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

Livers from normal and nephrotic rats were perfused by the nonrecirculating technique. Nephrosis was studied on the 7th d after the injection of puromycin animonucleoside. Amino acid-labeled lipoproteins (d < 1.21) were isolated from the perfusion medium by agarose column chromatography or by sequential density ultracentrifugation. In both groups of animals, in addition to very low density lipoproteins and nascent high density lipoproteins, column chromatography revealed the presence of a peak of 2-3 x 10(6) daltons. This peak contained lipoproteins of densities corresponding to <1.006, 1.006 < d < 1.02, and 1.02 < d < 1.06, which indicated that rat liver secretes a heterogeneous mixture of triglyceride-rich lipoproteins. The amount of these lipoprotein density classes was measured and their lipid and apoprotein composition and their apoprotein specific activity were determined. In both groups of rats there was a progressive rise in phospholipid and decrease in triglyceride content as the isolation density increased from 1.006 and 1.06. The lipoproteins from the nephrotics had higher amounts of cholesterol. The livers from the nephrotic rats secreted two to three times as much lipoprotein as controls in all density classes in the first 20 min, but during the next 40 min only the 1.02 < d < 1.06 and nascent high density lipoproteins remained at this high level compared to controls. A larger total liver pool of apolipoproteins in nephrotic livers was inferred from their lower specific activities during the first 20 min. The apoprotein composition of liver perfusate lipoproteins from nephrotics differed from controls. There was a 40% decrease in the amount of low molecular weight apoproteins in all density classes, with corresponding increases in apo B and apo E in the triglyceride-rich fractions. The apo A-1 content of nascent HDL was increased from 16% in controls to 52% in nephrotics, with corresponding decreases in apo C and apo E. When these results were combined with specific activity measurements of the individual apoproteins and the net secretion rate of total protein in each lipoprotein class, it was possible to estimate the total amount of each apoprotein secreted and the total incorporation of labeled amino acids into each. The incorporation of label gave results similar to those obtained by direct measurement of the amounts of apoproteins. Apo E secretion was increased by a factor of 1.8, apo B by 2.8, and apo A-1 by 8.4, whereas the secretion of apo C was not significantly altered. We explain these results by postulating that the primary stimulus to hepatic plasma protein synthesis in response to proteinuria is general and that subsequent negative feedback regulation affects individual apolipoprotein synthesis rates. A corollary of this hypothesis is that the biosynthesis and secretion of an apoprotein may be regulated independently of the lipoprotein density class in which it is found.
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PMID:Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis. 22 28

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria. 131 86

Retarded growth and extremely high cholesterol levels have been reported in infants with congenital nephrotic syndrome of the Finnish type (CNF). In an attempt to normalize growth and lipid disturbances the high-calorie diet (130 kcal/kg/d) containing protein 4 g/kg/d and supplemented with unsaturated fatty acids (mean P/S-ratio 1.40) was given to ten infants with CNF from birth. Growth, lipoprotein and apoprotein concentrations were measured. All patients exhibited normal growth, which allows renal transplantation, the only life-saving treatment in CNF, already at an early age. In spite of the diet lipid profiles at 3 and 9 months revealed marked elevation of triglyceride in all lipoproteins, especially in VLDL fraction, compared to controls. The abnormalities increased significantly with time (p for VLDL-TG 0.04). The elevation of serum cholesterol was mainly attributable to the increase of cholesterol in triglyceride-rich particles (chylomicrons, VLDL, IDL). Analysis of VLDL, LDL and HDL revealed significant triglyceride enrichment and cholesterol deficiency in all lipoproteins. The concentrations of the low-molecular weight apoproteins A-I and A-II were significantly decreased, but the concentration of high-molecular apo B was high. Urinary analysis revealed progression and decreasing selectivity of proteinuria with time. Thus the mechanisms leading to lipid abnormalities in CNF are multiple including stimulated hepatic lipoprotein synthesis, impaired conversion of VLDL and IDL to LDL, compositional changes, urinary loss of low-molecular apoproteins and presumably reduced LPL activity. The abnormalities indicate an increased risk of arteriosclerosis in CNF patients.
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PMID:Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis. 145 38

The relationship between blood-lipid levels and severity of proteinuria was examined retrospectively in 30 patients (12 males, 18 females; mean age 39 [18-58] years). All patients had histologically confirmed glomerulonephritis (minimal change: n = 7, perimembranous: n = 8, focal sclerosing: n = 6, rapid progressive: n = 3, mesangio-proliferative: n = 4, membrano-proliferative: n = 1, diabetic glomerulosclerosis: n = 1). None was taking lipid-lowering drugs. Patients were classified according to the degree of proteinuria. In group 1 (proteinuria less than 5 g/d, n = 13) the LDL-HDL ratio averaged 4.4; in group 2 (proteinuria 5.0-10.0 g/d, n = 10) the average ratio was 8.8, and in group 3 (proteinuria greater than 10.0 g/d, n = 7) 13.3. Total cholesterol concentration also rose with increasing proteinuria (to 300 +/- 87 mg/dl, 375 +/- 168 mg/dl and 464 +/- 143 mg/d, respectively). The size of the LDL-HDL ratio and the level of total cholesterol did not correlate with the degree of excretory renal failure. These results point to an impressive correlation between the degree of proteinuria and the level of LDL-HDL ratio as a measure of atherogenic risk for a given patient.
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PMID:[Proteinuria and atherogenic risk]. 150 44

Rats of the Milan Normotensive Strain (MNS) develop a dyslipoproteinemia that is associated with a spontaneous, age-dependent and slowly progressive nephropathy characterized by proteinuria and hypoalbuminemia (nephrotic syndrome). We assumed that the MNS strain might be a suitable model for studying the features of nephrotic dyslipoproteinemia and its relationship with proteinuria, hypoalbuminemia, and hepatic apolipoprotein production. Plasma lipoproteins were investigated in MNS rats at various ages (4-48 weeks) and in another rat strain (Milan Hypertensive Strain, MHS), genetically related to MNS but free of nephropathy, that was used as control. In MNS rats, abnormal proteinuria was detectable at 20 weeks and increased 2-fold up to 34 weeks with no reduction of plasma albumin (compensated stage). During this stage we found increased levels of plasma cholesterol (+ 34%), high density lipoprotein-1 (HDL1) (+ 73%), and HDL2 (+ 31%) that were positively correlated with proteinuria but not with plasma albumin. The later stage (34-48 weeks) (nephrotic stage) was characterized by a further increase of proteinuria, moderate hypoalbuminemia (- 25%), a 2-fold increase of plasma cholesterol, triacylglycerols, low density lipoprotein (LDL), and HDL1, and a 1.2-fold increase of HDL2. In this stage the levels of LDL, HDL1, and HDL2 were positively correlated with proteinuria, and negatively correlated with plasma albumin. The most striking change in apolipoproteins was a progressive increase of the relative content of apoA-I in HDL (in 48-week-old MNS rats the A-I/E ratio was 3-fold that found in MHS rats) that was associated with a similar increase of plasma apoA-I. None of these lipoprotein changes were observed in age-matched MHS rats. At the end of the compensated stage, the hepatic levels of A-I, B, A-II, and albumin mRNA were 5.3-, 3.5-, 1.3-, and 2.0-fold, respectively, those found in age-matched MHS rats. During the nephrotic stage, albumin mRNA continued to increase, whereas A-I, B, and A-II mRNAs decreased toward the levels found in age-matched MHS rats. Thus, nephrotic dyslipoproteinemia in MNS rats starts to develop in the compensated stage before the onset of hypoalbuminemia, is characterized by an early elevation of HDL1 + HDL2, and is associated with an increased content of hepatic mRNAs of some apolipoproteins, especially apoA-I. The slow progression of nephrotic syndrome with the long-standing proteinuria and no reduction in plasma albumin renders the MNS strain the most suitable animal model for the study of the effect of proteinuria on plasma lipoprotein metabolism.
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PMID:Dyslipoproteinemia in an inbred rat strain with spontaneous chronic progressive nephrotic syndrome. 179 47

High dietary protein intake, in the past recommended for nephrotic syndrome, does not improve hypoproteinemia and may accelerate progressive renal damage. In contrast, low-protein diets reduce proteinuria and preserve renal function in experimental renal models of nephrotic syndrome. In this study, 20 steroid-resistant, nephrotic patients were treated with a pure vegetarian, low-protein diet, supplemented with essential amino acids and ketoanalogues (supplemented vegan diet, SVD) for 4.6 +/- 3.1 months. Before the study, these patients followed an unrestricted protein, low-sodium diet (LSD). Proteinuria, daily urea nitrogen excretion and creatinine clearance decreased significantly on SVD. A similar lowering effect of SVD was observed on serum total cholesterol. Seven of the 20 patients changed from LSD to SVD and vice-versa on 3 occasions, and in all cases, we found an increase of proteinuria during the LSD period. Serum albumin, HDL cholesterol, triglycerides and anthropometric measurements did not change on SVD. Our data suggest that SVD exerts a favorable effect on proteinuria and hypercholesterolemia in nephrotic patients, without inducing clinical or laboratory signs of malnutrition.
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PMID:A special, supplemented 'vegan' diet for nephrotic patients. 180 35

Racial differences in lipoprotein (LP) and cardiovascular (CV) abnormalities have been noted in the general population and in the population of patients on dialysis. Few studies have investigated the interaction of race and LP and CV disturbances in other renal disease groups. We studied lipid profiles and risk ratios (total cholesterol (TC)/high density lipoprotein-cholesterol) (HDL-C) and apolipoprotein (apo) A-I/apo B (A-I/B)) and the influence of race across a spectrum of renal disease groups (normal renal function (NRD), nephrotic range proteinuria (NS), hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), post-transplant (TR), renal insufficiency (RI)). We also performed a longitudinal study of lipid profiles in patients with end stage renal disease (ESRD) and the relationship of these profiles to race and other variables. There was a general tendency towards a better CV risk profile for blacks than whites in all the groups. Blacks tended to have lower TC, higher HDL-C, lower TC/HDL-C, higher apo A-I, lower apo B, and higher A-I/B. We analyzed four yearly cross-sections of the HD and CAPD populations using ANOVA with adjustment for appropriate covariates. Whites had lower HDL-C and a higher TC/HDL-C risk ratio than blacks. HD patients had lower TC, TC/HDL-C, apo A-I, and apo B than CAPD patients, and women had higher TC than men. When lipid profiles were studied longitudinally by yearly intervals, no consistent significant changes were seen, but over two years, levels of apo B fell and A-I/B rose. Race had no significant effect on any of the longitudinal data.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipid abnormalities in black renal patients. 185 70

To determine the possible role of a glycaemic control in lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM) patients, serum lipid and apolipoprotein levels were measured in well-controlled and poorly controlled lean NIDDM without proteinuria and hypertension. A sample of 96 lean NIDDM patients (body mass index less than 25 kg m-2 in men and less than 27 kg m-2 in women) were divided into two groups: group I, where the HbA1c concentration had been less than 6% for the previous 3 months, and group II, where the HbA1c concentration had been greater than 8% for the previous 3 months. Serum total cholesterol, triglyceride, and HDL-cholesterol levels showed no significant differences between groups I and II. Furthermore, serum levels of apolipoproteins AI, AII, B, CII, CIII, and E did not differ significantly between groups I and II. These results suggest that glycaemic control did not influence lipid metabolism in lean NIDDM patients.
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PMID:Serum lipid and apolipoprotein levels in non-hypertensive lean NIDDM patients. 186 64


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