Dyslipidaemia as predictor of progressive renal failure and the impact of treatment with atorvastatin.

BACKGROUND: In patients with chronic renal disease, other lipid markers than total cholesterol or low density lipoprotein (LDL)-cholesterol are probably more appropriate to detect a potential lipid-related risk for progression to renal failure. Statin therapy might be protective. METHODS: From 1999 to 2001, 177 consecutive patients with renal disease from our out-patient clinic were included and 169 could be followed-up for a mean period of 4.1 years. Seventy-two progressive patients (end-stage chronic renal disease or >5 ml/min/year decrease of creatinine clearance) were compared in 97 patients with stable or slowly progressive disease (<5 ml/min/year decrease). Throughout the study all patients were treated according to nephrology guidelines. Atorvastatin was instituted in patients with elevated LDL-cholesterol (LDL-C) after the baseline determinations RESULTS: Proteinuria, mean arterial pressure and the type of underlying renal disease were independently associated with progressive renal disease. After adjustment for these factors and whether or not statin therapy was started, an increase in plasma apo B concentration was the most predictive lipid parameter for renal failure. An increase in apo B from 0.77 g/l (10th percentile) to 1.77 g/l (90th percentile) was associated with progressive loss of renal function, represented by an odds ratio of 2.63 (95% CI: 1.02-6.76; P = 0.045). Treatment with atorvastatin in the dyslipidaemic patients to lower LDL-C, was also accompanied by a reduction of proteinuria in this group (P < 0.001). The patients who reached the target level for LDL-C of <2.6 mmol/l in response to atorvastatin showed less often progression than patients with higher LDL-C (P = 0.010). CONCLUSIONS: A high apo B at baseline appeared to be the strongest risk factor among various lipid parameters for progression of renal failure during the following years. Atorvastatin, aimed at lowering LDL-C, reduced proteinuria. Renal outcome was better in patients with the lowest LDL-C on treatment.     

他汀类药物对急性心肌梗死患者肾功能的影响

目的回顾性分析阿托伐他汀、辛伐他汀、氟伐他汀对急性心肌梗死患者肾功能的作用。方法选择105例急性心肌梗死患者,其中服用阿托伐他汀（A组）27例、辛伐他汀（B组）26例、氟伐他汀（C组）26例,未服用他汀类药物（对照组）26例。观察各组患者在治疗2周前后总胆固醇（TC）、低密度脂蛋白C（LDL-C）、肾小球滤过率（GFR）的变化值及之间的相关性。结果A、B、C三组患者经治疗后TC、LDL-C、GFR均较治疗前有所改善,并且与对照组比较有统计学差异（P〈0．05）,其中TC、LDL-C改善水平与GFR改善有相关性。结论阿托伐他汀、辛伐他汀、氟伐他汀对急性心肌梗死患者具有肾保护作用,该作用与其降脂作用有一定相关性。     

联合使用阿托伐他汀和贝那普利对IgA肾病蛋白尿的影响

目的 探讨阿托伐他汀联合贝那普利治疗对IgA肾病患者蛋白尿的影响。方法 将62例IgA肾病患者随机分为对照组30例,应用贝那普利治疗;治疗组32例,应用阿托伐他汀联合贝那普利治疗;2组疗程均为6个月,比较2组治疗前、后,血压、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、尿蛋白（U-pro）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）等指标的变化情况。结果 治疗组治疗后6个月,TC、LDL-C、L卜Pro等指标明显下降,与对照组比较有统计学差异（P〈0．05）;而2组治疗前、后比较,TG、HDL-C、ALT、AST、CK、CK-MB均无统计学差异（P〉0．05）。结论 阿托伐他汀联合贝那普利,能有效降低IgA肾病患者的TC、LDL-C、U-pro水平。     

Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study

OBJECTIVE: There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min). MATERIAL AND METHODS: The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat. RESULTS: Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was 20%. Atorvastatin was withdrawn in 20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months. CONCLUSIONS: Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.     

Impact of fluvastatin on hyperlipidemia after renal transplantation

BACKGROUND: Renal transplant recipients are at increased risk of atherosclerotic vascular disease with hyperlipidemia. Many recipients have preexisting cardiovascular disease at the time of transplantation, and immunosuppressive therapy may aggravate existing risk factors or promote development of new risk factors, notably hyperlipidemia and hypertension. Fluvastatin is one of the statins, an HMG-CoA reductase inhibitor, which has been shown to be effective in lowering cholesterol levels. We treated hyperlipidemia after renal transplantation with Fluvastatin for more than 6 months.We attempted to clarify the efficacy of fluvastatin on hyperlipidemia in renal transplant recipients. MATERIALS: Forty-five renal transplant recipients with hyperlipidemia were enrolled in this study. The mean age was 44.2 years, with 23 men and 22 women. Thirty-seven transplantations were from a living related donors and eight from cadaveric donors. Thirty-three recipients were ABO-compatible, seven recipients had minor mismatches, and five recipients were ABO-incompatible. The dose of fluvastatin was 20 mg per day. Levels of total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), serum creatinine (s-Cr), ALT, ALP, uric acid (UA), hematocrit (Ht), CPK, and blood pressure were examined in all recipients before treatment as well as 1, 3, and 6 months after Fluvastatin administration. RESULTS: The mean levels of TC and TG were significantly reduced from 256, to 224 and 215 mg/dL, and from 188 to 170 and 147 mg/dL at 1 and 6 months after treatment, respectively. The mean levels of HDL-C were 72 mg/dL before treatment, 81 mg/dL at 1 month, and 80 mg/dL at 6 months after treatment. The mean levels of LDL-C were 153 mg/dL before treatment, 145 mg/dL at 1 month, and 145 mg/dL at 6 months after treatment. Fluvastatin significantly produced a reduction rate in TC of 16%, TG of 22%, and LDL-C of 5% after 6 months of treatment, respectively. The mean levels of HDL-C of were increased 10% after 6 months of treatment. The serum creatinine and CPK were not significantly different. There were no clinically significant differences in other factors. No significant adverse effects were observed. CONCLUSIONS: Fluvastatin seemed to be safe and highly effective to control TC, TG, LDL-C, and HDL-C in renal transplant recipients.     

Use of atorvastatin in hyperlipidemic hypertensive renal transplant recipients

The aim of the present short-term study was to evaluate the use of a new HMG-CoA reductase inhibitor, atorvastatin, in the treatment of hyperlipidemia and the effect on blood pressure in a group of hypertensive stable renal transplant recipients with hypercholesterolemia who received kidney grafts before 18 years of age. Eight patients (aged 10.8-30.1 years) with inadequately controlled total cholesterol (TC) levels by a lipid-lowering diet (8 weeks) were treated daily for 12 weeks with atorvastatin at an initial dose of 2.5 mg. The dose was increased monthly by 2.5 mg in order to lower TC levels to less than 200 mg/dl. Serum lipoprotein profile, cyclosporin A (CsA), serum creatinine (SCr), and liver and muscle enzyme levels were measured before starting the lipid-lowering diet, at the start of treatment (baseline), and during treatment. Ambulatory blood pressure monitoring (ABPM) (24-h) was carried out in each patient at both baseline and the end of the follow-up. During the lipid-lowering diet, no significant changes in lipoprotein parameters were observed. Atorvastatin was tolerated well and no clinical side effects were noted during the follow-up. The final dose of atorvastatin ranged from 2.5 to 7.5 mg/day. At the end of the study, TC was reduced by 32.2% ( P<0.05), low-density lipoprotein cholesterol (LDL-C) by 41.8% ( P<0.05), and apo B by 29.5% ( P<0.05). No significant changes in HDL-C, VLDL-C, apolipoprotein AI, and lipoprotein(a) were observed. SCr and CsA levels were unaffected. Overall, no significant changes in mean 24-h, daytime, and nighttime ABPM values between the first and the second recordings were observed. However, both daytime and nighttime systolic and diastolic ABPM values dropped in four patients. In conclusion, low-dose atorvastatin appears to be safe, well tolerated, and effective in the treatment of post-transplant hyperlipidemia. In addition, the capacity of atorvastatin to reduce blood pressure, whether or not related to its lipid-lowering action, deserves further investigation.     

Atorvastatin preserves renal function in chronic complete unilateral ureteral obstruction

PURPOSE: The pleiotropic effects of hMG-CoA (3-hydroxy-3-metylglutaryl coenzyme A) reductase inhibitors may provide renal protection in chronic kidney disease. We examined whether atorvastatin administration preserved renal function in rats with chronic unilateral ureteral obstruction. MATERIALS AND METHODS: Renal clearance experiments were performed in sham operated rats and rats subjected to 3 or 12-day unilateral ureteral obstruction. Hemodynamics parameters and urinary microalbumin levels from the obstructed kidney were also measured. The rats were maintained on a regular diet or the same diet but supplemented with atorvastatin (50 mg/kg daily). RESULTS: Atorvastatin administration did not alter plasma total cholesterol but it significantly decreased triglyceride levels. In sham operated and 3-day unilateral ureteral obstruction rats atorvastatin treatment did not have effects on the glomerular filtration rate or effective renal plasma flow and it also did not affect urinary microalbumin levels. In rats with 12-day unilateral ureteral obstruction the glomerular filtration rate but not effective renal plasma flow was significantly higher and urinary microalbumin was significantly lower in atorvastatin treated rats than in those without atorvastatin treatment. CONCLUSIONS: Atorvastatin treatment decreased microalbuminuria and helped preserve filtration function in chronic unilateral ureteral obstruction without altering plasma cholesterol levels, suggesting that pleiotropic renal protection is offered by this statin.     

Lipoprotein profiles at different stages of chronic renal insufficiency

BACKGROUND: Lipoprotein abnormalities characteristic of renal dyslipoproteinemia are significantly associated with different stages of chronic renal insufficiency. The renal dyslipoproteinemia may contribute not only to accelerated development of atherosclerosis but also to progression of human chronic renal insufficiency. METHODS: The purpose of the studies was to estimate the lipid and lipoprotein profiles in 52 not dialysed patients with various renal insufficiency advancement. Basing on creatinine level the patients were divided into 3 groups. CR1-A--serum creatinine 2-5 mg/dL (n = 16), CR1-B--serum creatinine 5-10 mg/dL (n = 19), CR1-C--serum creatinine > 10 mg/dL (n = 17). RESULTS: In CR1-A and CR1-B dyslipoproteinemia was found at different stages of renal insufficiency which was manifested by the significant increase of TG, TC, LDL-C, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and significant decrease of HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in comparison with controls. We also observed decreased TG, TC, LDL-C, apo AI, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and unchanged HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in cm-c in comparison to CR1-A. The decrease of the lipoprotein parameters in CR1-C might result from malnutrition (statistically decreased albumin level) and metabolism disturbances connected with the renal insufficiency advancement. Negative correlation between IG, HDL-C levels (r = -0.43, p < 0.001) and TG, IIDL-C/apoAI (r = -0.56; p < 0.001) were found, which confirmed the abnormal composition of HDL molecules and indicated a high risk of atherosclerosis. CONCLUSION: Our results may indicate that of atherosclerosis in CR1 patients is connected with dyslipoproteinemia and disturbances in HDL molecular composition and with different stages of chronic renal insufficiency.     

A prospective proof of concept study of the efficacy of tacrolimus ointment on uraemic pruritus (UP) in patients on chronic dialysis therapy.

BACKGROUND: Uraemic pruritis (UP) is a serious symptom of chronic dialysis patients and patients with end-stage renal disease. UP causes skin damage, discomfort, sleeping disorders and diminished quality of life. Since UP is considered to be in part an immune-mediated inflammatory process, immunosuppressive drugs like tacrolimus may be beneficial. METHODS: We conducted a prospective study on the effect of 6 weeks treatment with two sequential concentrations of tacrolimus ointment on the severity of UP in chronic dialysis patients and again after 2 weeks wash-out. Twenty-five patients with UP were enrolled in the study; 21 patients completed the study. UP was measured using a validated modified pruritus assessment score and a Visual Analogue Scale (VAS). RESULTS: The modified pruritus assessment score decreased significantly by 81.8% after 6 weeks treatment from [median score 11 (interquartile range: IQR 6-16) on day 0 to median score 2 (IQR 0-5.25) at week 6: P<0.0001]. After 2 weeks wash-out, the median score returned to 72.7% of baseline levels [8 (IQR 2-16)]. Using the VAS score an identical evolution could be demonstrated. Tacrolimus ointment was well tolerated and no serious adverse events were noted. Transient stinging and burning sensation was reported by four patients in the first weeks of the trial, one patient suffered a mild skin rash. No systemic exposure to tacrolimus was detected. CONCLUSION: This prospective study has shown that 6 weeks treatment with tacrolimus ointment significantly reduces the severity of UP in chronic dialysis patients and is well tolerated. Randomized placebo-controlled studies are necessary to confirm these encouraging preliminary results.     

Effect of atorvastatin therapy and conversion to tacrolimus on hypercholesterolemia and endothelial dysfunction after renal transplantation

BACKGROUND: Hypercholesterolemia is a frequent complication in renal transplant patients treated with cyclosporine A (CsA). Whether it is preferable to treat hypercholesterolemia with statins or to switch patients from CsA to tacrolimus (TRL) has not been investigated. METHODS: Twelve CsA-treated kidney transplant recipients with hypercholesterolemia were successively crossed over from CsA alone to: CsA plus atorvastatin; TRL alone; and TRL plus atorvastatin. Total cholesterol (C), Low density lipoprotein (LDL)-C, high density lipoprotein (HDL)-C, LDL and HDL alpha-tocopherol content, lag-time of LDL oxidation, plasma levels of oxidized LDL and the percentage of small dense LDL were assayed at the end of each treatment period. Endothelial function was assessed by high resolution ultrasound measurement of flow-mediated brachial artery vasodilatation (FMD). RESULTS: Atorvastatin therapy was more efficient in reducing total cholesterol and LDL-C levels than conversion from CsA to TRL. Combining TRL with atorvastatin further reduced LDL-C levels as compared to TRL alone, but was no more efficient than the CsA-statin combination. Neither atorvastatin therapy nor conversion to TRL significantly changed the proportion of dense LDL, lipoprotein alpha-tocopherol contents or the lag time of LDL oxidation. Addition of atorvastatin to CsA increased FMD from 4.0+/-1.8% to 6.5+/-4.0% (P<0.05 vs. CsA). Conversion from CsA to TRL caused a slight improvement in FMD (5.1+/-2.1%, P<0.05 vs. CsA). Adding atorvastatin to TRL had no detectable effect on FMD (5.5+/-2.3%, P=NS vs. TRL). CONCLUSIONS: Atorvastatin was more efficient in reducing total and LDL cholesterol levels of CsA-treated renal transplant patients than conversion to TRL and significantly improved endothelial dysfunction.     

短期服用氟伐他汀对血脂及C反应蛋白的影响

目的:观察氟伐他汀在短期(4周)内对血脂及 C-反应蛋白的影响。方法:将80例高脂血症患者随机分为治疗组40例和对照组40例。治疗组在饮食和生活方式调整基础上,每天晚上服用氟伐他汀20mg,连续4周。分别测定治疗前后患者血浆总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(HDL-C),高敏感 C-反应蛋白(hsCRP)的水平。结果:4周后治疗组 TC、LDL-C 分别下降了21.7%和21.8%。HDL-C 升高了6.5%,hsCRP 下降了7.8%,hsCRP 的下降与血浆 TC、LDL-C 降低无相关性(P>0.05),而与 HDL-C 的升高呈显著负相关(r=0.22,P<0.01)。对照组无明显变化。结论:短期服用氟伐他汀即可调整血脂代谢异常,并且 hsCRP 的降低与血脂的下降无关,而与 HDL 的升高相关。     

Effects of long-term pravastatin treatment on serum and urinary monocyte chemoattractant protein-1 levels and renal function in type 2 diabetic patients with normoalbuminuria

To explore the renoprotective and anti-inflammatory effects of pravastatin, we analyzed the changes in renal function and urinary monocyte chemoattractant protein-1 (MCP-1) level as a renal tubulointerstitial inflammatory biomarker and serum MCP-1 level as a systemic inflammatory biomarker following the introduction of treatment with 10 mg/day of pravastatin in 10 hyperlipidemic type 2 diabetic patients with normoalbuminuria. Twelve months of the pravastatin treatment did not affect urinary levels of albumin, transferrin, N-acetylglucosaminidase, or MCP-1 in the hyperlipidemic diabetic patients, whereas the treatment significantly reduced serum levels of MCP-1 in the patients. The pravastatin treatment effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in the hyperlipidemic diabetic patients to levels nearly to those in 11 non-hyperlipidemic type 2 diabetic patients with normoalbuminuria. Interestingly, serum MCP-1 levels were significantly lower in the hyperlipidemic patients treated with pravastatin than in the non-hyperlipidemic patients. No significant correlation was observed between serum LDL-C and MCP-1 levels in all the data in the hyperlipidemic patients before and after the pravastatin treatment and in the non-hyperlipidemic patients. These results collectively indicate that pravastatin may ameliorate systemic vascular inflammation rather than local renal inflammation in hyperlipidemic type 2 diabetic patients with normoalbuminuria, independent of its cholesterol-lowering effects.     

Combined hyperlipidemia in a single subject with tetraplegia: ineffective risk reduction after atorvastatin monotherapy

BACKGROUND/OBJECTIVE: Effects of atorvastatin (Lipitor) drug monotherapy (10 mg daily) on fasting blood lipid profiles and cardiovascular disease (CVD) risks were examined for a single subject with C5-C6 tetraplegia. Routine fasting lipid profiles were analyzed by standard biochemistry techniques for total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C). Lipid profiles were analyzed on 3 occasions before drug therapy was initiated and 3 months after therapy commenced. The TC:HDL and LDL:HDL ratios were computed for all sampling times and used to assess pretreatment and post-treatment CVD risk. RESULTS: Fasting TC, TG, and LDL-C were all significantly reduced by therapy. The pretreatment HDL-C of 35 mg/dL was lowered to 21 mg/dL. As a result, the TC:HDL risk ratio was only marginally reduced from 6.6 to 6.4, whereas the LDL:HDL risk ratio remained unchanged by treatment. CONCLUSIONS: In this man with tetraplegia, atorvastatin drug monotherapy rapidly lowered TC, TG, LDL-C, and HDL-C. However, the TC:HDL ratio, considered the best predictor of CVD risk, was unchanged.     

Assessing the benefits and harms of statin treatment in patients with chronic kidney disease

This Practice Point commentary discusses a meta-analysis by Strippoli et al. that included 50 randomized and quasi-randomized trials of statins in patients with different stages of kidney disease (predialysis, dialysis and transplantation; n = 30,144). The authors found that statins safely reduced lipid concentrations and the risk of cardiovascular events and cardiovascular mortality, but that the agents had no effect on all-cause mortality overall and had uncertain renoprotective effects. The analysis was comprehensive and well executed. A decreased risk of all-cause mortality with statins was found in studies of predialysis patients but not in studies of renal transplant recipients or patients on chronic dialysis. Statin doses used in the trials were well tolerated and safe in all subgroups of patients with chronic kidney disease; therefore, we feel that statin use to maintain LDL cholesterol below 100 mg/dl (2.6 mmol/l) should be initiated to potentially decrease cardiovascular risk in such patients. The benefits of statin therapy on all-cause mortality and the clinically significant benefits of this treatment on progression of kidney disease are still unclear, and additional trial evidence in patients with chronic kidney disease is needed.     

Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: Rationale and design of the ASsessment of clinical Usefulness in CKD patients with Atorvastatin (ASUCA) trial

Background

Since dyslipidemia has been shown to be an independent risk factor for the progression of chronic kidney disease (CKD), low-density lipoprotein cholesterol (LDL-C)-lowering therapy can be potentially associated with inhibition of CKD progression. The ASsessment of clinical Usefulness in CKD patients with Atorvastatin (ASUCA) trial was designed to determine whether atorvastatin has protective effects on renal function in patients with dyslipidemia and CKD.

Methods

We decided to carry out a prospective multi-center, open-labeled, randomized trial to compare the reno-protective effects between diet therapy alone and atorvastatin plus diet therapy in patients with dyslipidemia (LDL-C ≥ 140 mg/dL if not treated or LDL-C ≥ 100 mg/dL if treated with lipid-lowering drugs in subjects taking dyslipidemia-treating agents other than statins) and CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²]. The primary endpoint is the change in eGFR (mL/min/1.73 m²) as calculated by the modified MDRD equation for Japanese after 2 years of treatment.

Results

Enrollment began in April 2009 and was completed in March 2011. A total of 334 patients (213 male and 121 female) were randomly assigned to either diet therapy alone or atorvastatin plus diet therapy and included in an intent-to-treat population. In the atorvastatin and control groups, the mean ages were 63.2 and 63.1 years, mean eGFRs were 55.9 and 54.0 mL/min/1.73 m², and median urinary albumin/creatinine ratios were 24.9 and 29.1 mg/g, respectively.

Conclusions

This study distinguishes itself from similar studies by increasing statistical accuracy derived from its significantly larger sample size and longitudinal magnitude. The results of this study will help to determine whether atorvastatin has reno-protective effects in patients with dyslipidemia and CKD.     

Plasma phospholipid transfer protein activity is decreased in type 2 diabetes during treatment with atorvastatin: a role for apolipoprotein E?

Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the potential role of apolipoprotein E (apoE). PLTP activity and apoE were measured in patients with type 2 diabetes from the DALI (Diabetes Atorvastatin Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was positively correlated with waist circumference, HbA(1c), glucose, and apoE (all P < 0.05). Atorvastatin treatment resulted in decreased PLTP activity (10 mg atorvastatin: -8.3%, P < 0.05; 80 mg atorvastatin: -12.1%, P < 0.002). Plasma apoE decreased by 28 and 36%, respectively (P < 0.001). The decrease in apoE was strongly related to the decrease in PLTP activity (r = 0.565, P < 0.001). The change in apoE remained the sole determinant of the change in PLTP activity in a multivariate model. The activity of PLTP in type 2 diabetes is decreased by atorvastatin. The association between the decrease in PLTP activity and apoE during statin treatment supports the hypothesis that apoE may prevent PLTP inactivation.     

Effects of Long-Term Pravastatin Treatment on Serum and Urinary Monocyte Chemoattractant Protein-1 Levels and Renal Function in Type 2 Diabetic Patients with Normoalbuminuria

To explore the renoprotective and anti-inflammatory effects of pravastatin, we analyzed the changes in renal function and urinary monocyte chemoattractant protein-1 (MCP-1) level as a renal tubulointerstitial inflammatory biomarker and serum MCP-1 level as a systemic inflammatory biomarker following the introduction of treatment with 10 mg/day of pravastatin in 10 hyperlipidemic type 2 diabetic patients with normoalbuminuria. Twelve months of the pravastatin treatment did not affect urinary levels of albumin, transferrin, N-acetylglucosaminidase, or MCP-1 in the hyperlipidemic diabetic patients, whereas the treatment significantly reduced serum levels of MCP-1 in the patients. The pravastatin treatment effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in the hyperlipidemic diabetic patients to levels nearly to those in 11 non-hyperlipidemic type 2 diabetic patients with normoalbuminuria. Interestingly, serum MCP-1 levels were significantly lower in the hyperlipidemic patients treated with pravastatin than in the non-hyperlipidemic patients. No significant correlation was observed between serum LDL-C and MCP-1 levels in all the data in the hyperlipidemic patients before and after the pravastatin treatment and in the non-hyperlipidemic patients. These results collectively indicate that pravastatin may ameliorate systemic vascular inflammation rather than local renal inflammation in hyperlipidemic type 2 diabetic patients with normoalbuminuria, independent of its cholesterol-lowering effects.     

Effect of low doses of atorvastatin on adiponectin, glucose homeostasis, and clinical inflammatory markers in kidney transplant recipients

INTRODUCTION: Various studies describe the pleiotropic antiinflammatory and antioxidant effects of atorvastatin, in addition to its hypolipemic effects. It has been suggested that statins modify glucose homeostasis via their antiinflammatory effects. A further hypothesis suggests that the incidence of posttransplantation diabetes is lower in statin-treated patients. This study sought to ascertain whether atorvastatin modifies glucose homeostasis, adiponectin, and inflammatory markers in kidney transplant recipients. PATIENTS AND METHODS: Sixty-eight kidney transplant recipients (41 men, 27 women; mean age, 53 +/- 12 years) with stable renal function and dyslipidemia were treated with atorvastatin (10 mg/d) for 12 weeks. Glucose, insulin, homeostasis model assessment (HOMA-IR) index, adiponectin, tumor necrosis factor (TNF)-alpha, and serum C-reactive protein (CRP) concentrations were determined at baseline and at 3 months. The lipid profile, renal function parameters (creatinine, creatinine clearance, and proteinuria), as well as GOT, GPT, and CK were determined at baseline and at 3 months. RESULTS: Treatment with atorvastatin achieved a statistically significant decrease in lipid profile. After 3 months of treatment, 74.6% of patients had total cholesterol and 78.7% low-density lipoprotein (LDL) cholesterol concentrations within reference range (<5.2 and 3.3 mmol/L, respectively). Furthermore, 47.5% of patients attained an LDL concentration <2.59 mmol/L. A greater reduction in total cholesterol (P = .05) and LDL cholesterol (P = .04) was achieved in patients with creatinine clearance <60 mL/min. Atorvastatin did not modify glucose homeostasis parameters, adiponectin, TNF-alpha, or CRP. At baseline and after 3 months of treatment, an inverse correlation was found between adiponectin and glucose, insulin, HOMA- IR index, and creatinine clearance, and a positive correlation was found between adiponectin and high-density lipoprotein (HDL) cholesterol. CONCLUSION: Atorvastatin at a dose of 10 mg/d in kidney transplant recipients does not modify glucose homeostasis or alter inflammatory markers, despite its hypolipemic effects. Its efficacy to reduce total cholesterol and LDL cholesterol was greater in patients with worse renal function.     

Efficacy, safety and tolerability of atorvastatin in dyslipidemic subjects with advanced (non-nephrotic) and endstage chronic renal failure

Background Patients with dyslipidemia and advanced renal failure are at markedly increased risk of cardiovascular morbidity and mortality. We evaluated the efficacy, safety, and tolerability of atorvastatin in non-nephrotic, dyslipidemic patients with chronic renal failure (CRF) or endstage renal failure (ESRF) receiving dialysis. Methods Following a 6-week baseline period, adult patients meeting Australian Heart Foundation treatment guidelines received atorvastatin for 16 weeks: 19 with CRF (predialysis), 17 on hemodialysis (HD), and 13 on continuous ambulatory peritoneal dialysis (CAPD). Dose (10–40 mg daily) was titrated to achieve lipid-lowering targets. Efficacy was determined by monitoring lipids (principally triglycerides and low-density lipoprotein [LDL] cholesterol); safety and tolerance by monitoring clinical and laboratory parameters. Results Atorvastatin was effective in reducing LDL cholesterol from baseline at each of weeks 4, 8, 12, and 16 in all study groups, with reductions of more than 40% at week 16. Sixty-two percent of PD, 73% of HD, and 100% of CRF patients were at or below target (<2.6 mmol/l) for LDL cholesterol at week 16. Significant reductions in triglycerides (approximately 27%) were seen in the CRF and combined HD/CAPD groups at all time points. Depending on the group, 65%–83% of patients were at or below target (<2.0 mmol/l) for triglycerides at week 16. The majority of patients received the 10-mg dose. Atorvastatin also reduced total cholesterol and apolipoprotein B levels in all groups and very-low-density lipoprotein (VLDL) cholesterol in the CRF group. Significant increases in LDL particle size were found in the HD and combined HD/CAPD groups. Minor, particularly gastrointestinal, symptoms were common. Three patients reported musculoskeletal symptoms, but creatine kinase was raised in only one. Conclusion Atorvastatin is an effective lipid-lowering agent for dyslipidemic subjects with advanced and endstage renal failure, and was reasonably well tolerated.     

Assessment of the efficiency of treatment of dyslipidaemia in renal outpatients

BACKGROUND: Lipid abnormalities, together with other co-existent risk factors, contribute to the accelerated atherosclerotic process, and consequently to the high incidence of cardiovascular disease, observed in end-stage renal patients. The objectives of this study were to determine the prevalence of dyslipidaemia and to assess how it is managed in a range of patients at four UK renal units. METHODS: Patients with renal disease were recruited from the outpatient clinics of 4 UK hospitals. Individuals meeting the entry criteria were required to provide one sample of venous blood following a 12-hour fast. Lipid profiles were measured for each patient. RESULTS: The study population consisted of 677 patients of which 276 (40.8%) were pre-dialysis patients with existing renal disease, 233 patients (34.4%) were receiving haemodialysis and 168 patients (24.8%) were receiving CAPD. Analysis showed that 64% of all patients had hypercholesterolaemia (defined according to Joint British Societies guidelines as LDL-cholesterol [LDL-C] >3.0 mmol/L [115 mg/dL] and/or total cholesterol [TC] >5.0 mmol/L [190 mg/dLl). Despite the high incidence of hypercholesterolaemia, only 16% of study participants were receiving lipid-lowering therapy. An LDL-C goal of <3.0 mmol/L (115 mg/dL) was achieved in 50.0% of patients receiving lipid-lowering treatment. CONCLUSIONS: The widespread failure to treat hypercholesterolaemia in patients with renal dysfunction given their high risk of future cardiovascular events is a major cause for concern. The observation that many dialysis patients receiving lipid-lowering therapy had not achieved recommended LDL-C and TC levels suggests that more efficient treatment of dyslipidaemia may be indicated in this patient population.