Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dyslipidemia is commonly observed in nephrotic syndrome, in chronic renal failure, and after renal transplantation. The patterns of dyslipidemia, however, differ among these three conditions, and the origins and mechanisms responsible for abnormalities in lipoprotein metabolism in each are not well understood. Whether these dyslipidemias contribute to the development of atherosclerosis and coronary heart disease is uncertain, but it is probable that they do. Important questions are whether an attempt should be made to treat the various renal dyslipidemias, and if so, by what means. Also of current interest are dyslipidemias in the nephrotic syndrome, chronic renal failure (uremia), and the post-renal transplantation state.
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PMID:Mechanisms and treatment of dyslipidemia of renal diseases. 792 19

Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome or chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease. Studies on animals with lupus nephritis, aminonucleoside nephrosis, reduced renal mass, diabetes mellitus or systemic hypertension have shown that cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of lipid induced glomerular damage. Apo E-containing lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells, and increase the synthesis of mitogens and extracellular matrix protein. The pathogenic role of oxidized lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that lipoproteins may play a critical role in mediating the development of glomerulosclerosis.
Atherosclerosis 1994 May
PMID:The role of lipids in nephrosclerosis and glomerulosclerosis. 794 52

To determine the effects of the nephrotic syndrome (NS) on atherogenic risk, we studied the lipoprotein composition and the activities of lecithin-cholesterol acyltransferase (LCAT), lysolecithin acyltransferase (LAT), and cholesteryl ester transfer (CET) in the plasma of 11 NS patients and 10 control subjects. NS plasma had lower ratios of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and HDL2/HDL3 and an elevated free cholesterol (FC) to phosphatidyl choline (PC) ratio (1.09 +/- 0.27 in NS and 0.72 +/- 0.21 in controls, P < .02), all of which indicate an increased atherogenic potential. LCAT activity was normal in NS plasma when assayed with an exogenous substrate, but was 40% lower than in control plasma when assayed with the endogenous substrates. However, in vitro addition of serum albumin to NS plasma failed to normalize the LCAT activity. The LAT reaction, which is catalyzed by LCAT protein in the presence of LDL, was 60% to 80% higher in NS plasma, and consequently the ratio of LAT/LCAT activities was increased twofold. CET activity was significantly increased (+160% of control), and this abnormality was attributable to changes in both the acceptor (very-low-density lipoprotein [VLDL] + LDL) and donor (HDL) lipoproteins and possibly in CET protein. These results suggest that the NS may increase the risk of atherosclerosis not only by adversely affecting the concentrations of lipoproteins, but also by altering their composition and function.
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PMID:Abnormal acyltransferase activities and accelerated cholesteryl ester transfer in patients with nephrotic syndrome. 808 87

Hyperlipidemia so commonly complicates heavy proteinuria that it has come to be regarded as an integral feature of the nephrotic syndrome (NS). Characteristically, total plasma cholesterol and triglyceride levels are elevated, as are very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol. Although high-density lipoprotein (HDL) concentrations may be normal, HDL subtypes are abnormally distributed, with a reduction of HDL2 and an increase in HDL3. In addition, lipoprotein (a) [Lp (a)] levels may be elevated. The mechanisms underlying these abnormalities are multifactorial, involving both increased rates of lipoprotein synthesis and defective clearance and catabolism of circulating particles. Although recent dietary and therapeutic studies have demonstrated that nephrotic hyperlipidemia can be effectively treated, the need for such intervention has not been clearly established. This pattern of lipoprotein abnormality is associated with an increased risk of cardiovascular disease in the general population, and several studies have suggested that nephrotic individuals are more likely to develop atherosclerosis. However, no prospective trials have evaluated the relationship between deranged lipid metabolism and coronary or cerebral artery disease in patients with NS. In addition, although recent experimental studies suggest that lipid abnormalities may accelerate renal injury and that lipid-lowering agents may protect renal function, there is little current evidence to suggest that such intervention is of value in preserving residual renal function in humans. Further studies are clearly required to assess the potential long-term benefits of lipid-lowering intervention in individuals with NS. In the meantime, based on data generated from other population groups, a rational approach to the clinical management of hyperlipidemia in these patients is presented.
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PMID:Lipid abnormalities in the nephrotic syndrome: causes, consequences, and treatment. 812 33

Large-scale and systemic epidemiological, pathological and experimental studies emphasized and documented the childhood origin of atherosclerosis. There is increasing consensus that lipid levels in children to a large extent determine the rate of coronary artery disease (CAD) in the adult population. Minimal sudanophilic intimal deposits, and the presence of intracellular and extracellular lipid, and a slight increase in interstitial ground substance in 3 years of age or older patients are found. In the Bogalusa Hearth Study aortic fatty streaks were strongly related the antemortem levels of both total cholesterol and low-density lipoprotein cholesterol (LDL-C) independent of race, sex, and age, and were negatively correlated with the ratio of high-density lipoprotein (HDL-C) to low-density plus very-low-density lipoprotein cholesterol (LDL-C+VLDL-C). The potential for primary prevention is real and the strongest piece of evidence for its is the remarkable trend in CHD mortality rates in recent times, rapidly downward in many western countries. A number of factors influence plasma levels of lipid and lipoproteins in newborn, in infants, in children and adolescents and their relevance as possible predictors of adult coronary artery disease. They are certain inherited disorders of dyslipoproteinemia (familial hypercholesterolemia, familial combined hyperlipidemia, hyperapobetalipoproteinemia, and hypoalphalipoproteinemia) and secondary causes of hyperlipidemia (congenital biliary atresia, glycogen storage diseases, hypothyroidism, diabetes mellitus and nephrotic syndrome, etc).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Atherosclerosis and juvenile dyslipidemias]. 818 5

Patients with nephrotic syndrome (NS) are believed to be at increased risk of atherosclerosis and coronary heart disease (CHD), although existing evidence for this association has not been persuasive. The risk of CHD among 142 persons with NS documented by protein-uria > or = 3.5 g daily was compared with that among 142 matched controls randomly selected from the membership of a large Northern California health plan. Controls were matched for sex, year of birth, and presence in the health plan when the referent case was diagnosed. No diabetics were included in this study. Mean follow-up for nonfatal CHD events was 5.6 years for NS subjects and 11.2 years for controls. Among the NS subjects myocardial infarction (MI) developed in 11, and there were 58 deaths, seven because of CHD. Among the controls, there were four MIs and 10 deaths, three because of CHD. In matched-pair analysis, there were 11 MIs among NS subjects and none among controls [P = 0.001, lower bound of 95% confidence interval for relative risk (CI), 2.8]. In an unmatched analysis adjusted for hypertension and smoking at diagnosis of NS, the relative risk of MI was 5.5 (95% CI 1.6 to 18.3) and the relative risk of coronary death was 2.8 (95% CI 0.7 to 11.3). Omitting data of NS subjects with minimal change disease and systemic lupus erythematosus yielded similar results. These data suggest that persons with NS are at increased risk of CHD.
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PMID:The increased risk of coronary heart disease associated with nephrotic syndrome. 823 Oct 39

Hyperlipidaemia is an invariable complication of the nephrotic syndrome. The quantitative and qualitative changes in lipoproteins which occur may accelerate atherosclerosis. The pathogenetic mechanisms of the hyperlipidaemia are complex and poorly understood. Increases in lipoprotein production are compounded by reduced lipolysis of very low density lipoprotein and impaired catabolism of low density lipoprotein. Both proteinuria and hypoalbuminaemia have been implicated in the genesis of these abnormalities. The optimum treatment of the hyperlipidaemia has not been determined. 3-Hydroxy-3-methyl-glutaryl co-enzyme A reductase inhibitors appear to be the most effective lipid-lowering drugs, although their ability to reduce ischaemic events or prevent/delay renal failure remains to be proven.
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PMID:Pathogenesis of lipid abnormalities in patients with nephrotic syndrome/proteinuria: clinical implications. 823 98

Existing evidence suggests that dyslipidemia associated with long-lasting nephrotic syndrome and with chronic renal insufficiency may favor in the long run the occurrence of cardiovascular complications, and also aggravate glomerular damage with a pathological mechanism analogous to atherosclerosis. Correction of hypercholesterolemia and hypertriglyceridemia is therefore mandatory in both clinical conditions. This goal can be achieved with the combination of dietary intervention and the administration, even for long periods of time, of hypolipemic drugs (hydroxymethylglutaryl coenzyme A, HMGCoA, reductase inhibitors, to correct hypercholesterolemia in nephrotic syndrome, and fibric acids, to correct hypertriglyceridemia in uremic and dialyzed patients are the drugs of choice). In end-stage renal failure, the choice of the type of dialysis is also important. The value of extracorporeal LDL cholesterol removal is still to be proven.
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PMID:Treatment of hyperlipidemia in human renal disease. 823 7

Hyperlipidemia is an important characteristic of nephrotic syndrome (NS). Elevation of plasma total cholesterol, or more specifically low-density lipoprotein cholesterol, is the major lipid abnormality in NS, although hypertriglyceridemia may develop as the disorder progresses. The pathophysiology of nephrotic hyperlipidemia is complex. The prevailing view is that both hepatic synthesis of lipids and of apolipoproteins is increased, and that the clearance of chylomicrons and very low-density lipoproteins is reduced. The precise contribution of increased lipogenesis and decreased lipid catabolism to hyperlipidemia, and their relationship to urinary protein loss, hypoalbuminemia and reduced serum oncotic pressure remain controversial. There are two potential risks of elevated plasma lipids: atherosclerosis and progression of glomerular injury. Although neither of these complications has been proved with certainty, there is growing evidence that both may be long-term consequences of NS. Therefore, the diagnosis and treatment of lipid abnormalities, important aspects of the management of nephrotic children, is summarized here to provide pediatric nephrologists with an informed choice.
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PMID:Hyperlipidemia in childhood nephrotic syndrome. 825 23

This article has focused on the appropriate indications for lipid-lowering drugs in adult patients with different lipoprotein disorders, which we have divided into primary hypercholesterolemia, combined hyperlipidemia,and hypertriglyceridemia. The mechanism of action, efficacy, and safety profile of the major drugs have been reviewed, and based on this information, we have presented our views on the appropriate drugs of first choice and appropriate second-choice agents for treatment of adult patients with different dyslipidemias. The rationale for the use of hypolipidemic drugs is strongest in patients with hyperlipidemia who concurrently have evidence for coronary or peripheral vascular disease, in whom the goal of secondary prevention is to retard further progression of atherosclerosis and potentially induce some regression, whereas in selected high-risk patients without evidence of atherosclerosis, the goals of therapy are to prevent the premature development of CAD or, in patients with severe hypertriglyceridemia, prevent the adverse sequelae of hepatomegaly, splenomegaly, and potentially pancreatitis. We have focused on the use of hypolipidemic drugs in adult patients, and the guidelines discussed are not appropriate for use in children with hyperlipidemia, in whom drug therapy should be undertaken selectively and in consultation with a lipid specialist. Many areas of controversy in the use of lipid-lowering drugs remain to be addressed by future studies; these include the use of lipid-lowering drugs in patients with secondary causes of hyperlipidemia (e.g., the nephrotic syndrome), the use of lipid-lowering drugs in women, and recommendations for drug therapy in older patients.
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PMID:Drug treatment of dyslipoproteinemia. 828 33


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