Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal renal diseases including nephrotic syndrome and chronic renal failure are associated with hyperlipidemia, significance of abnormal lipid metabolism has been thought to be limited in some inherited renal diseases. However, recent studies have postulated that glomerulosclerosis is induced by hyperlipidemia and is in common with atherosclerosis. This involvement is found in the progressive renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and glycogen storage disease. Interaction between macrophages and mesangial cells may play an important role in such conditions. This evidence is supported by experimental models with hyperlipidemia. On the other hand, discovery and new hereditary metabolic disorders, such as type III hyperlipoproteinemia and lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy has specific features different from those of lipid-induced renal diseases. In this disease, apo E Sendai which results from new substitution (Arginine 145-->Proline) may induce intraglomerular lipoprotein thrombi characteristic of lipoprotein glomerulopathy.
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PMID:Abnormal lipid metabolism and renal disorders. 916 48

Hypercholesterolemia and mesangial cell proliferation have been proposed to play a role in the progression of glomerulosclerosis in diabetic nephropathy and other renal diseases. Although LDL is mitogenic for and cytotoxic to mesangial cells, the effect of HDL on these cells is unknown. HDL stimulates fibroblast mitogenesis and is the principal cholesterol-bearing lipoprotein in the rat, the experimental model for studying the effect of hyperlipidemia on renal disease. Insulin is mitogenic in several cell systems, and its levels are increased in serum in non-insulin-dependent diabetes mellitus. This study investigates whether HDL acts as a growth factor in mesangial cells and whether it functions in parallel with insulin. It was found that HDL at protein concentrations between 10 and 500 microg/ml, both alone and in the presence of 100 nM insulin, increased DNA synthesis in mesangial cells (129 to 165% of control for HDL alone; 140 to 235% for HDL plus insulin), whereas HDL at 1000 microg/ml and greater inhibited mesangial cell proliferation. Insulin alone at 100 nM stimulated [3H]thymidine incorporation in the same cell system (145% of control); the mitogenic effect of insulin was additive to that of HDL. Purified apo A-I had a similar effect, but at significantly lower concentrations. Specific binding of HDL to mesangial cells was demonstrated (B(max) [binding constant] of 5.19 +/- 0.70 x 10(-7) micromol of HDL bound/mg cell protein and K(b) of 2.83 +/- 0.22 nM). Tetranitromethane alters apo A-I, preventing binding to its cognate receptor. Tetranitromethane-modified HDL did not bind to mesangial cells and had no effect on [3H]thymidine incorporation. Addition of HDL to mesangial cells caused an immediate transient increase in free intracellular calcium in several representative mesangial cells, similar to the response seen with platelet-derived growth factor. The mitogenic effect of HDL was not altered after attenuation of cellular protein kinase C activity, but the stimulatory effect of HDL alone and in combination with insulin on DNA synthesis was completely eliminated after inhibition of cellular tyrosine kinases by 24-h pretreatment with 0.25 microM herbimycin A. Thus, HDL binds to a specific apo A-I-dependent receptor, promotes DNA synthesis, and initiates second-messenger events by a tyrosine kinase-dependent and protein kinase C-independent mechanism.
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PMID:HDL causes mesangial cell mitogenesis through a tyrosine kinase-dependent receptor mechanism. 925 51

Plasma lipoproteins (LP) may be identified on the basis of density properties or apolipoprotein (apo) composition. ApoB-containing LP occur in VLDL, IDL and LDL. There are several types of apoB-containing LP characterized by specific composition of minor apolipoproteins (apoC, apoE etc.) and lipid constituents (triglycerides and cholesterol), metabolic properties and relative atherogenicity. The alterations of lipoprotein metabolism in renal disease resulting in elevated levels of apoB-containing LP may be reflected in hyperlipidemia. Whereas nephrotic syndrome and heavy proteinuria are associated with increased formation of cholesterol-rich apoB-containing LP in LDL and VLDL, the characteristic feature in renal failure is the accumulation of intact or partially metabolised triglyceride-rich LP in IDL and VLDL. The potentially atherogenic apoB-containing LP have been linked to the pathogenic processes that result in progressive glomerular and interstitial lesions and ultimate loss of renal function. The mechanisms of injury are not fully understood. Receptor- and non-receptor mediated uptake of LP by mesangial cells may induce or accelerate proliferative and sclerotic processes in the glomerular mesangium that are analogous to atherosclerosis in the arterial wall. Changes in glomerular permeability can result in increased filtration of LP that may be internalized by tubular cells and elicit corresponding lesions in the interstitial tissues. The negative impact of proteinuria on the prognosis of renal disease could be mediated in part through an increased filtration of lipoproteins. Induction of hyperlipidemia accelerates glomerular and interstitial damage in experimental renal failure. This can be attenuated by treatment with hypolipemic agents. In patients, increased concentrations of apoB-containing LP are associated with more rapid progression of renal insufficiency in both primary renal disease and diabetic nephropathy. It is, however, presently not known to what extent treatment of the renal dyslipidemia can modify the progression of chronic renal failure. Experimental and clinical evidence suggest that apoB-containing LP may play a pathogenetic role in the progression of renal disease.
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PMID:Progression of renal failure: role of apolipoprotein B-containing lipoproteins. 940 33

Sodium-lithium countertransport (SLC) in erythrocytes represents one of the transmembrane sodium transport systems. SLC activity is elevated in arterial hypertension, diabetes mellitus type I (IDDM) complicated with nephropathy, hyperlipidemia, hyperuricemia and pregnancy. Increase of SLC is considered as a genetic marker of primary arterial hypertension. In present paper SLC was assessed in 12 patients with IDDM without nephropathy (group I), 12 patients with IDDM complicated with diabetic nephropathy on hemodialytic treatment (group II), 15 patients treated with haemodialysis due to non-diabetic nephropathy (group III) and 12 healthy subjects (group IV). All groups were matched in respect of age. Serum creatinine concentration and inulin clearance were similar in groups I and IV as well as in groups II and III. SLC was assessed according to method described by Canessa and coworkers (1980). SLC activity in group II (0.60 mmol/l litre of erythrocytes/h; 0.43-0.94; 0.28-1.22) (median, 25%-75%, min.-max.) was significantly higher than in other groups-group I (0.30; 0.20-0.38; 0.12-0.57), group III (0.24; 0.16-0.33; 0.11-0.38) and group IV (0.20; 0.15-0.25; 0.12-0.27). In 3 patients of group I the values were higher than in all examined of groups III and IV and approximated to mean values of group II. The results confirm a significant rise of SLC activity in patients with IDDM complicated with end-stage diabetic nephropathy. SLC activity in end-stage renal disease due to non-diabetic nephropathy does not differ from values in healthy subjects. It seems that elevated SLC activity in IDDM might be a genetic marker foretelling development of nephropathy.
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PMID:[Activity of sodium-lithium cotransport in erythrocytes of patients with diabetes mellitus type I (IDDM) complicated by diabetic nephropathy in the renal failure stage]. 944 Dec 88

Current opinions on the relationships between erythrocyte sodium-lithium countertransport kinetics and primary hypertension, hyperlipidaemia and diabetic nephropathy are reviewed. Problems associated with the assay are analysed. Some possible mechanisms that could modify the kinetics of ion exchange are examined. The question of what catalyses sodium-lithium countertransport is discussed, but not answered. Some models are put forward showing how a study of sodium-lithium countertransport kinetics could further our understanding of important disease processes.
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PMID:Sodium-lithium countertransport: physiology and function. 953 10

A case of acquired perforating dermatosis associated with diabetic nephropathy is described. The case is unusual in that the dermatosis first developed approximately 1 year after renal transplantation rather than at a time when renal function was more severely impaired or during haemodialysis. There was a partial response to treatment with isotretinoin but the use of this drug was limited by the development of hyperlipidaemia. The relevant literature is reviewed.
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PMID:Acquired perforating dermatosis and diabetic nephropathy--a case report and review of the literature. 960 58

Diuretics have again been recommended by the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) as one of the first-choice medications in the management of hypertension. This recommendation is based on the results of numerous randomized, diuretic-based, long-term controlled clinical trials that have demonstrated a reduction in both cerebrovascular and cardiovascular morbidity. Despite this and other national recommendations, the use of diuretics has steadily decreased over the past 15 years. Reasons include heavy promotion of other medications and the perception that diuretics produce adverse metabolic effects and do not reduce coronary heart disease events. Data, however, indicate that (1) changes in glucose and cholesterol metabolism are minor, especially with the smaller doses now being used; (2) cardiovascular morbidity and mortality have been reduced in hypertensive patients, even in those with hyperlipidemia or diabetes, when diuretics are used; and (3) concerns about hypokalemia-induced arrhythmias have been overstated. While special indications exist for other medications in the treatment of hypertension, for example, use of an angiotensin-converting enzyme inhibitor (usually in addition to a diuretic) for a patient with heart failure or diabetic nephropathy, most patients, including those with hyperlipidemia or glucose intolerance, can be effectively treated with a diuretic as initial therapy or as part of a combination regimen. Diuretics should be used more not less frequently; use of diuretics would reduce the number of resistant hypertensive patients.
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PMID:Why are physicians not prescribing diuretics more frequently in the management of hypertension? 1045 Jul 8

In this review the usefulness of the measurement of erythrocyte Na+/Li+ countertransport (Na+/Li+ CT) activity is evaluated. In particular, the association between enhanced erythrocyte Na+/Li+ CT activity and essential hypertension, hyperlipidaemia and diabetic nephropathy is discussed. The conclusion of this review is that elevated erythrocyte Na+/Li+ CT activity is associated with essential hypertension and hyperlipidaemia. A relationship between Na+/Li+ CT activity and diabetic nephropathy is less evident. Despite a significant link of Na+/Li+ CT activity with hypertension and hyperlipidaemia, the diagnostic significance of Na+/Li+ CT activity is low. This is due to the large overlap between the results of control subjects and patients. The factors that contribute to this broad range are discussed in detail.
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PMID:Relevance of erythrocyte Na+/Li+ countertransport measurement in essential hypertension, hyperlipidaemia and diabetic nephropathy: a critical review. 965 6

To determine whether high prevalence of small dense low-density lipoprotein (LDL) in non-insulin-dependent diabetes (NIDDM) with nephropathy is directly associated with kidney damage, we measured LDL particle size by non-denaturing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic patients with primary renal disease and compared the results to particle size in NIDDM patients with diabetic nephropathy. The average LDL particle diameter was significantly smaller in patients with diabetic nephropathy (245+/-3 A mean +/- SEM) compared to the controls (263+/-1 A), diabetics without nephropathy (257+/-2 A), patients with primary renal disease (254+/-2 A) or non-diabetic patients treated with hemodialysis (HD) (260+/-1 A). The incidence of small LDL (mean diameter is < or =255 A) was remarkably increased in diabetic nephropathy (67%) compared to diabetes without nephropathy (27%), patients with renal disease (24%), HD patients (15%) and controls (10%). LDL size in patients with primary renal disease was significantly smaller than those in controls. However, because there was an excellent correlation between LDL size and plasma triglyceride (TG) levels, when hypertriglyceridemic subjects (TG >1.7 mM) were excluded, no difference of LDL size was observed between the renal disease group (260+/-2 A) and the control group (264+/-1 A). On the other hand, even when hypertriglyceridemic subjects were excluded, LDL size was still smaller in diabetic nephropathy (250+/-4 A). We performed an oral fat load test in normotriglyceridemic subjects (fasting TG <1.7 mM) of control, diabetes with and without nephropathy and primary renal disease. The TG responses in plasma and TG-rich-lipoprotein (TRL) (d <1.006) after the oral fat load were significantly greater in NIDDMs with nephropathy compared to controls or NIDDMs without nephropathy, while such a marked postprandial lipemia was not observed in patients with primary renal disease. In these fasting normotriglyceridemic subjects, LDL size was significantly inversely correlated with postprandial TG responses, which is totally independent from fasting TG levels. These results suggest that high prevalence of small dense LDL in NIDDM patients with nephropathy is not directly associated with kidney damage. Postprandial lipemia may play an important role in reducing LDL particle size in these patients.
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PMID:High prevalence of small dense LDL in diabetic nephropathy is not directly associated with kidney damage: a possible role of postprandial lipemia. 986 40

The progressively growing number of patients with end-stage renal failure (ESRF) associated with diabetes mellitus and requiring renal replacement therapy (RRT) stimulated both nephrologists and diabetologists to investigate the mechanisms linking hyperglycaemia to diabetic renal failure and to set up measures to prevent the onset and slow the progression of diabetic nephropathy. Over the last few decades, a large number of studies have investigated both the incidence of diabetic nephropathy and the relationship between metabolic control and the development of diabetic nephropathy. Chronologically, the first type of diabetes and diabetic nephropathy to be studied was type I, and it is only in recent years that metabolic control has been proven to be a contributor to the development of nephropathy in such patients. Recently, the DCCT demonstrated that metabolic control in the prealbuminuric phase was effective in reducing the incidence of microalbuminuria, even if it was unable to reduce the incidence of overt proteinuria in patients with type I diabetes and established proteinuria. On the other hand, in type II diabetes, the number of studies demonstrating a favourable effect of metabolic control on onset and progression of diabetic nephropathy is only slightly greater than those that failed to show a favourable effect. This feature may suggest that in type II patients, genetic and ethnic differences, nutritional aspects, lifestyle and other confounding factors may play a relevant role in the course of the disease. However, the trials performed and the retrospective analyses generally agree that glycated haemoglobin two standard deviations greater than the mean is related to a worsening in progression of diabetic nephropathy and to an enhanced risk of other complications. In general, a glycated haemoglobin < or =8% seems advisable. Moreover, in both type I and type II, greater emphasis should be placed on the major risk factors such as hypertension, smoking habits and hyperlipidaemia.
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PMID:The effect of metabolic control on development and progression of diabetic nephropathy. 987 Apr 24


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