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)

Urinary enzyme excretion and proteinuria were studied in 316 children with different underlying diseases. Activities on N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase decreased progressively with age in the urine of 66 healthy prematures, newborns, infants or children. In 51 children with nephrotic syndrome, tubulopathies or chronic renal failure, excretion of NAG and AAP rose 3 to 30 fold. Contrary to molecular weight dependent protein analysis, determination of enzymuria did not allow to differentiate between glomerular and tubular disorders. After renal transplantation, 31 out of 52 children had a pathological enzymuria. NAG and AAP were more frequently elevated during treatment with cyclosporine A (21/29), than with azathioprine (10/23). The influence of nephrotoxic drugs upon enzymuria was documented in 14 children with cystic fibrosis or septicaemia treated with tobramycin. Activities of NAG and AAP rose transiently, whereas proteinuria remained almost unchanged. Only three out of 45 children receiving nonsteroidal antiinflammatory drug therapy for juvenile rheumatoid arthritis or spondylarthritis showed a pathological increase in enzymuria. Mean urinary NAG and AAP excretion in 154 children with insulin dependent diabetes mellitus were not different from controls and were unrelated to either duration of disease or HbA1 concentration. The determinations of urinary enzymes as non-invasive tests of renal integrity in medicine and toxicology provide a very sensitive indicator of renal damage. The assays of NAG and AAP have proven to be most valuable; however, due to a lack of specificity for the type and origin of renal dysfunction, these urinary enzyme assays are most useful when carried out in conjunction with electrophoretic analyses of proteinuria.
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PMID:[Enzymuria and kidney diseases in childhood]. 288 Nov 98

We measured the excretion rates of six urinary enzymes that either originate from the proximal renal tubule, like alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), or that are typical low-molecular-mass proteins, like lysozyme (EC 3.2.1.17) and pancreatic ribonuclease (EC 3.1.27.5). These rates were compared with those of total protein and albumin in urine of 36 insulin-dependent diabetic men and 30 healthy men. Seventeen of the diabetics had "clinical proteinuria," defined as excretion of more than 7.5 g of protein per mole of urinary creatinine (group B). Group A comprised the 19 diabetics without proteinuria. Except for gamma-glutamyltransferase, the excretions of enzymes and proteins were significantly higher in diabetics than in controls and were greater in group B than in group A. N-Acetyl-beta-D-glucosaminidase was the analyte most often increased in group A (89%), followed by albumin and alkaline phosphatase (each 32%). All patients in group B showed increased excretion of N-acetyl-beta-D-glucosaminidase. We conclude from the comparative data that this enzyme may be useful as an early predictor of diabetic nephropathy.
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PMID:Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy. 289 6

The nephrotoxicity of three different dose levels of propyleneimine (10, 20 and 30 microliter/kg body wt) administered intraperitoneally to rats was studied and 20 microliters/kg body weight was found to be the most appropriate sublethal dose. Injection of propyleneimine (10 microliters/kg body wt) produced a small rise in N-acetyl-beta-D-glucosaminidase (NAG) activity, minor histological damage but no change in urine volume. Six rats were injected with 20 microliters/kg body weight, and urine was collected over the following 16 days. An immediate increase in urine volume, osmolality together with a concomitant decrease in specific gravity, was accompanied by a small increase in creatinine excretion and a more marked increase in the sodium and potassium content of urine after the administration of the nephrotoxin. NAG activity increased immediately and peaked on day 3, the activity remained elevated until day 12 when it fell to near normal levels. The activity of both beta-D-galactosidase and beta-D-glucosidase increased 9 days after administration of the nephrotoxin. In contrast, no consistent change was found in the excretion of the brush border marker enzymes, leucine aminopeptidase (LAP), alanine aminopeptidase (AAP) or alkaline phosphatase (ALP). Proteinuria increased sharply the day after injection and remained abnormal. Increased urinary albumin excretion and the predominance of low molecular weight proteins was demonstrated by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Evidence is presented that propyleneimine exerts its early toxic effect on the renal papilla.
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PMID:Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat. 309 1

Calves (n = 4) were given neomycin (2.25 or 4.5 mg/kg) twice daily IM and were compared with 2 calves given penicillin IM. The 2 hallmarks of aminoglycoside toxicosis, nephrotoxicosis and ototoxicosis, were seen with both dosages of parenterally administered neomycin. Nephrotoxicosis was confirmed by abnormal findings in urinalysis (granular casts, proteinuria, low specific gravity), renal biopsy results (tubular degeneration and necrosis), and increased 24-hour amounts of urinary enzymes (alanine aminopeptidase and gamma-glutamyltranspeptidase). Azotemia, decreased creatinine clearance, polyuria, and polydipsia also were documented in calves given neomycin. Clinically, deafness was suspected in 2 calves and was documented by electrical auditory-evoked response tests. Abnormalities in partial thromboplastin times and renal residues of neomycin were seen in all 4 calves that were given neomycin, but not in calves that were given penicillin.
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PMID:Neomycin toxicosis in calves. 611 66

A possible tubulotoxicity of drugs can be judged with the help of the excretion of tubular membrane proteins in the urine. The brush border of the proximal tubular epithelia which react particularly sensitive to toxic influences contains surface antigens which easily release themselves from the membrane core membrane under pathological conditions and become provable in the urine by means of biochemical and immunological methods as signs of an early structural cell damage. Apart from these soluble membrane proteins which above all correspond to enzymes such as alanine aminopeptidase and gamma-glutamyl transpeptidase in severe lesions high molecular brush border fragments transformed to vesicles can appear. The clinical relevance of a pathological tissue proteinuria (histuria) of proteins of renal membranes is among others explained at the instance of the renal effects of cytostatics, antibiotics and x-ray contrast medias.
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PMID:[Assessment of drug nephrotoxicity by the excretion of tubule-specific membrane antigens and enzymes]. 614 70

Following experimental rhabdomyolysis, animals become resistant to heme protein-induced acute renal failure (ARF). The goals of this study were to: (a) ascertain whether this resistance, previously documented only in vivo, is expressed directly at the proximal tubular cell level; (b) determine whether heme proteinuria (vs. other consequences of rhabdomyolysis) is its trigger; and (c) ascertain some of its subcellular determinants. Rats were injected with a borderline toxic dose of glycerol and 24 hours later proximal tubular segments (PTS) were isolated for study. Their vulnerability to diverse forms of injury (FeSO4-induced oxidant stress, hypoxia, Ca2+ ionophore, cytochalasin D, PLA2) was compared to that found in normal PTS. Post-glycerol PTS manifested significant resistance to each insult (decreased lactate dehydrogenase +/- N-acetyl-beta-D-glucosaminidase release). Protection against FeSO4 was virtually complete and it was associated with a 50% decrease in membrane lipid peroxidation. No decrease in hydroxyl radical generation was noted during the FeSO4 challenge (salicylate trap assessment), suggesting a primary increase in membrane resistance to attack. That PLA2 addition caused less deacylation, plasma membrane enzyme (alanine aminopeptidase) release, and LDH leakage from post-glycerol versus normal tubules supported this hypothesis. To test whether cytoresistance was specifically triggered by heme proteins (vs. being a non-specific filtered protein effect, or a result of endotoxin cascade activation), rats were injected with purified myoglobin, non-heme containing filterable proteins, or endotoxin. Only myoglobin induced cytoresistance. In vivo heme oxygenase inhibition (tin-protoporphyrin) did not block the emergence of cytoresistance and it was expressed despite Na,K-ATPase inhibition (ouabain) or cytoskeletal disruption (cytochalasin D). In vivo heat shock failed to protect. In conclusion, (1) rhabdomyolysis induces broad based proximal tubular cytoresistance; (2) heme proteinuria is its trigger; and (3) it is most easily explained by a primary increase in plasma membrane resistance to attack.
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PMID:Heme protein-induced tubular cytoresistance: expression at the plasma membrane level. 763 63

Aminoglycosides, among the most commonly used antibiotics in neonates, have frequently been implicated in nephrotoxic reaction. Studies in adults have indicated that phospholipiduria (PLU) is rapidly increased during aminoglycoside therapy, in relation to the renal phospholipidosis these drugs are known to induce in renal cortex. We studied the effect of amikacin (AK) on PLU in male prematurely-born neonates (gestational age > 34 weeks; postnatal age < or = 2 days) by assessing the urinary excretion of 4 enzymes (N-acetyl-beta-D-glucosaminidase [NAG], alkaline phosphatase, tau-glutamyltransferase and alanine aminopeptidase) and 4 low-molecular-weight proteins (beta-2-microglobulin, clara cell protein, microalbumin and retinol-binding protein) which are currently used to monitor the development and extent of renal tubular damage. Twenty-two patients and 8 healthy (as control) neonates were enrolled in the study. Patients were treated with AK (15 mg/kg per day) given in one (qd, n = 10) or two equal injections (b.i.d., n = 12) for durations of 7-11 days. PLU and proteinuria were determined in 24-h urine sample collections, and enzymes were assessed in spot urine collected at 9 a.m. We found that in neonates, AK causes a significant increase in PLU, and in enzymuria except for NAG in the qd group. Proteinuria showed no significant change due to AK treatment. No significant differences were observed between qd and b.i.d. administrations of AK for all parameters tested. We conclude that PLU could be used in neonates as well as in adults as a non-invasive method to monitor the development of the renal phospholipidosis during aminoglycoside therapy.
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PMID:Urinary phospholipids excretion in neonates treated with amikacin. 767 71

Neonates, especially preterms, are known to have low glomerular filtration rates (GFR). This may result in elevated trough concentrations during multiple administration of aminoglycosides (AGs), potentially leading to nephro- and ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential pharmacodynamic and nursing advantages. No data, however, are available for neonates. As a consequence, this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen, in relation to the pharmacokinetics of the drug under these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose (trough level) and 1 h after completion of infusion (peak level) and after 3 and 6 h only at day 1. Due to the small size of the samples, no difference in efficacy could be assessed and was not the aim per se. Glomerular dysfunction was assessed by creatinine clearance, and tubular injuries by the urinary excretion of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as controls. All patients showed a normal and similar increase of GFR during the first postnatal days. Proteinuria did not increase, but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups. BAEPs at day 9 were not significantly different between treated and untreated patients. We conclude from this pilot study that, in the absence of more toxicity, the q.d. administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages.
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PMID:Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity. 782 57

The present study was performed to compare renal injury induced by high acute doses of both the nonacetylated salicylate, salsalate (SSA) and the acetylated salicylate, aspirin (ASA). As a marker of renal injury, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) were measured after oral administration of 600 mg/kg of each drug. Other tests to detect renal injury were also performed. Serum salicylic levels after SSA or ASA were determined in a different experiment. Acetaminophen (APAP) was used as a standard of renal toxicity. Both drugs increase NAG and to a greater extent, AAP excretion. Proteinuria and polyuria appear after both drugs. Changes in urinary sodium and potassium were also shown. Our results support the view that both acetylated and non-acetylated salicylates induce renal injury at toxicological doses.
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PMID:N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) excretion after acute administration of acetaminophen, salsalate and aspirin in rats. 810 22


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