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)

In order to detect even subclinical hints of nephrotoxicity after application of carboplatin, sensitive non-invasive methods, e.g. determination of urinary enzyme (lactate dehydrogenase, leucine aminopeptidase, gamma-glutamyltransferase, N-acetyl-beta-glucosaminidase), glomerular and tubular protein excretion (albumin, alpha-1-microglobulin) and determination of the creatinine clearance, were used. Eighteen patients with small-cell lung cancer entered the study. All patients were treated with the three-drug combination chemotherapy: vincristine (1.5 mg i.v. on days 1, 8, 15, 22), etopside (escalating doses: 100-160 mg/m2 on days 1-3) and carboplatin (300 mg/m2 day 1). Investigations were made during the first, third and fifth treatment cycles. Deterioration of renal function occurred in 4 out of 18 patients in all three observed treatment courses. Abnormal amounts in the excretion of at least one of four urinary enzymes were found in 6 out of 18 patients during the first cycle and in 4 out of 8 patients during the third and fifth cycles. All patients with pathological enzymuria during the first treatment course also developed an increased enzymuria during cycles 3 and 5. Four patients developed pathological proteinuria during the first and 2 patients during the third and fifth cycles. These findings demonstrate that the new platinum analogue, carboplatin, is capable of inducing renal damage. In comparison with cisplatinum, the nephrotoxicity of this new analogue is reduced but not completely eliminated.
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PMID:Investigations on the acute and chronic nephrotoxicity of the new platinum analogue carboplatin. 218 39

Carbetimer (carboxyimamidate) is a low molecular weight derivative of ethylene/maleic anhydride polymer. This compound has demonstrated antitumor activity against several animal models with a daily x 5 schedule appearing most effective. A phase I clinical study of the daily x 5 schedule repeated every 28 days was therefore performed. Forty-one evaluable patients received 66 evaluable cycles of Carbetimer at daily doses ranging from 100-11,000 mg/m2. Hypercalcemia was the dose limiting toxicity with both patients at the 11,000 mg/m2 daily dose level and one patient who received 6 cycles of drug at the 4200 mg/m2 dose level developing severe hypercalcemia not explained by the underlying malignancy. Mild nausea, concentration and rate dependent arm pain at the site of infusion, proteinuria, and coagulopathy were also seen. Calcium balance studies revealed hypercalciuria, suggesting increased mobilization of calcium rather than renal retention. In vitro coagulation studies revealed concentration dependent prolongation of the partial thromboplastin time and thrombin time. No complete or partial responses were seen. However mixed response or biochemical response (reduction in serum lactic dehydrogenase) were seen in 5 patients with melanoma or renal cancer. Due to unacceptable toxicity at the 11,000 mg/m2 daily dose level, Carbetimer 8500 mg/m2 is the recommended dose for a 5-day treatment schedule every 28 days. Special attention should be directed toward possible activity against melanoma and renal cancer.
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PMID:Phase I trial of a 5-day course of carbetimer. 238 16

In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease in p-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2 x MELD(10) (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i.e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity.
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PMID:Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat. 259 97

To identify early markers of the preclinical stage of diabetic nephropathy, a study was made of the activity of the specific canalicular enzymes in urine: N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-G1), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) in patients with diabetes mellitus without (26) and with (15) proteinuria. Patients without the clinical signs of diabetic nephropathy manifested a significant rise of excretion of lysosomal enzymes of the proximal canaliculi (NAG and beta-G1). Concomitant elevation of the excretion of several enzymes (NAG, beta-Gl, GGT and AP) was observed in 50% of cases. Patients with diabetic nephropathy demonstrated an increase of the excretion of all enzymes under study. Puncture biopsy of the kidneys was made in 4 patients without proteinuria with insignificant duration of diabetes mellitus and concomitant elevation of the excretion of a number of enzymes. Light microscopy revealed minimal changes in the glomeruli, whereas electron microscopy changes both in the glomeruli and in the canaliculi. The morphological changes in renal tissue confirm the diagnostic importance of high concomitant excretion of canalicular enzymes (NAG, beta-Gl, AP) as a marker of the preclinical stage of diabetic nephropathy.
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PMID:[Urinary enzymes as a marker of the preclinical stage of diabetic nephropathy]. 262 51

A new case of acquired von Willebrand syndrome (AvWS) with Hashitoxicosis and pernicious anemia combined in a 73-years-old male is reported. He was admitted because of appetite loss and general malaise. Physical examination showed severe anemia and general edema. The red-cell count was 103 X 10(4)/microliters with a MCV of 122 fl; the white-cell count was 2,900/microliters with 24.5% hypersegmented neutrophils; the platelet count was 17.2 X 10(4)/microliters. the lactate dehydrogenase was 9,513 U/ml and vitamin B12 was 87 pg/dl. An aspirated specimen of bone marrow was diagnostic of megaloblastic anemia. The thyroid hormones were decreased with the thyroid stimulating hormone increased. From the immunological findings, the thyroid-test, microsome-test, and anti-intrinsic factor were positive, but M proteinemia and Bence Jones proteinuria were absent. Histology of the thyroid gland and the gastric mucosa established the diagnosis of chronic thyroiditis and chronic atrophic gastritis. Subcutaneous hemorrhages after veni-puncture were observed on admission. He had a normal bleeding time, but the coagulation studies indicated the presence of von Willebrand disease, but as his family and past history were negative, this suggested the presence of an AvWS. The analysis of von Willebrand factor (vWF) multimeric composition had showed the lack of the larger multimers in the plasma, but it was normalized after the administration of levothyroxine sodium and hydroxocobalamin with vWF: Ag/RCo ratio paralleled. As far as we know, this is the first report of AvWS with Hashitoxicosis and pernicious anemia combined.
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PMID:[Acquired von Willebrand syndrome associated with Hashitoxicosis and pernicious anemia combined]. 267 35

2-Bromo-(diglutathion-S-yl)hydroquinone [2-Br-(diGSyl)HQ] causes severe necrosis of the proximal renal tubules in the rat, elevations in blood urea nitrogen (BUN) and increased urinary excretion of protein, glucose, and lactate dehydrogenase. In contrast, 2-Br-3-(GSyl)HQ, 2-Br-5-(GSyl)HQ, and 2-Br-6-(GSyl)HQ caused differentially less toxicity than the diglutathionyl conjugate. None of these conjugates had any apparent effect on liver pathology and serum glutamate-pyruvate transaminase remained within the normal range. Pretreatment of rats with probenecid, an organic anion transport inhibitor, offered only slight protection against 2-Br-(diGSyl)HQ-mediated elevations in BUN, proteinuria, or glucosuria. In contrast, quinine, an organic cation transport inhibitor, potentiated the nephrotoxicity of 2-Br-(di-GSyl)HQ. Thus, in contrast to other nephrotoxic sulfur conjugates, probenecid-sensitive organic ion transport systems do not contribute to the kidney-specific toxicity of 2-Br-(diGSyl)HQ. However, inhibition of renal gamma-glutamyl transpeptidase by AT-125 completely protected rats from the nephrotoxic effects of 2-Br-(diGSyl)HQ. Aminooxyacetic acid, an inhibitor of cysteine conjugate beta-lyase, caused a 20-25% decrease in 2-Br-(diGSyl)HQ-mediated elevations in BUN and urinary excretion parameters. The isomeric 35S conjugates covalently bound to rat kidney 10,000 x g homogenate in the order 2-Br-6-(GSyl)HQ greater than 2-Br-5-(GSyl)HQ greater than 2-Br-3-(GSyl)HQ greater than 2-Br-(diGSyl)HQ. AT-125 (0.4 mM) decreased covalent binding by 25%, 17%, 33%, and 28%, respectively. Aminooxyacetic acid (0.1 mM) inhibited covalent binding by 26%, 10%, 17%, and 17% respectively. Ascorbic acid (1.0 mM) inhibited covalent binding by 63%, 87%, 62%, and 28%, respectively, and this inhibition correlated, inversely, with the redox potential of the conjugates. Thus, the covalent binding is mediated preferentially by oxidation of the quinol moiety, although the formation of reactive thiols cannot be excluded. In addition, the initial conjugation of 2-BrHQ with GSH does not result in the formation of a less redox-active species. However, the subsequent addition of a second molecule of GSH results in the formation of a more redox-stable compound, which, paradoxically, enhances toxicity. The metabolism of 2-Br-(diGSyl)HQ by renal proximal tubular gamma-glutamyl transpeptidase and trans-membrane transport of the cysteine conjugate(s) followed by oxidation of the quinol moiety is probably responsible for the target organ toxicity of this compound.
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PMID:2-Bromo-(diglutathion-S-yl)hydroquinone nephrotoxicity: physiological, biochemical, and electrochemical determinants. 317 33

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

Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical-independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation.
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PMID:Systemic complement activation, lung injury, and products of lipid peroxidation. 403 Oct 60

The effect of nickel on cadmium nephro-toxicity and hepato-toxicity in rats was investigated. The administration of nickel (6 mg per kg, i.p., three days) or cadmium (6 mg per kg, i.m., once) significantly enhanced the urinary excretion of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate oxaloacetate transaminase (GOT), amino acids, and proteins. In addition, it increased the activity of serum ALP, GOT, and glutamate pyruvate transaminase (GPT). These biochemical alterations in urine and serum were used as a measure of kidney and liver damage. Cadmium-induced enzymuria, proteinuria, amino aciduria and increase in the activity of serum enzymes were significantly less marked in animals pretreated with nickel than in controls. However, the accumulation of cadmium in kidneys and liver and its urinary excretion were unaffected by nickel pretreatment. The results suggest protection by nickel against cadmium nephro- and hepato-toxicity.
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PMID:Preventive effects of nickel on cadmium hepatotoxicity and nephrotoxicity. 647 83

The protean manifestations of Legionnaires' disease are described in an analysis of 12 sporadic cases. Two forms of the disease have been delineated. One variant (Group A) consisted of six patients who had a mild form of non-progressive pneumonia with minimum extra-pulmonary involvement. Six patients (Group B) were differentiated by rapidly progressive pulmonary infiltrates, severe hypoxia and respiratory failure, plus a higher frequency of band neutrophils and extra-pulmonary manifestations. Particularly notable were evidence of severe myositis (elevated creatinine phosphokinase and lactate dehydrogenase), anaemia, and neurological findings which included alterations in the sensorium, meningitis, and convulsions. Cerebrospinal fluid (CSF) abnormalities were seen frequently in patients with neurological manifestations, and necropsy findings in one patient suggested that the Legionnaires' bacillus was capable of producing a fatal leucoencephalitis. Renal findings included haematuria, proteinuria and oliguric renal failure. Hepatic transaminases (SGPT, SGOT) were elevated in six patients and serum bilirubin was abnormal in five. Alkaline phosphatase values were normal to minimally elevated. The gastrointestinal symptoms commonly considered to be a frequent initial manifestation of Legionnaires' disease were rare in this series. Recommendations for instituting empirical therapy, based upon recognition of a clinical syndrome which should suggest the diagnosis of Legionnaires' disease, are included.
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PMID:The protean manifestations of Legionnaires' disease. 663 Oct 29


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