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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nephrotic syndrome comprises proteinuria, oedema, albuminuria, hypoalbuminaemia, and hyperlipidaemia. Some of its manifestations are present throughout the course of progressive renal disease. Hyperlipidaemia is one of the most dramatic of the clinical manifestations of the syndrome, but has not been seen as relevant to the progression of renal disease. Recently, however, increasing interest has been shown in the lipid abnormalities of patients with persistent proteinuria, largely as a result of experimental data which have emphasised the connection between progressive disease and hyperlipidaemia in animal models. This review considers some aspects of the metabolic background against which the pathological changes in animal models of nephrotic syndrome take place. Attention is drawn to analogies between glomerular disease and atherosclerosis. Lack of information on the value of long-term lipid lowering therapy in patients with proteinuria, hyperlipidaemia, and progressive renal disease emphasises the need for long-term studies of lipid-lowering therapy in these individuals. A conceptual framework for understanding the role of lipids is discussed in relation to the underlying disease processes and possible therapeutic approaches in man.
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PMID:Lipids and progressive kidney disease. 204 69

Altogether, a growing amount of clinical and experimental data suggests that lipids may be important in the development and progression of chronic renal injury. Abundant clinical data have demonstrated that hyperlipidemia is associated with diabetes, decreased renal function, and the nephrotic syndrome. Although clinical correlations between plasma lipid levels and renal dysfunction do not prove a cause-and-effect relationship, potentially injurious lipid abnormalities are invariably present in those patients most likely to progress to end-stage renal disease. In several animal models, pharmacologic treatment of lipid abnormalities has been shown to ameliorate renal disease. Moreover, experimental data suggest that lipid-induced alterations in a number of immune and nonimmune mechanisms could explain the association between lipids and renal injury. A better understanding of these alterations and mechanisms may ultimately lead to more effective treatment of patients with chronic progressive renal disease.
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PMID:The role of lipid abnormalities in the pathogenesis of chronic, progressive renal disease. 206 7

Effect of corticosteroids (steroids) on some hemostatic parameters was serially studied in 23 children with minimal change nephrotic syndrome (MCNS). Increased platelet count, erythrocyte sedimentation rate (ESR), cholesterol, fibrinogen, fibrin(ogen) degradation products (FDP), alpha 2-macroglobulin (alpha 2M), alpha 2-antiplasmin (alpha 2AP) and protein C, and reduced antithrombin III (ATIII) and plasminogen (Plg) were noted in relapse before steroid therapy began. With institution of oral prednisolone, FDP started to fall, and platelet count, cholesterol, alpha 2M, ATIII, Plg, alpha 2AP and protein C started to increase despite unchanged nephrotic state from that before the therapy. In remission induced by prednisolone, platelet count, cholesterol, alpha 2M, ATIII, Plg, alpha 2AP and protein C were still increased, but normalized off therapy. ESR, fibrinogen, FDP, alpha 2M and protein C correlated inversely with serum albumin and directly with cholesterol and urine protein excretion. In contrast, ATIII and Plg correlated directly with serum albumin and inversely with cholesterol and urine protein excretion. A direct correlation was only noted between alpha 2AP and the dose of prednisolone. The data indicate that steroids appear to be a thrombogenic factor by accerelating thrombocytosis and hyperlipidemia, and by reducing plasma fibrinolysis in children with MCNS.
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PMID:Effect of corticosteroids on some hemostatic parameters in children with minimal change nephrotic syndrome. 207 95

The effect of lovastatin on the hyperlipidemia induced in rats with experimental nephrotic syndrome was investigated; toxicity and the effects on common blood chemistry parameters were also assessed. Hyperlipoproteinemia in this particular model is associated with an increase in hepatic synthesis of lipoproteins, and treatment with lovastatin could be the most suitable, since the drug inhibits cellular cholesterol synthesis. Lovastatin treatment resulted in a considerable reduction in plasma cholesterol and triglyceride levels. The decrease in cholesterol levels with treatment was mainly confined to the low-density lipoproteins (LDL) although there was a reduction in the nephrotic-syndrome-induced incremental level of high-density lipoprotein cholesterol. Other lipoprotein fractions were unaffected by lovastatin. LDL apoprotein B was increased in both groups of rats, but to a lesser degree in the lovastatin-treated group, suggesting a double effect, inhibition of both, cholesterol and apoprotein synthesis. Both groups of rats showed a certain degree of renal impairment as shown by significant elevations in plasma urea and creatinine levels. Hepatic damage was also observed, chemically and microscopically, in both groups of rats, being more pronounced in those rats treated with lovastatin in which a 50% mortality ensued after 2 weeks of treatment. At the dosage used this may have some implications in its therapeutic use in certain conditions.
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PMID:Toxicity of lovastatin in rats with experimentally induced nephrotic syndrome. 207 99

The authors report the case of a 18 year old man with a chronic corticosteroid-refractory nephrotic syndrome complicated by carotid artery thrombosis and myocardial infarction. Thromboembolism is one of the most serious complications of the nephrotic syndrome. Serious clotting factor disturbances are observed: changes in platelet function (hyperaggregability) increased plasma zymogens and cofactors, increased plasma fibrinogen, abnormalities of the fibrinolytic system and acquired deficiencies of coagulation inhibitors. The respective role of each of these abnormalities have not been clearly established, but it is likely that increased platelet aggregation and antithrombin III deficiency are important factors in producing a hypercoagulable state in the nephrotic syndrome. Hyperlipidemia is also a characteristic feature of the nephrotic syndrome: these is a wide spectrum of lipoprotein patterns with increased low density lipoproteins (LDL) or very low density lipoproteins (VLDL) or both; contradictory results have been reported with respect to the high density lipoproteins (HDL): decreased, normal or even increased plasma levels have been observed. In addition, changes in the distribution and composition of LDL and VLDL subclasses have been detected. Most of these changes have an atherogenic potential but controversy still surrounds the question of the prevalence of ischaemic heart disease in the nephrotic syndrome; it is unlikely that nephrotic syndromes of short duration have any influence on the incidence of coronary events, but patients with chronic heavy protein urea and long-term exposure to abnormalities of haemostasis and lipid profiles appear to have a significant risk of developing cardiovascular disease and may require long-term anticoagulant therapy.
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PMID:[Carotid artery thrombosis and myocardial infarction in nephrotic syndrome]. 210 97

Acquired hyperlipidemia (secondary dyslipoproteinemias) results from underlying disorders that lead to alterations in plasma lipid and lipoprotein metabolism. Secondary dyslipoproteinemias may mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased predisposition to premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to the development of pancreatitis and other features of the chylomicronemia syndrome. Diabetes mellitus and use of drugs such as diuretics, beta blockers, and estrogens are commonly encountered causes of secondary dyslipoproteinemia. Other conditions leading to acquired hyperlipidemia include hypothyroidism, renal failure, nephrotic syndrome, alcohol usage, and some rare endocrine and metabolic disorders. When secondary and familial forms of hypertriglyceridemia coexist, triglyceride removal mechanisms may be saturated and marked hypertriglyceridemia with fasting chylomicronemia might ensue. Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia. Specific lipid-lowering therapy may be required in certain circumstances.
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PMID:Acquired hyperlipidemia (secondary dyslipoproteinemias). 219 73

Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomerulopathy, suggesting that the "syndrome" of early onset nephrotic syndrome progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known.
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PMID:Left atrial atheromatosis in childhood nephrotic syndrome. 219 47

The inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase are highly effective in treating severe elevations of serum cholesterol, and are being widely used for this purpose. In our laboratory, these drugs have been used for the treatment of other forms of dyslipidemia including primary moderate hypercholesterolemia, primary mixed hyperlipidemia, diabetic dyslipidemia, hyperlipidemia of the nephrotic syndrome, and primary hypoalphalipoproteinemia. In these conditions, the HMG CoA reductase inhibitors proved effective in substantially decreasing levels of both low-density lipoproteins and very low density lipoproteins, as well as apolipoprotein B. In some patients, they may even increase levels of high-density lipoproteins. The primary mode of action of HMG CoA reductase inhibitors appears to be to increase the synthesis of hepatic receptors for lipoproteins containing apolipoprotein B, although a reduction in synthesis of these lipoproteins has not been ruled out with certainty. Regardless of mechanisms, drugs of this type appear to have the potential for effective therapy of various forms of dyslipidemia beyond primary severe hypercholesterolemia.
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PMID:Use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in various forms of dyslipidemia. 220 34

The pathophysiology of the nephrotic syndrome (NS), characterized by protenuria, edema, sodium retention and hyperlipidemia, is not clear. We studied the role of some systemic factors on sodium retention in an experimental model of NS. NS was induced in rats by a single subcutaneous injection of puromycin aminonucleoside (PA) (15 mg/100 g); control animals received vehicle. All rats were kept in metabolic cages for 24 days (3 days before and 21 days after PA-injection). Urine was collected daily. Blood samples were obtained every day until day 10, and then every other day up to the end of the study. The rats showed the following alterations after PA injection: a) a rise in serum angiotensin converting enzyme activity (ACEA) and plasma aldosterone (PAldo) at day 1; b) a rise in urinary aldosterone (UAaldoV), azotemia and sodium retention at day 2; c) massive proteinuria (UProt) and decrease in plasma angiotensinogen concentration (PAC) at day 4; d) increases in plasma renin activity (PRA), plasma renin concentration (PRC) and serum creatinine as well as hypoproteinemia, hypercholesterolemia, hypertriglyceridemia, ascitis and edema at day 5; e) increase in urine volume at day 6. PAldo became normal at day 7; urine sodium (UNaV), PRA and PRC at day 8; UAldoV at day 9; serum urea and ACEA at day 10; urinary volume at day 11; PAC, serum total protein and creatinine at day 12. The edema disappeared at day 11. UProt, hypercholesterolemia and hypertriglyceridemia persisted, though they decreased substantially by the end of the study (day 21). Light microscopy studies revealed normal glomerular morphology, but electron microscopy showed fusion of podocytes before proteinuria. These data suggest that: a) sodium retention was not a consequence of proteinuria or hypoproteinemia; b) sodium retention seems non-related to renin secretion, but may be partially mediated by a fall in glomerular filtration rate or by an increased tubular resabsorption secondary to other factors; c) the increase in PAldo, UAldoV and ACEA are non-related to renin secretion: all occurred before PRA rose; d) water retention, increase in PRA and PRC, hypercholesterolemia and hypertriglyceridemia are secondary to the hypoproteinemia.
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PMID:Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. I. The role of proteinuria, hypoproteinemia, and renin-angiotensin-aldosterone system on sodium retention. 223 72

Hyperlipidemia is a consistent feature of the nephrotic syndrome. In this study, low-density lipoprotein (LDL) metabolism has been investigated in nine patients with nephrotic syndrome and varying degrees of proteinuria. In subjects with moderate proteinuria (less than 10 g/d), total plasma cholesterol values were elevated to approximately 160% of normal due mainly to an increase in circulating LDL cholesterol. Metabolic studies showed that a defect in LDL clearance via the receptor pathway was responsible for its accumulation. The total amount of LDL apolipoprotein catabolized by this mechanism was only 55% of the value seen in controls; 60% more LDL was channelled into alternative, receptor-independent, catabolic pathways. Heavier proteinuria was associated with substantial increases in plasma triglyceride and very-low-density lipoprotein (VLDL) levels. The defect in LDL catabolism was aggravated by oversynthesis of the lipoprotein, which expanded the plasma LDL pool to 250% of normal. These observations indicate that the hyperlipidemia of the nephrotic syndrome is multifactorial in origin. The altered catabolism of LDL may be important in predisposing these subjects to premature atherosclerosis.
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PMID:Low-density lipoprotein metabolism in the nephrotic syndrome. 229 90


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