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)

The nephrotoxicities of gentamicin and three other experimental aminoglycosides were compared at a single 60 mg. per kilogram per day dose in rats. Renal function, lysosomal enzymuria, and antibiotic concentrations in plasma, urine, and renal tissue were measured at regular intervals throughout the course of treatment. Kidney tissue was examined by light and electron microscopy in animals killed at intervals throughout the period of antibiotic administration. Proteinuria and enzymuria were early indicators of nephron dysfunction, whereas endogenous creatinine clearance declined later in the course of treatment. All animals were killed 24 hours after a previous antibiotic injection and displayed sustained renal tissue antibiotic concentrations which were 5 to 10 times higher than those in serum or urine. When assayed separately, renal cortical tissue had a fivefold greater antibiotic concentration than renal medulla. Light microscopy displayed necrosis of the pars convoluta of the proximal tubule. Electron microscopy revealed appearance of cytosegrosomes with myeloid bodies. It is possible that impaired cytoplasmic degradation of sequestered organelle membranes, resulting from aminoglycoside accumulation, is responsible for the myeloid body formation and subsequent tubular necrosis.
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PMID:Experimental aminoglycoside nephrotoxicity. 16 76

The amount of forming pinocytic (coated) microvesicles on the apical plasma membrane of kidney proximal tubule cells was assessed in kidney biopsies of 10 patients suffering from chronic glomerulonephritis. A significant correlation was found between the amount of these vesicles and diurnal proteinuria levels (r = 0.889; p less than 0.01). The possible mechanisms of protein reabsorption via pinocytosis in both normal and pathological conditions are considered.
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PMID:Possible role of the proximal convoluted tubules of human kidney in chronic glomerulonephritis. A quantitative electron-microscopic study. 20 14

The study of renal function, primarily the tubular function, in 55 patients with idiopathic, recurrent renal stones showed a large number of abnormalities. 49% of the patients, especially the women were affected. The most common defect was a reduced acidification capacity of varying degrees of severity in 64% of the woman and in 20% of the men. Impairment of the acidification capacity of the distal tubule was found in 18% and of the proximal tubule in 11% of the patients. Inability to dilute the urine after water loading was found in 17% and tubular proteinuria also in 17% of the patients. Most patients with an impaired tubular function had a severe stone disease. The defects in acidification and dilution capacity ought to be of pathogenetic importance for stone formation and should be considered in the selection of preventive therapy.
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PMID:Tubular defects in patients forming calcium-containing stones. 34 51

The appearance of an acute renal insufficiency in the rabbit, after glycerol injection (10, 13 or 15 ml/kg of a 50% solution) is investigated. After a 24 hours of intoxication, especially in the ten following days, cylinders, erythrocytes and renal cells appear in the urine sediment. Proteinuria appears after 24 hours and practically disappears after 72 h. Glucosuria persists from 24 hours to 6 days. Haemoglobinuria is intense after 24 and 48 hours and persists slightly about 6 days. Na, K and Cl elimination in urine diminishes clearly in all animals. Plasma K increases in non-surviving animals and does not change in those surviving. Plasma Na does not change in the dying ones, and decreases in those surviving. In non-surviving animals, pH, pCO2 and CO3H minus decrease sharply. In the surviving ones pCO2 decreases clearly after 24 hours, increasing afterwards slowly to normal values. pH increases, slightly during the first 48 hours, and then neatly during approximately 6 days. Standard CO2H minus does not change during the first 48 hours, increasing afterwards during 6 to 7 days. Histologically, the chief lesion is a vacuolar degeneration of the proximal tubule. The possible mechanisms of such alterations are discussed.
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PMID:Acute renal insufficiency in the rabbit by glycerol. 116 59

Angiotensin-induced proteinuria was examined at the glomerular-tubular level in rats. Ultra-micro-disc electrophoresis was employed to determine albumin concentration of rat proximal tubular fluid samples under control conditions and during the infusion of 0.15 mug/min X 100 g body weight angiotensin II using micropuncture techniques. Under control conditions proximal tubular albumin concentration was 1.32 +/- 0.79 (SD) mg/100 ml (n = 71). There was no correlation between albumin concentration and (TF/P)-inulin ratio indicating an albumin reabsorption in the proximal tubule parallel to fluid reabsorption under control conditions. During angiotensin infusion using re-collection techniques, there is an average increase of 26 times in tubular albumin concentration, indicating an increase in albumin filtered. There was no change in GFR, SNGFR, transit time, (TF/P)-inulin ratio, an increase in urine flow rate, sodium excretion, protein excretion, mean arterial blood pressure during angiotensin infusion. Since effective glomerular filtration pressure was not increased during angiotensin it is concluded that angiotensin-induced proteinuria is due to an increase in filtered protien mediated by a change in glomerular permeability to proteins.
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PMID:Effect of angiotensin on glomerular filtration of albumin. 123 90

Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were purified to homogeneity from pooled urine concentrate of patients with renal damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration (Superdex). Based on the specific enzyme activity of the starting material, dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The relative molecular masses, Michaelis constants and isoelectric points were determined. Negative staining of the purified enzymes revealed globular proteins (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A reacted specifically with tubular and, in the case of anti-angiotensinase A sera, with tubular and glomerular structures. In addition, urinary membrane vesicles of proximal tubule origin were eluted with the void volume (Superdex-gel filtration), indicating heavy epithelial cell disintegration. Both soluble tissue enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from epithelia contribute to proteinuria, as was shown in patients with glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for angiotensinase A, in patients with essential arterial hypertension.
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PMID:Biochemical and immunological properties of urinary angiotensinase A and dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell injury. 136 94

Iron, which has been shown to accumulate within proximal tubule lysosomes in proteinuric models of renal disease, may play a role in the progression of chronic renal disease by the generation of reactive oxygen species. Therefore, renal biopsies from humans with proteinuria and/or chronic renal failure were examined at an ultrastructural level for iron by energy dispersive analysis and compared with normal biopsies. Iron accumulated in proximal tubular lysosomes in renal disease (P < 0.05 v normals), accompanied in some cases by phosphorus and silicon. Both the number of iron-containing lysosomes per tubular cross-section (1.86 +/- 0.41 v 0.66 +/- 0.22, P < 0.05) and the mean concentration of lysosomal iron (254.5 +/- 73.4 mg/dL v 81.2 +/- 23.8, P < 0.001) was greater in patients with nephrotic syndrome (n = 12) than in those without (n = 8). Iron accumulation (number of iron-containing lysosomes/tubule) correlated with protein excretion (r = 0.68, P = 0.003, n = 20), but not with glomerular filtration rate. Damaged tubules contained greater amounts of iron than tubules with less damage (288.5 +/- 68.5 mg/dL v 80.4 +/- 13.9, P < 0.01). Further studies are needed to define the possible role of iron in causing tubular damage and progression of renal disease.
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PMID:Iron accumulation in human chronic renal disease. 146 86

Long-term exposure to certain industrial chemicals (e.g. heavy metals, some halogenated hydrocarbons) may cause progressive degenerative changes in the kidney, possibly leading to renal insufficiency. The screening tests most widely used to assess the integrity of the kidney (i.e. serum creatinine or BUN and the quantitative or semi-quantitative measurement of total proteinuria) lack sensitivity; they do not permit the detection of renal disturbances at a stage when removal from exposure may prevent progression of the disease process and are not suitable to determine the no-effect levels of potentially nephrotoxic chemicals. During the last decades new markers have been proposed for the early detection of structural and/or functional changes at various sites of the renal parenchyma. Some tests mainly attempt to assess the integrity of the glomerulus (e.g. high Mr proteinuria such as transferrinuria and albuminuria; increased excretion of some components of the glomerular basement membrane or the mesangium matrix, increased plasma concentration of low Mr proteins such as beta 2-microglobulin and free retinol binding protein), the proximal tubule (e.g. urinary excretion of several low Mr plasma proteins, tubular enzymes and antigens), the loop of Henle and distal tubule (e.g. excretion of various prostanoids). Currently, the majority of these tests are of limited value at the individual level because their health significance, even when they are persistently abnormal, has not yet been sufficiently studied. In workers exposed to Cd, however, it has been shown that a persistent low Mr proteinuria is predictive of an exacerbation of the age-related decline of the GFR; this biological change should be considered as an adverse effect. Currently, the principal application of these tests lies in the framework of epidemiologic studies designed to assess permissible exposure levels to nephrotoxic pollutants. The study of dose-effects/response relationships based on a large battery of renal markers has allowed the better determination of the internal dose of Cd, which is not associated with significant renal risk.
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PMID:Monitoring of early nephrotoxic effects of industrial chemicals. 147 Nov 89

To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u. > 0.5 g/day, group IV had serum creatine level (Cr) > 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.
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PMID:Mitochondrial enlargement and basement membrane thickening of renal proximal tubules, possible initiators of microalbuminuria in non-insulin-dependent diabetics (NIDDM). 147 27

The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.
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PMID:Exogenous metallothionein and renal toxicity of cadmium and mercury in rats. 147 92


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