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)

Rats with a nephrotoxic serum nephritis reveal changes of proteinuria and content of serum proteins as well as serum cholesterol in the direction of a nephrotic syndrome as is seen after Daunomycin. Nevertheless, the morphological findings with TEM and especially with SEM are quite different. A striking feature of the nephritis is the rather good preservation of cell processes through all the time of experiment in spite of the elevated proteinuria. Moreover, podocytes with furrowed or ribbed surfaces originate and are most numerous when the signs of inflammation are most pronounced. These furrowed podocytes are interpreted as representing a special reactive, perhaps mobilized form. With SEM it is evident that the glomeruli are altered focally and segmentally in the nephrotoxic serum nephritis.
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PMID:Podocytes of rat kidneys with nephrotoxic serum nephritis. A combined transmission and scanning electron microscopic study. 121 24

Female CBA/H-T6T6 mice were given daily i.p. injections of 1 ml of saline containing 250 mg of human serum albumin (HSA) for 7 consecutive days. Control mice received the same volume of saline only. At approximately 24 hourly intervals for the 10 days after the first injection, groups of mice (3 HSA and 1 saline-injected) were killed and kidney tissue was taken for light (LM) scanning (SEM) and transmission (TEM) electron microscopy. Small numbers of glomeruli with Bowman's space filled with protein and fine, radially-disposed casts in collecting tubules were observed by LM. SEM revealed focal changes in both endothelium and epithelium, and in a few cases severely damaged epithelial cells were seen. TEM showed numerous small regions of loss or change in shape of foot processes. Epithelial cell branches became increasingly swollen. By the third day after the last injection glomerular morphology appeared to have returned to normal. Although the cause of the proteinuria was attributed to the effects of HSA-induced increased blood viscosity, the focal distribution of the observed morphological changes remains unexplained.
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PMID:Morphological changes in the kidneys of mice with proteinuria induced by albumin-overload. 661 9

Female Wistar strain rats injected intraperitoneally with 1 g of BSA per day for 5 days, a total of 5 g of BSA, developed heavy proteinuria. Characteristic morphological abnormalities were seen by both TEM and SEM in the large majority of glomeruli from these animals and were similar overall, but not identical to, those seen in puromycin aminonucleoside nephrosis. The heterologous protein overload model seems to present considerable opportunity for study of the basic mechanisms of glomerular visceral epithelial cell handling of protein.
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PMID:A scanning and transmission electron microscopic study of glomerular damage in the rat following heterologous serum albumin overload. 728 27

Complement-independent nephritis was induced in rats by intravenous injections of duck anti-rat nephrotoxic serum (DNTS). The kidneys were examined by light and immunofluorescent microscopy, plus electron microscopy (SEM and TEM) at 15, 30 and 60 minutes and on days 1 and 5. Additional experiments included pretreatment with heparin sulfate prior to DNTS and perfusion experiments 24 hours following DNTS using normal saline and heparin sulfate. Light microscopy demonstrated no increase in inflammatory cells. Immunofluorescent microscopy showed only linear staining against duct anti-rat immune globulin. TEM and SEM showed glomerular capillary wall changes at 24 hours which correlated roughly with the level of proteinuria and varied from minimal changes, grade I, to severe foot process effacement and partial detachment of endothelium and epithelium, grade III. Pretreatment with heparin sulfate exaggerated the severity of the Grade III changes. Perfusion of DNTS rats with normal saline result in detachment of loosened podocytes. Perfusion of DNTS rats with heparin sulfate resulted in severe podocyte detachment. Examination of DNTS rats on day 5 revealed reversion to normal structure. SEM and TEM complemented each other in demonstrating the unusual DNTS induced phenomenon of weakened cell attachment unrelated to classical complement and inflammatory cellular mechanisms.
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PMID:SEM of complement-independent nephrotoxic nephritis. 741 78

A mouse model for the autosomal form of Alport syndrome was produced. These mice develop a progressive glomerulonephritis with microhematuria and proteinuria, consistent with the human disease. End-stage renal disease develops at approximately 14 weeks of age. TEM analysis of the glomerular basement membranes (GBM) during development of renal pathology revealed focal multilaminated thickening and thinning beginning in the external capillary loops at 4 weeks and spreading throughout the GBM by 8 weeks. By 14 weeks, half of the glomeruli were fibrotic with collapsed capillaries. Immunofluorescence analysis of the GBM showed the absence of type IV collagen alpha-3, alpha-4, and alpha-5 chains and a persistence of alpha-1 and alpha-2 chains (these chains normally localize to the mesangial matrix). Northern blot analysis using probes specific for the collagen chains illustrate the absence of COL4A3 in the knockout, whereas mRNAs for the remaining chains are unchanged. An accumulation of fibronectin, heparan sulfate proteoglycan, laminin-1, and entactin was observed in the GBM of the affected animals. The temporal and spatial pattern of accumulation was consistent with that for thickening of the GBM as observed by TEM. Thus, expression of these basement membrane-associated proteins may be involved in the progression of Alport renal disease pathogenesis. The levels of mRNAs encoding the basement membrane-associated proteins at 7 weeks were unchanged.
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PMID:Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome. 895 99

To investigate how the interruption of the renin-angiotensin system (RAS) and reduction of blood pressure (BP) affect the lesions of chronic focal and segmental glomerulosclerosis (FGS), we studied the effects of high and low doses of angiotensin-converting enzyme inhibitors (temocapril - TEM) a newly developed ACE inhibitor with biliary tract excretion, on the hypertensive model of FGS. A high dose of TEM significantly lowered BP and suppressed both intense proteinuria and glomerular extracapillary lesions including macrophage infiltration. On the other hand, although a low dose of TEM did not significantly lower BP throughout the experimental period, it prevented renal lesions almost in the same manner as high-dose TEM with suppression of c-myc gene expression in glomeruli. These findings suggest that in PAN-induced chronic FGS, the systemic BP elevation could not be the major factor for the progression of renal damage which TEM could prevent without significant lowering of BP.
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PMID:Significant suppressive effect of low-dose temocapril, an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats. 1112 99

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP.
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PMID:Effects of exercise training on glomerular structure in fructose-fed spontaneously hypertensive rats. 1471 83

Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.
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PMID:Lipoprotein X Causes Renal Disease in LCAT Deficiency. 2691 98

Salt-sensitive (SS) hypertension is accompanied with an early onset of proteinuria, which results from the loss of glomerular podocytes. Here, we hypothesized that glomerular damage in the SS hypertension occurs in part due to mitochondria dysfunction, and we used a unique model of freshly isolated glomeruli to test this hypothesis. In order to mimic SS hypertension, we used Dahl SS rats, an established animal model. Animals were fed a 0.4% NaCl (normal salt, NS) diet or challenged with a high salt (HS) 4% NaCl diet for 21 days to induce an increase in blood pressure (BP). Similar to previous studies, we found that HS diet caused renal hypertrophy, increased BP, glomerulosclerosis, and renal lesions such as fibrosis and protein casts. We did not observe changes in mitochondrial biogenesis in the renal cortex or isolated glomeruli fractions. However, Seahorse assay performed on freshly isolated glomeruli revealed that basal mitochondrial respiration, maximal respiration, and spare respiratory capacity were lower in the HS compared to the NS group. Using confocal imaging and staining for mitochondrial H2O2 using mitoPY1, we detected an intensified response to an acute H2O2 application in the podocytes of the glomeruli isolated from the HS diet fed group. TEM analysis showed that glomerular mitochondria from the HS diet fed group have structural abnormalities (swelling, enlargement, less defined cristae). Therefore, we report that glomerular mitochondria in SS hypertension are functionally and structurally defective, and this impairment could eventually lead to loss of podocytes and proteinuria. Thus, the glomerular-mitochondria axis can be targeted in novel treatment strategies for hypertensive glomerulosclerosis.
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PMID:Renal Glomerular Mitochondria Function in Salt-Sensitive Hypertension. 3211 33