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)

Gentamicin is a nephrotoxic agent known to damage the proximal tubule,--a site of low molecular weight (LMW) protein reabsorption and catabolism. The effect of gentamicin was investigated on three LMW proteins--amylase, light chains, and beta 2 microglobulin--and the effects were correlated on the latter to renal function as determined by creatinine clearance (GFR). The renal excretion of beta 2 microglobulin (beta 2M) was studied in 18 patients receiving gentamicin and eight control patients. Both gentamicin and control patients had similar mean ages and serum beta 2M. Twelve of the 18 gentamicin treated patients had marked increases in beta 2M excretion. The mean daily 2 beta microglobulin excretion for the gentamicin treated group was 10,511 microgram while that of the control group was 102 microgram. Serial determinations in 10 of the gentamicin treated patients revealed an increase in beta 2M excretion within 48 hours of starting therapy. No deterioration of GFR was seen in any patient. In four patients, beta 2M excretion decreased while still receiving gentamicin. The renal handling of amylase was found to be normal in four patients and mildly abnormal in three patients receiving gentamicin who also had increased beta 2M excretion. Urinary light chains were determined in four of these seven patients and found to be normal. It is concluded that gentamicin induces an early and often transient tubular proteinuria. This tubular proteinuria is not associated with clinical nephrotoxicity.
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PMID:The significance of beta-2 microglobulinuria associated with gentamicin therapy. 617 9

In contrast to healthy persons, microvillous antigens of the proximal tubule were excreted at an increased rate in patients with kidney diseases as could be shown using specific antisera against brush border (BB) fragments (tissue-proteinuria, histuria). These urinary membrane components were immunologically completely identical with those antigens prepared from isolated kidney cell membranes. A glycoprotein of 240 000 dalton, containing mannose and N-acetylglucosamine was identified as a major immunoreactive constituent of the brush border surface and found to be part of a multienzyme complex. BB-antigens were excreted in urine of patients with glomerulonephritis, hypertension, pyelonephritis, multiple myeloma, after operations, after kidney transplantation, under cytostatic treatment, and after administration of radiopaque agents. Histuria of BB-antigens was significantly higher in patients with multiple myeloma and Bence-Jones-proteinuria compared to those patients where no Bence-Jones L-chains in urine became apparent. Selective kidney angiography and intravenous urography caused a significantly higher output of BB-antigens as compared to the control period (2 p less than 0,005). In a volunteer model, on the basis of BB-histuria, a different nephrotoxic potency of cephalosporins and aminoglycosides arose. In addition, beside soluble BB-antigens, also high molecular weight membrane vesicles were discovered in urine of patients after cytostatic treatment (cis-platinum), after x-ray contrast media, and after kidney transplantation. Both, soluble as well as supramolecular membrane vesicles were isolated from urine applying immunospecific affinity chromatography (anti-BS-agarose beads). Labeled antisera directed against the vesicle material of urine revealed a specific immunofluorescence of cortical tubule only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunodiagnosis of kidney tubular cell injuries using specific anti-membrane antibodies]. 638 21

The brush border of the proximal tubule of human kidney consists of peripheral, integral as well as of transmembranous antigens. Peripheral (surface) antigens are associated with the presence of 5-7 nm globular particles sensitive to limited proteolysis; particles were found to contain a multienzyme complex and exhibited strong affinity towards ConA and WGA. PM-antigens can be solubilized from different portions of PM by differential treatment with proteases and detergents. Labelled antisera against isolated surface glycoproteins reveal a specific reaction with luminal PM of the proximal tubule only, supporting their value for quantitative image analysis (histometry) of kidney tissue sections and for screening of tissue-proteinuria. PM were capable of binding cationic serumproteins (esp. immunoglobulin) and certain O/K-antigens from E.coli, where adhesion was observed on peripheral and intrinsic PM-antigens as well. Major markers of the distal tubule are Tamm-Horsfall protein (cytoplasmic compartment) and a PNA-binding glycoprotein originating from the luminal PM. PM from renal adenocarcinoma exhibit not the globular surface structure found in renal PM, show low immunogenicity, a modulation in the glycosylation pattern of the marker gamma-Glu-transpeptidase and are characterized by a marked depletion of normally differentiated renal antigens. Due to solubilization experiments the presence of cryptic antigens are likely. In addition common determinants between cancer antigens and distinct proteins of the distal tubule and placental trophoblast became apparent.
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PMID:[Characterization of membrane antigens from human kidney and renal adenocarcinoma]. 639 70

The combined use of ultrastructural morphometry and X-ray microanalysis in conjunction with biochemical analysis is one approach to elucidating mechanisms of metal nephrotoxicity at the cellular level. Ultrastructural morphometry conducted on proximal tubule cells of rats exposed to low levels of methyl mercury for prolonged periods of time showed statistically significant increases in the volume densities of the lysosomal and mitochondrial compartments. These findings were associated with marked changes in lysosomal marker enzymes and mitochondrial heme biosynthesis enzymes leading to the detection of a renal porphyrinuria that occurred before changes in standard tests of renal function. Ultrastructural morphometry, X-ray microanalysis, and biochemical studies of the low-molecular-weight tubular proteinuria produced by injection of cadmium metallothionein (CdMT) showed a rapid proximal tubule cell lysosome uptake and degradation of the CdMT complex, which led to a subsequent decrease in the numerical density (Nv) and average diameter of lysosomes and to an increase in the Nv of apical pinocytolic vesicles with time. The data indicate disruption of the normal primary lysosome-pinocytolic vesicle fusion process and related development of tubular proteinuria. Ultrastructural techniques may provide information useful in elucidating mechanisms of ongoing metal-induced nephrotoxic processes when consideration is given to sampling strategies for morphometric analysis and the inherent detection limits, elemental volatility, translocation effects, and limitations of quantification for X-ray microanalysis in soft biological tissues.
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PMID:Role of ultrastructural techniques in understanding mechanisms of metal-induced nephrotoxicity. 661 93

Cadmium metallothionein (CdMT) nephrotoxicity was studied in rats injected i.p. with a single nonlethal dose of CdMT (0.6 mg of Cd per kg). Within 8 hr of CdMT injection, urine volume and urine sodium excretion were increased and sodium dodecyl sulfate gel electrophoresis of urine proteins showed that elevated levels of low molecular weight proteins were present in the urines of CdMT-treated rats. Urine RNAase activity was also elevated, approximately 7-fold, by CdMT but not by zinc metallothionein (ZnMT) or lysozyme at equivalent protein doses, demonstrating that a proteinuria indicative of proximal tubule cell dysfunction develops as an early response to CdMT exposure. Ultrastructural alterations were also present in animals injected with CdMT but not ZnMT or lysozyme. The earliest alterations occurred in the lysosome compartment of the cell. By 1 hr, the number of small lysosomes in renal proximal convoluted tubule cells increased significantly with no changes in other organelle compartments. By 4 and 8 hr, there was a further increase in lysosome number with a concomitant decrease in size and a marked increase in the number of small clear apical vacuoles. Lysosomal cathepsin D activity was decreased at 4 and 8 hr after CdMT injection, and in vitro studies indicated that this effect was not due to a direct inhibition of the enzyme by Cd++ or CdMT. Thus, both lysosome size and protease activity were rapidly altered by CdMT exposure. Studies of Cd binding in the kidney suggest that non-MT-bound Cd is an important factor in CdMT-associated toxicity. Approximately 97% of the Cd present in the cytoplasm at 1 hr was non-MT-bound. Prior induction of renal MT by treatment with zinc (20 mg of Zn per kg as ZnSO4, i.p. 16 hr before CdMT injection) markedly reduced non-MT binding of Cd++ in kidneys of treated animals and inhibited the alterations in urine volume and low molecular weight protein reabsorption induced by CdMT. These data suggest that acute CdMT exposure provides an excellent system for studying the mechanism of cadmium tubular proteinuria and that the intracellular renal MT pool plays a key role in regulating this process.
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PMID:Cadmium-Metallothionein nephropathy: relationships between ultrastructural/biochemical alterations and intracellular cadmium binding. 670 45

Protein excretion and protein fractions according to their molecular weight (SDS polyacrylamide-gelectrophoresis) were studied in the urine of male and female rats before and after castration. The polyacrylamide-gels were investigated qualitatively as well as quantitatively by densitometry. Male rats excrete considerably more protein in the urine than female rats. The values for the absolute protein quantity in 24-h-urine and the relative proteinuria (mg protein per 24 h and 100 g body weight) are five and three times higher, respectively, in males than in females. After castration proteinuria decreases significantly in both sexes, in males, however, more considerably (by about 75%) than in females (by about 30%), so that there is no significant difference in relative proteinuria between castrated males and females. The electrophoresis method used in this study allows to distinguish at least 10 to 11 protein fractions in the total urinary protein of both sexes within a molecular weight range from about 94.000 d to 14.000 d. Low molecular weight proteins (about 31.000 d to about 14.000 d) represent in both sexes the main part of the urinary protein. Females, however, excrete relatively more high molecular weight proteins (about 94.000 d to 60.000 d; about 25% of total urinary protein) than males (about 15% of total urinary protein). Concerning the relative parts in total urinary protein there are sex differences in all protein fractions, especially, however, in the fraction with a molecular weight of about 19.000 d (males more than 50%, females about 17% of total urinary protein). Castration causes in males more distinct changes in the relative parts of protein fractions in total urinary protein (drastic decrease of the 19.000-d-fraction) than in females. The results can be interpreted among other things in connection with a sex different handling of proteins in the proximal tubule of the rat kidney. The lysosomal catabolism of proteins in the proximal tubule is probably lower in males than in females, thus contributing to a higher proteinuria and a higher excretion especially of low molecular weight proteins in males in comparison with females.
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PMID:[Sex differentiated protein pattern in the urine of the rat following castration]. 672 23

The localization of various peptidases in the renal section of the rat was investigated histochemically, and their activities were determined fluorometrically in renal homogenate. The membrane-bound peptidases aminopeptidase A (APA), aminopeptidase M (APM), gamma-glutamyl-transferase (gamma-GT), dipeptidylpeptidase IV (DAP IV), and the lysosomal dipeptidyl peptidases I (DAP I) and II (DAP II) were investigated in male and female (estrus) rats both before and 30 days after castration. In addition, protein excretion and APA, APM, DAP I and DAP IV activities were measured in the urine of these animals. Histochemically, the membrane-bound peptidases are demonstrable mainly in the brush borders of the proximal tubules. In addition, APA and DAP IV are found in the glomeruli, gamma-GT and DAP IV in the thin descending limbs of the loops of Henle, and gamma-GT in the basal labyrinth of the S2 and S3 segments. The lysosomal peptidases are most concentrated in the S1 and S2 segments of the proximal tubule, in the distal tubule, and in certain cells of the connecting tubule and collecting duct, where they are contained in lysosomes of varying size. Sex differences and castration effects are demonstrable both histochemically and biochemically for the investigated peptidases. Histochemically these effects are most pronounced in the S3 segments for the membrane-bound peptidases, and in the lysosomes of the proximal tubule for the lysosomal peptidases. Biochemical tests in controls show significantly higher lysosomal peptidase activities in the renal homogenate of females than of males. After castration the lysosomal peptidase activities in males increase, approaching those of females. This appears to have bearing on the sex-dependent proteinuria in rats, for lysosomal peptidases and proteinases are particularly important in the degradation of filtered proteins that are reabsorbed in the proximal tubule. In females high lysosomal peptidase activities correlate with a low proteinuria, while males demonstrate lower lysosomal peptidase activities and a significantly higher proteinuria than females. After castration, the lysosomal peptidase activities and proteinuria in males approach those in females. Renal peptidases are also excreted in the urine, again with sex differences, and so these excreted peptidases contribute to the proteinuria in rats.
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PMID:Peptidases in the kidney and urine of rats after castration. 704 50

The sequential changes in renal morphology that occurred for 5 subsequent days after a subcutaneous injection of uranyl nitrate (10 mg. per kg.) were examined in saline- and water-drinking rats using light microscopy, transmission electron microscopy, and scanning electron microscopy. The cortical proximal tubule exhibited diffuse focal brush border loss and increased vacuolization by 1 hour after administration of the nephrotoxin. By 5 days, the P2 and P3 segments were completely necrotic. Cells of P1 segments accumulated large vacuoles throughout their cytoplasm, and distal nephron segments exhibited considerable cellular swelling and vacuolization. Scanning electron microscopy revealed abnormalities in glomerular epithelial cells similar to those seen in humans with chronic renal disease and in experimental animal models characterized by proteinuria. There was essentially no difference in the morphologic response of saline- and water-drinking rats. Although uranyl nitrate administered at this dosage resulted in the relatively slow development of tubular necrosis, changes in renal morphology could be seen within an hour and progressed insidiously throughout the study with little evidence of regeneration.
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PMID:Morphologic changes in uranyl nitrate-induced acute renal failure in saline- and water-drinking rats. 706 22

During the last decade enormous progress has been made in the study of the ultrastructure of the glomerular capillary wall, the mechanism of protein filtration and excretion, and the pathophysiology and biochemistry of proteinuria. However, current knowledge concerning each of these problems is incomplete. Nonetheless the mechanisms of proteinuria can be categorized, using available biochemical measurements of plasma and urinary proteins, into four groups of causes. The mechanism most commonly underlying proteinuria is a defect of glomerular permeability but proteinuria may also result from the presence in the plasma of high concentrations of low molecular weight protein, failure of the proximal tubule to reabsorb protein filtered by the normal glomerulus, and protein derived from the renal parenchyma. Glomerular proteinuria may cause the nephrotic syndrome or may persist without symptoms. Investigation and follow-up of persistent asymptomatic proteinuria is important although the natural history of this condition is still uncertain.
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PMID:Symptomless abnormalities proteinuria. 707 61

Renal changes following hypophysectomy are investigated. Particular attention is given to sex differences in the ultrastructure of proximal tubule cells and in protein excretion. Regardless of gender, hypophysectomy is followed by an increase in urine volume. However, there is a concomitant reduction of proteinuria, which is much more pronounced in males than in females. Partial hypophysectomy with anterior pituitary function preserved also leads to increased urine excretion, but does not alter proteinuria. In both sexes there is a reduction of the tubule circumference, which again is more pronounced in males thereby moderating the sex difference. The proximal tubule cells display a segment- and sex-independent reduction in surface area, a decrease of Golgi areas and reduction of ribosomes. Mitochondrial changes (condensation of cristae) selectively affect the S3 segment. The changes in the lysosomes and microbodies are segment- and sex-dependent. The volume density of microbodies in the S3 segment increases considerably, particularly in females. The volume density of lysosomes undergoes an increase in the S1 cells of the males and a decrease in the S2 cells. In the females the volume density of these organelles shows little change in these tubule segments; a sex-dependent difference is not longer apparent in the S1 and S2 segments. By contrast, in S3, there is an increase in the volume density of lysosomes in both sexes. The present study confirms a connection between the morphology of lysosomes in the proximal tubule and proteinuria. The findings also point to a possible involvement of male sex hormones in the reabsorption of protein in the renal proximal tubule.
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PMID:Sex-dependent changes in the rat kidney after hypophysectomy. 722 15


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