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 angiotensin I-converting enzyme (ACE) activity was studied in 2 experimental models of acute renal failure: (a) rats treated with a single injection of mercuric chloride (1.5 mg/kg) and (b) rats treated with a single injection of potassium dichromate (15 mg/kg). Rats were sacrificed 24 and 48 h after mercuric chloride or potassium dichromate injection. ACE activity was measured in urine, serum, and kidney. These data were compared with vehicle-treated rats. Rats with acute renal failure had proteinuria, polyuria, and decreased creatinine clearance. The damage to the kidney proximal tubule was evident by (a) the histological analysis at light and electron microscopy, (b) the augmentation in the urinary excretion of dipeptidyl aminopeptidase IV and N-acetyl-beta-D-glucosaminidase, and (c) the low molecular weight proteinuria pattern. In addition, the histological analysis at the ultrastructural level showed normal glomeruli appearance. The above data suggest that the increased urinary excretion of enzymes and proteins in rats with acute renal failure is a consequence of tubular injury. Urinary and serum ACE activities increased and kidney ACE activity decreased. Our data suggest that the increase in urine ACE activity may be due to the kidney proximal tubule damage. This work supports the contention that an increase in urine ACE may be an indicator of injury to the proximal tubule.
 ...
PMID:Urinary angiotensin I-converting enzyme activity is increased in experimental acute renal failure. 871 86

Maleate treatment of rats induces transport defects similar to those seen in the Fanconi syndrome (glycosuria, aminoaciduria, phosphaturia, proteinuria, etc.) and causes an accumulation of apical vesicles in proximal tubule epithelial cells. Because the apical membrane glycoprotein, gp330, is a receptor associated with the apical endocytotic and recycling apparatus in these cells, we examined the effect of maleate on the distribution of this protein and other brush border markers. Rats received sodium maleate (400 mg/kg ip) and were killed at various times between 45 min and 3 h; kidneys were perfusion fixed with paraformaldehyde-lysine-periodate before processing for immunofluorescence and immunoelectron microscopy. In control rats, staining with a polyclonal or monoclonal gp330 antibody showed a uniform distribution on the brush border and in coated pits of all proximal tubule cells. In the S3 segments, the immunofluorescence labeling of the microvilli was generally uniform but at times showed spike labeling, suggesting that gp330 sheds easily from the apical membrane. After maleate treatment, the staining intensity of the brush border was decreased in all proximal tubule segments, and cytoplasmic streaks as well as an intense vacuolar staining were seen. In the S3 segment, a remarkable mosaic pattern of staining was observed, with the brush border of some cells being completely negative, while adjacent cells showed an apparently normal staining pattern. These results were confirmed at the electron microscope level, using the protein A-gold technique. Maleate had no effect on the distribution or staining intensity of four other brush border markers, dipeptidyl peptidase IV, and various lectins (Helix pomatia lectin, peanut lectin, elderberry bark lectin). The urinary excretion of gp330 occurs in normal rats and was already increased as early as 1 h after maleate injection and remained at a twofold increment between 6 and 24 h. These data suggest that the generalized membrane transport derangement seen in this experimental Fanconi syndrome could occur via a specific effect on gp330, which seems to block endocytosis and the recycling apparatus at the late endosome level and inhibits the formation of new dense apical tubules.
 ...
PMID:Specific effect of maleate on an apical membrane glycoprotein (gp330) in proximal tubule of rat kidneys. 889 22

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C(Li) was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.
 ...
PMID:The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy. 895 33

Tenidap is a novel antirheumatic agent that causes a mild, reversible proteinuria in human clinical trials. In order to achieve a mechanistic understanding and safety perspective of the proteinuric effects of tenidap observed in clinical trials, female Sprague-Dawley rats were treated with up to 100 mg/kg/day of tenidap in the diet for 4 to 6 weeks followed by a 1- to 6-week reversal period. Pharmacokinetics and measurements of renal function and histology were assessed during the study. Sustained high plasma concentrations of tenidap [area under the plasma concentration curve (0-24 hr) of 941-1021 micrograms. hr/ml and peak plasma concentration of 61-67 micrograms/ml] increased urinary protein, albumin and phosphate excretion (2- to 8-fold) in rats. These renal effects were reversible within 9 days after removal of the drug. These effects preceded later occurring changes in renal morphology (papillary degeneration and necrosis). There was no evidence of glomerular damage, proximal tubule degeneration or necrosis or tubulointerstitial nephritis at the light microscopic level. Other indices of overall renal function (glomerular filtration rate, electrolyte and glucose excretion) were unaffected. Examination in situ of microperfused proximal tubules from treated rats revealed a 68% decrease in the rate of proximal tubule albumin absorption compared to controls (19 +/- 4 vs. 59 +/- 7 pg/min/mm, respectively). Fluid absorption rate and bicarbonate handling by the proximal tubule, along with blood bicarbonate concentrations, pH, PCO2 and PO2, were unaffected by treatment. It was concluded that tenidap caused a rapid, stable and reversible phosphaturia, microalbuminuria and proteinuria in the rat. The proteinuric effects were due to impaired proximal tubule albumin reabsorption that were not associated with other signs of impaired renal function or histological evidence of tubulointerstitial nephritis or proximal tubule/glomerular damage.
 ...
PMID:Model development and analysis of tenidap-induced proteinuria in the rat. 896 56

The evaluation of a new drug in normotensive volunteers can provide important information, as long as the compound has a specific mechanism of action which can be evaluated in healthy subjects as well as in patients. The purpose of the present paper is to review the renal effects of new specific angiotensin II receptor antagonists observed in normotensive subjects and to compare them to those of angiotensin-converting enzyme (ACE) inhibitors. Blockade of the renin-angiotensin system with ACE inhibitors and angiotensin II antagonists induces an expected increase in plasma renin activity and plasma angiotensin I levels. Plasma angiotensin II levels decrease with ACE inhibitors, whereas they increase with angiotensin II receptor blockade. So far, the expected decrease in plasma aldosterone levels has been difficult to demonstrate with most angiotensin II antagonists. In normotensive subjects, ACE inhibitors, as well as angiotensin II antagonists, cause no change in glomerular filtration rate and either no modification or an increase in renal blood flow. Both approaches to block the renin-angiotensin system are natriuretic, and the natriuresis is more pronounced in salt-depleted subjects. Finally, in contrast to ACE inhibitors and other angiotensin II receptor antagonist, losartan markedly increases uric acid excretion and lowers plasma uric acid levels. This unique property of losartan is due to a direct interference of losartan with the uric acid transport system in the proximal tubule. The data obtained in normal subjects therefore suggest that ACE inhibitors and angiotensin II receptor antagonists have comparable renal properties. Whether this is also true in hypertensive patients and in patients with proteinuria and chronic renal failure remains to be demonstrated.
 ...
PMID:Renal effects of angiotensin II receptor blockade and angiotensin-converting enzyme inhibition in healthy subjects. 900 96

There are reports concerning profitable influence of unsaturated acids administration on blood pressure, inflammation and proteinuria. The aim of presented study was to estimate the effect of Omega-3 on plasma lipids and renal function in patients with primary glomerulopathies. The tested group consisted of 13 patients (7F and 6M) aged from 22 to 60 years, with primary glomerulopathies and normal renal function. They received Omega-3 (Fishproduct, iceland) 3 x 2 caps for three months. Before, after 2 and 3 months of treatment and 3 months after its discontinuation following parameters were estimated: total cholesterol, HDL and LDL cholesterol (HDL, LDL), triglycerides and an order parameter of erythrocyte lipid bilayer (S). Simultaneously N-acetylglutamate (NAG), creatinine clearance and 24-hours proteinuria were measured. For calculation t-Student test was used. In our study we found statistically significant increase of HDL after 2 and 3 months and decrease of LDL after 3 months of Omega-3 administration (p < 0.05). During the 2 and 3 months of treatment statistically significant decrease of NAG was noticed but a month after its discontinuation significant increase of NAG excretion was observed (p < 0.05). The S parameter in tested group of patients was higher than in healthy population but during Omega-3 administration the value of an order parameter of erythrocyte bilayer increased significantly (p < 0.01). On the base of given results we could conclude that unsaturated acids may have profitable influence on plasma lipids, functional status of erythrocyte membrane and probably proximal tubule function in patients with primary glomerulopathies.
 ...
PMID:[The effect of administering Omega-3 acids on lipids in serum, functional state of erythrocyte membrane and function of the kidneys in patients with primary glomerulonephritis]. 916 8

Post-exercise proteinuria is a common phenomenon in healthy subjects. Previous studies have used albumin (Alb) and beta 2-microglobulin (beta 2-m) molecules as representatives of high- and low-molecular-weight proteins. Recently, more specific markers of the human kidney proximal tubule have been used to identify the precise site of alterations. Active male subjects underwent two strenuous runs, one 400-m run and one 3000-m run. Urine was collected from the subjects before and after each event. Total protein (TP), Alb, alpha 1-microglobulin (alpha 1-m), beta 2-m, intestinal alkaline phosphatase (IAP), tissue-nonspecific alkaline phosphatase (TNAP) and N-acetyl-beta-D-glucosaminidase (NAG) were determined for each sample. The short-distance run (400 m) resulted in the largest increases (P < or = 0.05) in TP (31-fold), Alb (100-fold) and beta 2-m (164-fold) as compared to the long-distance run (3000-m). The alpha 1-m excretion rates were increased to a lesser extent by the exercises. The IAP activity was slightly increased (+90%) by the 400-m run while the TNAP and NAG activities showed a 6.8-fold and a 3.6-fold increase, respectively, after this event. Smaller increases were recorded for the long-distance run (P = 0.05). To conclude, the present investigation showed that: (1) post-exercise proteinuria is related to the absolute intensity of exercise; (2) the impairment of protein reabsorption is revealed better by changes in Alb and beta 2-m; (3) changes in TNAP and NAG activities could reveal biochemical modifications that occur in the proximal tubule, particularly at the S1-S2 segment.
 ...
PMID:Evidence of differential renal dysfunctions during exercise in men. 924 75

Proteinuria has been invoked as a cause of tubulointerstitial injury in chronic renal disease, and in vivo studies have suggested indirectly the particular nephrotoxicity of one urinary protein holotransferrin (Tf-Fe). However, to date there has been no direct evidence for the nephrotoxicity of Tf-Fe. To examine the potential cytotoxicity of Tf-Fe and the mechanism involved, and to compare this to another urinary protein albumin, rat proximal tubule cells were studied in primary culture. Tf-Fe at pH 6.0 caused functional and ultrastructural injury, but no cytotoxicity was seen with cells exposed to albumin, apotransferrin (transferrin), or Tf-Fe at pH 7.4. The influence of pH on Tf-Fe-induced cytotoxicity was not due to pH per se, but could be explained by an effect on Tf-Fe uptake. At pH 6.0, uptake of 125I-Tf-Fe (3.55 +/- 0.05 versus 1.25 +/- 0.10 fmol/dish, P < 0.01) and intracellular iron concentration (1.14 +/- 0.25 versus 0.46 +/- 0.23 nmol/dish, P < 0.01) were increased compared with values at pH 7.4. In contrast, pH 6.0 did not increase iron uptake from FeCl3. Lysine (100 mM) inhibited Tf-Fe uptake, decreased intracellular iron concentration, and attenuated Tf-Fe-induced cytotoxicity. The iron chelator des-ferrioxamine (200 microM) and hydroxyl radical scavenger dimethylpyrroline N-oxide (32 mM) abolished lactate dehydrogenase leakage induced by Tf-Fe at pH 6.0. Lipid peroxidation, as assessed by production of malondialdehyde, preceded lactate dehydrogenase leakage. In summary, holotransferrin, but not albumin, is toxic to rat proximal tubule cells, a pH-dependent effect involving its uptake into tubule cells, its iron moiety, and its lipid peroxidation.
 ...
PMID:Toxicity of holotransferrin but not albumin in proximal tubule cells in primary culture. 944 90

To avoid renal loss of large amounts of proteins, filtered proteins are reabsorbed by endocytosis along the proximal tubule. However, although protein reabsorption is a task of proximal tubular cells, it is also a threat because it may cause cell injury. This study determines whether exposure to bovine serum albumin (BSA) leads to regulatory changes in endocytosis of FITC-BSA in proximal tubule-derived opossum kidney cells. Preincubation with BSA led to a decrease of FITC-BSA endocytosis with an IC50 value of 0.58 g/L. Specific binding of FITC-BSA to the apical membrane was also reduced (IC50 = 0.69 g/L). Kinetic analyses revealed that maximal uptake rate and maximal binding capacity were decreased with no change in affinity. Similar effects were observed after preincubation with equimolar amounts of other proteins (lactalbumin, transferrin, and conalbumin), but not after preincubation with dextran. The effect of preincubation with BSA could be mimicked by preincubation with some amino acids. Preincubation with L-Ala, L-Gln, or NH4Cl, but not with L-Leu, L-Glu, or L-Asp, reduced FITC-BSA endocytosis and binding. Preincubation with BSA, but not with dextran, reduced protein degradation and increased ammonia production, vesicular pH, as well as the rate of lactate dehydrogenase release. Apical fluid-phase endocytosis and apical uptake of neutral amino acids were not reduced. It is concluded that proximal tubular cells reduce the uptake rate for proteins, but not for other substrates, in response to increased protein load. This reduction is achieved by reducing the number of apical binding sites, partially in response to increased ammoniagenesis with deranged vesicular pH and enzyme activities. Thus, increased protein filtration could result in reduced protein reabsorption, thereby enhancing proteinuria.
 ...
PMID:Long-term protein exposure reduces albumin binding and uptake in proximal tubule-derived opossum kidney cells. 962 Dec 78

Loss-of-function mutations of the ClC-5 chloride channel lead to Dent's disease, a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones. We show that ClC-5 is expressed in renal proximal tubule cells, which normally endocytose proteins passing the glomerular filter. Expression is highest below the brush border in a region densely packed with endocytotic vesicles, where ClC-5 colocalizes with the H+-ATPase and with internalized proteins early after uptake. In intercalated cells of the collecting duct it again localizes to apical intracellular vesicles and colocalizes with the proton pump in alpha-intercalated cells. In transfected cells, ClC-5 colocalizes with endocytosed alpha2-macroglobulin. Cotransfection with a GTPase-deficient rab5 mutant leads to enlarged early endosomes that stain for ClC-5. We suggest that ClC-5 may be essential for proximal tubular endocytosis by providing an electrical shunt necessary for the efficient acidification of vesicles in the endocytotic pathway, explaining the proteinuria observed in Dent's disease.
 ...
PMID:ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells. 965 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>