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

Nephrotic syndrome is defined as proteinuria sufficiently severe to result in hypoalbuminaemia, oedema and hyperlipidaemia. The early modern history of this illness was characterised by the serendipitous development of renal biopsy technique at approximately the same time as the use of corticosteroids for nephrotic syndrome. The coincidence of these events set the stage for evaluating therapeutic response to corticosteroids and cytotoxic agents in relation to renal histology and ultimate clinical outcome. The International Study of Kidney Disease in Children (ISKDC) was initiated in the 1960s as a multicentre study examining these relationships in children. Over the next decade this study, as well as contributions from other investigators, helped define optimum therapy for these children. It was determined that a child with nephrotic syndrome under the age of 6 years, who did not present with hypertension, azotaemia, hypocomplementaemia or signs of systemic illness, had an approximately 85% chance of responding to corticosteroid therapy. If only those children who had minimal change histology on biopsy were considered, 94% responded. The original regimen which is still used today, was 60 mg/m2 bsa/day prednisone administered on a 3 times per day dosage schedule for 4 weeks, followed by an additional 4 weeks of therapy at a dose of 40 mg/m2 bsa given as a single oral dose every other day. Of those who respond roughly one-third will have no relapses, while almost half will have frequent relapses (greater than or equal to 2 in 6 months) and the rest will have infrequent relapses. Patients in relapse are treated as at presentation but are usually converted to the 40 mg/m2 bsa dose when the urine has been free of protein for 3 days, and are then tapered off or maintained on this dose for several weeks, depending on the individual's history of relapses and incidence of side effects from corticosteroids. For those children who are suffering frequent relapses and severe corticosteroid side effects (e.g. growth failure, morbid obesity, aseptic necrosis of bone), cytotoxic agents were identified as providing long term remission. After inducing remission with conventional corticosteroid dosages, cyclophosphamide is administered at a dose of 2 mg/kg/day given as a single dose for 8 weeks. This regimen was shown to lead to approximately 70% of patients being in remission 2 years after completion of this course of therapy. Chlorambucil given at a dose of 0.2 mg/kg/day as a single oral dose has been equally efficacious.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of nephrotic syndrome in childhood. 171 84

The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism. Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipid-lowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in poly- and monounsaturates fatty acids, has been recently tested by the author, with very promising results.
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PMID:Lipid changes in the nephrotic syndrome: new insights into pathomechanisms and treatment. 175 84

An unusual case of severe hypercholesterolemia and hypertriglyceridemia is described in a child with nephrotic syndrome. The severe hyperlipidemia in this patient was most likely induced by multiple interacting factors which included the metabolic abnormalities of nephrotic syndrome, steroid therapy, the underlying genetic predisposition of ApoE-2 homozygosity as well as diet and diuretic therapy. The result of these factors was an extremely severe type III hyperlipoproteinemia. The pathogenesis of hyperlipidemia in this setting is discussed.
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PMID:Severe hyperlipidemia due to multiple factors in a child with nephrotic syndrome. 175 19

Recent reports of risk factors for and survival of patients with diabetic retinopathy do not include exudative maculopathy as a separate entity. We therefore studied a group of hypertensive Type II diabetic subjects with exudative maculopathy (n = 26) compared to a carefully matched hypertensive diabetic comparison group without retinopathy (n = 26) over seven years. Diabetic maculopathy patients had higher mean diastolic blood pressure (101.6 +/- 14 versus 94.8 +/- 10 mmHg, p less than 0.05), serum cholesterol (6.65 +/- 2.2 versus 5.9 +/- 1.31 mmol/l), HDL2 subfraction levels (0.46 +/- 0.23 versus 0.32 +/- 0.18 mmol/l) and a higher prevalence of hyperlipidaemia (54% versus 35%) compared to the comparison group. After seven years, the maculopathy group showed a strikingly higher prevalence of renal failure and nephrotic syndrome (42% versus 8%, p less than 0.05) and of macroproteinuria (58% versus 15%, p less than 0.01) compared to the comparison group. Mortality and cardiovascular disease event rate was 12% and 38% in the maculopathy and 15% and 31% respectively in the comparison group. We conclude that although mortality is not significantly higher in diabetics with exudative maculopathy, proteinuria, renal failure and nephrotic syndrome may be associated features on long term follow-up. Hypertension and hypercholesterolaemia may also be risk factors in the development of diabetic maculopathy.
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PMID:Long-term follow-up of and underlying medical conditions in patients with diabetic exudative maculopathy. 180 Jan 69

Hyperlipidemia associated with nephrotic syndrome was treated with probucol and the changes in plasma lipoprotein lipid concentration and urinary protein excretion were examined in puromycin aminonucleoside-induced nephrotic rats. Rats made nephrotic exhibited severe hyperlipidemia with increases in all major lipoprotein fractions. Probucol treatment of nephrotic rats significantly lowered plasma triglyceride (TG), cholesterol (Ch) phospholipid (PL) and apoprotein B associated with very-low-density and low-density lipoprotein and Ch and PL in high-density lipoprotein (HDL). Malondialdehyde (MDA) associated with the lipoproteins was significantly elevated in nephrotic rats and probucol treatment also lowered MDA concentration in all major lipoproteins. In control rats probucol moderately, but significantly, reduced plasma TG and HDL-Ch concentrations. Proteinuria associated with nephrosis was decreased significantly by treatment with probucol. Probucol treatment did not affect blood urea nitrogen and plasma creatinine levels. A significant positive correlation existed between the amount of protein excreted in urine and the plasma lipid concentrations in all nephrotic rats, suggesting that the hypolipidemic effect of probucol may attenuate proteinuria associated with nephrosis. These results suggest that probucol may be a favorable treatment for hyperlipidemia associated with nephrotic syndrome.
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PMID:The lowering effect of probucol on plasma lipoprotein and proteinuria in puromycin aminonucleoside-induced nephrotic rats. 185 87

Although hyperlipidemia is a well recognized complication of the nephrotic syndrome, the precise disturbances of lipoprotein metabolism which cause the elevated plasma lipid and lipoprotein concentrations have not been clearly defined in humans. This study examines the metabolism of apolipoprotein B-containing lipoproteins in patients with nephrotic-range proteinuria and in healthy controls. Two radioiodinated tracers of very low density lipoproteins (VLDL1, Sf60 to 400, and VLDL2, Sf20 to 60), were used to trace the metabolism of apolipoprotein B through the delipidation cascade from very low density lipoproteins (VLDL) to low density lipoproteins (LDL). The data from the apoB specific radioactivity curves and the pool sizes of apoB in four subfractions were analyzed by a multicompartmental modeling procedure using the SAAM 30 program. The main findings in the nephrotic group were: 1.) a consistent decrease in the fractional rate of apoB transfer from VLDL1----VLDL2 (median values-nephrotic 0.92 pools/day vs. controls 3.66, P less than 0.02) and from VLDL2----IDL (1.49 vs. 2.74, P less than 0.05); 2.) increased secretion of apoB into VLDL2 (14.5 mg/kg/day vs. 4.2, P less than 0.02); 3.) a trend towards decreased removal of IDL and LDL attributable to a defect in LDL receptor-mediated removal as previously shown (Metabolism 39:187-192, 1990). These findings suggest that catabolic defects of the apo B-containing lipoproteins are as important as increased hepatic synthesis in the pathogenesis of nephrotic hyperlipidemia in humans.
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PMID:Metabolism of apolipoprotein B-containing lipoproteins in subjects with nephrotic-range proteinuria. 192 Nov 48

Nephrotic syndrome, uremia, hemodialysis, peritoneal dialysis, and renal transplantation are accompanied by alterations in lipoprotein metabolism In nephrotic patients, total cholesterol, LDL, VLDL and triglycerides are elevated, while HDL may be increased, normal, or decreased. The pathophysiology includes increased hepatic synthesis of VLDL and cholesterol, decreased activity of lipoprotein lipase, and increased urinary excretion of HDL. The risk of coronary heart disease (CHD) is increased in nephrotic patients and elevated LDL-cholesterol may contribute to this risk. Cholesterol lowering diet and drugs are indicated. Presently, Lovastatin and Simvastatin are the most potent cholesterol lowering drugs in nephrotic patients with good evidence of long-term safety. Most patients with impaired renal function or on hemodialysis have moderate hypertriglyceridemia due to decreased lipoprotein lipase activity. HDL may be slightly decreased. Although the risk of CHD is increased in these patients, triglyceride lowering drugs are not indicated, since no benefit can be expected. Peritoneal dialysis is accompanied by elevated VLDL in addition to hypertriglyceridemia. Reabsorption of large amounts of glucose from peritoneal dialysis fluid increases the carbohydrate load and stimulates hepatic VLDL synthesis. Cholesterol lowering therapy may be advantageous, but the experience is very limited. Side effects of lipid lowering drugs may be aggravated in renal failure. Total cholesterol, LDL, VLDL, and triglycerides are elevated in 50% of patients following renal transplantation. Corticosteroids and cyclosporin are major causes of hyperlipidemia. Cholesterol lowering therapy is indicated since the incidence of CHD is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pathophysiology and therapy of lipid metabolism disorders in kidney diseases]. 192 Dec 28

Hyperlipidemia is common in patients with the nephrotic syndrome. The main cause is probably increased hepatic lipogenesis, a non-specific reaction to falling oncotic pressure secondary to hypoalbuminemia. Cardiovascular morbidity and mortality are increased in patients with the nephrotic syndrome, with the exception of patients with minimal change disease. It is not clear whether this is caused by the hypercholesterolemia or secondary to uremia or medical treatment. Experiments suggest that hypercholesterolemia may cause glomerulosclerosis, a common complication of the nephrotic syndrome. The hypercholesterolemia of the nephrotic syndrome can now be treated effectively with HMG coenzyme A reductase inhibitors.
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PMID:[Hyperlipidemia in nephrotic syndrome]. 194 40

Nephrotic syndrome refers to the symptoms caused by renal injury in which large amounts of protein are lost in the urine. Common manifestations of the syndrome are proteinuria, edema, hypoalbuminemia, hyperlipidemia, and hypercoagulability. Recent research has presented findings that contradict some of the accepted theories regarding the pathophysiology of some symptoms of the syndrome. Accurate understanding of these pathophysiological mechanisms underlying the symptoms seen in nephrotic syndrome is necessary for caregivers to determine the appropriate treatment for these patients.
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PMID:Nephrotic syndrome: pathophysiology and treatment. 195 84

The effects of the nephrotic syndrome in rats on the cholesterol content and the biosynthesis of apolipoprotein E (apoE) by resident peritoneal macrophages have been investigated. Since the nephrotic syndrome has been associated with an increased risk of coronary atherosclerosis, we hypothesized that macrophages from nephrotic rats would accumulate cholesterol and undergo transformation into foam cells, with a concomitant increase in apoE biosynthesis. The nephrotic syndrome was induced in rats with puromycin aminonucleoside. Peritoneal macrophages exposed in vivo for 7-21 d to ascites fluid derived from plasma containing sixfold elevations of lipoproteins did not accumulate unesterified or esterified cholesterol. Nevertheless, immunoprecipitation assays after incubation of the isolated cells with [35S]methionine, or immunoblot analysis of the incubation medium demonstrated a 2.6-fold increase in apoE secretion compared with normal macrophages. This increase was accompanied by 5- to 10-fold increases in cellular apoE messenger RNA as determined by quantitative solution hybridization assay. Peritoneal macrophages cultured from nephrotic rats during the period of hypercholesterolemia also showed distinct and highly reproducible morphologic changes. The dissociation between apoE biosynthesis and macrophage cholesterol content provides new insight into the response of peritoneal macrophages in vivo to endogenous hyperlipemia.
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PMID:Macrophages from nephrotic rats regulate apolipoprotein E biosynthesis and cholesterol content independently. 199 33


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