Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The exact role of urinary proteins in kidney stone formation remains an area of controversy. Some investigators believe that urinary proteins are selectively incorporated within urinary calculi and as such have an active role in stone formation. Other investigators believe that urinary proteins are nonspecifically adsorbed into urinary crystals and thus have only a passive role in stone formation. In the current investigation a previously described stone-forming animal model (hyperoxaluric rat) was utilized along with an animal model for renal tubular injury (gentamicin nephrotoxicity) in an effort to clarify the role of urinary proteins in kidney stone formation. Urine specimens were collected before and after the induction of stone formation and after the induction of renal tubular injury. The purified proteins from each urine specimen were separated in two dimensions by electrophoresis resulting in a characteristic "map" of protein spots for each urine specimen. All animals in the stone-forming group had pathologic evidence of early stone formation (diffuse intranephronic calculosis). Early stone formation was consistently associated with a reduction in the excretion of low molecular weight urinary proteins (30,000 dalton and less than 20,000 dalton ranges). Alcian blue staining confirmed the presence of matrix within clumps of intranephronic calcium oxalate crystals. Renal tubular injury was associated with an increase in the excretion of low molecular weight proteins (approximate 20,000 dalton range) consistent with classical tubular proteinuria. These results suggest that low molecular weight urinary proteins are selectively incorporated within the crystalline structure of the stone early during its formation.
 ...
PMID:The evaluation of urinary protein patterns in a stone-forming animal model using two-dimensional polyacrylamide gel electrophoresis. 200 20

Compensatory renal and glomerular hypertrophy accompanies the many functional and structural changes associated with a reduction in functional renal mass. Increased levels of dietary sodium supplementation ranging from deficient to 2.3% Na+ (38-fold above the minimal daily requirement for the rat) in rats with subtotal nephrectomy were associated with a progressive rise in proteinuria and renal size without any significant change in arterial pressure. To further define these relationships, groups of rats on two intermediate levels of sodium intake were studied in detail. Single-nephron filtration rate and glomerular capillary pressure were similar in subtotally nephrectomized rats fed the 0.06 and 0.46% Na+ diets. Both the volume fraction and absolute volume of periodic acid-Schiff staining mesangial lesions in the glomerulus were greater in the 0.46% Na+ group. Glomerular volume and the mean glomerular capillary radius was larger in the 0.46% Na+ group. Increased glomerular tension, as predicted by the Laplace law, may represent a final common pathway by which compensatory growth and/or glomerular hypertension result in glomerular injury.
 ...
PMID:Adverse effects of growth in the glomerular microcirculation. 233 56

Morphologic studies were performed in a passive model of in situ immune complex glomerulonephritis in rats. The formation and fate of subepithelial immune complexes as well as the role of glomerular polyanion in the induction of disease were examined. Unilateral in situ immune complex glomerulonephritis was induced in rats by perfusion of cationised horse spleen ferritin (pI greater than 9.5) (400 micrograms/rat) into the left kidney followed by systemic injection of 0.2 ml (= 400 micrograms precipitating antibody) of sheep anti-ferritin antiserum 2 h later. This schedule induced glomerulonephritis with proteinuria (mean maximum 100 mg/24 h between the 5th and the 12th day). Rats were sacrificed at intervals between 1 h and 42 days after induction of glomerulonephritis, samples of renal tissue were examined by light, immunofluorescence and electron microscopy (including staining of anionic sites by polyethyleneimine). The lesion induced closely resembled that of membranous glomerulonephritis in man as massive subepithelial deposits were seen with very little cellular infiltration or proliferation. The antigen (ferritin) deposits were initially located subepithelially; from 2 weeks onwards intramembranous deposits in the thickened basement membrane were present, the apparent translocation being due to excessive newly synthesised basement membrane material which encloses the deposits. A loss of anionic sites in the lamina rara interna, lamina rara externa and on the epithelial cell surface coat preceded the development of proteinuria.
 ...
PMID:Ultrastructural studies in passive in situ immune complex glomerulonephritis. A rat model for membranous glomerulonephritis. 248 73

This paper reviews experimental findings which support the concept that vasopressin (VP) and the process of urine concentration may be involved in the progression of chronic renal failure (CRF). The influence of dietary protein intake on the progression of CRF may also involve VP and the operation of the concentrating process. VP receptors have been identified in glomeruli and VP is able to constrict mesangial cells as does angiotensin II. Acute VP infusion increases the glomerular transcapillary hydraulic pressure difference, and chronic VP infusion increases GFR. In rats with CRF (induced by 5/6 nephrectomy), VP levels were found elevated. In rats with 5/6 nephrectomy, we increased experimentally water intake in order to decrease circulating VP levels, urine concentration, and free water reabsorption. Several indices of progression of CRF, including proteinuria, hypertension and glomerulosclerosis, were significantly reduced, thus suggesting a contribution of VP in progression. Lowering protein intake in CRF could be beneficial because proteins, but not carbohydrates or lipids, produce metabolic end products (mainly urea, ammonia, protons, etc.) that are excreted by the kidney, and concentrated in the urine. In healthy subjects (man or rat), high protein (HP) intake favors urine concentration and causes changes in kidney function and morphology very similar to those induced by chronic VP infusion or water restriction. These changes involve an increase in transport activity of the thick ascending limb (where the initial active step of the concentrating process takes place) and may affect filtration rate and/or glomerular hemodynamics secondarily, by decreasing salt concentration at the macula densa and depressing tubuloglomerular feedback.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Possible involvement of vasopressin and urine concentrating process in the progression of chronic renal failure. 270

The fawn-hooded rat (FH rat) develops hypertension accompanied with focal and segmental glomerulosclerosis and proteinuria, resulting in premature death. In a first experiment the relationship between renal lesions and blood pressure at various ages was investigated. In a second experiment blood pressure was measured weekly from 10 to 38 weeks of age in a number of male FH rats, followed by examination of renal tissues at 40 weeks of age. Plasma renin activity (PRA) had also been determined in individual FH rats. FH rats aged 4.5 weeks had no renal morphological abnormalities. The severity of the glomerulosclerosis increased with age and showed a positive relationship with blood pressure. The scores of the proteinaceous tubular casts also increased with age and they, too, showed a positive correlation with blood pressure. The severity of glomerulosclerosis and proteinaceous casts at 40 weeks of age was related positively to the course of blood pressure throughout life. The final blood pressure level showed a positive correlation with final PRA values. Only FH rats with malignant nephrosclerosis had high PRA values. The renal glomerular and vascular lesions in the FH rat, most likely caused by the hypertension, progressively deteriorate to malignant nephrosclerosis. At that stage PRA values are increased and may be contributing to the development of renal vascular lesions and acceleration of the hypertension.
 ...
PMID:Relationship between blood pressure level, renal histopathological lesions and plasma renin activity in fawn-hooded rats. 355 93

Alterations of glomerular basement membrane (GBM) anionic (charge sites, CSs) in the development of proteinuria in a model of idiopathic nephrotic syndrome in man (puromycin aminonucleoside nephrotic syndrome [PAN] in the rat) were assessed quantitatively and sequentially early after disease induction. GBM CSs (known to consist mainly of heparan sulfate-rich proteoglycans) were stained in vivo and, in a separate group of animals by an in vitro method, with the cationic marker polyethyleneimine (PEI) studied by electron microscopic examination. Four hours after administration of PAN, there was a significant decrease in GBM lamina rara externa CSs: 18 +/- 0.7 versus 22.0 +/- 2.2 per 1000 nm GBM in controls by PEI injection and 17.2 +/- 2.7 versus 21.1 +/- 1.6 per 1000 nm GBM in controls by PEI in vitro staining. This CS alteration coincided with changes in glomerular epithelial cell morphologic characteristics (increased cytoplasmic organelles and rough endoplasmic reticulum) and preceded the detection of foot process broadening (at 24 hours) and increased urinary albuminuria (suggested at 12-24 hours, statistically significant at 36-48 hours). These results suggest that GBM CS-heparan sulfate proteoglycan alterations consisting of either decreased number and/or less anionic charge occur early in PAN and support a role for glomerular epithelial cell maintenance of GBM CS for normal glomerular function.
 ...
PMID:Glomerular basement membrane anionic charge site changes early in aminonucleoside nephrosis. 378 94

1 The effects of aspirin, prednisolone, and indomethacin on nephrotoxic serum nephritis in rats was studied. The nephritis was induced by a single intravenous injection of nephrotoxic serum (NTS, rabbit anti-serum against the water-soluble renal antigen of the rat). The injection of NTS induced the heterologous phase of proteinuria (within a day after NTS injection) and then the autologous phase (5 to 7 days after NTS injection). The effect of drugs given before the NTS (i.e. prophylactically) or after the NTS (i.e. therapeutically) was investigated. 2 Aspirin, which was given orally at doses of 150 and 250 mg/kg daily from the day before NTS injection, suppressed the development of proteinuria in both the heterologous and the autologous phase, and lowered the serum cholesterol level towards the normal level. Aspirin (250 mg/kg daily, orally) had no significant effect against the established proteinuria in the autologous phase. 3 Prednisolone, which was given orally at doses of 3 and 5 mg/kg daily from the day before NTS injection, elevated the proteinuria in the heterologous phase, while inhibiting the development of proteinuria in the autologous phase. Prednisolone (5 mg/kg daily, orally) was ineffective against established proteinuria in the autologous phase. 5 Indomethacin (3 mg/kg daily, orally) did not exert any significant effect on proteinuria in either the heterologous or the autologous phase.
 ...
PMID:Effects of aspirin, prednisolone and indomethacin on nephrotoxic serum nephritis in the rat. 707 88

Ulinastatin is a potent protease inhibitor purified from the human urine that has been used clinically to treat acute pancreatitis and circulatory shock. In the current study, we evaluated the therapeutic effects of Ulinastatin in a rat model of crescentic glomerulonephritis (CrGN) and investigated its putative mechanisms. Wistar-Kyoto rats were injected with nephrotoxic serum and received daily intraperitoneal injection of Ulinastatin. Ulinastatin treatment significantly reduced proteinuria and glomerular crescentic formation. Moreover, glomerular infiltration of neutrophils and ED1+ cells (monocytes/macrophages) was significantly suppressed by Ulinastatin. In contrast, the glomerular deposition of heterologous (rabbit) and autologous (rat) antibodies was not changed. Neither serum complement activation nor the anti-rabbit immune response was affected by Ulinastatin administration. Our results suggest that Ulinastatin has preventive effects on rat experimental CrGN, mediated at least in part by inhibiting intraglomerular infiltration of inflammatory cells.
 ...
PMID:Therapeutic effects of ulinastatin on experimental crescentic glomerulonephritis in rats. 1075 12

Adenovirus (Ad)-mediated gene transfer of immunoregulatory molecules prevents acute allograft rejection. It is here analyzed for the first time whether this approach may prevent the development of chronic renal allograft injury in rats. Renal allografts (F344-->Lewis rat) were ex vivo transduced in group I with control Ad-construct, group II with three different therapeutic Ad-constructs expressing the immunoregulatory molecules vIL-10, TNFRp55-Ig, and IL-12p40, and group III with AdIFN-gamma. Group IV served as untreated controls. Control grafts (IV) showed increasing proteinuria during the 24-wk follow-up. Chronic graft injury was accelerated by Ad-control (I) and even more by AdIFN-gamma (III). All rats carrying the AdIFN-gamma-transduced grafts died within 12 to 13 wk by advanced chronic renal failure associated with strong immune cell infiltration and immune gene expression. By contrast, the Ad-therapy group II showed less inflammation and improved graft histology and function if compared with the groups I and III. Moreover, significantly less infiltrating ED-1(+) macrophages and an improved histologic score even if compared with untreated controls (IV) was observed. However, after disappearance of therapeutic gene expression, group II showed increasing proteinuria probably as result of late T cell activation to the Ad-encoded proteins. Ex vivo transduction of allografts with Ad-control or even more AdIFN-gamma expression promotes intragraft inflammation and chronic graft injury. Targeting macrophage activation by a cocktail of therapeutic genes improved the results. These data support the pathogenetic role of cytokines in chronic graft injury; however, they also show the limitations of the Ad-mediated gene transfer.
 ...
PMID:Targeting of macrophage activity by adenovirus-mediated intragraft overexpression of TNFRp55-Ig, IL-12p40, and vIL-10 ameliorates adenovirus-mediated chronic graft injury, whereas stimulation of macrophages by overexpression of IFN-gamma accelerates chronic graft injury in a rat renal allograft model. 1250 54

After renal transplantation, persistent glomerular disease affecting the native kidneys typically causes albuminuria, at least for a period of time, making it difficult to determine in a noninvasive fashion whether proteinuria originates in the native kidneys or the renal allograft. To address this problem, dynamic contrast-enhanced magnetic resonance imaging (MRI) using gadolinium (Gd)-based albumin-bound blood pool contrast agent (MS325) to localize proteinuria was investigated. Glomerular proteinuria was induced in Sprague-Dawley rats by intravenous injection of puromycin aminonucleoside (PAN), whereas control rats received physiologic saline vehicle. Both groups of animals underwent a 40-min dynamic contrast-enhanced MRI using radio frequency spoiled gradient echo imaging sequence after injection of Gd-labeled MS325. Contrast uptake and clearance curves for cortex and medulla were determined from acquired MR images. Compared with controls, proteinuric rats exhibited significantly lower elimination rate constants. The use of gadopentetate dimeglumine (Gd-DTPA) as a contrast agent showed smaller and less specific differences between proteinuric and control groups. In rats with one proteinuric kidney (PAN-treated) and one normal kidney (transplanted from a normal rat), MRI using MS325 was able to differentiate between the two kidneys. The results suggest that MRI with an albumin-bound blood pool contrast agent may be a useful noninvasive way to localize proteinuria. If this technique can be successfully applied in human patients, it may allow for the localization of proteinuria after kidney transplant and thereby provide a noninvasive way to detect disease affecting the renal allograft.
 ...
PMID:Detection and localization of proteinuria by dynamic contrast-enhanced magnetic resonance imaging using MS325. 1587 75


1 2 Next >>