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)

Chronic renal failure is characterized by abnormalities in glucose metabolism. In fact there are present a normal fasting plasma glucose level )or mild hyperglycemia) in the presence of hyperinsulinemia, blunted decrease in the plasma glucose concentration in response to exogenous insulin administration, and diminished effect of intravenous insulin on glucose uptake in forearm perfusion studies. The glucose intolerance is not the result of reduced insulin secretion, or circulating insulin antagonists, and does not correlate with the coexisting metabolic acidosis. Glucose intolerance exists because the peripheral insulin-sensitive tissue (muscle, adipose tissue, liver) of the patients with chronic renal failure are insulin resistant. However there are two subgroups of uremic patients with regard to glucose tolerance: about half of uremic patients can augment their insulin secretion sufficiently to maintain normal glucose tolerance despite glucose intolerance. In the other half, insulin secretion following glucose loads is not different from normal values, so that glucose intolerance results. The cause of the peripheral insulin resistance remain unclear. Besides deranged renal function can result in the development of hypoglycemia. The most important predisposing mechanism to hypoglycemia is diminished glucose availability due to substrate limitation; the second important mechanism (alcohol, insulin, propranolol, etc.). Finally, in chronic renal failure persistent hyperinsulinemia can contribute hyperlipemia and to high incidence of cardiovascular disease.
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PMID:[Glucose metabolism and chronic renal insufficiency]. 801 26

A 61-year-old woman with hyperlipidemia was treated with gemfibrozil. She also had insulin-treated diabetes mellitus and chronic renal failure and was admitted because of severe chest pain. The ST segment was depressed and creatine kinase levels were elevated. The original diagnosis was acute myocardial infarction. In the presence of increasing chest pain, the onset of limb muscle tenderness, and increasing levels of creatine kinase, the diagnosis of myopathy secondary to gemfibrozil therapy was made and the drug was discontinued. All symptoms then subsided and creatine kinase levels returned to normal. Myopathy is a well-known complication of blood lipid-lowering drugs, especially in patients with renal failure.
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PMID:[Gemfibrozil-induced myopathy]. 825 19

Catabolism of low-density lipoprotein is altered in experimental chronic renal failure. In patients with chronic renal failure, cardiovascular disease accounts for a significant proportion of all deaths. Several factors contribute to the "accelerated" atherosclerosis in this population, including hyperlipidemia, the pathogenesis of which is multifactorial. We investigated low-density lipoprotein (LDL) metabolism in a remnant model of chronic renal failure in the guinea pig. After one and two-thirds nephrectomy, creatinine clearance decreased to one-sixth normal. Plasma cholesterol and triglyceride (TG) levels increased with induction of renal failure. Analysis of lipoprotein composition disclosed significant TG enrichment of both uremic very-low-density lipoprotein (VLDL) and uremic LDL compared with control lipoproteins. Plasma clearance of homologous LDL was evaluated in turnover studies in control and uremic guinea pigs. To discriminate between differences in catabolism related to the uremic lipoprotein particle and to the uremic host milieu, a crossover protocol was used comparing the fractional catabolic rate (FCR) after simultaneous injection into control and uremic animals of 125I-control LDL and 131I-uremic LDL. The FCR of native LDL was slower in uremic animals than in controls. In addition, FCR of uremic LDL was significantly less than that of control LDL in both groups. Degradation studies in cultured fibroblasts indicated substantially reduced degradation of uremic LDL compared with control LDL. These results suggest dual abnormalities of LDL catabolism in renal failure that are not only related to alterations in clearance mechanisms in the uremic environment, but also suggest important functional differences in the LDL particle itself isolated from uremic animals.
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PMID:Catabolism of low-density lipoprotein is altered in experimental chronic renal failure. 847 12

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

1. The primary aim of this study was to assess the impact of renal haemodynamics on the pharmacokinetic behaviour of ibuprofen enantiomers. Thirty-two patients and ten age-matched healthy volunteers participated in this study. These patients had at least one of the following risk factors for cardiovascular disorders: hypertension, diabetes mellitus, hyperlipidaemia and hyperuricaemia with or without consequent complications such as coronary artery disease, congestive heart failure, cerebral vascular disease, and chronic renal failure. Renal function in these patients was thus characterized by unstable renal haemodynamics that might render them susceptible to ibuprofen-incurred renal damage. 2. Each subject received a single oral dose of 800 mg of racemic ibuprofen. The pharmacokinetic parameters of (S)- and (R)-ibuprofen, t 1/2(S), t 1/2(R), AUC(S), AUC(R), V/F(R), and CL/F(R), for each individual were determined from respective plasma concentration-time curves. To assess the effect of individual clinical conditions on the disposition of ibuprofen enantiomers, the arithmetic means of these pharmacokinetic parameters for each disease group were compared with those of the healthy volunteers by a t-test. 3. All of these disease groups showed elevated AUC(S) and higher (S)/(R) AUC ratios. These disease states along with gender and age were analyzed by multiple linear regression to discern significant factors for elevating AUC(S). Of these, advanced age (P = 0.02) and hypertension (P = 0.03) were identified as independent factors contributing to AUC(S) increase in this population. Thus, patients with these two clinical conditions are at particular risk from the adverse renal effect of ibuprofen.
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PMID:Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics. 852 70

Hypertension, diabetes and hyperlipidemia are risk factors for life-threatening complications such as end-stage renal disease, coronary artery disease and stroke. Why some patients develop complications is unclear, but only susceptibility genes may be involved. To test this notion, we studied crosses involving the fawn-hooded rat, an animal model of hypertension that develops chronic renal failure. Here, we report the localization of two genes, Rf-1 and Rf-2, responsible for about half of the genetic variation in key indices of renal impairment. In addition, we localize a gene, Bpfh-1, responsible for about 26% of the genetic variation in blood pressure. Rf-1 strongly affects the risk of renal impairment, but has no significant effect on blood pressure. Our results show that susceptibility to a complication of hypertension is under at least partially independent genetic control from susceptibility to hypertension itself.
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PMID:Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat. 852 50

We designed a short-term randomized controlled study in 12 adult patients with chronic renal failure to assess the metabolic effects of a low-protein diet (LPD) supplemented or not with ketoacids (Cetolog, Clintec Corp., France). Dietary survey included a monthly 3-day food record and a 24-hour urinary urea measurement. After a baseline period (1.11 g protein, 31.7 kcal/kg BW/day), patients reduced their protein intake (PI) to 0.71 g/kg BW/day. Energy intake (EI) was kept constant (31.4 kcal/kg BW/day) during the 3-month period. Baseline plasma lipids did not show overt hyperlipemia. After reducing PI, a significant increase in apolipoprotein AI and the Apo-AI/Apo-B ratio was observed. Plasma Lp(a) levels were elevated at baseline and did not change during the 3-month LPD period. There was no difference between groups receiving ketoacids or not. Thus, in adult chronic renal failure, under a sufficient EI, reducing PI by 40% had a beneficial effect on plasma lipid profile. This improvement in lipid profile might reduce the high cardiovascular risk in these patients.
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PMID:Effects of low-protein diet supplemented with ketoacids on plasma lipids in adult chronic renal failure. 867 7

In children with steroid-resistant nephrotic syndrome (SRNS) hyperlipidaemia may in the long term be associated with progressive renal insufficiency and increased risk of coronary heart disease. We have assessed the efficacy and tolerability of diet prior to and in combination with a hydroxymethylglutaryl CoA reductase inhibitor, simvastatin, in seven children with SRNS with a mean age of 8 years (range 1.8-16.3 years). Dietary advice to maintain adequate energy and protein intakes with reduced saturated fat and cholesterol intake had little impact on lipid levels pre treatment (mean reduction in cholesterol 1 mmol/l, triglyceride 1.1 mmol/l) but was maintained throughout the study duration. The mean cholesterol and triglyceride concentrations pre treatment were 12.1 +/- 2 (SEM) mmol/l and 8 +/- 2.1 (SEM) mmol/l, respectively. On a median simvastatin dose of 10 mg/day (range 5-40 mg) there was a 41% reduction in cholesterol to 6.6 +/- 0.77 (SEM) mmol/l and a 44% reduction in triglyceride to 3.9 +/- 1.38 (SEM) mmol/l at 6 months which was sustained at 12 months in five patients. The drug was well tolerated with no clinical side effects being noted. Over 6 months the mean plasma albumin concentrations increased from 18.2 +/- 1.26 (SEM) g/l to 23 +/- 2.51 (SEM) g/l, accounted for by three patients (1 complete remission, 1 partial remission, 1 end-stage renal failure). Plasma creatinine concentrations remained stable in five patients with two having progressive chronic renal failure. Growth parameters for both weight and height were maintained. Simvastatin has a beneficial effect on abnormal lipid levels in SRNS but the effectiveness of long-term therapy needs to be evaluated.
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PMID:Hyperlipidaemia, diet and simvastatin therapy in steroid-resistant nephrotic syndrome of childhood. 870 4

Lipoprotein abnormalities are common in patients with chronic renal failure (CRF) on either dialysis or conservative therapy. In order to investigate the changes in lipid and apolipoprotein pattern from early CRF to dialysis treatment, plasma lipids with apoproteins AI, B, E, CII, CIII, CII/CIII ratio, E/CIII ratio, parathyroid hormone (PTH) and insulin levels were examined in 72 patients with different degrees of CRF and 31 patients on hemodialysis (HD), and compared the values of 28 controls. A significant decrease in the Apo CII/CIII ratio was the earliest lipoprotein abnormality to occur in CRF. Hypertriglyceridemia (HTG) with reduced high-density lipoprotein cholesterol levels, increased Apo CIII and decreased Apo E/Apo CIII ratio only occurred in more advanced renal failure (creatinine clearance < 31 ml/min). HD patients showed a general worsening of the lipoprotein profile with elevated Apo E levels and indirect evidence of remnant accumulation. While PTH did not have any significant influence on lipoprotein pattern, increased insulin levels during HD might partly account for the HTG of these patients. Our results point to elevated Apo CIII, reduced Apo CII/Apo CIII and Apo E/ Apo CIII ratios as typical features of uremic hyperlipidemia and show that a defective triglyceride removal is the major pathogenetic mechanism of uremic HTG. HD treatment seems generally to worsen the lipid and apolipoprotein pattern observed in the predialytic stage of CRF.
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PMID:Lipoprotein abnormalities in chronic renal failure and dialysis patients. 873 41

The effect of hyperlipidemia on the progression of chronic renal failure was investigated in 104 chronic renal failure patients, aged 39.3 +/- 2.9 years. The follow up period was 4.1 +/- 2.9 years. The serum creatinine level was 2.1 +/- 1.1 (mean +/- SD) mg/dl at the beginning of study and increased to 8.7 +/- 4.4 mg/dl at the end of the study. The reciprocal serum creatinine concentration (1/Cr) was plotted against the observation time, and the slope was calculated. The absolute value of the slope was used as the progression rate of renal impairment. The progression rate was positively related to total cholesterol level or urinary protein score, while it was negatively related to total protein level. Without the influence of urinary protein score, the progression rate correlated with total cholesterol level. The result suggests that hypercholesterolemia may be an independent aggravating factor in the progression of renal dysfunction in chronic renal failure patients.
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PMID:Hypercholesterolemia and the progression of the renal dysfunction in chronic renal failure patients. 900 82


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