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)

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

We present a six-year follow-up of a boy with a novel type of hypolipoproteinemia, with clinical and biochemical features distinct from classical hypoalphalipoproteinemias. There were abnormally low concentrations of total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) B, apo A-I, and apo A-II, and the phospholipids were decreased. The most striking abnormality was an extra fraction containing mainly phospholipids and apo A-I in the HDL3 subfraction. This fraction is reminiscent of concentric 20- to 50-nm-diameter lamellar phospholipid liposomes. Plasma lecithin:cholesterol acyltransferase activity was strongly decreased. We noted a persisting polyclonal hypergammaglobulinemia, hematological abnormalities (hemolytic anemia and thrombocytopenia), and a progressive splenomegaly. After the five-year follow-up, the patient had recurrent severe infections; moderate hematuria and proteinuria developed gradually. Treatment with corticosteroids and immunoglobulins improved thrombocytopenia and hypolipoproteinemia. These clinical and biochemical findings differ from those in the known primary and secondary hypo-alpha-lipoproteinemia syndromes. Although investigation of the relatives suggests a familial predisposition for hypo-alpha-lipoproteinemia, the subject's condition can be regarded as acquired.
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PMID:Acquired hypolipoproteinemia. 158 35

Lecithin: cholesterol acyltransferase (LCAT) is an enzyme that catalyzes the esterifying reaction of cholesterol in plasma high density lipoprotein (HDL). Deficiency of LCAT is a rare hereditary disease characterized by several clinical symptoms such as proteinuria, corneal opacity, and anemia due to a shortened life span of erythrocytes. In this communication, we report a case of 40 year-old female patient of LCAT deficiency. She visited a hospital for work-up of proteinuria, corneal opacity and anemia. Activity of her serum LCAT was found to be extremely low, and characteristic changes in plasma lipids due to deficiency of LCAT was observed: those were marked decreases in HDL-cholesterol, degree of esterification in serum cholesterol, and apoprotein A-I, A-II, B and C-II levels. The diagnosis of LCAT deficiency was finally made. We studied about histopathological changes in the patient's kidney, and erythrocyte membrane lipid composition and fluidity. Histopathological findings in renal biopsy were follows: a) Light microscopy showed spherical deposits stained with periodic acid-Schiff in mesangial matrix and adjacent capillary loops, and hyaline deposits in arterioles, b) Electron microscopy showed vacuoles in mesangial matrix and along the glomerular basement membranes. In erythrocyte membrane lipids, increase of cholesterol to phospholipid molar ratio was evident, being accompanied by changes in phospholipid fractions: increase of phosphatidylcholine, and decreases of phosphatidylethanolamine, sphingomyelin and lysophosphatidylcholine. In phospholipid acyl chains, increase of C18:2 and decreased of C18:1 were evident in the patient. Erythrocyte membrane fluidity was found to be decreased in the patient in a measurement by pyrene, probably being related to the changes in membrane lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of familial lecithin: cholesterol acyltransferase deficiency]. 163 33

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

Both increased synthesis and decreased clearance of lipoproteinemia may contribute to the hyperlipoproteinemia which frequently complicates the nephrotic syndrome with increased levels of total and low-density lipo-protein (LDL) cholesterol as the most characteristic abnormality. The hyperlipoproteinemia may also be characterized by elevated levels of triglycerides, increased concentrations of Apo B, Apo C and Apo E and reduced levels of Apo A-I and Apo A-II. The increased lipoprotein synthesis occurs in partly undefined mechanisms related to proteinuria, hypoalbuminemia and, possibly, increased availability of mevalonate as a substrate for cholesterol synthesis. Urinary loss of high-density lipoprotein (HDL) components and other liporegulatory factors may contribute to decreased activity of lipolytic enzymes and result in impaired clearance of cholesterol- and triglyceride-rich lipoproteins of lower densities and altered composition of HDL. The variability in these two metabolic abnormalities may account for the corresponding variability in lipoprotein profiles of patients with the nephrotic syndrome.
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PMID:Pathogenesis of hyperlipidemia in the nephrotic syndrome. 225 78

A high-resolution two-dimensional electrophoretic method for protein, with silver staining, has been used to characterize and identify urinary high-density-lipoprotein apolipoproteins (HDL-Apos) and their isoforms in healthy subjects and in patients with kidney disease. Analytical techniques based on both molecular mass and ultracentrifugal flotation properties were used to isolate urinary lipoprotein particles with characteristics identical to those of HDL in plasma. HDL-Apos identified in urine of normal subjects and patients with glomerular proteinuria were Apos A-I, A-II, and C. Five isoforms of Apo A-I were present. Immunostaining of electroblotted proteins further confirmed the presence of HDL-Apos in urine. Creatinine clearance rate was decreased in the patients with proteinuria, and ranged from 32.5 to 40 mL/min. Concentrations of cholesterol and triglycerides in serum were greater in the patients' group, whereas mean HDL-cholesterol (0.68, SD 0.10 mmol/L) and Apo A-I (0.953, SD 0.095 g/L) were significantly (each P less than 0.01) lower. Results of this study suggest that measurement of urinary Apo A-I will reflect excretion of HDL in urine.
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PMID:High-density lipoprotein apolipoproteins in urine: I. Characterization in normal subjects and in patients with proteinuria. 313 41

We have developed a capture antibody, noncompetitive, enzyme-linked immunoassay for urinary apolipoprotein A-I (Apo A-I) in urine, with use of affinity-purified polyclonal antisera against Apo A-I. A 96-well microtiter plate format is used, with unconcentrated urine as sample and dilutions of serum or high-density lipoprotein (HDL) as standards. The intra- and interassay variation (CV) averaged 7.4% and 9.4%, respectively. The limit of detection is low (1.25 ng/L), and no cross-reactivity with Apo B, C, E, or A-II was detected. The mean (+/- SD) concentrations of Apo A-I in urine of patients with glomerular proteinuria were a thousandfold greater (38.4 +/- 23.1 mg/L) than in normal subjects (16.3 +/- 11.3 micrograms/L in men, 17.97 +/- 7.7 micrograms/L in women, a significant difference, P less than 0.001). Apo A-I measurements correlated very well (r = 0.92) with selectivity index assessment. The diurnal variation of the concentration of Apo A-I in urine appears to result from dilution related to fluid intake. This enzymatic method is easy to perform, can be used with large numbers of samples, and is adaptable for use in the routine clinical laboratory. The method holds promise for discriminating between normal and subclinical kidney disease populations by measuring the concentrations of urinary Apo A-I excreted on HDL particles.
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PMID:High-density lipoprotein apolipoproteins in urine: II. Enzyme-linked immunoassay of apolipoprotein A-I. 313 42

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.
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PMID:Lipoprotein distribution and composition in the human nephrotic syndrome. 398 19

The relationship of plasma levels of high density lipoprotein (HDL) cholesterol, apolipoproteins A-I and A-II (the major apolipoproteins in HDL), low density lipoprotein (LDL) cholesterol, triglyceride, and glucose to microangiopathy was evaluated in 49 insulin-dependent diabetic subjects. Although the HDL cholesterol/LDL cholesterol ratio (a risk determinant for macroangiopathy) was lower in women with proteinuria, no other relationships between HDL cholesterol or the A apolipoproteins and renal microangiography were found. The only independent association between HDL and retinal microangiopathy was found in women, where an inverse correlation was found between the apo A-I/apo A-II ratio and the number of microaneurysms (rs = -0.561, P less than 0.05). Men showed strong relationships of glucose, triglyceride, cholesterol, and LDL cholesterol to renal microangiopathy whereas women, in general, had stronger correlations of these variables with retinal microangiopathy. Thus, several alterations in lipoprotein cholesterol distribution and HDL composition are associated with diabetic microangiopathy. In addition, differences between sexes suggest that previously undescribed hormonal factors may influence the severity of this process.
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PMID:Plasma lipids and microangiopathy in insulin-dependent diabetes mellitus. 704 28

A 43-year-old woman and her 47-year-old brother were studied because of corneal opacity. They showed a marked decrease in plasma high density lipoproteins (HDL) and a decrease in the ester ratio of plasma total cholesterol. Discoidal particles were found in the HDL2 fraction (d 1.063-1.125). A marked heterogeneity of low density lipoproteins was disclosed in both patients by electron microscopy. Apoprotein analysis revealed an increase in apo E and a decrease in apo A-I and A-II in both patients. These abnormalities were similar to the data reported in other cases with hereditary lecithin : cholesterol acyltransferase (LCAT) deficiency. However, several interesting dissimilarities have been disclosed as compared with the previously reported cases. Neither patient had proteinuria, and their kidney functions were within the normal limits. The ester ratios of plasma cholesterol of both patients were the highest among the cases reported thus far. Their plasma LCAT activities were 14.4 and 15% of the normal mean values determined by Glomset-Wright's common-substrate method. The enzyme activities determined by Stokke-Norum's self-substrate method were 40.2 and 29% respectively. These results may indicate that this inherited disorder is not characterized by absence of plasma LCAT or presence of inhibitory factors in plasma, but by the presence of partially inactive LCAT in patients' plasma.
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PMID:Familial plasma lecithin: cholesterol acyltransferase deficiency. A new family with partial LCAT activity. 714 18


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