS- or m-IgA-treated rats. In conclusion, an acute form of IgA-mediated nephritis in rats was induced by p-IgA but not by m-IgA. This reproducible model provides a basis for further study into the mechanisms of IgA-mediated glomerular inflammation.
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PMID:An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies. 809 59

To identify genes expressed predominantly in the kidney with chronic and progressive glomerulosclerosis but not in acute and transient form of glomerulonephritis, we induced progressive glomerulosclerosis in rats by applying unilateral nephrectomy prior to injection of monoclonal anti-Thy1.1 antibody (OX-7), which cause acute and transient glomerulonephritis with single injection. In rats with nephrectomy and OX-7 injection (Nx group), proteinuria increased with time and mesangial expansion accompanied with interstitial fibrosis was recognized, whereas transient proteinuria and mesangiolysis followed by mesangial hypercellularity were seen in rats with sham operation and OX-7 injection (Sham group). Four weeks after the induction of glomerulonephritis, mRNAs were isolated from kidney cortex of both groups and used for cDNA synthesis. By subtraction hybridization of cDNAs from Nx with excess amount of those from Sham, we isolated and sequenced several genes expressed specifically in the Nx group. These included genes, which contain identical sequences with serine protease inhibitors, cytokine receptors, osteopontin as well as genes with unknown function. These genes may play important roles in the process which promotes acute glomerular damage advance to chronic and progressive glomerulosclerosis.
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PMID:Identification of genes specifically expressed in chronic and progressive glomerulosclerosis. 940 63

There is accumulating evidence that matrix metallo-proteinases (MMP) play a prominent role in glomerular inflammatory diseases. The aim of the present study was to determine the anti-inflammatory effects of the synthetic MMP inhibitor BB-1101 in acute anti-Thy1.1 nephritis. Sixty-three male Wistar rats were studied: healthy rats (n = 9), treated healthy rats (n = 9), nephritic rats (n = 18), and treated nephritic rats (n = 27). BB-1101 therapy (30 mg/kg body wt per d) of nephritic animals was initiated either 2 d before (n = 18) or 2 d after (n = 9) disease induction. Renal histology was analyzed 11 d after induction of the nephritis, at the peak of MMP-2 production and total glomerular cellularity. Pretreatment of nephritic rats by BB-1101 resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, extracellular matrix deposition, and size of glomerular cross-sections. These beneficial effects were less pronounced, but in part still significant, in animals treated by BB-1101 after induction of anti-Thy1.1 nephritis. Proteinuria, expressed as area under the curve of the protein:creatinine ratio versus time, was clearly decreased in both groups of treated nephritic rats. Healthy control rats were not affected by MMP inhibitor treatment. In summary, the present study demonstrates for the first time in vivo that mesangial cell proliferation can be effectively suppressed by MMP inhibition. Thus, MMP inhibition by synthetic compounds may represent a new approach to the therapy of mesangial cell-mediated forms of glomerulonephritis.
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PMID:Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis. 951 1

Injection of rats with mouse monoclonal IgG2a anti-Thy1.1 antibodies (ER4G) results in rapid development of proteinuria in Wistar rats, reaching average values of 160 mg/24 h on day 3 after antibody administration. In contrast, no overt proteinuria was observed in PVG/c+ rats (maximum, 40 mg/24 h on day 3). This study investigates whether differences in the inactivation of C5b-9 complexes in the glomerulus by complement inhibitors are responsible for the differences in proteinuria between the two rat strains. Regardless of the presence of proteinuria, an increased expression of Crry by mesangial cells (MC) was observed within 24 h after injection of ER4G in both Wistar and PVG/c+ rats. Double-label immunofluorescence using goat anti-mouse Ig antibodies demonstrated an expression of Crry exclusively on MC. Furthermore, Crry colocalized with C5b-9 complexes on MC, as detected by a monoclonal antibody against the rat C5b-9 neo-antigen. In PVG/c+ rats, C5b-9 complexes persisted in the mesangial area for at least 7 d and colocalized immediately (within 1 h) and homogeneously with vitronectin. However, in proteinuric Wistar rats, C5b-9 complexes disappeared from the glomerular mesangium within 6 d. In these rats, mesangial colocalization of C5b-9 with vitronectin could only occasionally be detected. Pretreatment of PVG/c+ rats with antibodies against vitronectin, followed by administration of ER4G, resulted in the immediate development of proteinuria (maximum, 119 mg/24 h on day 3; P < 0.05), whereas Wistar rats did not become more proteinuric. This study provides evidence that differences in susceptibility of PVG/c+ and Wistar rats to complement-mediated damage of the glomerulus may be related to the degree of inactivation of C5b-9 complexes by complement regulatory factors.
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PMID:Anti-vitronectin antibodies enhance anti-Thy-1-induced proteinuria in PVG/c, but not in Wistar rats. 962 Dec 82

Mycophenolate mofetil (MMF) represents a powerful immunosuppressant in organ transplantation. The aim of this study was to determine the anti-inflammatory effects of MMF on mesangial cells. Cultured rat mesangial cells were exposed to mycophenolic acid (MPA) in concentrations of 0.1 to 10 microM. MPA inhibited the proliferation of these cells in a dose-dependent manner. A maximum of 98% inhibition was obtained by a 2-d exposure of mesangial cells to > or =5 microM MPA. As expected, the addition of > or =75 microM guanosine prevented the antiproliferative effect of MPA completely. Subsequently, in vivo studies were performed in the anti-Thy1.1 nephritis model. Sixty-six male Wistar rats were investigated: healthy rats (n = 15), treated healthy rats (n = 6), nephritic rats (n = 15), and treated nephritic rats (n = 30). MMF therapy (40 mg/kg body wt per d) of nephritic animals was initiated 2 d before (n = 3) and 6 h (n = 15) or 2 d (n = 12) after induction of nephritis. Renal histology was analyzed at days +6 and +9 after initiation of disease. Therapy of nephritic rats by MMF resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, synthesis of alpha-smooth muscle actin, extracellular matrix deposition, and glomerular hypertrophy. Proteinuria, expressed as areas under the curve of protein/creatinine ratios versus time, showed a clear tendency toward a reduction by MMF therapy. Healthy control rats were not negatively affected by exposure to MMF. In summary, this study shows that mesangial cell proliferation can be significantly inhibited by MPA in vitro and in vivo. MMF represents a new approach to the therapy of experimental mesangial cell-mediated forms of glomerulonephritis.
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PMID:Mycophenolic acid: a new approach to the therapy of experimental mesangial proliferative glomerulonephritis. 980 91

Recent studies have shown that glomerular-filtered albumin appears to be processed by two distinct cellular pathways. The major pathway, a high-capacity retrieval pathway, returns most of the filtered albumin to the blood supply intact. The albumin not taken up by the retrieval pathway is degraded by lysosomes during renal passage and excreted as fragments in urine. We studied the interplay of the albumin retrieval pathway and the degradation pathway in the disease models of anti-Thy1 nephritis, a model of mild proteinuria, and anti-glomerular basement membrane (anti-GBM) disease, a model of severe proteinuria. This is achieved by investigating the integrity of urinary albumin and its excretion rate. Total albumin excretion (intact plus fragments) did not change significantly in the rats with anti-Thy1 nephritis. However, it was established that intact albumin excretion had a strong positive correlation with increasing total-protein excretion, which showed that the degradation pathway was being predominantly affected in this disease. For the rats with anti-GBM disease, total protein excretion increased 26-fold compared with the control group, and intact albumin excretion increased 250-fold. The profound changes in albumin excretion in anti-GBM disease are consistent with inhibition primarily of the retrieval pathway.
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PMID:Characteristics of albumin processing during renal passage in anti-Thy1 and anti-glomerular basement membrane glomerulonephritis. 1069 67

Hyperglycemia, although necessary, alone is insufficient for the development of progressive diabetic nephropathy. Two factors implicated in its pathogenesis are mesangial cell activation and/or proliferation and monocyte/macrophage influx. We have shown that prolonged hyperglycemia in the Goto-Kakizaki (GK) rat is associated with renal structural changes similar to those in patients with diabetes before the onset of progressive nephropathy. The aim of the current study is to examine the role of mesangial cell injury and macrophage influx on renal structure and function. After induction of nephritis in either hyperglycemic GK rats or normoglycemic Wistar rats by the administration of Ox-7 antibody, the degree of mesangiolysis and subsequent mesangial proliferation was no different between GK and Wistar rats. Similarly, macrophage influx and mesangial cell activation (assessed by alpha-smooth actin expression) was no different between the two groups. Wistar rats developed marked albuminuria; conversely, no significant proteinuria or albuminuria was seen in GK rats. Analysis of glomerular proteoglycans (PGs) showed an increase in (35)S incorporation into heparan sulfate PGs of GK compared with Wistar rats, with no alteration in glycosaminoglycan chain size or charge density. These changes were kidney specific and not seen in spleen, lung, or heart tissue. Western blot analysis showed increased agrin core protein expression in whole-kidney homogenates of untreated GK rats. Induction of Thy1.1 nephritis was associated with reduced expression of agrin in both GK and Wistar rats. However, agrin expression was greater in GK rats at all times. In summary, acute mesangial cell injury associated with a macrophage influx did not initiate progressive diabetic nephropathy in GK rats. Despite a similar magnitude of glomerular/mesangial injury, GK rats, in contrast to normoglycemic Wistar rats, did not develop proteinuria after the administration of anti-Thy1 antibody. We postulate that altered expression of agrin in this model accounts for the lack of proteinuria and thus may protect against progressive nephropathy.
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PMID:Goto-Kakizaki rat is protected from proteinuria after induction of anti-Thy1 nephritis. 1197 42

IFN-inducible protein-10 (IP-10/CXCL10) is a potent chemoattractant for activated T lymphocytes and was recently reported to have several additional biologic activities. In this study, the expression and the function in normal glomeruli and in Thy1.1 glomerulonephritis (GN) were investigated. The expression of IP-10 was detected in normal rat glomeruli mainly in the podocyte. The expression of IP-10 was also detected on the cultured podocyte. The IP-10 expression was elevated at the early phase of Thy1.1 GN. The double staining immunofluorescence study clearly demonstrated that the elevated expression of IP-10 was mostly detected in the podocyte and very partly in mesangial area. A receptor for IP-10, CXCR3, showed similar expression patterns to that of IP-10. Expressions of neither of IP-10 nor of CXCR3 were detected on the inflammatory cells. For elucidating the role of IP-10, the blocking study was carried out with monoclonal anti-IP-10 antibody. The monoclonal anti-IP-10 antibody treatment decreased the expression of IP-10 and podocyte-associated proteins such as nephrin and podocin that are reported to be essential for maintaining the podocyte function (IP-10, 53.0% to control; nephrin, 43.5%; podocin, 60.4%). The findings indicated that the anti-IP-10 treatment disturbed the podocyte function. The anti-IP-10 treatment given to the rats with Thy1.1 nephritis exacerbated proteinuria, mesangiolysis, and matrix expansion. Collectively, the findings indicated that IP-10 plays a role in maintaining the podocyte function. Also, the findings suggested that anti-IP-10 treatment exacerbated the glomerular alterations in Thy1.1 GN by disturbing the podocyte function.
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PMID:IFN-inducible protein-10 has a differential role in podocyte during Thy 1.1 glomerulonephritis. 1463 10


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