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)

Prolonged cadmium exposure has been associated with proteinuria, calcuria and loss of calcium from bones in humans. Previous studies have shown that kidney uptake of cadmium in vivo results from proximal tubule absorption of the circulating cadmium metallothionein complex (CdMT), and intracellular release of the Cd2+ ion prior to induction of renal metallothionein. Parenteral administration of CdMT has been found to selectively damage the proximal tubule cell lysosome system with development of a tubular proteinuria pattern similar to that observed under chronic exposure conditions. The present studies also demonstrate a concomitant calcuria but no changes in the excretion of other electrolytes or glucose using this model. These marked changes in renal calcium metabolism occurred in the absence of mitochondrial damage, changes in total, Na/K or Mg-stimulated ATPase activities, renal ATP levels, membrane 45Ca2+ transport or overt tubule cell necrosis during an 8 hour period following CdMT injection. Proteinuria and calcuria were prevented by prior zinc induction of the renal MT pool. Data from these studies indicate that renal proximal tubule cell uptake and degradation of the circulating CdMT complex produces both a marked proteinuria and calcuria. The calcuria does not appear to stem from changes in renal energy metabolism or membrane transport of this element but is probably a secondary result of calcium binding to excreted proteins which are increased in urine to a similar extent. The studies also suggest that zinc status and maintenance of the renal ZnMT pool may play an important role in regulating cadmium-induced renal proteinuria and calcuria by preventing Cd2+ perturbation of the proximal tubule cell lysosome system.
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PMID:Mechanism of cadmium-metallothionein-induced nephrotoxicity: relationship to altered renal calcium metabolism. 282 68

The effects of maleate on membrane-bound and lysosomal peptidases were studied histochemically in the kidney and biochemically in the kidney and the urine of male and female rats 6 h after the administration of two different doses of sodium maleate (150 and 300 mg/kg body weight). Additionally, the proteinuria of experimental animals was electrophoretically analysed to detect maleate-induced alterations in the urinary protein composition. The histochemistry of the brush-border peptidases (aminopeptidase A, gamma-glutamyltransferase) showed dose-dependent maleate effects in the late pars convoluta and the pars recta of the proximal tubule (blurring of the brush-border enzyme reaction pattern). The female animals were more severely affected by both maleate doses. After maleate treatment, enzyme-activity measurements in the kidney homogenate supernatant and urine indicated dose-dependent structural destruction of the proximal tubule, especially of brush-border membranes, and revealed an increase in enzyme excretion. Both the maleate-induced enzyme excretion and proteinuria were more pronouncedly increased in females than in males. Electrophoretic analysis of urinary proteins revealed alterations in the urinary-protein composition after maleate treatment, which favoured the excretion of proteins with a molecular weight higher than 20,000 daltons. Again, sex-related differences in the maleate effects were demonstrated. The results indicate that maleate causes alterations in the brush-border membranes and, especially at higher doses, results in cellular destruction selectively in the late proximal tubule of rat kidneys. Selectivity was also encountered in the maleate effects on urinary-protein composition, suggesting that the tubular alterations lead to an inhibition of the reabsorption of mainly high-molecular-weight proteins. Although the nature of the effects was independent of sex, it appears that females are less well protected against tubular damage caused by maleate.
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PMID:Maleate effects on kidney peptidases and proteinuria of male and female rats. Histochemical and biochemical studies. 285 59

1-(2-Chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin (CZ; 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose) are structurally related anticancer agents which differ by virtue of the increased water solubility, and comparatively low carbamylating activity, of CZ relative to MeCCNU. In the present study, a single sc injection of either of these chloroethylnitrosoureas was nephrotoxic to male Fischer 344 rats. However, at equimolar doses, CZ was shown to be a much more potent nephrotoxicant. A lethal 40-mg/kg dose of CZ (127 microM) initially resulted in acute tubular necrosis of the proximal tubules of the cortex, followed later by a necrosis of papillary collecting ducts. In contrast, lethal doses of MeCCNU (100-180 mg/kg; 400-730 microM) produced only minimal proximal tubule injury. A 250-mg/kg (1 mM) dose of MeCCNU resulted in massive papillary necrosis within 7 days, with only limited necrosis to the proximal tubules. Sublethal doses of either drug, resulted in a similar, chronic, progressive nephropathy which was delayed in onset and was characterized by polyuria, enzymuria, a decrease in urine concentrating ability, and in renal slice organic ion accumulation. Alterations in less sensitive indicators of renal toxicity (i.e., proteinuria, glucosuria, and elevated blood urea nitrogen) were observed no earlier than 3 to 7 days after administration of only the highest tested doses of CZ (40 mg/kg) or MeCCNU (250 mg/kg). At sublethal doses, administration of either drug resulted in karyomegaly to the collecting ducts in the renal medulla within 2 to 4 weeks. These studies demonstrate that carbamylation-mediated reactions may not be necessary for nephrotoxicity to develop following administration of this class of antitumor agent.
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PMID:Comparative nephrotoxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin: functional-structural correlations in the Fischer 344 rat. 293 79

1. Experimental proteinuria (262.9 mg protein/24 hr urine) was induced in rats by repeated intraperitoneal injections of BSA. 2. Hypertrophy of the kidney cortex was significant 8 days after the start of the BSA injections, and the activities of lysosomal enzymes in kidney cortex and urine were significantly higher in proteinuric compared to nonproteinuric rats. 3. Lysosome populations in the kidney cortex were examined by rate sedimentation of the homogenate and by rate zonal and isopycnic centrifugation of the lysosome-rich ML fraction. 4. The activity of lysosomal enzymes in the kidney cortex increased slightly, essentially in the large, fragile lysosomes mainly recovered from the proximal tubule. 5. Proteinuria induced a shift/reduction in the density of small lysosomes from 1.235 and 1.20 g/ml to 1.225 and 1.185 g/ml, respectively. 6. Proteinuria induced a new population of small lysosomes (density 1.185 g/ml) enriched in cathepsin D.
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PMID:Changes in lysosome populations in the rat kidney cortex induced by experimental proteinuria. 304 82

Previous studies from our laboratory have shown that human immunoglobulin light chains (LC) can be toxic to the epithelium of the rat proximal tubule. To examine the toxicity of monoclonal LC's in man, 11 kidney specimens (EXP group) obtained from patients with monotypical LC-related renal disease (7 lambda, 4 kappa), documented by the presence of monoclonal LC's in the serum or urine and in the tissue, were examined by light, immunofluorescence, electron, and immunoelectron microscopy. This EXP group had monotypical LC deposition in the tubules and/or the glomeruli and did not have evidence of intraluminal LC precipitation and cast formation, which alters tubule morphology. A control group (CON; N = 12) of kidney specimens was obtained from patients who had proteinuria greater than 2.5 g/24 hr and mean age (49 +/- 4 vs. 59 +/- 3 years; P = NS), serum creatinine concentration (2.4 +/- 0.5 vs. 3.2 +/- 1.5 mg/dl; P = NS) and creatinine clearance (65 +/- 13 vs. 63 +/- 12 ml/min; P = NS) similar to the EXP group. All of the EXP specimens demonstrated varying degrees of proximal tubule damage, manifested by cell vacuolation, desquamation, loss of the luminal brush border, and, often, coagulation necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphologic alterations of the proximal tubules in light chain-related renal disease. 313 19

Acute passive Heymann glomerulonephritis in rats induced heavy proteinuria and highly increased urinary activity of N-acetyl-beta-D-glucosaminidase, acid beta-galactosidase and acid phosphatase. The cortical activity of these acid hydrolases was increased essentially in the large lysosomes as demonstrated by subfractionation of the lysosome-rich mitochondrial-lysosomal fraction, by rate zonal centrifugation. Banding density of small lysosomes shifted or reduced to slightly lower value (1.225 g/ml), which is between the banding densities of small 'light' (1.20 g/ml) and small 'dense' lysosomes (1.235 g/ml) in normal rat kidney cortex. Labelled protein reabsorbed in the proximal tubule is recovered in these populations of small lysosomes as well as in the large lysosomes or 'protein droplets'. Glomerulonephritis also induced a new population of small 'light' lysosomes (density 1.185-1.195 g/ml) enriched in cathepsin D. The previously demonstrated morphological, biochemical, and physiological heterogeneity of renal lysosomes was confirmed and emphasized in the kidney cortex of glomerulonephritic rats. The main changes in the lysosomal populations appear to reflect the increased protein reabsorption as confirmed by the proteinuria.
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PMID:Changes in lysosome populations in the rat kidney cortex induced by passive Heymann glomerulonephritis. 313 21

The effect of food restriction (FR) on the kidney cortex lysosomes prepared by rate and isopycnic zonal centrifugation was studied in rats with passive Heymann glomerulonephritis (PHN). FR reduced the renal mass by 41%, but the capacity for handling of labelled endocytosed proteins by the lysosomes was not different from fed PHN rats. While PHN with heavy proteinuria increased the recovery of lysosomal enzymes in the large lysosomes located in the proximal tubule, no changes were observed in FR-PHN rats in spite of significant proteinuria. The density of the small lysosomes was significantly shifted/reduced (from 1,200 and 1,235 g/ml to 1,185 and 1,225 g/ml, respectively) in both fed and FR-PHN rats, suggesting that the handling of extra loads of protein may enhance the absorptive function of small lysosomes found in the lower part of the nephron. FR reduced the mechanical fragility of lysosomes in the kidney cortex of PHN-rats. The highly increased urinary excretion of lysosomal enzymes in fed PHN rats was not observed in FR-PHN rats. As a conclusion, FR reduces both the fragility of lysosomes and the proportion of digestive enzymes in fragile lysosomes. These lysosomal enzymes may be of pathogenic importance in PHN causing cell damage when liberated from disrupted lysosomes.
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PMID:Effect of fasting on lysosomes in kidney cortex of glomerulonephritic rats. 321 May 36

We have proposed that the deposition in vivo of anti-brush border antibodies on proximal tubule cells in Heymann nephritis stimulates those cells to divide. To evaluate that hypothesis, we have investigated the temporal relationship between antibody deposition and kidney cell proliferation, using autoradiography to detect dividing cells in rats with Heymann nephritis and in age-matched controls treated with Freund's adjuvant alone. To assess the possible stimulation of proximal tubule cell proliferation by factors associated with proteinuria and/or nephrotic syndrome, kidney cell proliferation was measured in rats with chronic serum sickness glomerulonephritis. Proteinuric rats with chronic serum sickness also served as recipients of anti-brush border antibodies in passive transfer experiments. Cell division rates were not altered by adjuvant treatment or ageing. In both active Heymann nephritis and passive transfer experiments, a highly elevated stimulation of 3H-thymidine incorporation, reflecting mitotic activity, was detected in the proximal tubule epithelium immediately following the deposition of antibodies on the brush border. Significant enhancement of cell division was not noted in other nephron segments. A much smaller increase in proximal tubule cell proliferation accompanied proteinuria in chronic serum sickness. A similar small elevation compared to controls was also detected in late stages of Heymann nephritis when the proximal tubules were free of immunoglobulin deposits. It appears that the reaction of divalent antibodies with plasma membrane antigens can produce proliferative pathology of the proximal tubule epithelium. Furthermore, a significant, if less dramatic, enhancement of cell proliferation may be secondary to proteinuria and/or other manifestations of the nephrotic syndrome.
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PMID:Antibody-mediated proliferation of proximal tubule cells. 325 99

Howie and Brewer recently described a novel glomerulopathy: the glomerular tip lesion (GTL). The characteristic feature of this entity is a collection of intracapillary foam cells and marked vacuolization of the epithelial cells of the glomerular segment adjacent to the origin of the proximal tubule. Although this lesion resembles focal segmental glomerulosclerosis (FSGS), Howie and Brewer suggested that it constitutes a distinct entity, differing also clinically from FSGS, in that it would have a better response to steroid treatment. We treated five patients fulfilling the criteria of Howie and Brewer. However, neither corticosteroids (1.5 mg/kg/day for 1 month in five patients) nor cyclosporin-A (5 mg/kg/day for three months in four patients) caused a decrease in proteinuria to below 4 g/day. In two patients, renal function deteriorated and in one of them, recurrence of classical FSGS was found in the renal transplant. A sixth patient was observed in whose biopsy a combination of GTL with membranous glomerulopathy was present. We conclude that GTL is not a distinct entity and that in the clinical course and response to treatment it does not differ from FSGS.
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PMID:The glomerular tip lesion: a distinct entity or not? 328 Jul 67

Proximal tubule pathology in Heymann nephritis has been attributed to anti-brush border antibodies, but antibodies with other specificities might also be important. To determine whether injury to the basolateral membranes of proximal tubules could occur independently of brush border injury, LEW rats were immunized either with partially purified basolateral or brush border membrane vesicles. Both immunogens produced glomerular immunopathology and pathophysiology identical in magnitude and time course to that seen in Heymann nephritis. Antibodies eluted from the kidneys of rats immunized with either antigen preparation stained the brush border in vitro. However, circulating anti-brush border antibodies were in significant titers only in rats immunized with brush border vesicles, whereas antibodies that stained the cytoplasm of both proximal and distal tubules predominated in rats immunized with basolateral membranes. With the onset of proteinuria, rats immunized with brush border membranes developed the proximal tubule pathology of Heymann nephritis. In rats immunized with basolateral membranes, the brush border and apical aspect of proximal tubule cells remained essentially normal. However, defects of basolateral membrane transport function were present, indicating that those defects need not necessarily be secondary to brush border damage. The dissociation of brush border damage from glomerular injury suggests that different antibody populations may account for each. Furthermore, anti-brush border antibodies may not account for all aspects of proximal tubule pathology in Heymann nephritis.
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PMID:Kidney immunopathology and pathophysiology in rats immunized with proximal tubule cell brush border or basolateral membrane vesicles. 331 82


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