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)

Intravenous administration of the aminonucleoside of puromycin produces the nephrotic syndrome (proteinuria, hypercholesterolemia, hypoproteinemia and edema) in rats. This model is very similar to human nephrotic syndrome caused by various disease states. The current study was designed to assess the nature of urinary lipoproteins in the urine of nephrotic rats, including studies related to the urinary loss of the "activator" apolipoproteins for the lipoprotein lipase-triglyceride interaction. Sprague-Dawley rats were given a single intravenous injection (10 mg/100 g) of puromycin aminonucleoside. Plasma and urine were collected before and 7, 18, 29, 36, and 53 days after injection of puromycin. Urine was fractionated in the preparative ultracentrifuge into density (d) fractions less than 1.006 (very low-density lipoproteins), d = 1.006-1.063 (low-density lipoproteins), and d = 1.063-1.210 (high-density lipoproteins--HDL). The cholesterol, triglyceride, phospholipid, and protein content of these fractions was analyzed. Lipoprotein electrophoresis was performed in agarose agar. Urine from normal and nephrotic rats was added to an in vitro system containing lipoprotein lipase and triglyceride. The free fatty acids (FFA) liberated were then measured as an index of urinary activator property on this system. Measurable urinary lipoproteins were present only on days 7 and 18 after induction of the nephrotic syndrome. Coelectrophoresis of these urinary lipoproteins with rat plasma revealed a single band having alpha- (HDL) electrophoretic mobility. The total mean protein content of day-7 urinary lipoproteins (64.3%) was greater than the content of plasma HDL (52.9%). The protein content of urinary lipoproteins also increased with time. When day-7 and day-18 postinjection urine at nephrotic rats was added to the lipoprotein lipase system, the hydrolysis of triglyceride yielded a mean of 0.320 and 0.235 muEq FFA/ml/20 min, respectively. Control rat urine yielded 0.030 muEq FFA/ml/20 min and 0.000 muEq FFA/ml/20 min 7 and 18 days after injection of normal saline, respectively. It is inferred that in this experimental model (1) high-density lipoproteins are probably excreted in the glomerular filtrate, (2) alterations in the composition of the excreted lipoproteins may occur during their passage through the nephron. The possibility that only a selective portion of the HDL spectrum is excreted into the glomerular filtrate cannot be excluded. It is suggested that the urinary or renal loss of this functionally important lipoprotein may contribute to the pathophysiology of hyperlipoproteinemia in the nephrotic syndrome.
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PMID:High density lipoproteinuria in nephrotic syndrome. 18 67

Plasma lipoproteins and postheparin plasma were investigated in a patient with familial LCAT deficiency with normal renal function and without proteinuria. As revealed by gelfiltration the large molecular weight LDL2 was not present, and myelin structures were not found in LDL1 or LDL2 when she was on her ordinary diet. After 60--65% fat diet for one week the large molecular LDL2 was found, but only in low concentration. We have no explanation for the difference in the lipoprotein abnormalities of this patient and others with this disease. There is no major difference in the fat content in the ordinary diet of the Norwegian patients with familial LCAT deficiency, nor has our patient any clinical signs of malabsorption. Furthermore, there was no difference in lipoprotein lipase or hepatic lipase activity in postheparin plasma between our patient and others with the same disease. However, whereas hepatic lipase activity was within the reference values, lipoprotein lipase activity was rather low in all patients investigated. We suggest that impaired VLDL catabolism in plasma, because of LCAT deficiency and low lipoprotein lipase activity, may partly explain the low HDL concentration consistently found in patients with familial LCAT deficiency.
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PMID:Familial lecithin:cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function. 21 75

Post-prandial lipaemia was investigated in a group of nine subjects with nephrotic syndrome by following the concentrations of triglyceride and retinyl palmitate in the d < 1.006 g ml-1 fraction of plasma after a standard oral fat load containing vitamin A. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in post-heparin plasma. Subjects with other renal disease but insignificant proteinuria acted as controls. The time course of the lipaemic response was similar in both groups although individual patients demonstrated a prolonged lipaemia. Overall, there were no significant differences in the rise in triglyceride at 6 h (nephrotic--median 2.53 mmol l-1; range 0.87-4.76 vs. control 1.88; 0.38-4.12, P = 0.34), the peak concentration of retinyl palmitate (nephrotic 0.87 mg dl-1; 0.27-2.16 vs. control 0.65; 0.24-1.89, P = 0.97) or the areas under the curve from 0-24 h for triglyceride (nephrotic 10.5 mmol. h l-1; 2.9-43.6 vs. control 9.7; 4.3-27.0, P = 1.0) or retinyl palmitate (5.5 mg.h dl-1; 1.0-23.4 vs. 4.3; 1.5-12.4, P = 0.7). At baseline, the particles in the d < 1.006 g ml-1 fraction of plasma from nephrotic subjects had a higher free cholesterol:phospholipid ratio but this difference was no longer apparent 6 h after the test meal. There were no differences in total heparin-releasable lipase, lipoprotein lipase or hepatic triglyceride lipase activities between the two groups. These data suggest that impaired clearance of chylomicrons is not a major contributor to nephrotic hyperlipidaemia in man.
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PMID:Post-prandial lipoprotein metabolism in nephrotic syndrome. 147 53

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.
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PMID:Pathophysiology of hyperlipidemia in diabetes mellitus. 171 Jul 39

Hyperlipidemia is common in patients with glomerular proteinuria. It may contribute to atherosclerotic complications and accelerate glomerular damage. Early trials of the fibric acid derivative clofibrate led to a myositis syndrome causing many nephrologists to abandon attempts at treatment of nephrotic hyperlipidemia. Recent trials with lipid-lowering medications have been successful without major side effects. The bile acid sequestrants colestipol and cholestyramine bind bile acids in the gut and deplete the hepatic cholesterol pool, thus inducing LDL hepatocyte receptors. Recent studies showed a reduction of total cholesterol of 8-20% and LDL cholesterol of 19-31% without significant changes in HDL cholesterol. Probucol has reduced total cholesterol 23-30% and LDL cholesterol 23-25% in nephrotic patients. Although HDL cholesterol was reduced, the LDL/HDL ratio remains favorably changed. The fibric acid derivative gemfibrozil inhibits adipose lipolysis and enhances lipoprotein lipase activity thus decreasing LDL synthesis and increasing its removal. It caused a large decrease in triglycerides with a 13-15% decrease in total and LDL cholesterol in a recent trial. HDL cholesterol increased 18%. The HMG-CoA reductase inhibitors inhibit the rate-limiting step in cholesterol biosynthesis hence inducing an increase in LDL receptors on hepatocytes. Trials have shown decreases of 18-36% in total cholesterol and 18-47% in LDL cholesterol, while HDL cholesterol was either increased or unchanged. The use of lipid-lowering agents of several classes has been effective in ameliorating the progression of glomerular damage in a number of different models of glomerulosclerosis. Nevertheless, so far in humans lipid lowering drugs have not been established to have an effect on either the degree of proteinuria or the progression of glomerulosclerosis.
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PMID:Lipid-lowering agents in proteinuric diseases. 225 70

It has been established previously that nephrotic hyperlipidemia is characterized by both an increase in lipid synthesis and a defect in removal of lipoproteins. The relationship between these defects and altered albumin metabolism is uncertain. One hypothesis is that hepatic lipogenesis increases in parallel with albumin synthesis. To test this hypothesis, albumin synthesis was increased in nephrotic rats fed an 8.5% protein diet (LPN) by increasing dietary protein to 40% (HPN). Proteinuria was modulated in half of the rats fed 40% protein by enalapril (HPE). Albumin synthesis was the same in both HPN and HPE, but proteinuria was reduced in HPE compared to HPN, and so were serum cholesterol and triglycerides (TG). To examine the effect of serum albumin on lipid clearance in the absence of proteinuria, plasma clearance of chylomicrons (CM) and VLDL was measured in Nagase analbuminemic rats (NAR) and found to be no different than in normal SD rats. When proteinuria was induced in NAR and in SD rats, a severe and identical defect in both CM and VLDL clearance was acquired in both groups and blood lipid levels were increased to a similar degree in both groups. Neither hyperlipidemia nor defective removal of lipoproteins from the circulation are linked to albumin synthesis or serum albumin concentration but result, at least in part, from proteinuria. Postheparin lipoprotein lipase (LPL) activity was reduced slightly in nephrotic animals compared to nonnephrotic controls, but the most striking finding was a highly significant decrease in postheraprin LPL activity in normal NAR compared to SD rats (P less than 0.001), suggesting that reduced LPL activity is not responsible for reduced clearance of CM and VLDL in nephrotic rats.
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PMID:Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. 238 6

Hyperlipoproteinemia corresponding to the IIb type was developed in the most patients with diffuse chronic glomerulonephritis and nephrotic syndrome. In blood concentration of very low density lipoproteins (VLDL) was increased with simultaneous accumulation of cholesterol in the fraction. Under conditions of nephrotic syndrome most distinct increase of the Sf 20-12 fraction and content of triglycerides, as compared with the Sf 12-0 fraction, was found in lipoproteins of low density (LDL) Content of cholesterol in high density lipoproteins (HDL) was decreased as compared with donor blood. Activity of postheparin lipoprotein lipase decreased in the most patients. Inspite of cholesterol accumulation in VLDL, triglycerides containing in the Sf 400-100 fraction of the patients were hydrolyzed by rat lipoprotein lipase at the high rate; hence, alteration of VLDL composition should be considered as a factor responsible for impairment of lipoprotein metabolism in blood. Content of VLDL was increased in blood of the patients within the first week of dexamethasone treatment. Within the subsequent period the hormone exhibited distinct hypolipidemic effect. In presence of the hormone heparin-dependent lipoprotein lipase was activated. Increase of lipolytic activity was observed in urine of patients simultaneously with distinct proteinuria.
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PMID:[Characteristics of lipoprotein metabolism impairments in nephrotic syndrome]. 685 31

The aim of the study was to document postheparin plasma lipoprotein lipase (LPL) and hepatic lipase activities and relate these to serum lipid, lipoprotein and apolipoprotein concentrations in 85 patients with kidney function ranging from normal to dialysis dependency. Strict selection criteria were applied in order to exclude conditions other than renal failure which may influence lipid metabolism. Stress was laid on minimizing proteinuria and inflammatory activity. The changes in the lipoprotein pattern were numerically strikingly modest compared to those previously reported. This probably reflected the intention to elucidate the contribution of reduced renal function as such to the dyslipoproteinemia of renal failure, a condition often associated with confounding factors. Significant increases in serum concentrations of triglycerides and apolipoprotein CIII were already observed in moderate renal failure, whereas serum concentrations of high density lipoprotein cholesterol and plasma LPL activities were decreased only in severe renal failure. Plasma LPL activities were not significantly reduced in hemodialysis patients (probably due to anticoagulation with low molecular weight heparin), but serum concentrations of triglycerides and apolipoprotein CIII were significantly increased. A multiple regression analysis, taking glomerular filtration rate, LPL and apolipoprotein CIII into account, showed that both plasma LPL activity and serum apolipoprotein CIII concentration independently predicted serum triglyceride concentration. However, serum apolipoprotein CIII concentration was a much stronger predictor than plasma LPL activity. Thus, a decrease in LPL activity does not seem to be a prerequisite for the hypertriglyceridemia of uremia, but it probably accentuates this condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure. 747 64

The effects of amino acid-fortified low casein and fish oil (FO) diets on hyperlipidemia and proteinuria were studied in rats with nephrotoxic serum nephritis. After an antiserum injection, rats were maintained for 14 d on four different experimental diets: a 20% casein diet containing corn oil (CO) or FO, or an 8% casein diet supplemented with cystine plus threonine containing CO or FO. The 8% casein diets reduced urinary protein excretion in nephritic rats without inducing severe growth retardation or fatty liver compared with the basal 20% casein diets. Both the 8% casein diet and the FO diet decreased serum cholesterol, triglyceride and phospholipid levels in nephritic rats, and nonesterified fatty acid levels were decreased by FO feeding. In nephritic animals, hepatic cholesterol synthesis was decreased by the 8% casein diets compared with the 20% casein diets, and tended to be reduced by FO feeding between groups at the same casein levels. No effect of diet was observed on fatty acid synthesis among the nephritic rats. FO administration to the nephritic animals suppressed fecal steroid excretion. While lipoprotein lipase activity was unchanged among the nephritic rats, hepatic triglyceride lipase activity was reduced by either the 8% casein or FO diet. The results suggest that the hypolipidemic action of low casein diets may, at least in part, be due to reduced hepatic cholesterol synthesis and suppressed triglyceride secretion from the liver. They also suggest that the hypolipidemic action of FO may, at least in part, be due to reduced hepatic cholesterol synthesis and decreased fatty acid mobilization from peripheral adipose tissue.
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PMID:Effects of low casein and fish oil on hyperlipidemia and proteinuria in nephritic rats. 786 59

It has been reported that focal and segmental glomerulosclerosis (FSGS) with pronounced proteinuria rapidly develop in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. We found that even when they are fed a standard rat chow (0.3% NaCl), DS rats, especially males, exhibit marked proteinuria, hypoalbuminemia, and hypertriglyceridemia without marked hypertension at 32 to 38 weeks of age. The nephrosis was associated with spontaneously developed FSGS. We therefore investigated the mechanism of hypertriglyceridemia in nephrotic animals. Plasma triglyceride (TG) and apoprotein (apo) B levels were markedly increased in DS rats compared with Sprague-Dawley (SD) rats, and this was mainly attributable to an increase in the concentration of very-low-density lipoprotein (VLDL). The TG secretion rate estimated by the Triton WR1339 method was significantly greater in DS rats. VLDL-TGs isolated from both the DS and SD rats were endogenously radiolabeled with different isotopes, and a mixture of these was then injected into DS and SD recipients. The half-life of VLDL-TG was about three times longer in DS recipients, regardless of the source of VLDL. In SD recipients, VLDL from DS rats was cleared at a slower rate than VLDL from SD rats. The activity of lipoprotein lipase in postheparin plasma was substantially decreased in DS rats. Isoelectric focusing gel electrophoresis (IEF) showed that the ratio of apo E/C or apo C-II/C-III in VLDL was markedly decreased and the ratio of apo E or apo C to apo A1 in high-density lipoprotein (HDL) was slightly decreased in DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of hypertriglyceridemia in Dahl salt-sensitive rats, an animal model of spontaneous nephrotic syndrome. 812 10


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