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 hemolytic-uremic syndrome (HUS) is an acute disorder, characterized by the triad of microangiopathic hemolytic anemia, nephropathy and thrombocytopenia. The great majority of patients are children, usually under 4 years of age, although adults can be affected. The onset is abrupt and usually follows gastroenteritis or upper respiratory infection. Later, clinical manifestations based on the triad, such as pallor, jaundice, edema, hypertension and purpura soon develop. The urinary output is reduced and the urine may appear dark yellow or tea-colored. Laboratory tests of peripheral blood show severe hemolytic anemia associated with fragmented red blood cells and thrombocytopenia, usually below 50,000/microliters. The blood urea nitrogen, serum creatinine and lactate dehydrogenase concentrations are elevated. Proteinuria and microscopic hematuria, which are indicative of active glomerular damage are also seen. Profound understanding of these manifestations is sufficient to permit an early diagnosis of HUS.
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PMID:[Diagnosis and clinical features of hemolytic uremic syndrome]. 843 21

Three cases of multiple false-positive drug tests are described. Postmortem urine specimens were screened using the enzyme-multiplied immunoassay technique. All patients had proteinuria and lactic aciduria. These false-positive reactions were due to the presence of lactate dehydrogenase (LDH), lactic acid, and protein. This finding was confirmed by creating a multiple false-positive sample with a solution of LDH and lactate in 5% bovine serum albumin at pH 6.
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PMID:False-positive postmortem EMIT drugs-of-abuse assay due to lactate dehydrogenase and lactate in urine. 857 77

Among N-(halophenyl)succinimides. N-(3,5-dichlorophenyl)succinimide (NDPS) is a potent nephrotoxicant as well as an agricultural fungicide. Although two chloride groups on the phenyl ring are essential to induce optimal nephrotoxicity, the role of halogen groups in NDPS nephrotoxicity is not clear. In this study, N-(3-bromophenyl)-2-hydroxysuccinimide (NBPHS) was prepared as a monohalophenyl derivative of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS), an oxidative and nephrotoxicant metabolite of NDPS. The nephrotoxic potential of NBPHS was evaluated in vivo and in vitro to determine the role of halogen groups in N-(halophenyl)succinimide nephrotoxicity. Male Fischer 344 rats (four/group) were administered a single intraperitoneal (i.p.) injection of NBPHS (0.1, 0.4 or 0.8 mmol/kg) or vehicle (25% dimethyl sulfoxide in sesame oil) and renal function monitored for 48 h. Administration of NBPHS (0.8 mmol/kg) induced nephrotoxicity, while very mild changes or no changes in renal function were observed following administration of 0.4 mmol/kg or 0.1 mmol/kg of NBPHS, respectively. Nephrotoxicity induced by NBPHS (0.8 mmol/kg) was characterized by diuresis, transiently increased proteinuria, glucosuria and hematuria elevated kidney weight and reduced tetraethylammonium (TEA) uptake by renal cortical slices, and was not as marked as nephrotoxicity induced by NDHS (0.1 mmol/kg) or NDPS (0.4 mmol/kg). In the in vitro studies the effects of NBPHS on organic ion accumulation, pyruvate-stimulated gluconeogenesis, and lactate dehydrogenase (LDH) release were measured using renal cortical slices. NBPHS decreased p-aminohippurate (PAH) and TEA accumulation at NBPHS bath concentrations of 0.05 mM and 0.5 mM and 0.5 mM or greater, respectively. Renal gluconeogenesis was inhibited by NBPHS at 1 mM bath concentration, while LDH leakage was not increased at NBPHS bath concentrations up to 1 mM. The results demonstrate that NBPHS is a mild nephrotoxicant in vivo and in vitro, but does not have cytotoxic effects to renal tissues at the concentrations tested. From these results, it appears that halogen groups are essential to the nephrotoxic potential of N-(halophenyl)-2-hydroxysuccinimides or N-(halophenyl)succinimides and play an important role in the mechanism of NDPS nephrotoxicity following NDHS formation.
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PMID:Nephrotoxicity of N-(3-bromophenyl)-2-hydroxysuccinimide: role of halogen groups in the nephrotoxic potential of N-(halophenyl) succinimides. 865 56

Aminophenols and halogenated anilines induce nephrotoxicity and mild hepatotoxicity in rats. In this study, the in vivo and in vitro nephrotoxic potential of 4-amino-2-chlorophenol and 2-amino-4-chlorophenol, monochlorinated aminophenols and potential metabolites of 3-chloroaniline, was evaluated. Hepatotoxicity of both compounds was also examined in vivo. Male Fischer 344 rats (four/group) were administered 4-amino-2-chlorophenol hydrochloride (0.4, 0.8 or 1.0 mmol/kg), 2-amino-4-chlorophenol hydrochloride (0.4, 0.8 or 1.2 mmol/kg) or vehicle intraperitoneally (i.p.) and renal and hepatic function monitored for 48 h. Administration of 4-amino-2-chlorophenol (0.8 mmol/kg) induced nephrotoxicity, while only minor changes in kidney function were observed following administration of 0.4 mmol/kg of 4-amino-2-chlorophenol or 0.8 mmol/kg of 2-amino-4-chlorophenol. Increasing the dose of 4-amino-2-chlorophenol to 1.0 mmol/kg or 2-amino-4-chlorophenol to 1.2 mmol/kg resulted in lethality. Nephrotoxicity induced by 4-amino-2-chlorophenol was characterized by diuresis, increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, and marked proximal tubular damage, while 2-amino-4-chlorophenol induced milder effects on renal function and transient oliguria instead of diuresis. No hepatotoxicity was observed with either compound at any dose tested. In the in vitro studies, the direct effects of 4-amino-2-chlorophenol or 2-amino-4-chlorophenol on organic ion accumulation, pyruvate-stimulated gluconeogenesis and lactate dehydrogenase (LDH) leakage were determined using renal cortical slices. 4-Amino-2-chlorophenol and 2-amino-4-chlorophenol were almost equally effective in inhibiting organic anion or cation uptake and gluconeogenesis or increasing LDH leakage, although small differences in the minimum effective concentrations were present (minimum effective concentration, 0.01-0.5 mM range). These results demonstrate that 4-amino-2-chlorophenol is a more potent nephrotoxicant than 2-amino-4-chlorophenol in vivo. The results also indicate that the addition of a chloride group to aminophenols enhances renal toxicity.
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PMID:Nephrotoxicity of 4-amino-2-chlorophenol and 2-amino-4-chlorophenol in the Fischer 344 rat. 865 59

The activity of gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDG), N-acetyl-beta-D-glucosaminidase (NAG) was assessed in 53 patients with psoriasis (PS), 24 PS patients with affected kidneys, 50 patients with type 1 diabetes mellitus(DM). Enhanced activity of the enzymes occurred not only in nephropathy patients but also in those without proteinuria. AP and NAG were more active in PS, while LDG and NAG in DM. Both in PS and DM, NAG activity rose 3-4-fold compared to control. A direct correlation was found between enzymuria and uremia, glycemia (in hyperglycemia only) and cholesterolemia. An inverse relationship existed between enzymuria and uricosuria. The above changes in enzymic activity are attributed to impairment of tubules of the kidney induced by PS and DM. Diagnostic significance of enzymuria as a marker of early tubular involvement is confirmed by investigations of renal biopsies.
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PMID:[Urinary enzymes in the assessment of the early stage of kidney involvement in psoriasis and diabetes mellitus]. 877 18

In progressive renal disease the degree of renal failure correlates with interstitial scarring and the rate of progression correlates with the degree of proteinuria. This has led to the hypothesis that proteinuria may cause interstitial scarring. Human tubular cells (HTC) grown on permeable membrane supports were characterized to be predominantly of proximal tubular origin. HTC produce the matrix protein fibronectin in a polarised fashion the ratio of basolateral to apical secretion being 2.9 +/- 0.2 at 48 hours. The addition of serum proteins (1.0 mg/ml) to the apical medium resulted in increased basolateral secretion of fibronectin, 2.62 +/- 0.23-fold after 24 hours and 2.40 +/- 0.16-fold after 48 hours. Serum fractionation revealed that the stimulant to fibronectin production had a molecular weight 40 to 100 kDa. Platelet derived growth factor secretion was also stimulated to apical exposure to serum but transforming growth factor beta secretion was not detected. Addition of neutralizing anti-PDGF antibodies did not decrease fibronectin secretion. The activity of serum was not reproduced by albumin or by transferrin. Exposure of HTC to serum resulted in increased release of lactate dehydrogenase, suggesting a degree of cytotoxicity. This evidence could provide a mechanism for the link between proteinuria and interstitial scarring.
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PMID:Fibronectin production by human tubular cells: the effect of apical protein. 898 25

Nephrotoxic potential of laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa PCC 7806 (Pasteur Institute) was assessed in male rats. The animals were injected intraperitoneally with 0.5, 1.0 and 2.0 LD50 doses of lyophilized cell extract. Elevated plasma urea and creatinine levels were accompanied by decrease in protein and albumin levels, followed by hematuria, proteinuria and bilirubinuria. Also decrease in kidney lactate dehydrogenase and glutamic oxaloacetic transaminase indicated possible nephrotoxic potential of the cyanobacteria. The extract also produced various hematological changes associated with stagnant type of hypoxia. High performance liquid chromatography of the culture identified the active principle (toxin) as Microcystin-LR.
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PMID:Toxicity evaluation of freshwater cyanobacterium Microcystis aeruginosa PCC 7806: II. Nephrotoxicity in rats. 909 31

We describe a case of peripheral T cell lymphoma that is remarkable for its fulminate course and selective targeting of both kidneys. The patient was a 6-year-old girl who was in her usual state of good health until the onset of abdominal pain and fever. She was treated for acute oliguric renal failure and visual disturbances. A renal biopsy was performed. Biopsy findings were interpreted as suggestive of a vasculitic process, and treatment was initiated for a presumptive diagnosis of Wegener's granulomatosis. The patient died 3 days following admission, and autopsy revealed extensive bilateral kidney infiltration by a peripheral T cell lymphoma. The remainder of the body was spared with the exception of mild infiltration of the pulmonary parenchyma and choroid plexus by neoplastic lymphocytes. The neoplastic nature of the disease was confirmed utilizing immunoperoxidase stains and T cell receptor gene rearrangement. Primary renal lymphoma and renal failure attributable to involvement by lymphoma are rare findings that should be considered when other more common causes of renal insufficiency have been excluded. The presenting clinical complaints are generally of short duration, nonspecific, and atypical. Most patients exhibit oliguria. Physical examination may reveal hepatosplenomegaly, lymphadenopathy, and flank and/or abdominal mass(es). Laboratory findings frequently include an elevated serum creatinine, blood urea nitrogen, lactate dehydrogenase, and a mild proteinuria. Electrolyte abnormalities are variably present. Possible radiographic findings include hypodense or hypoechoic renal lesions and diffuse bilateral renal enlargement. Although the prognosis is dismal, survival may be prolonged utilizing current treatment modalities, and rare patients may be "cured" of disease. The clinical presentation, radiological findings, and prognosis of patients with clinically evident renal involvement by non-Hodgkin's lymphoma are discussed.
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PMID:Rapidly progressive T cell lymphoma presenting as acute renal failure: case report and review of the literature. 918 23

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.
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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.
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PMID:Long-term protein exposure reduces albumin binding and uptake in proximal tubule-derived opossum kidney cells. 962 Dec 78


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