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)

The pathophysiology, clinical features, complications, and pharmacologic management of adult idiopathic nephrotic syndrome are reviewed. Loss of plasma proteins in the urine is the primary process leading to the nephrotic syndrome, which is characterized by hypoalbuminemia, hyperlipidemia, and edema. The four principal causes, or subclasses, of adult idiopathic nephrotic syndrome are membranous nephropathy (MN), minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranoproliferative glomerulonephritis (MPGN); definitive diagnosis requires histologic examination of a renal biopsy specimen. Treatment of nephrotic syndrome may be directed at the specific cause of the proteinuria, the proteinuria itself, or the complications induced by the syndrome. The four subclasses of nephrotic syndrome vary in their response to therapy. Corticosteroids, alone or in combination with cytotoxic agents, and cyclosporine have been used to induce partial or complete remission in patients with MN, MCD, and FSGS; combinations of corticosteroids, cytotoxic agents, platelet inhibitors, and anticoagulants have been used to treat patients with MPGN. Treatment of proteinuria involves dietary protein restriction with the possible addition of an angiotensin-converting-enzyme inhibitor or a nonsteroidal anti-inflammatory drug. Management of the complications of nephrotic syndrome encompasses the use of diuretics; a low-cholesterol, low-fat diet; lipid-lowering agents; and anticoagulants. Patients with nephrotic syndrome are in a constant state of flux with respect to fluid status, organ function, and critical protein balance. Treatment is based on the histologic subclass of the disease.
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PMID:Pharmacologic management of adult idiopathic nephrotic syndrome. 840 14

Hyperlipidemia has been associated with glomerulosclerosis and a glomerular monocyte infiltrate in models of progressive renal insufficiency. The pathogenesis of hyperlipidemia-induced renal injury remains unknown. We postulated that the effect of hyperlipidemia may be mediated through LDL-induced activation of mesangial cells, which have recently been shown to possess LDL receptors. To test this hypothesis, cultured human mesangial cells were co-incubated with human LDL. Monolayers treated with LDL demonstrated a greater level of tissue culture supernatant fibronectin than control mesangial cells. This correlated with enhanced expression of fibronectin mRNA in LDL-treated mesangial cells. Additionally, LDL conditioning of mesangial cells caused a dose- and time-dependent increase in the expression of monocyte chemoattractant protein-1 mRNA, a monocyte specific chemotactic factor, as well as an increase in the monocyte chemotactic activity of mesangial supernatants. Thus, the deleterious effects of hyperlipidemia on the kidney may be mediated by the mesangial cell through an increase in production of mesangial matrix and recruitment of inflammatory cells to the glomerulus.
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PMID:LDL stimulates mesangial fibronectin production and chemoattractant expression. 843 62

Hyperlipidemia is associated with accelerated glomerular sclerosis in experimental renal insufficiency. To investigate whether the dyslipoproteinemia seen in human renal failure also influences the future course of renal insufficiency, we have correlated plasma levels of lipids and apolipoproteins at start of follow-up with the subsequent change in renal function in 34 adult patients with chronic renal disease. Nineteen patients had primary renal disease, and 15 patients had diabetic nephropathy. Except for antihypertensive therapy no specific treatment to modify the progression of the disease was given during the follow-up. The rate of progression was determined by repeated measurements of the glomerular filtration rate (GFR). The time of follow-up ranged from 12 to 91 months with an average of 39.7 +/- 16.7 months. The mean initial GFR was 34.7 +/- 13.9 ml/min x 1.73 m2 body surface area and the average decline in renal function was -0.27 +/- 0.26 ml/min/month. The entry levels of triglycerides (TG; p = 0.04), very-low-density lipoprotein cholesterol (p = 0.03), apolipoprotein-B (ApoB; p = 0.008) and systolic blood pressure (SBP; p = 0.04) were significantly correlated with the rate of progression. Among lipoprotein variables, ApoB showed the strongest correlation with the decline in GFR. Patients with a progressive course of their disease also tended to have initially higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (NS), whereas the initial plasma concentration of high-density lipoprotein cholesterol did not show an association with the progression of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein-B-containing lipoproteins and the progression of renal insufficiency. 772 19

Two adult patients with type I glycogen storage disease (I-GSD) had chronic renal disease with heavy proteinuria. Renal biopsies showed focal glomerular sclerosis, interstitial fibrosis, tubular atrophy or vacuolation, and prominent arteriosclerosis. Marked glomerular hypertrophy was demonstrated histometrically. Oil red O staining in one patient revealed numerous lipid deposits in the glomerular mesangium, tubular epithelial cells and interstitium. Electron microscopy in the other patient revealed diffuse thickening of the glomerular basement membrane (GBM) and lipid droplets within the mesangium. The glomerular hypertrophy, thickening of the GBM, and subsequent sclerosis were similar to those in insulin-dependent diabetes mellitus. These findings may explain the similarities between the natural histories of renal involvement in the two disorders. Particularly, glomerular hypertrophy may be a key step leading to glomerular sclerosis, which is the predominant finding I-GSD. Hyperlipidemia, which is commonly seen in I-GSD, may also accelerate the glomerular sclerosing process.
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PMID:Renal histology in two adult patients with type I glycogen storage disease. 844 18

Results of recent animal studies have lent support to the hypothesis that hyperlipidaemia may contribute to renal injury. This report documents the case of a 15-year-old boy with drug-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FGS) who showed an improvement in renal function and proteinuria as a result of treatment with low-density lipoprotein aphaeresis (LDL-A) combined with pravastatin. Although further work is required to determine the efficacy of lipid-lowering therapy in progressive glomerular disease in humans, the combination of LDL-A and pravastatin is likely be included in the choice of treatment modalities available for patients with drug-resistant nephrotic syndrome due to FGS.
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PMID:Treatment with a combination of low-density lipoprotein aphaeresis and pravastatin of a patient with drug-resistant nephrotic syndrome due to focal segmental glomerulosclerosis. 847 19

The purpose of this review has been to summarize the effects of lipids on the progression of renal disease in chronic renal failure. Animal studies show that hypercholesterolemia as induced by a high cholesterol diet can aggravate the progression of renal disease in experimental models of chronic renal failure. Hypolipidemic treatment, when given to animals with chronic nephropathy associated with endogenous hyperlipidemia such as in reduced renal mass, obese Zucker rat, PAN nephrosis and the Dahl salt-sensitive rat, results in a reduction in serum lipids levels concomitant with a decrease in the renal damage. Enrichment of the diet with omega-6 PUFA given to rats with reduced kidney mass leads to a reduction in renal damage, probably due to beneficial changes in renal fatty acid composition, while supplementation of a fish oil diet to rats with immune complex nephritis resulted in a similar beneficial effect, probably due to a suppression in the local immunologic processes. The pathogenesis of this effect is still only partially understood. Lipid deposition and oxidation in the renal mesangium, migration of circulatory monocytes into the renal mesangium and their transformation to foam cell, and alterations in renal PUFA metabolism and composition are the main known alterations that accompany lipid-induced renal damage. These alterations, which are similar to those observed in atherosclerosis, lead to alterations in the normal biologic processes in the renal mesangium and terminate in glomerulosclerosis. Extrapolating the data from experimental studies to human renal diseases, it may be assumed that lipid metabolism has a significant impact on the gravity and progression of renal disease in a selected patient population, namely in patients with chronic renal disease. If so, hypolipidemic treatment or administration of certain types of PUFA can be important in the prevention of progression of the renal disease in these patients. Clinical studies are needed to elucidate this issue.
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PMID:Role of lipids in the progression of renal disease in chronic renal failure: evidence from animal studies and pathogenesis. 849 78

Recent evidence suggests focal glomerulosclerosis may be analogous to atherosclerosis. To investigate the role of hypertension and hypercholesterolemia in the appearance of glomerular foam cells, 2, 6 or 9-month-old stroke-prone SHR (SHRSP) were fed the high fat cholesterol diet (2% cholesterol, 0.5% cholic acid, 7% lard, 0.2% methylthiouracil; HFC) for 4 weeks. Serum total cholesterol was significantly elevated in HFC. Form cells were observed in glomeruli of 6- and 9-month-old, but not 2-month-old SHRSP with dietary-induced hypercholesterolemia. The glomerular foam cells varied in quantity almost in parallel with the duration of severe hypertension. Glomeruli with foam cells prominently situated in juxtamedullary region. Foam cells were frequently seen in glomerular sclerotic area. These results suggest that hypertension rather than hyperlipidemia may be more important for glomerular deposition of lipid, especially in early lesions, and hyperlipidemia may play a role in the foam cells accumulation.
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PMID:[Study on the glomerular foam cells in stroke-prone SHR]. 851 96

Hyperlipidemia has been implicated in the pathogenesis of experimental progressive glomerulosclerosis, but its role in human renal injury is controversial. This report describes a 12-yr-old boy presenting with massive proteinuria, hepatomegaly, anemia, severe mixed hyperlipidemia, and progressive renal failure. The initial renal biopsy disclosed large numbers of foam cells that were shown to be monocytes. Evidence is presented suggesting that apoprotein-E2 homozygosity in our patient, together with an 88% reduction in plasma lipoprotein lipase activity associated with severe nephrotic syndrome, is responsible for the atypical clinical features, lipoprotein phenotype III with chylomicronemia, and renal lipidosis. A regimen of dietary lipid restriction, gemfibrozil, and niacin resulted in significant but partial improvement of the dyslipidemia and resolution of the hepatomegaly and ascites. This report stresses the importance of characterizing unique lipid disorders in patients with nephrotic syndrome in order to prescribe effective lipid-lowering strategies. Moreover, the striking resemblance of the clinical and nephrohistologic features of this patient to those occurring in experimental models of coexisting glomerular injury and hyperlipidemia led to the speculation that, in this setting, the hyperlipidemia may contribute to the development of progressive glomerulosclerosis.
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PMID:Atypical hyperlipidemia and nephropathy associated with apolipoprotein E homozygosity. 858 83

Rats of the Milan normotensive rat strain (MNS) spontaneously develop severe proteinuria and excessive glomerular thromboxane (Tx)A2 production at a young age. These abnormalities are accompanied by podocyte alterations, progressive focal glomerulosclerosis (FGS), and interstitial fibrosis, resembling human FGS. Since it has been shown that pharmacologic Tx-synthase inhibition protects MNS rats from these changes, it was hypothesized that a fish oil (FO) enriched diet, by enhancing TxA3 production instead of TxA2, might afford similar protection, compared with diets enriched in safflower oil (SO) or lard (LD). Rats were pair-fed 11% fat diets from age of 1 to 11 months. Glomerular TxA2 at 11 months was significantly lower in PO-fed rats than in SO- and LD-fed rats (11 +/- 3.0, 69 +/- 3.0, 59 +/- 19.0 nanograms per min/mg, respectively; P < 0.001). At 3 months, urinary albumin excretion was similar among the groups. Over the course of the study, rats fed FO developed significantly less albuminuria than the SO and LD groups (P < 0.001 by analysis of variance for repeated measures), such that the values at 11 months were 25 +/- 5.8, 49 +/- 8.7, and 68 +/- 13.0 mg/24h, respectively. Serum cholesterol and triglycerides were also significantly lower in FO-fed rats than in SO- and LD-fed rats. The extent of FGS was similar in the three groups, but FO-fed rats had less interstitial injury than the other groups. It was observed that a fish-oil diet substantially alleviated albuminuria, normalized nephrotic hyperlipidemia, and reduced interstitial injury, but did not prevent the development of FGS in the MNS model.
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PMID:Fish oil ameliorates renal injury and hyperlipidemia in the Milan normotensive rat model of focal glomerulosclerosis. 858 25

Disturbances of lipid metabolism are considered to play a pathogenetic role in glomerulosclerosis. Since intraglomerular have been proposed to be involved in the pathogenesis of the glomerulosclerosis, we have investigated the influence of LDL on the activity of the cellular proteases. Cathepsins B and L were measured with the aid of fluorometry, and 7-amido-4-methylocoumarin derivates were used as substrates; Z-Arg-Arg-AMC for cathepsin B, Z-Phe-Arg-AMC for cathepsins B and L together. Rat mesangial cells cultured 24 h in medium supplemented with LDL revealed inhibition of cathepsin B activity at concentrations of 250 micrograms LDL/ml medium, lower LDL concentrations were without apparent effect. Since the glomerular accumulation of structural and nonstructural proteins plays an important role in glomerulosclerosis, we conclude that the augmented proteolytic activity of mesangial cells might be one of the pathways located by which hyperlipidemia causes an increased susceptibility to glomerular damage.
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PMID:Low-density lipoprotein suppresses cathepsins B and L activity in rat mesangial cells. 867 24


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