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 production of tumor necrosis factor (TNF) by nephritic glomeruli and glomerular macrophages was studied in antiglomerular basement membrane antibody induced glomerulonephritis (anti-GBM GN) in rabbits. Autologous phase injury was associated with glomerular macrophage infiltration and augmented TNF production by isolated nephritic glomeruli (day 8, 1.15 +/- 0.10 ng/10(3) glomeruli/24 hours; normal, 0.01 +/- 0.01 ng/10(3) glomeruli/24 hours; p less than 0.05). In contrast, during the heterologous phase, in which macrophages were not prominent, injury was not associated with augmented glomerular TNF production. Glomerular TNF bioactivity had a molecular weight and isoelectric point consistent with rabbit TNF and was inhibitable by an anti-TNF antibody. TNF was also identified in nephritic glomerular supernatants by Western blotting. Macrophages isolated from glomeruli of rabbits developing autologous phase anti-GBM GN produced significantly more TNF (0.14 +/- 0.02 ng/10(3) macrophages/24 hours) than blood monocytes (0.03 +/- 0.02 ng/10(3) monocytes/24 hours, p less than 0.05) from the same rabbits. Macrophage depletion of rabbits with autologous phase anti-GBM GN significantly reduced proteinuria, prevented glomerular macrophage accumulation, and blocked augmentation of glomerular TNF production. These studies demonstrate the association of glomerular TNF production with the development of glomerular macrophage infiltration and injury in anti-GBM GN and suggest that infiltrating glomerular macrophages are the major source of glomerular TNF.
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PMID:Tumor necrosis factor production by glomerular macrophages in anti-glomerular basement membrane glomerulonephritis in rabbits. 189 Aug 5

We have utilized specific, irreversible inhibitors of cysteine proteinases to examine the role of renal cathepsin B and cathepsin L in the proteinuria which occurs in an experimental model of human glomerular disease. Administration of trans-epoxysuccinyl-L-leucylamido-(3-methyl)butane (Ep475) a specific, irreversible inhibitor of cysteine proteinases, including cathepsins B and L, significantly reduced proteinuria in rats with experimentally induced, neutrophil-independent, anti-GBM antibody disease (controls: 10 +/- 1 mg/24 h, N = 8; anti-GBM antibody disease: 203 +/- 30 mg/24 h, N = 8; anti-GBM antibody disease + Ep475: 112 +/- 13 mg/24 h, mean +/- SEM, N = 6, P less than 0.05). There was a marked reduction in the activity of both cathepsin B and cathepsin L in renal cortices obtained from Ep475-treated rats compared to either saline-treated controls or rats treated with anti-GBM IgG only. Administration of Z-Phe-Tyr(O-t-butyl)CHN2, a specific, irreversible cysteine proteinase inhibitor with a high degree of selectivity toward cathepsin L, also caused a reduction in anti-GBM antibody-induced proteinuria (90 +/- 18 mg/24 h, N = 6, P less than 0.05). This reduction in proteinuria was accompanied by a marked decrease (-84%) in the specific activity of renal cortical cathepsin L in Z-Phe-Tyr(O-t-butyl)CHN2-treated rats. However, cathepsin B activity was unchanged. There was no significant change in the renal anti-GBM antibody uptake, plasma urea nitrogen, or plasma creatinine values in the Z-Phe-Tyr(O-t-butyl)CHN2-treated rats compared to rats treated with anti-GBM IgG only or saline-treated controls. These data document the ability of cysteine proteinase inhibitors to decrease the proteinuria which occurs in a neutrophil-independent model of human anti-GBM antibody disease and suggest an important role for cathepsin L in the pathophysiology of the proteinuria which occurs in this model.
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PMID:Evidence suggesting a role for cathepsin L in an experimental model of glomerulonephritis. 189 42

1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused albuminuria, decreased creatinine clearance, increased numbers of intra-glomerular neutrophils and increased excretion of TXB2, 2,3-dinor-TXB2 (products of TXA2) and 6-oxo-PGF 1 alpha and 2,3-dinor-6-oxo-PGF 1 alpha (products of PGI2) at 24 h. 3. Interleukin-1 (IL-1 beta; 5 micrograms) alone caused an increase in PGI2 metabolite excretion but had no effect on TXA2 metabolites. It had no effect on creatinine clearance but increased numbers of glomerular neutrophils by approximately 4-5 fold compared to a-GBM. 4. Pretreatment of rats with IL-1 beta before a-GBM synergistically increased albumin excretion but only additively increased eicosanoid excretion. Numbers of intra-glomerular neutrophils and creatinine clearance were unchanged compared to IL-1 beta alone. 5. The cyclo-oxygenase inhibitor, ibuprofen (10 mgkg-1 i.p., twice daily for 4 days) inhibited both serum TXB2 production and urinary prostaglandin excretion. It also caused an almost complete attenuation of albumin excretion. Creatinine clearance and glomerular neutrophils remained unchanged after a-GBM/IL-1 beta. 6. We conclude that the 50% inhibition of thromboxane production induced by ibuprofen does not modify the fall in creatinine clearance of accumulation of neutrophils in the glomerulus caused by the a-GBM. This degree of inhibition of eicosanoid production was associated with a striking decrease in proteinuria, but this may reflect a haemodynamic rather than a disease modifying action.
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PMID:Excretion of metabolites of prostacyclin and thromboxane by rats with nephrotoxic nephritis: effects of interleukin-1. 193 30

This report examines the correlation between glomerular injury and glomerular dysfunction in murine lupus nephritis. Glomerular filtration rate was measured by the clearance of inulin in conscious NZB/W female mice and shown to vary 12-fold in the animals tested. Detailed morphometric measurements were made on the perfused fixed kidneys. As disease progressed the surface density (Sv) of the open capillary loops decreased by 73%. This drop in Sv correlated with a 4-fold increase in mean glomerular volume (MGV, r = -0.79, p less than 0.0001). The "compensating" increase in MGV maintained or increased filtration surface area despite the loss of some capillary loops to proliferating and/or infiltrating cells. Filtration slit length/glomerulus and the filtration slit number/micron glomerular basement membrane varied 10-fold and were found to correlate directly with glomerular filtration rate (r = 0.64, p less than 0.0007 and r = 0.70, p less than 0.0001, respectively). When linear and multiple regression analyses were applied, all other structural measures, including filtration surface area, correlated with glomerular filtration rate poorly if at all. Glomerular permselective dysfunction (proteinuria) was measured as the fractional clearance of albumin (fractional clearance of albumin) and of IgG. Stepwise multiple regression analysis revealed the percentage of the glomerular basement membrane occupied by dense deposits, slit number/glomerular basement membrane, and glomerular basement membrane thickness statistically explained most (81%) of the variation in fractional clearance of albumin and IgG. These results suggest that epithelial slit length is the most important structural determinant of GFR and that the increase in MGV maintains filtration surface area despite evidence of an extensive inflammatory insult. The mechanism(s) of proteinuria in this model of lupus nephritis are consistent with either a focal increase in GBM permeability due to immune deposits and/or a diffuse increase in permeability due to GBM charge neutralization. The study provides insight as to why previous structure-function reports failed to find correlates of glomerular injury to glomerular dysfunction.
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PMID:Murine lupus nephritis. A structure-function study. 207 65

Hepatitis B virus carriers, a 30-year-old man (case 1) and a 31-year-old man (case 2), associated with nephrotic syndrome were treated with interferon-beta. The nephrotic syndrome did not respond to corticosteroid therapy. Their HBs-Ag, HBe-Ag and HBc-Ab were positive. Renal biopsies revealed membranous glomerulonephritis in case 1 and mixed membranous and proliferative glomerulonephritis in case 2. Direct immunofluorescence studies showed strong granular staining of the GBM with IgG and using sandwich technique with anti-HBe antiserum, granular deposits were seen throughout the GBM. Patients were administrated mainly 3-6 x 10(6) IU/day interferon-beta intravenously for four weeks. After transitory elevation of serum transaminase, HBe-Ag and DNA-polymerase have disappeared with development of HBe-Ab (seroconversion) about six months after the end of interferon-beta administration. Then nephrotic syndrome has recovered in incomplete remission after a year and a half follow-up. The secondary renal biopsy in case 1 showed less intense deposits of HBe-Ag along GBM. These facts suggest that the improvement of proteinuria is associated with the decrease in HBV replication due to interferon therapy.
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PMID:[Clinical and histological observation of HBV glomerulonephritis treated with interferon-beta]. 208 50

This article describes a case of Goodpasture's syndrome controlled by double filtration plasmapheresis (DFPP) combined with steroid and immunosuppressant therapy. A 48-year-old male, clerk, complaining of fever, dry cough and macroscopic hematuria, was admitted to our hospital. Microscopic hematuria was first pointed out at age 40 on an annual check up. His laboratory data on admission revealed severe anemia, azothemia, macroscopic hematuria and proteinuria. His chest radiograph and CT revealed diffuse nodular densities in bilateral lung fields. Specimens obtained by transbronchial lung biopsy and open renal biopsy revealed linear deposition of IgG by direct immunofluorescent antibody methods. Circulating antiglomerular basement membrane antibody level determined with radioimmunoassay was 1.8% on admission, but one week later it elevated to 5.6% with progression of dyspnea, hypoxemia, and renal failure. Steroid pulse therapy and a total of 6 double filtration plasmaphereses were performed in the first month. Subsequently hypoxemia and dyspnea disappeared, and the chest radiograph of the 40th hospital day showed no abnormal shadows. Two months later recurrence of pulmonary hemorrhage was noticed. Immunosuppressant administration (Cyclophosphamide 100 mg/day) and a total of 10 DFPP procedures were performed with success. By DFPP, circulating anti-GBM antibody fell rapidly to within normal ranges, and anti-GBM antibody level elevated in removed plasma. We think DFPP is effective to remove circulating anti-GBM antibody in Goodpasture's syndrome.
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PMID:[Double filtration plasmapheresis in case of Goodpasture's syndrome]. 221 5

Recurrence of anti-glomerular membrane antibody glomerulonephritis seems to be an unusual clinical phenomenon. We report a 57-year-old man with recurrence of anti-glomerular basement membrane antibody glomerulonephritis. He developed a rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibody (anti-GBM Ab), and recovered with a combined treatment of prednisolone, anticoagulant and antiplatelet agents. After a 2-year remission, hematuria and proteinuria followed by renal functional deterioration occurred without any obvious cause. The second renal biopsy revealed cellular crescents with linear IgG deposition along GBM, a finding similar to the first one. The aforementioned combined treatment resulted in a gradual recovery from proteinuria and renal functional derangement.
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PMID:Recurrence of anti-glomerular basement membrane antibody glomerulonephritis. 227 9

Authors studied the dispersion of immunoreactive HSPG with monoclonal antibody specific to protein nucleus of HSPG in renal diseases associated with nephrosis syndrome. Their results showed that the dispersion of HSPG in GBM does not fully agree with dispersion of anion linkage places known in literature. In membrane and diffuse proliferative lupus glomerulonephritis immunoreactive HSPG cannot be demonstrated in the place of immune deposits, concurrent with dispersion of anion places, while it appears in GBM newly developed round the deposits. Inconsistent with this, in glomerulonephritis having minimal changes, the anion loss of GBM is not associated with absence of nuclear protein, the immunoreactive HSPG remains intact. These observations reflected in literature indicate that--similarly to proteinuria--presumably, deficiency of anion linkage places of GBM is caused by different pathomechanisms.
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PMID:[Heparan sulfate proteoglycan distribution in the glomerular basal membrane in human glomerulonephritis]. 253 43

In order to investigate the early renal damage in diabetes mellitus, 89 diabetics without proteinuria by dipsticks and 67 normal control subjects were examined by means of SDS-PAGE. The relationships between electrophoretic patterns of urinary protein and duration of diabetes, age of patients, metabolic controls and stages of retinopathy were examined. 1) The percentage of higher molecular weight (MW) proteins (67,000 less than or equal to MW) was larger in diabetics than that in controls. Especially the percentage of proteins with MW between 67,000 and 94,000, which include transferrin was 13.9 +/- 6.9% in diabetics, significantly higher than that in controls (10.3 +/- 5.1%) (P less than 0.01). On the contrary, the percentage of low MW proteins (MW less than 67,000) was relatively small in diabetics. 2) The excretion of higher MW proteins increased until 16 years of diabetic duration, however that decreased after 16 years. Especially in the group with duration longer than 20 years, excretion of low MW proteins increased. 3) Electrophoretic patterns of urinary proteins in patients with good metabolic control were similar to those in normal controls. 4) Excretion of higher MW proteins increased in patients with retinopathic complication suggesting the progression to microangiopathy. From the above results, we concluded that increased excretion of higher MW proteins in diabetics may be the results of GBM damages in protein selectivity. In patients with longer history of diabetes, predominant excretion of urinary low MW proteins may be the result of tubular dysfunction due to macroangiopathy.
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PMID:[A study of microproteinuria in patients with diabetes mellitus]. 259 18

The relative contributions of chemo-attractant and terminal components of complement to heterologous phase glomerular injury was studied in anti-GBM glomerulonephritis in rabbits. Normal rabbits (complement intact) were given anti-GBM antibody at a dose which resulted in 140 micrograms specific kidney-fixed antibody per gram of renal cortex, and developed significant proteinuria (1910 +/- 327 mg/24 h; control 18.2 +/- 6.1 mg/24 h; P less than 0.01). Leucocyte depletion significantly reduced but did not abolish proteinuria (574 +/- 186 mg/24 h, P less than 0.05). Complement depletion of neutrophil-depleted rabbits resulted in a further significant reduction in proteinuria 50.1 +/- 12.2 mg/24 h, P less than 0.05; versus neutrophil-depleted, complement-intact rabbits), indicating that both neutrophil accumulation and complement activation independent of neutrophils contribute to injury in this model. Rabbits congenitally deficient in the sixth component of complement (C6D) developed similar levels of proteinuria (2099 +/- 796 mg/24 h) to normal rabbits given an identical dose of antibody. However, after leucocyte depletion, C6D rabbits developed significantly less proteinuria (135 +/- 56 mg/24 h) than did leucocyte-depleted, complement-intact rabbits (P less than 0.05). These studies show that terminal complement components are not necessary for the full expression of acute anti-GBM antibody-initiated injury in leucocyte-intact rabbits. However, in the absence of leucocytes, C6 and the terminal complement components are apparently responsible for the majority of the complement-dependent glomerular injury.
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PMID:Relative contributions of chemo-attractant and terminal components of complement to anti-glomerular basement membrane (GBM) glomerulonephritis. 261 54


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