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)

Adriamycin (ADR), selectively toxic to glomerular epithelial cells, was administered (5 mg/kg BW, i.v.) to MWF/Ztm rats to study its early effects on glomerular barrier function with respect to albumin and high molecular weight (HMW) proteins. After 7 days of ADR incubation (glomerular filtration rate remains unchanged), protein excretion was significantly increased in treated rats. The proteinuria was due to a nonselective glomerular lesions resulting in an increase in both, but not a changed ratio of HMW proteins to albumin. However, this ADR-induced proteinuria seen in the final urine was not confirmed by free-flow micropuncture studies of superficial glomeruli. The albumin and HMW protein concentrations in samples taken from Bowman's capsular space of ADR-treated rats did not significantly differ from control samples. These data suggest that cortical nephrons are less sensitive to ADR than juxtamedullary nephrons.
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PMID:Heterogeneity of glomerular barrier function in early adriamycin nephrosis of MWF rats. 320 83

The effect of steroids, heparin and specific PAF-acether antagonists (BN 52021 and triazolobenzodiazepines) on proteinuria and renal histological changes induced in rats by adriamycin was studied. Adriamycin evoked a marked proteinuria that was unaffected by methylprednisolone and slightly reduced by heparin. In contrast, adriamycin-injected rats treated with PAF-acether antagonists had a low proteinuria, if any, and no ultrastructural glomerular alterations. These data suggest that PAF-acether could play a major role in the occurrence of proteinuria and that PAF-acether antagonists might provide a new therapeutic approach in certain human nephropathies.
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PMID:Role of platelet-activating factor in adriamycin-induced nephropathy in rats. 362 4

Adriamycin (ADR) induces glomerular damage in rats with persistent proteinuria which develops 13 to 15 days after a single intravenous (i.v.) injection (5 mg/kg). Electron microscopy (EM) shows alterations of glomerular visceral epithelial cells with foot process fusions. The disease resembles minimal change nephropathy in humans. We studied the effect of two isocaloric diets with different protein content on urinary protein excretion, renal function, and glomerular morphology in rats treated with ADR. Six groups of rats were used. Group 1 received a single i.v. injection of ADR and was fed a standard diet containing 20% protein. Group 2 was fed a low-protein diet containing 6% protein starting 7 days before ADR. Group 3 was fed a low-protein diet starting the day after ADR. Group 4 served as control. Two additional groups of rats (5 and 6) were used to study the kidney distribution of ADR. Unlike animals fed the standard diet, animals fed the low-protein diet did not develop proteinuria. The kidney distribution of ADR measured at different intervals after drug injection was not influenced by the diet. Renal function as determined by glomerular filtration rate (GFR) and renal plasma flow (RPF) was not significantly modified in nephrotic rats receiving the standard diet compared to control animals. The low-protein regimen induced a significant elevation in RPF compared to the standard diet, but had no influence on GFR. Light and transmission EM studies showed alterations of glomerular visceral epithelial cells with fusion of foot processes in rats fed the standard diet, whereas no significant abnormalities of glomerular epithelial cells were detectable in animals receiving the low-protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-protein diet prevents glomerular damage in adriamycin-treated rats. 404 23

Adriamycin has been suspected of causing experimental nephrotoxicity. We report here that adriamycin induces a nephrotic syndrome in rats, proteinuria beginning 4 to 5 days after a single intravenous injection (7.5 mg. per kg. of body weight). The full expression of the syndrome develops 13 to 15 days later. Minimal alterations at light microscopy, negative immunofluorescence, and only some focal "fusion" of foot processes can be observed by electron microscopy in the early phase after injection (28 hours). At 13 days, loss of foot process architecture, and replacement by flattened epithelial cytoplasm, was invariably found. These ultrastructural findings became extensive at 28 days follow-up. Colloidal iron staining of kidney biopsies revealed loss of glomerular polyanions as early as 3 hours and very marked loss at 28 hours after adriamycin injection. Polyanions were totally absent at 13 days and were still undetectable at 28 days. Thus, the loss of polyanionic charges associated with the sialic acid coat precedes the ultrastructural changes and the onset of proteinuria. These changes appeared similar to those reported in rats treated with daunomycin or puromycin animonucleoside. The present study supports in a different animal model the concept that both morphologic changes and proteinuria are the consequence of a common primary event that is the loss of glomerular fixed negative charges.
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PMID:Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. 617 62

Alterations in glomerular permeability were studied in Adriamycin-induced proteinuria in rats by measuring fractional clearances (C/GFR) of uncharged labeled dextrans of varying molecular radii (ae) and of anionic, native, and cationic horseradish peroxidases (HRP) in experimental and control animals. Experimental animals were studied between days 14 and 55 after a single intravenous dose of Adriamycin (doxorubicin), 7.5 mg/kg. Mean proteinuria in the experimental animals was 98 mg/24 hr. Glomerular morphology showed few changes except for epithelial cell swelling, vacuolization, and foot process obliteration, and a significant reduction of glomerular colloidal iron staining. Polyethyleneimine staining revealed a similar distribution of anionic sites in the laminae rarae interna and externa in proteinuric rats as compared with controls. Inulin clearances revealed reduction in GFR and RPF of 20 and 15%, respectively. Dextran C/GFR values showed in experimental animals a size defect for molecules with an ae exceeding 40 A, with a four- to fivefold increase over the values found in control animals for dextrans with ae of 58 and 60 A. The peroxidase clearances showed a slight increase in C/GFR of anionic HRP in experimental animals, as could be expected on the basis of the sieving defect, whereas the C/GFR values for native and cationic HRP were virtually unchanged, indicating an intact functional charge barrier in the proteinuric animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glomerular permeability and polyanion in adriamycin nephrosis in the rat. 619 86

Passive Heymann nephritis (PHN) is an experimental model of membranous glomerulopathy in the rat ascribed to in situ formation of immune complexes. Very recently the demonstration that the aminonucleoside of puromycin provides some protection against PHN has highlighted the role of intrinsic properties of the glomerulus in immune complex formation. Adriamycin, a widely employed chemotherapeutic agent, is known to induce a nephrotic syndrome in rats characterized by severe ultrastructural changes of glomerular epithelial cells and by loss of glomerular polyanionic charges. We have studied the effect of pre-treatment with adriamycin on glomerular immune deposits in PHN using immunomorphological and quantitative techniques. In normal rats (group 1) injection of heterologous antibodies to proximal tubular brush border antigen (anti-FxIA), rapidly induces subepithelial immune deposits, as observed by immunofluorescence. Pre-treatment of rats with adriamycin (group 2) 48 hr before injection of anti-FxIA antibodies, when proteinuria is absent, does not alter the immunohistological findings of PHN. Heavily proteinuric rats (group 3) pre-treated with adriamycin 13 days before injection of anti-FxIA did not show any significant difference from groups 1 and 2. Species binding of injected anti-FxIA antibodies, studied by paired label techniques, was similar in normal rats and in proteinuric and non-proteinuric rats treated with adriamycin. The only difference was in the group of proteinuric rats treated with adriamycin, in which at 5 hr binding in the kidney was higher, due to tubular brush border binding as shown by immunofluorescence. This study indicates that local changes of the glomerulus and loss of glomerular histochemical properties do not invariably alter the glomerular deposition of immune complexes.
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PMID:Severe glomerular epithelial cell damage does not prevent passive Heyman nephritis in rats. 633 25

Adriamycin induces a nephrotic syndrome in rats characterized by severe ultrastructural changes of visceral epithelial cells similar to those observed in puromycin aminonucleoside (PA) nephrosis and in human 'minimal changes' glomerulopathy. Since steroids have been shown to be effective in human 'minimal changes' glomerulopathy and in PA nephrosis, we undertook the present study to assess whether steroids had a therapeutic effect on adriamycin nephrosis. Groups of rats injected with different doses of adriamycin were subsequently treated with prednisolone. No significant differences were observed in proteinuria and in ultrastructural findings between the control and the steroid-injected animals. This study suggests that the mechanism underlying adriamycin-induced nephrotic syndrome might be different from that responsible for PA nephrosis or human 'minimal changes' glomerulopathy.
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PMID:Steroids and Adriamycin nephrosis. 652 17

Adriamycin induced hyperlipemia: its features and mechanism(s) in rats were investigated. Massive hyperlipemia occurred 14-21 days after a single dose of adriamycin (7.5 mg/kg i.v.). All lipoprotein fractions were affected. Mild but significant changes in tissues were observed (liver and intestine triglycerides and kidney phospholipids were reduced). Lipid synthesis and secretion was decreased, as shown by the Triton WR1339 test 7 days after treatment, but subsequently returned to normal. Mitochondrial oxidation of long-chain fatty acids was markedly reduced in kidney, and a slight reduction was also observed in heart. Lipoprotein lipase activity was reduced in adipose tissue. These results suggest that adriamycin hyperlipemia is due to reduced lipid storage and utilization. Carnitine did not counteract hyperlipemia and proteinuria after adriamycin. Analogies to hyperlipemia following puromycin aminonucleoside-induced nephrotoxicity are discussed.
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PMID:Adriamycin causes hyperlipemia as a consequence of nephrotoxicity. 666 4

To determine whether preexistent glomerular injury and the nephrotic syndrome increase renal susceptibility to ischemic renal injury, normal rats and rats with either experimental minimal-change disease (Adriamycin nephropathy) (AN) or membranous nephropathy (passive Heymann nephritis) (PHN) underwent renal functional and histologic studies under either basal conditions or 18 h after bilateral renal artery occlusion (over 30 min). Prior to renal ischemia AN and PHN rats had minimally depressed glomerular filtration rate (GFR), normal (AN) or increased (PHN) renal blood flow (RBF), heavy proteinuria, hypoalbuminemia, decreased urine sodium excretion, extensive glomerular foot process fusion, and intratubular hyalin cast formation. Losses of GFR in response to ischemia were comparable among the three groups of rats (controls, 0.29; AN, 0.28; PHN, 0.25 ml X min-1 X 100 g body wt-1) despite prevailing differences in postischemic hemodynamics. Neither light nor transmission electron microscopy showed any differences in the degree of ischemic renal injury. These results suggest that 1) glomerulopathy and the nephrotic syndrome do not significantly increase renal susceptibility to ischemic renal injury; 2) the syndrome of acute renal failure that occurs in patients with minimal-change glomerulopathy is not due to a marked susceptibility of these kidneys to clinically occult ischemic events; and 3) foot process fusion is probably not a pathophysiologically significant lesion in ischemic acute renal failure, as previously suggested.
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PMID:Glomerulopathy does not increase renal susceptibility to acute ischemic injury. 670 61

We have measured the response to arachidonic acid (AA) in platelet-rich plasma (PRP) of rats with Adriamycin-induced nephrotic syndrome. For this purpose we measured the kinetics of generation of malondialdehyde (MDA), a stable product of cyclooxygenase activity, in response to platelet stimulation with different concentrations of the substrate. The apparent Km of platelet cyclo-oxygenase for AA was similar in PRP from control rats and rats treated 1-5 days previously, whereas it was significantly reduced, as compared to controls, in PRP of rats treated 2-5 weeks previously. Such a difference was not observed when washed platelet suspensions were tested instead of PRP. Experiments with crossed platelet/plasma systems indicated that in rats treated from 2-5 weeks, a plasmatic abnormality was indeed responsible for the increased affinity of platelets for AA. It is conceivable that in this nephrotic syndrome model characterized by heavy proteinuria, some plasmatic component would be lost with the urine which is normally modulating the platelet response to AA. The observed increase in platelet affinity for AA could at least partially contribute to the enhanced thrombotic tendency reported in the same experimental model.
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PMID:Enhanced affinity for arachidonic acid in platelet-rich plasma from rats with Adriamycin-induced nephrotic syndrome. 681 45


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