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

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels.
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PMID:Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects. 186 98

Cumulative carnitine losses through dialysis membranes may worsen hyperlipidemia during long-term hemodialysis. However, carnitine supplementation has not shown a consistent beneficial response in hyperlipidemia. We have compared in a double-blind, cross-over study the effect of dialysate buffer composition (acetate or bicarbonate) on the serum lipid response to L-carnitine supplementation during hemodialysis. We studied nine patients (mean age, 19 years; range, 14 to 23) with hyperlipidemia undergoing maintenance hemodialysis. Plasma levels of carnitines and lipids, including total and HDL cholesterol (HDL-C) and triglycerides (TG), were measured at baseline and monthly intervals after receiving 2 grams of L-carnitine or placebo added to dialysis bath for three months. One month of carnitine supplementation in acetate hemodialysis significantly reduced plasma TG (230 +/- 95 to 136 +/- 20 mg/dl; P less than 0.05) and elevated HDL-C (50 +/- 12 to 71 +/- 26 mg/dl; P less than 0.05). However, this effect was no longer observed at the end of three months of supplementation. Bicarbonate hemodialysis had lower baseline TG values, but carnitine supplementation did not modify plasma lipids (TG:144 +/- 87 to 158 +/- 115 mg/dl; HDL-C:50 +/- 23 to 50 +/- 19 mg/dl). Both groups had a significant increase in plasma carnitine levels after carnitine supplementation. These results suggest that bicarbonate hemodialysis may add a protective effect in hyperlipidemia by reducing requirements of carnitine supplementation. On the other hand, carnitine supplementation should be considered in patients with hyperlipidemia undergoing acetate hemodialysis. The observed difference in response between acetate and bicarbonate hemodialysis may be due to enhanced formation of acetyl-CoA and fatty acid synthesis during acetate hemodialysis.
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PMID:Effect of dialysate composition on the lipid response to L-carnitine supplementation. 269 97

To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4+, salicylate, and carnitine on the oxidation of [1-14C]palmitic acid to acid-soluble products (ASP) and to CO2 were investigated in rat liver slices. DL-carnitine (5 mM) increased total oxidation (ASP + CO2) more than oxidation to CO2. KCN (1.5 mM) inhibited more than 90% of the oxidation. NH4Cl inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to CO2 (63%) was larger than that of total oxidation (30%). Carnitine did not influence NH4+ inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90% at 3 mM salicylate but that of oxidation to CO2 reached 50%. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to CO2 was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to CO2 was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of CO2. The combination of 20 mM NH4Cl and 0.75 mM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4+ exerted a stronger inhibition of oxidation to CO2 than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to CO2 by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits.
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PMID:Effects of ammonium chloride, salicylate, and carnitine on palmitic acid oxidation in rat liver slices. 291 25

Carnitine facilitates the transport of activated fatty acids across the mitochondrial membrane and regulates energy metabolism through regeneration of intramitochondrial coenzyme A. In carnitine deficiency it may be a limiting factor for fatty acid oxidation and ketogenesis. Primary myopathic carnitine deficiency is characterized by low carnitine concentrations usually restricted to muscle; whereas systemic carnitine deficiency shows decreased concentrations in other organs and plasma as well. The latter condition features recurrent metabolic crises similar to those seen in Reye's syndrome and nonketotic hypoglycemia. A therapy with L-carnitine should be undertaken, but does not always prove effective. Similar symptoms may be caused by defects in beta-oxidation, Krebs cycle or respiratory chain enzymes. The conditions may be associated with secondary carnitine deficiency. Patients with organic acidurias exhibit an increased excretion of carnitine esters and an insufficiency of free carnitine. Carnitine supplementation may ameliorate the metabolic disturbance. Secondary carnitine deficiency has also been described in patients receiving chronic valproic acid therapy. Hemodialysed chronic renal patients may benefit from L-carnitine therapy and show improvement of their hyperlipidemia. Nutritional carnitine deficiency can be primarily expected in premature infants receiving a carnitine free diet, since these infants have an impaired capacity for carnitine biosynthesis.
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PMID:[Carnitine deficiency]. 301 17

1. Plasma carnitine levels in the spontaneously (endogenously) hyperlipidemic Watanabe (WHHL) rabbit are approximately 2-fold higher (P less than 0.001) than in normal rabbits of the New Zealand (NZ) or Netherland Dwarf (NDw) breeds. 2. Plasma carnitine levels in WHHL (44 +/- 3 nmol/ml) can be approximated in NZ and NDw which are rendered exogenously hyperlipidemic by supplementation of the stock chow diet with cholesterol and peanut oil. 3. The induction of endogenous hyperlipidemia in NZ by feeding a sucrose casein rich diet results in a biphasic response of plasma carnitine (elevation followed by normalization). 4. Plasma carnitine in WHHL is readily elevated by supplemental L-carnitine and the elevation is associated with a reduction in plasma triglyceride which shows differences in individual response time; plasma cholesterol is unaffected by supplemental L-carnitine.
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PMID:The influence of diet and carnitine supplementation on plasma carnitine, cholesterol and triglyceride in WHHL (Watanabe-heritable hyperlipidemic), Netherland dwarf and New Zealand rabbits (Oryctolagus cuniculus). 362 15

Once the decision is made to treat hyperlipidemia in a dialysis patient, several options for therapy are available. This review organizes a therapeutic approach into manipulations primarily by the patient (achievement of ideal body weight, exercise, various diets) and manipulations primarily by the physician. Dialytic options include the composition of the dialysate (buffer, glucose), peritoneal dialysis, hemodialysis and hemofiltration. The roles of dialysis efficiency and heparin are discussed in this context. Medicinal manipulations include drugs to avoid (beta adrenergic blockers, androgens, estrogens, glucocorticoids, ethyl alcohol, diuretics) and specific therapeutic agents (activated charcoal, nicotinic acid, clofibrate, L-carnitine).
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PMID:Therapy for uremic hyperlipidemia. 639 12

The lipid-lowering effect of carnitine and its precursors, namely lysine plus methionine, was examined in male Sprague-Dawley rats fed ethanol as 36% of the total calories. Ethanol caused typical hepatic steatosis characterized by significant accumulation of total lipids, triglycerides, cholesterols, phospholipids, and free fatty acids. Supplementation of the ethanol diet with 1% DL-carnitine, 0.5% L-lysine, and 0.2% L-methionine significantly lowered ethanol-induced increases of various lipid fractions, with the exception of free fatty acids. The lipid-lowering effect of carnitine was superior to that of its precursors and their effect together was no greater than that of carnitine alone. The triglyceride contents of liver and plasma were related inversely to the levels of carnitine and acyl carnitines. It is concluded that dietary carnitine more effectively than its precursors prevented alcohol-induced hyperlipemia and accumulation of fat in livers. Thus, a deficiency of functional carnitine may indeed exist in chronic alcoholic cases.
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PMID:Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver. 642 29

Adriamycin induced hyperlipemia: its features and mechanism(s) in rats were investigated. Massive hyperlipemia occurred 14-21 days after a single dose of adriamycin (7.5 mg/kg i.v.). All lipoprotein fractions were affected. Mild but significant changes in tissues were observed (liver and intestine triglycerides and kidney phospholipids were reduced). Lipid synthesis and secretion was decreased, as shown by the Triton WR1339 test 7 days after treatment, but subsequently returned to normal. Mitochondrial oxidation of long-chain fatty acids was markedly reduced in kidney, and a slight reduction was also observed in heart. Lipoprotein lipase activity was reduced in adipose tissue. These results suggest that adriamycin hyperlipemia is due to reduced lipid storage and utilization. Carnitine did not counteract hyperlipemia and proteinuria after adriamycin. Analogies to hyperlipemia following puromycin aminonucleoside-induced nephrotoxicity are discussed.
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PMID:Adriamycin causes hyperlipemia as a consequence of nephrotoxicity. 666 4

The mechanism of te development of hemodialysis hyperlipidemia was investigated in uremic patients on maintenance hemodialysis. Hemodialysis treatment lost large amounts of carnitine from blood into the dialysate fluid, resulting in the reduction in serum concentration of carnitine. After the treatments were repeated for more than 12 months, the serum concentration of carnitine reduced markedly and the serum triglyceride level increased significantly. In contrast, in patients who had been supplemented with commercial amino acids solution, the serum concentrations of carnitine and lipid were within normal ranges and remained unchanged even after repeated hemodialysis treatments. Carnitine administration also reduced the serum triglyceride level to or towards normal. The results suggest that carnitine depletion induced by hemodialysis treatments has a probable causal relationship to hyperlipidemia in uremic patients on long-term maintenance hemodialysis and that supplementation of carnitine or amino acids prevents carnitine depletion and improves hemodialysis hyperlipidemia.
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PMID:Carnitine depletion as a probable cause of hyperlipidemia in uremic patients on maintenance hemodialysis. 683 57

Twenty-three patients on regular dialysis treatment (RDT) were given 1-carnitine orally or in dialysate for six months. All patients remained in a stable biochemical state; hyperlipidaemia was reduced with an increase in HDL-cholesterol. Hormonal pattern was unmodified. Serum and muscle carnitine and acetylcarnitine constantly increased. L-carnitine in RDT, by restoring tissue reserves, improves metabolic alterations without any side-effects.
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PMID:Endocrine-metabolic effects of l-carnitine in patients on regular dialysis treatment. 687 45


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