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 nephrotoxic potential of alpha-interferon (IFN alpha-2b) was analysed in 21 patients with chronic myeloid leukemia. As particularly sensitive parameters in the detection of subclinical renal injury we measured the excretion of the following urinary enzymes: lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), leucine arylaminidase (LAP), beta-galactosidase (GAL) and N-acetyl-beta-glucosaminidase (NAG). Additionally, protein excretion and urinary sediment were analysed. In 18 of 21 patients a significant increase in the excretion of LDH, LAP, GGT and NAG was found, in 6 patients there was an additional rise in the output of GAL. Eleven patients developed proteinuria up to 2 g/l, one patient excreted up to 9 g/l. Enzymuria and protein excretion decreased in all patients after reduction of the IFN alpha-2b dosage and disappeared in two patients following cessation of therapy. The high incidence of nephrotoxic events in patients with CML during IFN alpha-2b therapy might be mostly due to immunological or substance-specific effects.
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PMID:[Detection of nephrotoxicity of human alpha 2b interferon with special reference to the analysis of urine enzymes in patients with chronic myeloid leukemia]. 347 5

In a group of 58 dogs with proven pyometra, 10 bitches developed renal failure, combined with increased (p less than 0.01) urinary excretion of protein, glucose, gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), amylase, lipase and casts. Thirty-two bitches without renal failure showed nevertheless signs of renal dysfunction as indicated by increased (p less than 0.01) urinary levels of protein, glucose, GGT, AP and amylase. Six bitches without significant proteinuria showed increased (p less than 0.02) urinary levels of GGT, AP as well as amylase. Thus renal injury was detected in 72 per cent of the bitches. Sixteen bitches showed normal urinary levels of protein, glucose, GGT, AP, amylase and lipase, indicating absence of renal disease.
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PMID:Renal injury in dogs with pyometra. 357 95

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

Chronic mercuric chloride intoxication in an aged horse given 0.8 mg Hg/kg/day for 14 weeks was manifest by signs of progressive respiratory difficulty and renal disease. The effects were not self-limiting after mercury was withdrawn, and the animal was destroyed six weeks later. Renal function changes included heavy glycosuria, modest proteinuria, phosphaturia, reduced urine osmolality, gradually increasing urine production, reduced glomerular filtration rate, and terminally, azotemia. The condition bore similarities to the Fanconi syndrome in man. Urinary gamma-glutamyl transpeptidase, alkaline phosphatase and amino-aspartate transferase activities were inconsistent indicators of tubular damage in random samples at this dose rate. The pathologic response was characterized by extensive granulomatous infiltration throughout the lungs, in particular, and to a lesser extent in the kidneys, liver and bone marrow. The renal changes included this marked interstitial reaction and proximal tubular degeneration. Mercury levels were negligible in the lungs and highest in the renal cortex. The granulomatous reaction was not encountered in previous mercury toxicity studies in horses and may indicate an individual sensitivity to the agent.
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PMID:Some effects of chronic mercuric chloride intoxication on renal function in a horse. 621 26

The effect of puberty on aspirin-induced renal necrosis in female Sprague-Dawley rats was observed. Rats aged 31 days were unaffected by aspirin administration, but 55-day-old rats showed segmental cortical tubular necrosis after a single dose of 1000 mg/kg of aspirin. Urinary gamma-glutamyl transpeptidase (gamma-GT) and proteinuria were useful non-invasive indicators of these necrotic changes.
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PMID:Age-related susceptibility to aspirin-induced nephrotoxicity in female rats. 662 43

To evaluate the effect of improved metabolic control on kidney function, urinary excretion rate of beta-2-microglobulin, lysozyme, and gamma-glutamyltransferase were evaluated in nine poorly controlled, newly diagnosed diabetic patients before and during treatment. In six poorly controlled insulin-dependent nephropathic diabetic patients, besides the parameters cited above, urinary albumin excretion rate and IgG/transferrin clearance ratio were further investigated to estimate the permeability and the selectivity of glomerular barrier during conventional treatment and after improvement of the metabolic control by a glucose-controlled insulin infusion system (GCIIS). The improved glycemic control resulted in a significant reduction of urinary beta-2-microglobulin and lysozyme excretion in all diabetic patients. Significant decreases of urinary albumin excretion and of IgG/transferrin clearance ratio (indicating a more selective proteinuria) during strict metabolic control were also observed in nephropathic diabetic patients. The reduction of urinary beta-2-microglobulin and lysozyme excretion indicates that a tubular reabsorptive dysfunction, reversible with the amelioration of glycemic control, can be observed in poorly controlled, newly diagnosed and in insulin-dependent nephropathic diabetic patients during conventional treatment. In the latter patients, the permeability and the selectivity properties of glomerular barrier also improved during GCIIS.
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PMID:Kidney function after improved metabolic control in newly diagnosed diabetes and in diabetic patients with nephropathy. 692 32

The glomerular filtration rate (creatinine clearance), glomerular permeability (qualitative and quantitative proteinuria), tubular reabsorption (k-lambda chains of immunoglobulins and lysozyme) and indexes of tubular cell lysis (alpha-glucosidase and gamma-glutamyltranspeptidase) were measured in the urine of 10 patients with moderate, uncomplicated essential hypertension during placebo therapy and after captopril given at increasing doses of 25, 50, 100 and 200 mg twice daily, the first three doses being given for 3 days and the last one for 4 weeks in all patients and for an additional 6 months in 5 patients. During placebo therapy, proteinuria was absent in eight patients and detectable (glomerular and selective) in two; selective proteinuria appeared in two and a decrease in selectivity was observed in two patients with previous proteinuria after 4 weeks of captopril therapy. No proteinuria was detectable in the five patients followed up to 6 months, not even in the one in whom a decrease in glomerular selectivity had occurred after 4 weeks. The glomerular filtration rate was unchanged as were lysozyme and gamma-glutamyltranspeptidase values, while light chains were always undetectable. Alpha-glucosidase showed some increase; however, increments were transient and always much lower than those observed with known tubular toxic drugs. These data show that under our experimental conditions captopril caused no evident changes in glomerular and tubular function.
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PMID:Effect of captopril on renal function in patients with essential hypertension. 704 2

Cysteinyl leukotrienes (LT) play an important role in the development of experimental glomerulonephritis (GN). We have partially purified and characterized LTC4 synthase, the enzyme responsible for cysteinyl LT formation, from rat renal microsomes and have investigated this enzyme activity in nephritic rats. LTC4 formation, measured in vitro, was linear for > 10 min at 25 degrees C in the presence of 50 mM serine borate (an inhibitor of gamma-glutamyl transpeptidase), with Km values for LTA4 and GSH of 56 microM and 8.5 mM, respectively. Detergent solubilization and anion-exchange chromatography of microsomal proteins resulted in a 7-fold increase in enzyme specific activity. Enzymatic and immunoblot analysis demonstrated that cytosolic and microsomal glutathione S-transferase (GST) activities were distinct from LTC4 synthase activity. Comparison of LTC4 synthase activity in nephritic rats over 21 days revealed an initial increase over the first 24 h following injection of nephrotoxic sera, followed by a subsequent decline until day 7 and a gradual recovery by day 21. Inhibition of LT biosynthesis with MK-0591 (10 mg kg-1 d-1) reduced GN-associated proteinuria by 72% (P < 0.05). These results suggest a potential mechanism for enhanced cysteinyl LT formation in the development of experimental GN and further support their causal role in the etiology of this disease.
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PMID:Renal leukotriene C4 synthase: characterization, partial purification and alterations in experimental glomerulonephritis. 782 26

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


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