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

The obese Zucker rat develops hyperlipidemia, proteinuria and focal glomerulosclerosis without prior changes in renal hemodynamics. To study the effects of oral fatty acid intake on the development of renal injury in this model, rats were fed standard chow or chow supplemented with either 14% fish oil or 14% beef tallow after unilateral nephrectomy at the age of 10 weeks. At 32 weeks post-nephrectomy animals were sacrificed and renal tissue saved to assess histology and glomerular eicosanoid production. Fish-oil treated rats had lower mean plasma cholesterol levels and developed less proteinuria than control or tallow-fed animals although there was no difference in plasma creatinine or blood pressure. Histological analysis showed significantly fewer sclerosed glomeruli in the fish oil group (4.0 +/- 0.8% vs. control 19.4 +/- 4.1%, P less than 0.0005 and vs. beef tallow 10.8 +/- 1.9%, P less than 0.005). Glomeruli derived from rats on fish oil supplements produced smaller amounts of prostaglandin (PG)E2 and of the stable metabolites of PGI2 (6-oxo-PGF1 alpha), PGF2 (PGF2 alpha) and thromboxane (TX)A2 (TXB2) than those from tallow-fed animals. This study demonstrates that oral fatty acid intake may influence the development of glomerulosclerosis. The apparent beneficial effects of fish oil have not been fully defined, but may relate to favorable changes in plasma lipid concentration and renal eicosanoid production.
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PMID:Effects of dietary fatty acids in an animal model of focal glomerulosclerosis. 206 9

The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain to be established. However, there is now evidence that renal disease clusters in families and that genetic factors are of central importance in determining liability. A predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Genetically controlled hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. This suggestion derives from the observation that the fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first sign of renal damage is the appearance of microalbuminuria and of a small elevation in arterial pressure, changes associated with significant mesangial expansion. Microalbuminuria is associated with abnormalities of lipoprotein profiles possibly as a consequence of insulin-resistance-induced hyperinsulinemia. It could be postulated that the environmental changes brought about by diabetes lead in susceptible individuals to increased systemic and intraglomerular pressure on the one hand and mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities would further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered of reduction in renal function, more hypertension, more proteinuria, more glomerular obsolence, more hyperlipidemia and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Mechanisms of diabetic renal and cardiovascular disease. 207 90

Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol + 1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak = 11.52 +/- 1.09 mmol l-1 vs. 4.73 +/- 0.31 on control diet, P less than 0.001) and triglyceride concentrations (peak = 2.31 +/- 0.27 mmol l-1 vs. 1.41 +/- 0.29, P less than 0.05) and a marked increase in beta-migrating lipoproteins. The severity of hypercholesterolaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, P less than 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, P less than 0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (P less than 0.05). The kidney total cholesterol content was increased from 29.2 +/- 0.8 to 47.7 +/- 3.3 mumols g-1 dry weight (P less than 0.0001), with esterified cholesterol increasing from 7.5 +/- 0.4% to 14.5 +/- 2.1% of total (P less than 0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition (rs = 0.7195, P less than 0.0001) and tissue total cholesterol content (rs = 0.6053, P less than 0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable.
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PMID:The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy. 210 41

Nephron loss is a common progression of a diverse range of kidney diseases. Recent experimental models of chronic renal disease have suggested that hemodynamic and nonhemodynamic mechanisms play key roles in progressive renal injury. Extensive renal ablation in the rat was followed by development of altered glomerular hemodynamics. Albuminuria and histologic damage leading to focal glomerulosclerosis were preceded by the development of increased glomerular pressures and were prevented by interventions such as severe dietary protein restriction and angiotensin-converting enzyme (ACE) inhibitor therapy. Both experimental interventions ameliorated glomerular hypertension. It was therefore concluded that these interventions ameliorated injury by glomerular hemodynamic effect. Similar findings were obtained in a rat model of type I diabetes mellitus induced by streptozotocin in which glomerular hemodynamic factors appeared important to the development of progressive renal disease. Recent studies have suggested that nonhemodynamic factors have important roles in the progression of glomerular injury. For example, although the predominant effects of ACE inhibitor therapy appear to be hemodynamically mediated, data are emerging which suggest that these agents may also influence growth/proliferation of glomerular cells. Because hyperplasia/hypertrophy may influence glomerular susceptibility to injury, this may also be a potential mechanism whereby ACE inhibitor therapy influences glomerular damage. In addition, a variety of studies have suggested that hyperlipidemia, which is frequent accompaniment of glomerular disease, is an important modulator of glomerular injury independent of glomerular hemodynamic effects. Coagulation factors, calcium phosphorus balance, as well as the genetic susceptibility of the glomerulus to injury, all appear to contribute to progressive nephron destruction.
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PMID:Renal protective effects of angiotensin-converting enzyme inhibition. 218 11

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

Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg.kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P less than 0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.
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PMID:Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. 223 87

Hyperlipidemia is common in patients with glomerular proteinuria. It may contribute to atherosclerotic complications and accelerate glomerular damage. Early trials of the fibric acid derivative clofibrate led to a myositis syndrome causing many nephrologists to abandon attempts at treatment of nephrotic hyperlipidemia. Recent trials with lipid-lowering medications have been successful without major side effects. The bile acid sequestrants colestipol and cholestyramine bind bile acids in the gut and deplete the hepatic cholesterol pool, thus inducing LDL hepatocyte receptors. Recent studies showed a reduction of total cholesterol of 8-20% and LDL cholesterol of 19-31% without significant changes in HDL cholesterol. Probucol has reduced total cholesterol 23-30% and LDL cholesterol 23-25% in nephrotic patients. Although HDL cholesterol was reduced, the LDL/HDL ratio remains favorably changed. The fibric acid derivative gemfibrozil inhibits adipose lipolysis and enhances lipoprotein lipase activity thus decreasing LDL synthesis and increasing its removal. It caused a large decrease in triglycerides with a 13-15% decrease in total and LDL cholesterol in a recent trial. HDL cholesterol increased 18%. The HMG-CoA reductase inhibitors inhibit the rate-limiting step in cholesterol biosynthesis hence inducing an increase in LDL receptors on hepatocytes. Trials have shown decreases of 18-36% in total cholesterol and 18-47% in LDL cholesterol, while HDL cholesterol was either increased or unchanged. The use of lipid-lowering agents of several classes has been effective in ameliorating the progression of glomerular damage in a number of different models of glomerulosclerosis. Nevertheless, so far in humans lipid lowering drugs have not been established to have an effect on either the degree of proteinuria or the progression of glomerulosclerosis.
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PMID:Lipid-lowering agents in proteinuric diseases. 225 70

Proteinuria is characteristic of many glomerular conditions, and often exceeds 2-3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from 'overload' proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinuria leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in hematuric conditions. Therapies designed to reduce proteinuria per se may have a role in the treatment of glomerulopathies.
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PMID:Proteinuria and progression in human glomerular diseases. 225 80

We chose to assess the role of cholesterol reduction in chronic aminonucleoside nephrosis by pharmacologically lowering serum cholesterol with cholestyramine. Two groups of rats were made nephrotic with a single intravenous dose of puromycin aminonucleoside (PA): one group (PA/resin) received 5% (w:w in diet) cholestyramine resin and the dietary control group (PA/cell) received 5% cellulose. Cholestyramine-treated rats demonstrated significant functional and histological protection. Recurrent proteinuria was significantly lower in PA/resin animals. Whole-kidney glomerular filtration rate in the PA/resin group was preserved at a level equivalent to normal age-matched control rats whereas the PA/cell group had a significantly lower value than did the normal animals. The extent of segmental glomerulosclerosis 24 wk after PA delivery was significantly lower in the PA/resin group. These results suggest a role for hyperlipidemia as one of the mechanisms involved in the pathogenesis of progressive glomerular disease.
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PMID:Cholestyramine resin ameliorates chronic aminonucleoside nephrosis. 232 67

The effect of exercise on the progression of experimental renal disease was studied in adriamycin (ADR)-treated rats, a model of sclerosing glomerulonephritis with nephrotic syndrome. Two hours of daily swimming exercise was carried out for 20 weeks in ADR-treated male Lewis rats fed with either an ad libitum intake of regular chow (group 1) or a restricted amount of food (group 3), which was equal to the amount of food freely ingested by ADR-treated rats not undergoing swimming exercise (group 2). Group 3 resulted in a significantly lower serum creatinine, higher inulin clearance and lower glomerular sclerosis index compared to group 2. The progress of renal dysfunction did not differ significantly between group 1 and group 2. Hyperlipidemia, especially, hypertriglyceridemia was significantly lower in the exercise groups than in the sedentary group. Among all the rats, inulin clearance was inversely correlated with either cholesterol (r = 0.560, p less than 0.01) or triglyceride (r = 0.423, p less than 0.05) and the glomerular sclerosis index correlated positively with cholesterol (r = 0.599, p less than 0.005). Systolic blood pressure was 10 mm Hg lower in group 3 than in group 2 and the difference was significant. It is concluded that swimming exercise with a relative restriction of food intake can improve hyperlipidemia and prevent progressive renal dysfunction in ADR-induced nephritic rats.
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PMID:Effect of swimming exercise on the progress of renal dysfunction in rat with focal glomerulosclerosis. 237 Sep 32


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