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

Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipid-lowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients.. We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population.. The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is similar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment.. Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Graft Rejection; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Kidney Failure, Chronic; Liver Transplantation; Middle Aged; Pravastatin; Primary Prevention; Prospective Studies; Proteinuria; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Time Factors

Premature atherosclerotic coronary heart disease driven by multiple risk factors is a major cause of morbidity and mortality among the 6 million patients in the United States with chronic renal failure. Consensus is that kidney failure and renal transplantation patients should be treated aggressively for dyslipidemia. Major medical literature databases were searched for published information about fluvastatin, a HMG-CoA reductase inhibitor, used in patients with impaired renal function. This article characterizes the dyslipidemia observed in these clinical settings and reviews the clinical experience with fluvastatin.

Topics: Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Lipids; Treatment Outcome

In comparison to the general population, individuals with chronic kidney failure experience an increased risk for atherosclerotic cardiovascular disease attributed predominantly to pronounced abnormalities in lipid metabolism. The emerging consensus is that patients with chronic kidney failure should be treated aggressively for dyslipidemia. Statins reduce the risk of cardiovascular disease in a range of at-risk patients; this class of lipid-lowering drugs should be considered first-line treatment of dyslipidemia observed in renal disease patients. Although the statins share a common lipid-lowering effect, there are differences within this class of drugs. The statins differ in their pharmacokinetic effects, drug interaction profiles, and risk of myotoxicity. This article characterizes the dyslipidemia observed in the renal failure setting and reviews the therapeutic considerations involved in selecting among the statins. Lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin are the available statins in the United States.

Topics: Atorvastatin; Comorbidity; Dyslipidemias; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Lovastatin; Pravastatin; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides

In patients with chronic kidney disease, vascular calcification contributes to increased cardiovascular (CV) morbidity and mortality. CV risk remains high after successful renal transplantation. Osteoprotegerin (OPG) is a glycoprotein, involved in the regulation of the vascular calcification process. Previous studies have shown that elevated OPG is predictive of mortality in high-risk populations. The aim of this study was to investigate the prognostic value of OPG for graft function, CV events and all-cause death, in a large transplant cohort.. OPG was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) study, a randomized placebo-controlled intervention study comparing fluvastatin and placebo. Patients were followed for 6.7 years with evaluation of pre-specified end points, graft loss, graft function, CV events and death.. OPG was analysed in 1889 renal transplant recipients, with a mean value of 4.69 ± 1.85 pg/L. The number of renal and CV events increased by quartiles of OPG. In the multivariate analysis, OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [hazard ratio (HR) 2.20 (1.56-3.11), P < 0.001], major CV events [HR 2.40 (1.58-3.64), P < 0.001], cardiac mortality [HR 2.80 (1.32-5.94), P = 0.007] and all-cause mortality [HR 2.31 (1.53-3.49), P < 0.001].. In a large cohort of kidney transplant patients with long-term follow-up, OPG was independently associated with renal events, CV events and mortality.

Topics: Adult; Aged; Anticholesteremic Agents; Biomarkers; Cardiovascular Diseases; Creatinine; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Graft Rejection; Humans; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Osteoprotegerin; Prognosis; Risk Factors; Survival Rate; Vascular Calcification

Anemia, low-grade inflammation and/or alterations in lipid metabolism are common findings in individuals with end-stage renal disease (ESRD) despite advances in dialysis treatment. Hepcidin, a key regulator of iron metabolism, may play an important role in the interdependence of inflammation and anemia in ESRD patients. Statins may reduce cardiovascular events in dialysis patients and have pleiotropic effects in addition to lowering total and low-density lipoprotein (LDL)-cholesterol.. Because there is a paucity of data on the effect of statins on serum prohepcidin levels in dialysis patients, this 8-week study was conducted to test the effect of fluvastatin (80 mg/day, n=22) compared with placebo (n=18) on circulating serum prohepcidin, a prohormone of hepcidin, and high-sensitive C-reactive protein (hs-CRP) in dyslipidemic ESRD patients with renal anemia.. Fluvastatin treatment decreased total cholesterol (P<0.05), LDL-cholesterol (P<0.01), hs-CRP (P<0.05) and serum prohepcidin levels (P<0.05) significantly.. Our pilot data suggest that short-term statin treatment may exert a beneficial effect on serum prohepcidin levels in ESRD patients. The potential clinical benefits of statins on renal anemia need to be confirmed and expanded with an appropriately powered long-term study.

Topics: Adult; Antimicrobial Cationic Peptides; C-Reactive Protein; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hepcidins; Humans; Indoles; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Protein Precursors; Renal Dialysis

According to the concept of apolipoprotein (apo)-defined lipoproteins, apoA-I-containing lipoproteins consist of two subclasses referred to as lipoprotein A-I (LpA-I) and lipoprotein A-I:A-II (LpA-I:A-II), and apoB-containing lipoproteins of five subclasses, namely lipoprotein B (LpB), lipoprotein B:C (LpB:C), lipoprotein B:E (LpB:E), lipoprotein B:C:E (LpB:C:E), and lipoprotein A-II:B:C:D:E (LpA-II:B:C:D:E). The purpose of this study was to determine the levels of apoA-I- and apoB-containing lipoprotein subclasses before and after fluvastatin treatment of patients with chronic renal insufficiency. ApoA-I- and apoB-containing lipoprotein subclasses were measured in 15 patients with chronic renal failure and 15 asymptomatic subjects. The effect of fluvastatin on lipoprotein subclasses was determined in a randomized, double-blind, placebo-controlled, two-way, treatment period crossover study. Patients were administered fluvastatin 40 mg/day or placebo during 8 weeks in a randomized order. Patients were characterized by significantly higher levels of LpB (P < 0.001), LpB:C (P < 0.001), and LpB:E (P < 0.05), and slightly higher levels of LpB:C:E and LpA-II:B:C:D:E than controls. The levels of LpA-I:A-II were significantly lower (P < 0.01) in patients than controls. Fluvastatin treatment reduced all apoB-containing subclasses, but only the reduced level of LpB subclass was statistically significant (P < 0.02). The levels of LpA-I and LpA-I:A-II were not affected. Fluvastatin treatment reduced and normalized LpB and LpB:E subclasses. Although slightly reduced, the levels of markedly atherogenic LpB:C subclass were not normalized. The potential role of LpB:C on the progression of coronary artery disease in chronic renal insufficiency remains to be determined in future studies.

Topics: Aged; Apolipoproteins B; Body Height; Body Mass Index; Cohort Studies; Cross-Over Studies; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Failure, Chronic; Lipoproteins; Male; Middle Aged; Treatment Outcome

Chronic renal insufficiency is characterized by specific abnormalities in lipoprotein metabolism, affecting both apolipoprotein A (apo A)- and apo B-containing lipoproteins. To evaluate the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on renal dyslipoproteinemia, we performed a randomized, double-blind, placebo-controlled, two-way, period cross-over study. Study patients were administered fluvastatin, 40 mg/d, or placebo during 8 weeks in randomized order. Forty-five nonnephrotic patients (28 men, 17 women) without diabetes with moderate to advanced chronic renal insufficiency participated in the study. Their mean age was 56.4 +/- 11.0 years. Glomerular filtration rate ranged from 12 to 44 mL/min/1.73 m2 of body surface area (mean, 27.5 +/- 10.5 mL/min/1.73 m2). Fluvastatin treatment resulted in significant reductions in the primary outcome variables low-density lipoprotein cholesterol (LDL-C; -26%; P < 0.001), apo B (-21%; P < 0.001), and lipoprotein B complex (Lp-Bc) (-14%; P < 0.01). There were statistically significant differences between fluvastatin and placebo treatment for the secondary outcome variables total cholesterol (-19%), triglycerides (TGs; -13%), VLDL-C (-13%), apo E (-13%), and Lp-B (-22%). There was no treatment effect on high-density lipoprotein cholesterol or lipoprotein(a). Fluvastatin treatment was well tolerated, with no serious adverse events during the study. In conclusion, fluvastatin treatment was well tolerated in patients with moderately advanced renal insufficiency and led to a significant reduction in cholesterol-rich, but to a lesser extent in TG-rich, apo B-containing lipoproteins. It remains to be clarified whether these positive changes in lipoprotein profile also will result in attenuation of the atherosclerotic process in these patients, as well as beneficially affect the progression of chronic renal failure.

Topics: Aged; Anticholesteremic Agents; Apolipoproteins; Cross-Over Studies; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gastrointestinal Diseases; Humans; Indoles; Kidney Failure, Chronic; Lipids; Lipoproteins; Male; Middle Aged; Treatment Outcome

Renal insufficiency is frequently associated with both quantitative and qualitative abnormalities in lipid and hemorheologic profiles. Although this may lead to increased risk of cardiovascular disease, a number of studies have also shown dyslipidemia to be a significant risk factor for the progression of renal insufficiency in human chronic renal disease. This double-blind, placebo-controlled trial aimed to assess the effect of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on these parameters in dyslipidemic patients with or without chronic renal insufficiency. After a 6-week placebo run-in, 42 patients who had been previously stratified into 2 groups on the basis of creatinine clearance levels (0.5-1.0 mL/sec or > 1.0-1.5 mL/sec) were randomized to treatment with fluvastatin (40 mg daily) or matching placebo. Significant differences (on analysis of variance with repeated measures) were seen between fluvastatin and placebo treatment groups for changes in total cholesterol (-15% vs 1%, respectively; p < 0.001), low density lipoprotein cholesterol (LDL-C; -21% vs -5%; p < 0.001), very low density lipoprotein cholesterol (-14% vs 14%; p = 0.017), very low density lipoprotein triglycerides (-1% vs 29%; p = 0.014) and total triglycerides (-7% vs 24%; p < 0.001). These effects on cholesterol levels were reflected in a significant decrease in apolipoprotein B levels with fluvastatin therapy (p < 0.001). Apolipoprotein A-I levels increased (p = 0.054) despite no significant change in the levels of high density lipoprotein cholesterol. Response to therapy did not differ between the 2 renal function groups for any of the lipid, lipoprotein, and apolipoprotein variables. Hemorheologic parameters were not altered with fluvastatin therapy, regardless of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticholesteremic Agents; Apolipoprotein A-I; Apolipoproteins B; Cholesterol; Cholesterol, LDL; Cholesterol, VLDL; Creatinine; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hemorheology; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemias; Indoles; Kidney Failure, Chronic; Lipoproteins, VLDL; Male; Middle Aged; Placebos; Safety; Triglycerides

Limited data are available on the relapse of statin intolerance after resumption of statins. We aimed to evaluate the relapse rates of statin intolerance in patients who subsequently received pravastatin or fluvastatin and to identify associated factors.. This retrospective, propensity score-matched cohort study screened data obtained from a tertiary university hospital between 2006 and 2015. Of 8073 patients screened, 488 with statin intolerance who received pravastatin or fluvastatin with regular follow-up were enrolled. After propensity score matching of patients, 384 were finally analyzed. The primary outcome variables were relapse of statin intolerance and stopping (ie, discontinuation or switching to other statins) rate for the 2 statins.. During the median follow-up period of 37 months, the rate of relapse of intolerance was 10.4% and 18.2% among users of pravastatin and fluvastatin, respectively (P = 0.04). However, the log-rank test showed no difference in the relapse-free rates between the 2 groups (P = 0.34). The stopping rates of the 2 statins were 36.5% and 42.2% (P = 0.30), respectively, for various reasons, including low efficacy of the drugs. After adjustment, chronic kidney disease (hazard ratio [HR] 1.83, P = 0.03) and previous creatine kinase elevation (HR 3.13, P = 0.001) were identified as independent determinants of relapse. Older age (HR 1.03, P = 0.057) and female sex (HR 1.70, P = 0.059) were associated, but not significantly, with relapse.. Although a small proportion of patients taking pravastatin or fluvastatin experienced a relapse of intolerance, many patients eventually discontinued or changed these agents. Chronic kidney disease and history of creatine kinase elevation were independent determinants of relapse.

Topics: Aged; Biomarkers; Creatine Kinase; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Kidney Failure, Chronic; Male; Middle Aged; Pravastatin; Propensity Score; Retrospective Studies; Risk Factors

To investigate the potential determinants of the pleiotropic effects of statins, we measured NK cell cytotoxicity in samples from normal subjects and patients, including patients receiving statin therapy. In a multivariate analysis, NK cell cytotoxicity was related to total plasma cholesterol concentration rather than statin use. In vitro, we investigated the role of lipid modification, specifically the effects on membrane rafts and raft-dependent signal transduction. We demonstrate that statins reduce NK cell cytotoxicity and that membrane cholesterol depletion by cyclodextrins has a similar effect. In contrast, isoprenyl transferase inhibitors had little or no effect on NK cell function. We hypothesise that the pleiotropic effects of statins reflect changes in membrane cholesterol and, specifically, the density of membrane rafts. Moreover, there is likely to be a relationship between membrane cholesterol, membrane rafts and cell function that may be involved in the pathogenesis of cardiovascular and metabolic diseases.

Topics: Adult; Aged; Cholesterol; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; K562 Cells; Kidney Failure, Chronic; Kidney Transplantation; Killer Cells, Natural; Male; Membrane Microdomains; Middle Aged; Myocardial Ischemia; Pilot Projects; Protein Prenylation; Signal Transduction; Simvastatin

Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population.. We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression.. The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001).. This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.

Topics: Adult; Aged; Cardiovascular Diseases; Creatinine; Death, Sudden, Cardiac; Diabetes Mellitus; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunosuppressive Agents; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mortality; Myocardial Infarction; Obesity; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Survival Analysis

Diabetic nephropathy is related to glomerular extracellular matrix (ECM) accumulation that leads to glomerulosclerosis. Fluvastatin as a lipid-lowering medicine significantly prevents diabetic nephropathy, probably not only through its lipid-lowering action, but also mainly through its direct suppression of glomerular ECM accumulation. To test this hypothesis, in the present study, a five-sixths nephrectomized (5/6Nx) rat model to induce a renal ECM accumulation without coexistence of hyperlipidemia was used to investigate the effect of fluvastatin on renal function, glomerular ECM accumulation and expression of connective tissue growth factor (CTGF). 5/6Nx induced a significant nephropathy in rats at 13 weeks, indicated by renal dysfunction including increases in blood urine nitrogen, creatinine and urinary protein excretion, and renal histopathological changes. Administration of fluvastatin significantly prevented the renal dysfunction and histological abnormalities in the 5/6Nx rats. Furthermore, both significant suppression of matrix metalloproteinases (MMPs) activity such as MMP-2 and significant activation of tissue inhibitors of MMP (TIMPs) such as TIMP-2 observed in the 5/6Nx rats were almost completely prevented by fluvastatin, resulting in a significant prevention of glomerular ECM accumulation. For upstream mediator of ECM accumulation, 5/6Nx significantly up-regulated CTGF mRNA expression, but fluvastatin treatment prevented CTGF up-regulation. These results suggest that fluvastatin, as one of well-known lipid-lowering agents, plays an important role in the prevention of nephropathy, likely through suppression of CTGF-mediated ECM accumulation. Therefore, fluvastatin may be a potential candidate for developing a pharmaceutical approach to the prevention of diabetic nephropathy due to its both lipid-lowering and direct anti-renal ECM accumulation actions.

Topics: Animals; Anticholesteremic Agents; Blood Urea Nitrogen; Connective Tissue Growth Factor; Creatinine; Disease Models, Animal; Extracellular Matrix; Fatty Acids, Monounsaturated; Fluvastatin; Immediate-Early Proteins; Indoles; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Kidney Glomerulus; Male; Matrix Metalloproteinase Inhibitors; Nephrectomy; Proteinuria; Rats; Rats, Wistar; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-2; Up-Regulation

Hemodialysis (HD) patients are frequently in an elevated inflammatory state which is correlated to the atherosclerosis-related and overall morbidity and mortality in this population. Statins, beyond their antilipidemic effects, are also considered to have anti-inflammatory, immunomodulating and antioxidant properties. The individual response of HD patients to a short course of fluvastatin, the mechanisms involved in the immunomodulating and anti-inflammatory effects of this drug and the time interval to the appearance of these effects are investigated in this longitudinal study.. In a group of 51 HD patients, fluvastatin 40 mg/day was administered for 4 weeks. Serial measurements of the lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin-10 (IL-10), and serum oxidized LDL (ox-LDL), were performed before, during, and after the treatment period.. Total cholesterol was significantly reduced after 14 days of treatment with fluvastatin (from mean +/- SD 216.7 +/- 34.3 to 179.2 +/- 42.3 mg/dl, p < 0.001). IL-6 and ox-LDL were reduced on day 28 (p < 0.001 and p < 0.01, respectively) and IL-10 was increased on day 14 (p = 0.05); CRP did not change significantly during the treatment period while sIL-6R was increased on day 28 of fluvastatin administration (p < 0.05). In a subgroup of patients with CRP, IL-6, sIL-6R, and ox-LDL baseline serum values > or = the median and IL-10 < or = the median, CRP was reduced on day 28 of fluvastatin treatment (p < 0.01), IL-6 and ox-LDL were reduced earlier, on day 14 (p = 0.05 and p < 0.05, respectively) while sIL-6R did not change significantly during the treatment period.. Treatment with fluvastatin rapidly modulates inflammation in HD patients. Enhancement of anti-inflammatory mechanisms and attenuation of the inflammatory and oxidative state contribute to this modulation. Patients in an elevated baseline inflammatory state respond more rapidly and effectively to the treatment. This immediate and multi-potent action of the statins could be clinically useful in acute atherosclerosis complications or in the treatment of chronic inflammation in HD patients.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; C-Reactive Protein; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Inflammation; Interleukin-10; Interleukin-6; Kidney Failure, Chronic; Lipids; Lipoproteins, LDL; Longitudinal Studies; Male; Middle Aged; Oxidation-Reduction; Receptors, Interleukin-6; Renal Dialysis; Time Factors

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Elasticity; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Kidney Failure, Chronic; Muscle, Smooth, Vascular; Oxidative Stress; Renal Dialysis

Fluvastatin, an HMG-CoA reductase inhibitor, was administered at a dosage of 20 mg/day for 24 weeks to 11 hemodialysis patients with a high plasma total cholesterol (TC) level (> or = 220 mg/dl). Serum lipids, apolipoprotein, and malondialdehyde (MDA) levels were measured every 12 weeks. After 24 weeks of fluvastatin administration, the TC level had decreased by 10.5% (238 +/- 15 mg/dl-->203 +/- 25 mg/dl), the low density lipoprotein cholesterol (LDL-C) level had decreased by 16.2% (142 +/- 32 mg/dl-->119 +/- 26 mg/dl), and the HDL-C level had increased by 23.4% (47 +/- 15 mg/dl-->58 +/- 19 mg/dl). These changes were statistically significant and resulted in a reduction of the atherogenic index (AI: TC-HDL-C/HDL-C). The triglyceride (TG) level did not change significantly. The apolipoprotein A1 level increased by 9.1% (121 +/- 22 mg/dl-->132 +/- 20 mg/dl) and the apolipoprotein B level decreased by 20.2% (114 +/- 25 mg/dl-->91 +/- 20 mg/dl). The MDA level also decreased significantly (1.16 +/- 0.92 nmol/ml-->0.58 +/- 0.38 nmol/ml). No particular side effects were observed during the 24 weeks of fluvastatin administration. In conclusion, fluvastatin may play an important role in preventing significant oxidative stress and was shown to be safe and effective in reducing the TC, LDL-C, MDA and AI levels in dialysis patients with hypercholesterolemia. The possibility that this improvement in the plasma lipid profile of dialysis patients may decrease atherogenic complications requires further investigation, including long-term clinical observations.

Topics: Aged; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Kidney Failure, Chronic; Lipid Metabolism; Male; Middle Aged; Oxidative Stress; Renal Dialysis