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)

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria. 131 86

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
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PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

One of the most prominent manifestations of the nephrotic syndrome is hyperlipidemia. Lipoprotein synthesis is increased and catabolism is reduced in nephrotic patients and animals. The observation that infusion of either albumin or dextran reduces lipid levels suggests that oncotic pressure (pi) may regulate lipogenesis. It has been postulated that prolonged plasma half-life of lipoproteins in nephrosis is a consequence of saturation of catabolic sites and is secondary to the hyperlipidemia that results from increased lipogenesis. However, the absolute rate of triglyceride catabolism is reduced in nephrotic rats in comparison to normal suggesting that defective lipid catabolism may be a cause rather than a consequence of hyperlipidemia. Furthermore, chylomicrons (CM) and very-low-density lipoproteins (VLDL) are cleared normally in rats with hereditary analbuminemia despite increased lipid synthesis. When we cause proteinuria in analbuminemic rats, the clearance of CM and VLDL becomes greatly prolonged, suggesting that proteinuria, and not reduced serum albumin or pi, is responsible for defective lipoprotein catabolism. Maneuvers that reduce proteinuria, such as administration of an angiotensin-converting enzyme inhibitor, reduce lipid levels in nephrotic patients and animals even when plasma albumin concentration is unchanged supporting a hypothesis that proteinuria may lead to reduced catabolism of lipoproteins.
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PMID:Nephrotic hyperlipidemia: primary abnormalities in both lipoprotein catabolism and synthesis. 146 61

The relationship between the secundaer hyperlipidaemia and pathological platelet activation was examined in 40 insulin-treated diabetic patients without nephropathy and 21 with nephropathy. Diabetic nephropathy was recorded with the measurements of serum creatinine, serum beta 2-microglobulin, and urine albumin excretion. Haemostasis and lipoprotein metabolism were characterized with determination of platelet aggregation, plasma beta thromboglobulin, thromboxane-B2, serum triglyceride, HDL and LDL cholesterol concentration, respectively. In the normalbuminuric group serum triglyceride and thromboxane-B2 positively correlated. In the nephropathic group serum cholesterol and beta thromboglobulin, as well as LDL and beta thromboglobulin, finally, LDL and thromboxane-B2 showed significant positive correlation. In diabetic patients without nephropathy platelet aggregate ratio was in positive correlation with the serum triglyceride, while the ED50-S elevated with the increase of serum cholesterol and LDL. The nephropathic group exhibited no such parallelisms. However, there were significant correlations of LDL with serum creatinine in both groups of diabetic patients. Our results seem to indicate that the increase of LDL could be associated with the change of LDL structure. Interactions of modified LDL and the platelet membrane might contribute to the platelet hyperactivation both in the nephropathy-free and nephropathic cases.
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PMID:[Relationship between platelet hyperactivation and dyslipoproteinemia in diabetic nephropathy]. 157 41

We have recently reported that a lipid-lowering agent, probucol, reduces proteinuria in puromycin aminonucleoside (PA)-induced nephrotic rats (PAN). In this study, we examined whether a long-term treatment of hyperlipidemia with probucol can suppress the development of focal and segmental glomerulosclerosis (FSGS) in chronic PAN. A chronic PAN model was made with repeated intraperitoneal injections of PA (initially 100 mg/kg body weight followed by 25 mg/kg 5 times at 2-week intervals). Two weeks after the first injection of PA, either normal rat chow with or without 1% probucol was given to the nephrotic rats for 10 weeks. Chronic PAN exhibited remarkable proteinuria, hypoalbuminemia and severe hyperlipidemia with all lipoprotein fractions increased. Probucol treatment significantly reduced the lipid concentration in all major lipoproteins, significantly reduced proteinuria and increased plasma albumin concentration. Plasma albumin inversely correlated with cholesterol or phospholipid in low-density and high-density lipoproteins, suggesting that the lipid-lowering effect of probucol may ameliorate the hypoalbuminemia associated with nephrosis. In light microscopic examination, various degrees of FSGS with tubulointerstitial lesions were observed in the renal cortex from chronic PAN. The degree of FSGS was scored from grades 1 to 4 according to severity. One half of the untreated PAN (4/8) was classified into grade 4 and the other into grades 2 or 3, whilst one half of treated PAN (4/8) was classified either into grade 1 or 2. The grading of FSGS correlated negatively with plasma albumin concentration. These results demonstrate that probucol is highly effective upon nephrotic hyperlipidemia and suggest that a long-term treatment of secondary hyperlipidemia can suppress progressive renal injury associated with chronic nephrosis.
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PMID:Treatment of hyperlipidemia with probucol suppresses the development of focal and segmental glomerulosclerosis in chronic aminonucleoside nephrosis. 158 21

The nephrotic syndrome results from altered glomerular permselectivity, causing urinary protein loss, reduced albumin concentration, oncotic pressure (pi), and hyperlipidemia. Hepatic lipid and apolipoprotein synthesis increases and lipoprotein catabolism decreases. Decreased lipoprotein catabolism follows the onset of proteinuria but is not associated with hereditary analbuminemia [Nagase analbuminemic rat (NAR)] if proteinuria is absent. We measured plasma apolipoproteins (apo) AI, B, and E levels, their mRNA concentrations in liver, and the transcription rate of each mRNA in rats with Heymann nephritis (HN) or NAR to determine which alterations occurred in NAR alone without proteinuria. Plasma apo AI, B, and E were increased in both HN and NAR. Cholesterol and apo AI were inversely proportional to pi and independent of urinary protein loss or the presence of albumin in plasma. In contrast, triglycerides (TGs) were significantly greater in HN and were increased out of proportion to apo B. The concentration of apo AI mRNA increased in liver of both HN and NAR as did apo AI transcription. Apo E mRNA increased in neither HN nor NAR, whereas apo B mRNA increased only in HN. Transcription of neither apo B nor E increased. Plasma apo AI levels are likely to be regulated transcriptionally at the level of protein synthesis, whereas plasma apo B and E levels are regulated either posttranscriptionally, at the level of protein catabolism, or at both sites. Lipoproteins rich in TG and poor in apo B appear after the development of proteinuria but not as a consequence of analbuminemia alone. The accumulation of TG-rich apo B containing lipoproteins in rats with HN may result from impaired lipolysis occurring as a consequence of proteinuria.
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PMID:Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis. 159 Apr 20

Serum triglycerides, free fatty acids, unconjugated bilirubin, and albumin were evaluated in 40 neonates receiving 0.5-3.5 g/kg/day of a 50/50 soybean-safflower lipid emulsion infused during 18 h. The purpose of the study was to evaluate lipid tolerance and unconjugated hyperbilirubinemia according to our total parenteral nutrition protocol, which initiates lipid on postnatal day 4. Mean serum triglycerides and free fatty acids were within the range of prelipid infusion values at all dosages, and no statistically significant differences were noted between very-low-birth-weight neonates and those greater than 1,500 g birth weight. Mean free fatty acid:albumin molar ratio was less than 1.0 at all dosages and no individual patient values exceeded a ratio of 3.0. Mean peak serum unconjugated bilirubin of 5.8 mg/dl on postnatal day 3 was stable or fell the next 10 days of lipid-inclusive total parenteral nutrition. Initiating intravenous lipid on the 4th postnatal day at 0.5 g/kg/day and increasing at 0.5 g/kg/day increments at the end of the 1st postnatal week appears to be tolerated well. However, 5% of serum triglyceride levels exceeded 200 mg/dl. Therefore, in view of the unpredictability of a given patient's tolerance to lipid infusion, there should be monitoring for lipemia.
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PMID:Use of intravenous lipid and hyperbilirubinemia in the first week. 159 67

The nephrotic syndrome is often accompanied by hyperlipidemia associated with an increased risk of accelerated atherosclerosis. The present study was undertaken to evaluate the effects of pravastatin, a novel competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the serum lipids and apolipoproteins in patients with this syndrome and marked hyperlipidemia. Eleven adult patients received 10 mg of pravastatin twice daily for 4 to 8 weeks. The total serum cholesterol decreased from 426 +/- 44 to 309 +/- 18 mg/dl (-27.4%, mean +/- S.E.; p less than 0.01) following administration of pravastatin. The serum triglyceride decreased from 332 +/- 122 to 229 +/- 50 mg/dl (-30.9%), although this change was not significant. Despite the fact that the HDL cholesterol level was barely changed (51 +/- 7 to 51 +/- 6 mg/dl), the LDL cholesterol fell from 313 +/- 30 to 211 +/- 16 mg/dl (-32.5%; p less than 0.005), and the LDL to HDL cholesterol ratio fell from 7.57 +/- 1.59 to 4.94 +/- 0.88 (-34.8%; p less than 0.05). These changes caused the atherogenic index to decline from 9.6 +/- 2.4 to 6.1 +/- 1.2 (-36.5%; p less than 0.05). No significant alterations could be found among apolipoproteins A-1, A-2, B, C-2, C-3, and E. During the present study period, pravastatin was well tolerated and did not affect the serum protein, albumin, serum urea nitrogen, creatinine levels, or urine protein excretion. Also, there were no serious adverse effects. Pravastatin appears to be effective for treating patients with hyperlipidemia of the nephrotic syndrome.
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PMID:Effects of pravastatin on serum lipids and apolipoproteins in hyperlipidemia of the nephrotic syndrome. 163 84

Simultaneous heparin extracorporeal LDL precipitation (HELP)-dialysis was carried out at weekly intervals in six patients with end-stage renal failure, associated hyperlipidemia, and a high risk of premature atherosclerosis. Evaluating 135 single treatments, a mean acute total cholesterol/LDL reduction of 31% and 39%, respectively, was found, while clearance of urinary substances was comparable to that in regular hemodialysis treatment. Treatment tolerance was excellent and no derangements in albumin, hemodialysis parameters, or blood coagulation were detected.
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PMID:Simultaneous heparin extracorporeal LDL precipitation and hemodialysis. First clinical experience. 175 Dec 49

In a group of 141 otherwise healthy subjects attending a lipoprotein clinic, urinary albumin excretion was measured to determine whether primary hyperlipidaemia was associated with evidence of early renal dysfunction. There was no evidence of increased urinary albumin concentrations or albumin:creatinine ratios when compared with data for normal controls. There were no differences in these parameters when the values for the upper and lower quartiles of the cholesterol distribution were compared, and no relationship existed between plasma cholesterol and albuminuria. A weak association was shown between plasma triglyceride and urinary albumin concentration after log transformation of the data. We conclude that hyperlipidaemia per se is not associated with renal disease as measured by sensitive assays of albuminuria.
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PMID:Primary hyperlipidaemia is not associated with increased urinary albumin excretion. 187 81


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