(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Nephrotic-Syndrome

Nephrotic syndrome is the collective name given to a group of symptoms that include proteinuria, lipiduria, hypoalbuminaemia, oedema, hypercholesterolaemia, elevated triglycerides, and hyperlipidaemia. Hyperlipidaemia is thought to aggravate glomerulosclerosis (hardening of blood vessels in the kidneys) and enhance progression of glomerular disease. Studies have established that reduction in total cholesterol and low density lipoprotein (LDL) cholesterol is associated with reduction in risk of cardiovascular diseases. In 2011, the European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidaemia recommended use of statins as first-line agents in the management of nephrotic dyslipidaemia. However, the effectiveness and safety of statins for people with nephrotic syndrome remains uncertain. Furthermore, the efficacy of second-line lipid-lowering drugs, such as ezetimibe and nicotinic acid, has not been proven in patients with nephrotic syndrome who are unable to tolerate statin therapy.. This review aimed to evaluate the benefits and harms of lipid-lowering agents in adults and children with nephrotic syndrome.. We searched the Cochrane Renal Group's Specialised Register (to 18 March 2013) through contact with the Trials Search Co-ordinator using search terms relevant to this review.. All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at participants with nephrotic syndrome that compared any lipid-lowering agent to placebo, no treatment or other lipid-lowering agents, given for not less than four weeks, were included.. Two authors independently assessed study eligibility and risk of bias, and extracted data. Statistical analyses were performed using a random effects model. Dichotomous results were expressed as risk ratios (RR) with 95% confidence intervals (CI). For continuous measures mean difference (MD) was used, or the standardised mean difference (SMD) where different scales had been used.. We included five RCTs enrolling a total of 203 participants. Of these, four studies compared statins with no treatment or placebo, and one compared fibrates with placebo. We found no published studies comparing second-line agents such as ezetimibe, bile acid sequestrants, and nicotinic acid with placebo or no treatment. Our assessment of the risk of bias found that one study was judged overall to be at low risk of bias and the remaining four were judged to be at high risk of bias.Most outcomes were supported by single study data. One study reported significantly increased high density lipoprotein (HDL) cholesterol among participants in the statin arm compared with the no treatment group (MD 5.40 mg/dL, 95% CI 2.31 to 8.49). Another study reported higher serum albumin in the statin group compared to those who received no treatment (MD 0.60 g/dL, 95% CI 0.14 to 1.06). No serious adverse events, such as rhabdomyolysis, were reported, however some minor events occurred. One study reported no significant difference in the number of participants with elevated liver enzymes (RR 3.00, 95% CI 0.13 to 69.52); three studies reported liver enzymes remained within the normal range (no data provided). Four studies reported creatinine phosphokinase (CPK). One study indicated that CPK values fluctuated in both the simvastatin and placebo groups (no data provided); the remaining three studies reported CPK either stayed within the normal range (one study) or there was no significant difference between the lipid lowering agents and placebo.. None of the included studies reported patient-centred outcomes including all-cause mortality, cardiovascular mortality, or non-fatal myocardial infarction; only single studies reported cholesterol (HDL, LDL and total cholesterol), triglycerides, serum creatinine, blood urea nitrogen, liver enzymes, and protein (serum, urine). High quality RCTs need to be conducted to assess the safety and efficacy of lipid-lowering drugs for people with nephrotic syndrome.

Topics: Adult; Child; Fatty Acids, Monounsaturated; Fluvastatin; Gemfibrozil; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Lovastatin; Nephrotic Syndrome; Randomized Controlled Trials as Topic; Simvastatin

Nephrotic dyslipidemia is a risk factor for development of systemic atherosclerosis; also it may aggravate glomerulosclerosis and enhance progression of glomerular disease. We aimed to assess the efficacy and safety of Monascus purpureus Went rice vs. fluvastatin therapy in the management of nephrotic dyslipidemia.. Seventy-two patients with idiopathic persistent nephrotic syndrome with secondary dyslipidemia were included. They were randomly allocated into 3 - age and sex - matched groups. The first group comprised of 20 cases and were given Monascus purpureus Went rice, second group comprised 30 cases were given fluvastatin. The remaining 22 received no anti-dyslipidemic therapy and constituted a control group. All of these patients were subjected to thorough laboratory investigations including renal function tests, lipogram and neurological assessment.. Our results showed that both fluvastatin and Monascus purpureus Went rice were well-tolerated with no significant side effects. Both of them significantly reduced cholesterol after 6 months and 1 year. In comparison to baseline values, fluvastatin achieved a significant and progressive reduction of serum cholesterol by 35%, 38% and 42% at 3 months, 6 months and after 1 year respectively (p<0.001). Similar reductions were observed in the Monascus purpureus Went rice group. After one year we observed that serum cholesterol was significantly lower in statin and Monascus purpureus Went rice groups compared to the control group.. Monascus purpureus Went rice is safe, effective cholesterol lowering agent for nephrotic dyslipidemia both in adults and children.

Topics: Adolescent; Adult; Anticholesteremic Agents; Atherosclerosis; Child; Drugs, Chinese Herbal; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Male; Monascus; Nephrotic Syndrome; Pilot Projects; Risk Factors; Young Adult

Nephrotic dyslipidemia is a risk factor for the development of systemic atherosclerosis; it may also aggravate glomerulosclerosis and enhance the progression of glomerular disease. We aimed to assess the efficacy and safety of Monascus purpureus Went rice versus fluvastatin therapy in the management of nephrotic dyslipidemia.. In total 72 patients with idiopathic persistent NS with secondary dyslipidemia were included. They were randomly allocated into three age- and sex-matched groups. The first group comprised 20 cases that were given M. purpureus Went rice in a dose of 600 mg twice per day for one month and then once daily. The second group comprised 30 cases that were given fluvastatin in a daily dose of 20 mg. The remaining 22 received no antidyslipidemic therapy and constituted a control group. All of these patients were subjected to thorough laboratory investigations, including renal function tests and lipograms. Moreover, neuromuscular status was evaluated with electromyography and nerve conduction velocity.. Our results showed that both fluvastatin and M. purpureus Went rice were well-tolerated with no evidence of significant side effects, including on neuromuscular function. Both M. purpureus Went rice and fluvastatin significantly reduced cholesterol after six months and one year, respectively.. Monascus purpureus Went rice is a safe, effective and economic treatment strategy for nephrotic dyslipidemia.

Topics: Adolescent; Adult; Anticholesteremic Agents; Child; Dose-Response Relationship, Drug; Electromyography; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Indoles; Male; Medicine, Chinese Traditional; Monascus; Muscle, Skeletal; Nephrotic Syndrome; Phytotherapy; Plant Preparations; Prospective Studies; Treatment Outcome

In this study 43 patients with idiopathic nephrotic syndrome were randomly distributed into 2 age- and sex-matched groups. The first group was given fluvastatin while the second was used as control. The cases in the 2 groups were evaluated clinically, biochemically (creatinine clearance, albumin, 24-hour proteinuria, and lipogram), neurologically, and histopathologically (examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin). In the fluvastatin-treated group but not in the control group, we observed a significant reduction in cholesterol, low-density lipoprotein, and triglyceride. Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients. Proteinuria, serum albumin and creatinine clearance values were significantly better in the statin-treated patients. There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group. The reduction in renal fat deposits in the statin-treated group was highly significant, while that of interstitial fibrosis was not. We conclude that: (1) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome; (2) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance; (3) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome, and (4) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression.

Topics: Adipose Tissue; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Indoles; Kidney; Nephrotic Syndrome; Prospective Studies

The influence of fluvastatin, a liver-selective, competitive inhibitor of the 3-hydroxymethyl-glutaryl-coenzyme A reductase, on the lipoprotein metabolism was investigated in 9 patients with nephrotic syndrome. All patients had biopsy-proven renal disease as cause of their nephrotic syndrome and exhibited severe hyperlipidemia [baseline: serum cholesterol 358 +/- 46 mg/dl (9.3 mmol/l), low-density lipoprotein cholesterol 236 +/- 18 mg/dl (6.1 mmol/l), triglycerides 333 +/- 28 mg/dl (3.8 mmol/l), and lipoprotein Lp(a) 46 +/- 11 mg/dl]. After 1 year of 40 mg of fluvastatin, significant reductions of total cholesterol by 31% to 242 +/- 26 mg/dl (6.3 mmol/l) and low-density lipoprotein cholesterol by 29% to 162 +/- 12 mg/dl (4.2 mmol/l) were observed. Furthermore, triglyceride values were also lowered significantly by 19% to 268 +/- 21 mg/dl (3.1 mmol/l). Lipoprotein Lp(a) and high-density lipoprotein-cholesterol remained unchanged by fluvastatin. These improvements in lipid profile were maintained during the entire follow-up period of 1 year. There were no adverse events, and the slight increase in serum creatinine observed during the study was considered to be due to the primary renal disease. In conclusion, long- term administration of fluvastatin in patients with nephrotic syndrome appears to be an effective and safe treatment of the hyperlipidemia associated with this disorder.

Topics: Adult; Cholesterol; Fatty Acids, Monounsaturated; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Indoles; Nephrotic Syndrome; Prospective Studies; Time Factors

The pharmacokinetics (PK) and safety of fluvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, were assessed in subjects with renal impairment and nephrotic syndrome. In a single-center, open-label, parallel-group study, a single dose of fluvastatin 40 mg was administered to subjects (8 per group, n = 48) with nephrotic syndrome (group II), healthy subjects (group I), and subjects with various degrees of renal impairment (groups III to VI). Subjects undergoing hemodialysis received two doses, one 2 days before and one just prior to hemodialysis. Blood samples to determine the PK parameters of fluvastatin were collected from 0 to 12 hours after drug intake. Noncompartmental PK evaluation and statistical analysis (descriptive and ANOVA) were performed. Safety was evaluated and vital signs were monitored. There was no difference in the PK parameters AUC0-infinity and Cmax of fluvastatin between healthy subjects and subjects with renal impairment. Fluvastatin was not removed from plasma by hemodialysis. In patients with nephrotic syndrome, the values for AUC0-infinity and Cmax were less than half of those obtained in the other groups; terminal half-life values, however, were comparable. Fluvastatin was well tolerated in all study participants. Only few adverse events of mild to moderate intensity were reported. There were no clinically relevant changes in laboratory parameters in the subjects with renal impairment. Renal impairment did not affect the PK of fluvastatin after a single oral dose. Exposure to fluvastatin was lower in subjects with nephrotic syndrome. Fluvastatin also was well tolerated in subjects with nephrotic syndrome.

Topics: Adult; Analysis of Variance; Area Under Curve; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Middle Aged; Nephrotic Syndrome; Renal Dialysis; Renal Insufficiency

Topics: Acute Disease; Aged; Anti-Inflammatory Agents; Anticholesteremic Agents; Cholestasis; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Male; Nephrotic Syndrome; Prednisolone

The effects of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the hyperlipidemia associated with nephrosis were studied. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma triglyceride (TG), total cholesterol and apoprotein (apo) B concentrations than controls. Fluvastatin was administrated as a 0.01% solution in drinking water for 14 days to either normal control or nephrotic rats. Concentrations of TG and apo B in plasma, and very low-density lipoprotein (VLDL) in nephrosis were completely normalized by the treatment with fluvastatin, but concentrations of cholesterol in plasma and each lipoprotein fraction were not altered by the treatment. The ratio of apo E to C in VLDL was significantly decreased in nephrotic rats, but the fluvastatin treatment increased this ratio. TG secretion rate estimated by the Triton WR1339 method was significantly increased in nephrotic rats, but was normalized by fluvastatin. Percent composition of TG in newly secreted VLDL particles in post-Triton plasma was not decreased by fluvastatin treatment, suggesting that the number of newly secreted VLDL particles was reduced by the treatment. Postheparin plasma lipolytic activities were not affected by the fluvastatin treatment. These results demonstrate that fluvastatin can effectively ameliorate the high concentration of VLDL by suppressing the hepatic secretion in nephrotic rats, and suggest that an inhibition of cholesterol biosynthesis suppresses VLDL secretion from the liver.

Topics: Animals; Anticholesteremic Agents; Apolipoproteins B; Cholesterol, LDL; Drinking; Eating; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Indoles; Isoelectric Focusing; Lipoproteins, VLDL; Male; Nephrotic Syndrome; Puromycin Aminonucleoside; Rats; Rats, Wistar; Triglycerides