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)

Chlorinated anilines are widely used as chemical intermediates in the manufacture of numerous dyes, pesticides, drugs and industrial compounds. The purpose of this study was to examine the nephrotoxic potential of the six dichloroaniline (DCA) isomers in vivo and in vitro. In the in vivo studies, male Fischer 344 rats (4-8 rats/group) were administered a single, intraperitoneal injection of a DCA isomer (0.4, 0.8 or 1.0 mmol/kg) as the hydrochloride salt or given vehicle (0.9% saline, 2.5 ml/kg), and renal function monitored at 24 and 48 h. Renal effects induced by DCA were characterized by decreased urine volume, increased proteinuria, hematuria, modest elevations in blood urea nitrogen (BUN) concentrations, decreased accumulation of p-aminohippurate (PAH) by renal cortical slices, and no change or a slight decrease in kidney weight. Renal morphological changes were observed as proximal tubular necrosis with lesser effects on distal tubular cells and collecting ducts. Based on the overall effects on renal function and morphology, the decreasing order of nephrotoxic potential was found to be 3,5-DCA greater than 2,5-DCA greater than 2,4-, 2,6- and 3,4-DCA greater than 2,3-DCA. The ability for the DCA to induce nephrotoxicity correlated well with the lipophilic properties of the DCA isomers and Hammett constants (sigma) for the various chloro substitutions. In the in vitro studies, renal cortical slices from naive male Fischer 344 rats were co-incubated with a DCA isomer (0-10(-3) M) and PAH or tetraethylammonium (TEA). All DCA isomers decreased PAH and TEA accumulation at 10(-3) M DCA concentration in the media with 3,5-DCA inducing the largest decrease at this concentration. These results indicate that DCA are capable of altering renal function in vivo and in vitro and that 3,5-DCA possesses the greatest nephrotoxic potential in vivo and in vitro.
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PMID:Acute nephrotoxicity induced by isomeric dichloroanilines in Fischer 344 rats. 239 36

Renal functions were examined in 102 patients with yusho in 1988, Frequencies of proteinuria, microhematuria and history of renal diseases were not different from 20 age-matched controls. The means of blood urea nitrogen, serum creatinine and serum uric acid levels of yusho patients did not differ from those of controls. The levels of serum beta 2-microglobulin and its urinary excretion showed no difference between two groups. Serum concentrations of sodium, potassium, chloride, calcium and phosphorus revealed no abnormality in all patients except for one who had hypophosphatemia. Urinary excretions of phosphorus, however, were significantly higher in yusho patients than in controls. Serum PCB levels, which were still higher in yusho patients, did not correlate with urinary excretions of phosphorus. The mechanism and the clinical significance of this phenomenon remain to be elucidated.
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PMID:[Renal function in patients with yusho]. 250 Dec

Toxic side effects of germanium dioxide contained in drugs that promote health, include nephropathy, anemia and peripheral neuropathy. Although the neuropathy, which we are interested in, is believed to occur in the patients taking excessive amounts of germanium dioxide, the pathogenesis of such neuropathy is not well understood. Therefore, we studied whether germanium dioxide causes the degeneration of the peripheral nerve in rats and monkeys. Our results showed that in rats, germanium dioxide administered orally and intraperitoneally, 100 mg/kg per day, 3 days a week for 8 weeks and 400 mg/kg per day, once a week for 8 weeks, respectively, did not produce a degeneration of myelinated fibers in teased fiber preparations and Epon-embedded sections of the peripheral nerve. In two monkeys also, germanium dioxide, administered orally, 30 to 40 mg/kg per day, 5 days a week for 8 months, did not produce a degeneration of myelinated fibers of the sural nerve on biopsy, although our results revealed proteinuria and elevated blood urea nitrogen. Further studies are warranted to elucidate the pathogenesis of germanium dioxide induced neuropathy.
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PMID:[Evaluation of germanium dioxide neurotoxicity in rats and monkeys]. 251 Feb 28

Forty-five adult clinic patients with chronic renal failure each supplied a 4-day weighed dietary record, a 24-h urine collection, and a nocturnal spot urine sample. Total nitrogen (N) losses derived from the urines were corrected for proteinuria and non-urea nitrogen excretion. Individual estimates of N intake were compared by correlation and assessing the level of agreement. Daily urea N excretion derived from the spot sample correlated well with the 24-h collection P less than 0.001, but the degree of agreement was poor, mean difference being +1.62 g with 95% limits of +5.7 to -2.47 g. The correlation between the spot-sample-derived N loss and dietary N intake was poor, r = 0.42; P less than 0.05. For 12 patients taking a low-protein diet, N intake correlated well with 24-h urine derived N losses, P less than 0.001, mean difference being +0.59 g, 95% limits +2.39 to -1.21 g. The correlation and agreement was less satisfactory for the subjects who had not received dietary instruction, due largely to individual variation in day-to-day protein intake. Use of spot urine samples is too inaccurate for routine clinical practice. Single 24-h urine derived estimates of N intake are only of value for assessing patients previously prescribed a low-protein intake.
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PMID:The estimation of dietary protein intake in chronic renal failure. 213 Mar 7

Spontaneous nephrotic mice (ICGN mice), a new mutant strain of mouse from outbred ICR, were clinically, macroscopically, histologically and immunohistochemically studied to establish their value as a model for human nephrotic syndrome. Most of the affected mice developed proteinuria, hypoproteinaemia and hypercholesterolaemia, and some of them developed systemic oedema. A high concentration of blood urea nitrogen (BUN) and a low haematocrit value were also observed. The kidneys of severe cases showed a decrease in size and had a yellowish granular surface. These findings indicated that the mice were terminally affected by chronic renal insufficiency. Histopathology demonstrated glomerular lesions consisting of thickened basement membranes of the capillary loops with irregular spike-like protrusions and enlargement of the mesangium unaccompanied by cellular proliferation. The immunofluorescence technique revealed positive granular staining for IgA, IgG and IgM and to a lesser extent for C3 along the capillary loops in affected mice. The similarity between this spontaneous disease and human nephrotic syndrome caused by idiopathic glomerular lesions is discussed. ICGN mice may be a useful animal model for this human disease.
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PMID:Characteristics of mutant mice (ICGN) with spontaneous renal lesions: a new model for human nephrotic syndrome. 252 1

MRL/Mp-lpr/lpr (MRL/l) mice spontaneously develop autoimmune kidney disease which resembles human systemic lupus erythematosus (SLE). Employing this strain of mouse, we examined the effect of several immunosuppressants and a newly synthetized anti-nephritic agent, 4-chloro-3',6'-dimethyl-2,2'-iminodibenzoic acid (TO-115) on both the development of immunological abnormalities and the clinical symptoms of autoimmune kidney disease. This study aimed to determine how much the magnitude of autoantibody suppression related to the degree of prevention of autoimmune nephritis. Immunological abnormalities were assessed by measuring the serum levels of anti-deoxyribonucleic acid and anti-trinitrophenyl antibodies, rheumatoid factor (RF), and immune complex (IC). The status of autoimmune kidney disease was monitored by means of the appearance of proteinuria and survival time and the measurement of serum levels of blood urea nitrogen (BUN) and cholesterol. Immunosuppressants such as cyclophosphamide (CY), 6-mercaptopurine (6 MP) and sodium aurothiomalate (SAT) remarkably suppressed the development of immunological abnormalities in a dose dependent manner. Interestingly, however, only CY showed the suppressive effect on the development of autoimmune kidney disease with prolongation of survival time and the excretion of proteinuria. In contrast, 6-MP and SAT did not inhibit the development of autoimmune kidney disease. On the other hand, TO-115 did not suppress the development of immunological abnormalities, but it restrained the symptoms of autoimmune kidney disease. Taken together, the suppression of autoantibody production does not always lead to prevention of the development of autoimmune kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of several kinds of drugs on the development of autoimmunity in MRL/Mp-lpr/lpr mice; lack of correlation between the suppression of autoantibody production and prevention of autoimmune disease. 252 11

1. We have investigated the effects of the non-renin-mediated actions of angiotensin converting enzyme inhibitors on the progression of chronic renal failure accelerated by hypertension. For this purpose, we studied the effects of captopril (a thiol-containing angiotensin converting enzyme inhibitor), enalapril (an angiotensin converting enzyme inhibitor without a thiol group) and cysteine (a thiol-containing amino acid which has no angiotensin converting enzyme-inhibitory action) in adriamycin-treated rats with deoxycorticosterone acetate-salt hypertension, in which the renin-angiotensin system was suppressed. 2. There were no significant differences in blood pressure between these groups and the control group [adriamycin-treated group with deoxycorticosterone acetate-salt loading, 206 +/- 7 mmHg (27.4 +/- 0.9 kPa) at week 10]. 3. Massive proteinuria occurred in all groups. At the end of the experiment (at week 10), urinary protein excretion was significantly reduced in the captopril and cysteine groups compared with the control group. No manifest improvements appeared in the enalapril group. 4. Levels of serum creatinine and blood urea nitrogen increased progressively. At week 10, the increases in the serum levels of creatinine were less in the captopril (87 +/- 16 mmol/l) and cysteine (80 +/- 19 mmol/l) groups than in the control group (124 +/- 27 mmol/l) (P less than 0.01). No marked differences were found between the control and enalapril groups. 5. Captopril and cysteine caused more than a three-fold reduction in the focal glomerulosclerosis score when compared with that in the control group, but enalapril did not decrease the score. The extent of tubulointerstitial change was parallel with the focal glomerulosclerosis score. 6. We conclude that the thiol group is possibly involved in the mechanism of the beneficial effects of some angiotensin converting enzyme inhibitors on the progression of chronic renal failure exacerbated by hypertension.
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PMID:Differences in the effects of angiotensin converting enzyme inhibitors with or without a thiol group in chronic renal failure in rats. 254 Sep 31

Streptozotocin (45 mg/kg) was intravenously administered to 7-week-old Wistar rats through their tail veins. After 11 days, the rats were divided into two groups. One group was fed a lipid-free diet (90%, w/w) plus lard (8%) and safflower oil (2%) for four weeks (Diet 1 group, n = 12). The other group was fed in the same way, except that safflower oil was replaced by 90% pure eicosapentaenoic acid (EPA) ethyl ester (Diet 2 group, n = 13). Twenty-four-hour urine was collected just before the diets started and during the experiment at 7-day intervals. In the second and third week, the levels of proteinuria were significantly lower in the Diet 2 group than they were in the Diet 1 group. There was no significant difference in the levels of creatinine, urea nitrogen, or lipids in plasma or in body weights between the two groups after four weeks on the diets. Because Diet 2 reduced proteinuria of diabetic rats compared to Diet 1, an EPA-rich diet may retard the development of diabetic nephropathy.
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PMID:Effect of eicosapentaenoic acid ethyl ester on proteinuria of streptozotocin-induced diabetes mellitus in rats. 255 48

A comparative clinico-pathological study was performed on 61 children and 51 adults with IgA nephropathy. Hematuria and/or proteinuria found by chance was the most common initial clinical sign, being observed in 82.0% of the children and 52.9% of the adults (p less than 0.001). At renal biopsy, hypertension and severe proteinuria were found in 9.8% and 33.3% of the adults and 0 and 14.8% of the children (p less than 0.05, p less than 0.05). Elevations of blood urea nitrogen and serum creatinine were found at the time of biopsy in 21.6% and 9.8% of the adults but in none of the children (p less than 0.001, p less than 0.05). On histological studies, proliferative changes of the glomerulus were similar in the two groups, and diffuse mesangial proliferation was found in 62.3% of the children and 51.0% of the adults (although the difference was not significant). Focal glomerulosclerosis and tubular atrophy were found in 52.9% of the adults and 32.8% of the children (p less than 0.05). These results suggest that focal glomerulosclerosis with tubular atrophy is correlated with deterioration of renal function, hypertension and age at renal biopsy, and has an important influence on the prognosis of patients with IgA nephropathy.
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PMID:[IgA nephropathy in Japanese children and adults: a comparative study of clinico-pathological features]. 258 35

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


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