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

Hyperlipidemia accelerates the progression of human renal disease, and its control is becoming an important component of therapy for patients with renal failure. The biologic basis for these observations remains poorly understood. This review summarizes recent data from animal models which show how lipoproteins interact with cells directly to cause renal injury. Data are presented from recent studies on the obese Zucker rat, a metabolic model of hyperlipidemia, obesity, and glomerular sclerosis, showing that triglyceride-containing lipoproteins may mediate glomerular injury. The biochemical basis for therapy is also discussed, including actions of lipid-lowering agents apart from their effect on serum lipids, and the use of polyunsaturated fatty acids as dietary therapy. Animal models are a crucial tool for the further elucidation of mechanisms of lipoprotein-mediated glomerular injury.
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PMID:Hyperlipidemia and renal disease: the use of animal models in understanding pathophysiology and approaches to treatment. 1037 11

Renal disease is accompanied by characteristic alterations of lipoprotein metabolism, which appear as a consequence of nephrotic syndrome or renal insufficiency and are primarily reflected in an altered apolipoprotein profile rather than elevated plasma lipid levels. Their full characterization requires identification of discrete lipoprotein particles. While nephrotic syndrome results in increased concentrations of both cholesterol- and triglyceride-rich apoB-containing lipoproteins, renal insufficiency is characterized by an accumulation of intact or partially metabolised triglyceride-rich apoB-containing lipoproteins. The dyslipidemia has been discussed as a contributory factor for the progression of renal insufficiency through development of glomerulosclerosis and tubulointerstitial lesions together with accelerated atherosclerosis. Several experimental studies have shown that hyperlipidemia accelerates renal damage. Lipid-lowering treatment can reduce renal lesions and preserve renal function. The documentation in human nondiabetic progressive renal insufficiency is more limited. We have found that increased concentrations of triglyceride-rich, but not cholesterol-rich, apoB-containing lipoproteins are, associated with a more rapid loss of renal function. The underlying pathophysiological mechanisms for the relation between triglyceride-rich apoB-containing lipoproteins and progression of renal insufficiency are not fully understood. Treatment with hypolipemic drugs may attenuate the renal dyslipidemia, but thus far there have been no reports about controlled clinical trials testing the possible effect of such treatment on the progression of renal insufficiency. In summary, there is evidence to suggest that some specific lipoprotein abnormalities are a risk factor for the progression of renal dysfunction, but the final test of such assumptions still rests on the results of urgently needed controlled intervention studies.
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PMID:Lipoprotein abnormalities as a risk factor for progressive nondiabetic renal disease. 1041 28

Cyclosporin (CsA) is widely used in the treatment of renal disease and transplantation, which are often complicated by alterations of lipid metabolism. Both chronic administration of CsA and hyperlipidaemia have been shown to evoke an early macrophage influx and have progressively led to glomerular and interstitial sclerosis. MCP-1 is the major monocyte chemoattractant secreted by stimulated mesangial cells and TGF-beta 1 is a key mediator of fibrogenesis in chronic progressive renal fibrosis. Thus, the combined effect of CsA and low-density lipoprotein (LDL) on the gene and protein expression of MCP-1 and TGF-beta 1 in cultured human mesangial cells (HMC) was explored. Both agents induced an early and persistent increase of MCP-1 and TGF-beta 1 mRNA levels and protein release. The simultaneous addition of CsA and LDL did not display any additive effect on target gene expression, but it caused a synergistic effect on MCP-1 and TGF-beta 1 protein secretion into culture medium. On the other hand, CsA and LDL had different effects on cell proliferation: the latter increased DNA synthesis, whereas CsA inhibited both spontaneous and mitogen-stimulated mesangial cell growth. The study concludes that CsA and LDL display an additive effect on TGF-beta 1 and MCP-1 synthesis and release by HMC, thus possibly co-operating to induce an early macrophage influx and the subsequent mesangial expansion and increased extracellular matrix deposition. However, in contrast they seem to modulate HMC proliferation differently, which is a further critical event intimately involved in the development of glomerulosclerosis.
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PMID:Low-density lipoproteins enhance transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemotactic protein-1 (MCP-1) expression induced by cyclosporin in human mesangial cells. 1044 70

Overall, 138 patients at teen age and youths were studied for the clinical course of their glomerulonephritis. In adolescence, the onset of glomerulonephritis presents as urinary syndrome with hematuria and nephrotic syndrome. Acute glomerulonephritis with hematuria is accompanied by a low level of proteinuria and slow progression. Apparent benefit from the treatment occurred in 73 +/- 5% of patients (complete and partial clinical and laboratory remission), unsatisfactory results of treatment were recorded in 27 +/- 5% of patients. Persistence of nephrotic syndrome in patients demonstrating unsatisfactory results of treatment coincide with far greater frequency of unfavourable morphological forms of glomerulonephritis (mesangiocapillary and focal-segmentary glomerulosclerosis (hyalinosis), changes in canaliculi and interstitium, with loss of the functional reserves of the kidneys and effect of plasmapheresis on hyperlipidemia being recordable.
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PMID:[The characteristics of the pathogenesis and clinical forms of the course of glomerulonephritis in adolescent patients]. 1047 54

Hyperlipoproteinemia can aggravate glomerulosclerosis and chronic tubulointerstitial (ti) damage in kidneys without primary immunologic disease. We evaluated whether the effect of hyperlipidemia on progression of renal damage differed between kidneys without preexisting glomerular disease and kidneys with mesangioproliferative glomerulonephritis and whether the renal actions of hyperlipidemia were dependent on oxidant-antioxidant balance. Hyperlipidemia was induced by high-fat and high-cholesterol diet in uninephrectomized rats. In rats without glomerulonephritis, hyperlipidemia led to a rise in glomerular and ti generation of reactive oxygen species (ROS). Oxygen radicals were mainly generated by enhanced xanthine oxidoreductase (XO), which rose with protein concentration and activity during hyperlipidemia; concurrently, glomerulosclerosis and chronic ti injury were noticed during hyperlipidemia [ti damage (% of total tubulointerstitium (TI) after 150 days): normolipidemia 0.1 +/- 0% vs. hyperlipidemia 3.4 +/- 0. 9%; P < 0.05]. In mesangioproliferative Thy-1 nephritis, ti injury was significantly accelerated by hyperlipidemia (ti damage after 150 days: normolipidemic Thy-1 nephritis 2.5 +/- 0.6% vs. hyperlipidemic Thy-1 nephritis 12.5 +/- 3.1%; P < 0.05). Antioxidant enzyme activities decreased and XO activity rose markedly in the TI (XO activity in TI after 150 days: normolipidemic Thy-1 nephritis 2.2 +/- 0.5 vs. hyperlipidemic Thy-1 nephritis 4.5 +/- 0.7 cpm/microg protein; P < 0.05). In hyperlipidemic Thy-1 nephritis rats, which had a higher urinary protein excretion than normolipidemic rats, hypochlorite-modified proteins, an indirect measure for enhanced myeloperoxidase activity, were detected in renal tissue and in urine, respectively. During hyperlipidemia, chronic damage increased in renal TI. Enhanced generation of ROS, rise in oxidant enzyme activity, and generation of hypochlorite-modified proteins in renal tissue and urine were noticed. These data suggest that oxidant stress contributed to the deleterious effects of hyperlipidemia on the renal TI.
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PMID:Oxidant stress in hyperlipidemia-induced renal damage. 1064 56

Chronic rejection is the most common cause of the long term renal graft loss. It is characterized by luminal thickening and obliteration, interstitial sclerosis, glomerulosclerosis and tubular atrophy development. The pathology is still unclear. Alloantigen-dependent factors (acute rejection, HLA mismatch) and allograft-independent factors (ischaemia-reperfusion, hyperlipidaemia, hypertension, infection, nephrotoxicity, reduced nephron dose) have been implicated in the etiology of chronic rejection. As a result of these factors, endothelial cells are activated and express a variety of adhesion molecules, cytokines and growth factors. Lymphocytes and macrophages infiltrate the areas of local damage and express other cytokines and growth factors (TGF, bFGF, PDGF). In the next step, vascular smooth muscle cells proliferate and migrate from the media into the vascular intima and produce local extracellular matrix. Which factors are the most important and which mechanisms are the key for the development of chronic rejection are in the focus of ongoing research.
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PMID:[Chronic rejection of renal allografts. Part 1. Present knowledge of etiopathogenesis]. 1074 33

1. We examined whether KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)-induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM-1K-SHR) or not. 2. The oral administration of KRH-594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM-1K-SHR. 3. In a histological study, KRH-594 (3 and 10mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently improved glomerulosclerosis and the hyalin cast of tubules in DM-1K-SHR kidneys. Both KRH-594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose-dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM-1K-SHR. 5. These results suggest that KRH-594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.
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PMID:KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates nephropathy and hyperlipidaemia in diabetic spontaneously hypertensive rats. 1077 24

To understand the effect of endothelin (ET) on the mesangium and matrix proliferation on the basis of hyperlipidemia, the model of mesangial proliferative glomerulonephritis (MSPGN) was established by intravenously giving calf serum albumin (250 mg/L) to the rabbits fed on feed containing 1% cholesterol for 4-8 weeks. Our results showed that in the 4th week of the experiment, the ET level in experiment group was significantly higher than that of normal controls (P < 0.01) and the pathological examination revealed development of MSPGN. In the 8th week of the experiment, the ET level was further elevated and pathological study demonstrated local glomerular sclerosis and infiltration of lymphocytes of interstitia. We are led to conclude that ET, as a newly identified hormone, is involved in the pathogenesis and development of MSPGN and acts as an important regulator in the proliferation of mesangium and accumulation of matrix of basal membrane.
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PMID:The role for endothelin in mesangial proliferative glomerulonephritis. 1080 41

The experimental model of Golden Syrian hamster subjected to concomitant hyperlipemia (diet-induced) and diabetes (by streptozotocin injection) for 24 weeks is characterised by the prevalence of micro- and macroangiopathies. We have used the hyperlipemic-diabetic (HD) hamsters to investigate: a) whether there is an alteration in the reactivity of the resistance arteries (mean internal diameter: 210-250 microm), b) if present, which are the structural and biochemical changes that accompany the functional modifications, and c) to examine the pathomorphological changes induced by the association of hyperlipemia and diabetes on vital organs such as myocardium and kidney glomeruli. To these aims, biochemical assays of plasma components, light- and electronmicroscopy, myographic, morphometric and spectrofluorimetric techniques were used. The mesenteric resistance arteries of HD hamsters exhibited (as compared to similar arteries in normals) a decreased contractile response to noradrenaline (1.86+/-0.35 vs. 2.43+/-0.21), and an impeded endothelium dependent relaxation to acetylcholine (approximately 61.40% vs. approximately 79.80%). The association of hyperlipemia with diabetes induced changes in morphology of the resistance arteries consisting in approximately 10% increase of the intima plus media cross-sectional area, approximately 20% decrease of the vascular lumen area, and approximately 2.85 fold augmentation of the wall to lumen ratio. The resistance arteries exhibited structural modifications of the endothelium (up to 8 copies of Weibel-Palade bodies/endothelial cell), and smooth muscle cells (secretory phenotype), and in the vessels media small calcification cores appeared embedded in a hyperplasic extracellular matrix. The vascular mesenteric bed of the HD hamsters contained approximately 2.30 and approximately 1.30 fold increased concentrations of AGE-collagen and pentosidine, respectively, above the normal values. The HD hamsters displayed also modifications that may be dependent on or may lead to an increase in blood pressure, such as: a) approximately 2 fold increase in the activity of serum angiotensin converting enzyme; b) approximately 4.8 fold enhancement of erythrocytes fragility (as a measure of the oxidative stress); c) left ventricular hypertrophy associated with a progressive disarray of cardiomyocyte contractile fibers, interruptions of the Z bands, and accumulation of collagen-rich extracellular matrix indicative of interstitial fibrosis; d) the kidney glomerular capillaries appeared partially or totally collapsed, with a thickened basement membrane which appeared polymorphic, and in some locations made up of successive layers connected by fine bridges and intercalated nodules; in addition, an increase (approximately 1.50 fold) of the mesangial volume was indicative of glomerulosclerosis.
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PMID:The effects of simultaneous hyperlipemia-hyperglycemia on the resistance arteries, myocardium and kidney glomeruli. 1087 2

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.
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PMID:Role of lipids in the progression of renal disease in systemic lupus erythematosus patients. 1102 Sep 63


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