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)

We have previously shown that the administration of a thromboxane A2 (TXA2) synthase inhibitor (FCE 22178) reduced the progression of glomerular lesions and proteinuria in MNS rats, an inbred strain which develops an age-related nephrotic syndrome. In the present study we investigated the effect of FCE 22178 on the plasma lipoproteins of MNS rats at 28 weeks of age (with mild proteinuria and moderate dyslipoproteinemia) and at 48 weeks of age (with heavy proteinuria and severe dyslipoproteinemia). Drug treatment reduced proteinuria (by 70% and 36% at 28 and 48 weeks of age, respectively) plasma cholesterol (by 36% and 27% at 28 and 48 weeks of age, respectively) and prevented the decrease of plasma albumin observed in untreated rats (C-MNS) 48 weeks old. In treated rats (T-MNS), the decrease of proteinuria was positively correlated with that of plasma cholesterol. FCE 22178 reduced the elevation in plasma HDL1 (by 17.4%) and HDL2 levels (by 30%), a key feature of nephrotic dyslipoproteinemia in the rat. From 28 to 48 weeks of age plasma apo A-I and apo E increased 217% and 128%, respectively, in C-MNS rats and 191% and 121%, respectively, in T-MNS rats. A significant increase of apo A-I/apo E ratio was found in C-MNS rats from 28 (2.28 +/- 0.36) to 48 weeks of age (3.84 +/- 0.9) but not in T-MNS rats. FCE 22178 altered the lipid composition of VLDL and HDL2 by reducing the content of cholesteryl esters and increasing that of free cholesterol and phospholipids. These findings suggest that the beneficial effect of FCE 22178 on the dyslipoproteinemia of nephrotic MNS rats is secondary to the amelioration in kidney function and to the reduction of proteinuria produced by this drug.
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PMID:The effect of a thromboxane A2 synthase inhibitor on the dyslipoproteinemia of an inbred rat strain with spontaneous age-related nephrotic syndrome. 789 85

The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progressively up to about 0.5 g/day (versus 0.07 g/day in controls; P < 0.001), while the creatinine clearance remained stable at about 80% of control values. Hypercholesterolaemia was observed 6 weeks after ADR, and increased progressively up to 7.0 +/- 1.0 mmol/l (versus 2.3 +/- 0.1 mmol/l in controls; P < 0.001). Cholesterol was primarily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (apo) A-I increased by more than 400% in the nephrotic rats (P < 0.001). Apo B and apo E increased by about 60% (P < 0.01), whereas apo A-IV remained unchanged. Focal sclerotic lesions in glomeruli had an incidence of 50 +/- 10% in ADR rats versus 2 +/- 1% in controls (P < 0.001). Immunohistochemistry revealed apo A-I and apo A-IV in the visceral epithelium. Apo E immunoreactivity and lipid deposits were observed in focal glomerular sclerotic lesions of ADR rats. Neither apolipoproteins nor lipids were detected in glomeruli of controls. Proximal tubular localization of apolipoproteins was extensive for apo A-I, apo A-IV and apo E, but no differences were observed in tubular deposition of apolipoproteins between ADR and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma lipoproteins and renal apolipoproteins in rats with chronic adriamycin nephrosis. 825 16

This study offers morphological evidence of the involvement of lipid abnormalities in human glomerular injury. Renal biopsy tissues from patients with several types of glomerular diseases were immunocytochemically examined using antibodies to apolipoproteins (apo) A-I, B-100, and E, and antibodies to low density lipoprotein (LDL) receptors and scavenger receptors. Immunofluorescent staining showed the predominant deposition of apo B and apo E in the mesangial area in mesangial proliferative types of glomerulonephritis; the distribution and staining intensity of these apolipoproteins correlated with the grade of mesangial proliferation and proteinuria, but were independent of plasma lipid levels. Immunoelectron microscopy revealed that apo B and apo E were distributed in droplets within glomerular epithelial and mesangial cells or in a granular pattern in the expanded mesangial matrix. Apo A-I was mainly localized in the visceral epithelial cells of normal human kidneys. Staining for apo A-I was increased in the glomerular epithelial cells of nephritic kidneys, compared to the pattern in normal human kidneys, and was decreased in the sclerosed areas of glomeruli. An immunogold technique revealed the expression of LDL receptors on the surface membranes of glomerular mesangial and epithelial cells. Dual immunofluorescent staining showed that apo B and LDL receptors were occasionally co-localized in nephritic glomeruli. Scavenger receptor was detected on the plasma membranes of mesangial and visceral epithelial cells. The glomerular expression of scavenger receptor was increased in glomeruli with marked mesangial proliferation. In addition, the expression of this receptor was intense in monocytes/macrophages occasionally infiltrating the glomeruli. Our present findings indicate that in human nephritic kidneys, glomerular epithelial and mesangial cells express both LDL receptors and scavenger receptors. The accumulation of apolipoproteins, whether receptor-mediated or mediated by other mechanisms, can occur independently of plasma lipid levels, and may be associated with mesangial expansion and proteinuria.
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PMID:Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases. 847 30

Decreased response to vasopressor agents characterizes pregnancy. Endothelium-derived relaxing factors and vasodilating prostaglandins play an important role in the vascular tone during pregnancy. Since inhibition of nitric oxide (NO) biosynthesis induced by NO2-arginine enriched diet produced hypertension we measured in vivo cardiovascular responses to PGF2 alpha, L-arginine (L-arg) and cicletanine (Cic, IPSEN, France) which enhances PGI2 production. From day 13 to day 20 of gestation 4 groups of female Wistar rats were fed NO2-arg (31 mg/kg/d), NO2-arg+Cic (10 mg/kg/d), Cic enriched or control diet (C). Mean arterial pressure (MAP) was measured via a carotid catheter in anesthetized rats. Injection of PGF2 alpha (50 micrograms/kg) in jugular vein significantly increased MAP in the NO2-arg group versus, NO2-arg+Cic, Cic and C group (+23.5 +/- 3.3 vs +15.7 +/- 2.2, +15.8 +/- 2.2 and +17 +/- 1.85 mmHg; p < 0.01). Injection of L-arg (100 mg/kg) or Cic (1 mg/kg) 5 min before PGF2 alpha produced no modification in MAP in C and Cic group. Likewise in NO2-arg group injection of L-arg or Cic produced a diminished pressor response to PGF2 alpha (+23.5 +/- 3.3 vs -17.5 +/- 1.7 mmHg; p < 0.05 and +15.2 +/- 2.4 mmHg; p < 0.01 respectively). In NO2-arg+Cic group, only injection of Cic induced a diminished pressor response to PGF2 alpha which is more important without L-arg (+15.7 +/- 2.2 vs +9.1 +/- 1.3 mmHg; p < 0.001) or with L-arg (+13.6 +/- 1.5 vs +9.1 +/- 1.3 mmHg; p < 0.01). Cicletanine also significantly diminished the proteinuria in the NO2-arg+Cic group versus NO2-arg group (13.9 +/- 4.36 vs 63.4 +/- 21.6 mmHg; p < 0.01). IN CONCLUSION, chronic NO synthesis inhibition enhanced blood pressure and pressor responses to PGF2 alpha during pregnancy in rats. Chronic administration of cicletanine in Wistar pregnant rats decreases the response to vasopressor agents like PGF2 alpha. Moreover acute and chronic administration of cicletanine blunted the pressor effect, which was lower than in normal gestation.
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PMID:[Chronic and acute effect of cycletanine in NO-dependent hypertensive pregnant rats]. 857 78

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi). Infusion of dextran or albumin reduces lipid levels suggesting that reduced plasma pi plays a role in causing hyperlipidemia in the nephrotic syndrome. To determine whether apolipoprotein (Apo) levels were affected by pi, passive Heymann nephritis (HN) was created in 20 rats. Hyperoncotic (25%) human albumin or ficoll was infused continuously into each of 5 HN rats adjusted to maintain a plasma pi above 20 mm Hg. Either saline or a mixture of amino acids calculated to approximate those released from catabolized human albumin were infused into 5 HN as controls. Urinary rat albumin loss was not different between the 4 groups of HN. Plasma apo A-I, B and E were all increased significantly in saline and amino acid infused HN, but apo A-IV was decreased. Infusion of either albumin or ficoll normalized apo A-I, and apo E levels in HN even though proteinuria continued unabated. In contrast, apo B remained significantly elevated in HN infused with albumin, but was reduced to normal by ficoll. Fifteen non-nephrotic control animals were studied in 3 groups of 5 animals each; one receiving human albumin, one ficoll, both adjusted to increase plasma pi to supranormal levels, and a 3rd group received saline. In contrast to HN, plasma apo A-I, E, and B levels were unaffected by albumin or ficoll infusion in control animals. Ficoll caused a significant reduction in apo A-IV in both HN and control animals to subnormal levels, but albumin infusion was without effect. Reduced plasma pi, but not reduced plasma albumin is necessary for increased apo A-I, and E levels in the nephrotic syndrome. When plasma pi is normal extensive proteinuria does not increase plasma apo A-I or E levels. Factors other than an albumin concentration or pi, such as persistent urinary protein loss, play a role in establishing increased apo B containing lipoproteins in the nephrotic syndrome. Ficoll may cause changes in plasma lipoprotein levels by means other than its ability to increase plasma pi.
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PMID:Effect of plasma oncotic pressure on apolipoprotein levels in rats with Heymann nephritis. 867 21

Nitric oxide (NO) synthesis is induced in glomeruli in glomerulonephritis; its role in the pathogenesis of glomerular injury is unknown. Interpretation of its role using the currently available analogues of L-arginine as in vivo inhibitors of NO is complicated by their lack of specificity for inducible NO synthase (iNOS). As NO synthesis by iNOS depends on extracellular L-arginine, we have here examined effects of L-arginine depletion on glomerular NO synthesis and the course of accelerated nephrotoxic nephritis (NTN). Arginase, which converts L-arginine to urea and L-ornithine, was used to achieve L-arginine depletion. A single dose of i.v. arginase produced complete depletion of plasma arginine for four hours. Two forms of NTN were induced in preimmunised rats by nephrotoxic globulin: (1) the systemic form of the model by intravenous nephrotoxic globulin; or (2) the unilateral form of model by left kidney perfusion with nephrotoxic globulin, which avoids the complications of systemic administration of nephrotoxic globulin. Arginase reduced plasma arginine levels and the synthesis of nitrite (the stable end-product of NO) by NTN glomeruli (95% inhibition). Proteinuria was exacerbated. There was no effect on early (24 hr) leukocyte infiltration. In the systemic form of the model arginine depletion by i.v. arginase increased glomerular thrombosis at 24 hours, and the severity of histological changes at four days, accompanied by systemic hypertension. In the unilateral form of the model, where i.v. arginase did not induce hypertension, there was no increase in thrombosis or histological severity of nephritis. These results show that arginine depletion, which inhibits glomerular NO synthesis in NTN, leads to increased proteinuria. Where injury is severe, or accompanied by systemic hypertension, the disease is further exacerbated by glomerular thrombosis. These results suggest that NO has an important role in limiting acute glomerular injury.
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PMID:L-arginine depletion inhibits glomerular nitric oxide synthesis and exacerbates rat nephrotoxic nephritis. 869 29

Two substrains of the fawn-hooded (FH) rat have been developed, one of which develops progressive hypertension and proteinuria, the FHH, and one which shows little increase in blood pressure and no renal damage, the FHL. Other hypertensive rodent models show primary metabolic disturbances before the development of renal damage, notably hypertriglyceridemia, which may also contribute to progression of renal disease. In this study we evaluated whether hyperlipidemia is a primary disturbance in FHH, or only occurs secondary to proteinuria. Lipid levels were determined before and after development of proteinuria, and compared to those found in age-matched FHL. We also determined whether reducing proteinuria with lisinopril would normalize lipid levels in aging FHH. At 4 weeks of age, proteinuria was very low (2-3 mg/day) in both FHH and FHL. While proteinuria increased steadily in aging FHH, reaching 350 +/- 62 mg/day at 40 weeks, much less increase was observed in FHL over the same period (32 +/- 5 mg/day at 40 weeks). Blood pressure was markedly higher in adult FHH than in FHL (158 +/- 2 vs. 129 +/- 2 mm Hg, p < 0.01). In 4-week-old FHL and FHH, plasma cholesterol levels were similar. Subsequently, cholesterol increased in FHH, reaching 3.4 +/- 0.9 mmol/l at 40 weeks, whereas cholesterol was barely affected by aging in FHL (2.1 +/- 0.2 mmol/l at 40 weeks). At 4 weeks, triglyceride levels were lowest in FHH. Subsequently, triglycerides increased in FHH, reaching 3.5 +/- 1.5 mmol/l at 40 weeks, as compared to 1.3 +/- 0.2 mmol/l in FHL. Besides a transient increase in triglyerides in lisinopril-treated FHH at 11 weeks, increments in blood pressure, proteinuria, cholesterol, triglycerides and apolipoproteins A-I, B and E aging FHH were effectively prevented by lisinopril. These data strongly suggest that there is no primary difference in lipid metabolism between FHH and FHL and that changes in plasma lipids in FHH as compared to FHL are all secondary to proteinuria.
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PMID:Hyperlipidemia is secondary to proteinuria and is completely normalized by angiotensin-converting enzyme inhibition in hypertensive fawn-hooded rats. 937 31

In a prospective, uncontrolled multicenter study, we have evaluated the effects of probucol on hyperlipidemia, proteinuria, and glomerular filtration rate (GFR) in hyperlipidemic children with persistent nephrotic syndrome. Probucol was started for a total of 12 weeks in 8 children and for 24 weeks in 14 children. Lipoprotein profiles, serum malondialdehyde (MDA) levels, proteinuria, renal function, and electrocardiogram were monitored every 4 weeks. Side effects were recorded by questionnaire. Treatment was completed by 7 of 8 patients for 12 weeks and by 7 of 14 children for 24 weeks. After 12 weeks, the mean serum concentrations of triglycerides (-15%), total cholesterol (-25%), very low-density lipoprotein-cholesterol (-27%), low-density lipoprotein-cholesterol (-23%), and high-density lipoprotein-cholesterol (-24%), as well as apolipoprotein (apo) A-I (-19%), apo B (-21%), and MDA (-32%) were reduced. The positive effects of probucol on the lipoprotein profile persisted over 24 weeks; however, there was no significant effect on either proteinuria or GFR. In conclusion, probucol had beneficial effects on lipoproteins and lipid peroxidation, but improved neither proteinuria nor GFR. The drug was generally tolerated well, but had to be discontinued because of a prolonged QT interval in 4 of 22 patients.
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PMID:Probucol for treatment of hyperlipidemia in persistent childhood nephrotic syndrome. Report of a prospective uncontrolled multicenter study. 1010 Feb 82

Lecithin: cholesterolacyltransferase (LCAT) transacylates the fatty acid at the sn-2 position of lecithin to the 3beta-OH group of cholesterol forming lysolecithin and the majority of cholesteryl ester found in plasma. LCAT participates in the reverse cholesterol transport pathway in man where it esterifies tissue-derived cholesterol following efflux from peripheral cells into HDL. Only 38 unique mutations in the human LCAT gene have been reported worldwide. Our French female proband presented with corneal opacity and no detectable plasma LCAT activity using either endogenous or exogenous assays. Her total plasma cholesterol and HDL cholesterol were low (2.34 mmol/l and 0.184 mmol/l, respectively) with a very high cholesterol/cholesteryl ester molar ratio (10.9:1). Plasma triglycerides were 0.470 mmol/l with low apo B (40.5 mg/dl), apo A-I (14.7 mg/dl), apo A-II (6.8 mg/dl) and apo E (2.1 mg/dl) levels. Plasma lipoprotein analysis by ultracentrifugation showed very low HDL concentrations and a characteristic shift of the lipoprotein profile towards larger, less dense particles. No proteinuria, renal dysfunction or signs of atherosclerosis were noted at age 45. Sequence analysis of her LCAT gene showed a novel homozygous TG-deletion at residues 138-139 that resulted in a frameshift causing the generation of a stop codon and premature termination of the LCAT protein at amino acid residue 144. Western blotting of the patient's plasma using a polyclonal IgY primary antibody against human LCAT failed to demonstrate the presence of a truncated LCAT protein. A 53 bp mismatched PCR primer was designed to generate an Fsp 1 restriction site in the wild type sequence of exon 4 where the mutation occurred. The 155 bp PCR product from the wild type allele produced a 103 bp and 52 bp fragment with Fsp 1 and no cleavage products with the mutant allele thus permitting rapid screening for this novel mutation.
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PMID:Classical LCAT deficiency resulting from a novel homozygous dinucleotide deletion in exon 4 of the human lecithin: cholesterol acyltransferase gene causing a frameshift and stop codon at residue 144. 1048 97

The purpose of this study was to assess the prevalence of dyslipoproteinemia and to analyze the clinical variables that are associated with it in a sample of premenopausal systemic lupus erythematosus (SLE) patients. We studied 53 premenopausal (34.5 y) SLE outpatients and 45 controls. Clinical variables studied included patient age, weight, height, body mass index (BMI), age at disease onset, disease duration, clinical activity of SLE, renal involvement and drug therapy. Total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides were measured using standard enzymatic techniques. Apolipoproteins (apo) A-I and B were determined by radial immunodiffusion. Twenty-nine patients (55%) and 14 controls (30%) had dyslipoproteinemia. An increase in TC, triglycerides, HDL3-C, apo A-I and apo B, and a decrease in HDL2-C and HDL-C/TC index was found in SLE patients in comparison with controls. TC (P = 0.007), apo B (P = 0.02), LDL-C (P = 0.03) and triglycerides (P = 0.0001) were significantly correlated with proteinuria. Patients on prednisone therapy had higher triglycerides levels (P = 0.03) than untreated patients. TC (P = 0.01), LDL-C (P = 0.006) and triglycerides (P = 0.04) were also correlated with the dose of prednisone. Dyslipoproteinemia is a common feature in adult SLE premenopausal patients which is characterized by an increase in TC, triglycerides and apo B, and an abnormal distribution of HDL subclasses. Corticosteroid therapy and proteinuria are the best predictors of dyslipoproteinemia in these patients.
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PMID:Lipid and lipoprotein levels in premenopausal systemic lupus erythematosus patients. 1140 67


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