Lipid profile during azathioprine or mycophenolate mofetil combinations with cyclosporine and steroids

BACKGROUND: Immunosuppressive therapy is the major cause of hyperlipidemia after renal transplantation. We sought to compare the effects of an azathioprine (AZA) combination (n = 26) with corticosteroid and cyclosporine (CyA; group 1) with a mycophenolate mofetil (MMF) combination (n = 71; group 2) in the first year following renal transplantation. METHODS: Ninety-seven renal transplant patients (71 men, 26 women; aged 34.7 +/- 13.1 years; renal transplantation duration, 44.9 +/- 12.9 months) underwent serum lipid profiles--total cholesterol, triglyceride, high-density lipoprotein (HDL); low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) at the initiation of as well as 3-month intervals after grafting for 1 year retrospectively. Serum creatinine for each patient was recorded at 12 months. We evaluated possible risk factors for hyperlipidemia. RESULTS: For all patients, the prevalence of hypercholesterolemia (>200 mg/dL) was 36.1% during the pretransplant period, 60.8% at month 3, 50.5% at month 6, and 38.1% at month 12 after renal transplantation. Total cholesterol and triglyceride levels significantly increased in both groups in the first year (P = .001 and P = .02, respectively). Three-month values for total cholesterol were higher in group 2 than group 1 (P = .001). No significant difference was observed between the groups with respect to total cholesterol and triglyceride levels (P > .05). In both groups, HDL, LDL, and VLDL levels did not change during the 12-month study (P > .05 for all). CONCLUSIONS: Independent of hyperlipidemia risk factors, serum total cholesterol and triglyceride levels tended to increase during CyA and steroid therapy among patients undergoing renal transplantation. Combination with MMF or AZA showed no advantage over one another regarding their effects on the lipid profile.     

Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.     

Effect of simvastatin on plasma asymmetric dimethylarginine concentration in patients with chronic kidney disease

BACKGROUND: The endogenous inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (ADMA), is a strong cardiovascular (CV) risk marker in patients with chronic renal insufficiency. Statins have pleiotropic effects and are currently considered as potential ADMA-lowering agents. METHODS: We investigated the effect of simvastatin on plasma ADMA levels in 35 patients with chronic kidney disease (CKD) by performing a secondary analysis of a randomized double-blind placebo-controlled trial where patients were randomized to receive simvastatin or placebo for 6 months. RESULTS: Plasma ADMA was higher in CKD patients (0.84 +/- 0.14 micromol/L) than in healthy subjects (0.69 +/- 0.10 micromol/L) (p<0.001). In CKD patients, ADMA at baseline was related directly with triglycerides (r=0.42, p=0.01) and inversely with HDL cholesterol (r=-0.37, p=0.03) and creatinine clearance (p=0.03). As expected, simvastatin caused significant reductions in total cholesterol, LDL cholesterol and triglycerides, as well as in C-reactive protein (CRP; -28%, p=0.001) and IL-6 (-20%, p=0.05) but failed to decrease plasma ADMA both in crude and adjusted analyses. CONCLUSIONS: Simvastatin does not modify plasma ADMA. Because raised ADMA is known to prevent the favorable effect of statins on myocardial blood flow, cointerventions aimed at lowering or antagonizing ADMA may either prompt or potentiate the cardiovascular protective effect of simvastatin.     

Low-density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end-stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low-density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n = 30) and peritoneal dialysis patients (PD; n = 17), and compared them to 40 asymptomatic, non-uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.     

Comparative effects of cerivastatin and fenofibrate on the atherogenic lipoprotein phenotype in proteinuric renal disease

Patients with nephrotic-range proteinuria have impaired clearance of triglyceride-rich lipoproteins. This results in the atherogenic lipoprotein phenotype (mild hypertriglyceridemia, low high-density lipoproteins [HDL], and excess small, dense low-density lipoproteins [LDLIII]). Excess remnant lipoproteins (RLP) are linked to hypertriglyceridemia and may contribute to the atherogenicity of nephrotic dyslipidemia. A randomized crossover study compared the effects of a statin (cerivastatin) and a fibrate (fenofibrate) on LDLIII and RLP in 12 patients with nephrotic-range proteinuria. Cerivastatin reduced cholesterol (21%, P: < 0.01), triglyceride (14%, P: < 0.05), LDL cholesterol (LDL-C; 23%, P: < 0.01), total LDL (18%, P: < 0.01), and LDLIII concentration (27% P: < 0.01). %LDLIII, RLP-C, and RLP triglyceride (RLP-TG) were unchanged. Plasma LDLIII reduction with cerivastatin treatment correlated with LDL-C reduction (r(2) = 34%, P: < 0.05). Fenofibrate lowered cholesterol (19%), triglyceride (41%), very low-density lipoprotein cholesterol (52%), LDLIII concentration (49%), RLP-C (35%), and RLP-TG (44%; all P: < 0.01). Fenofibrate also reduced %LDLIII from 60 to 33% (P: < 0.01). HDL-C (19%, P: < 0.01) increased with fenofibrate treatment; LDL-C and total LDL were unchanged. The reduction in LDLIII concentration and RLP-C with fenofibrate treatment correlated with plasma triglyceride reduction (LDLIII r(2) = 67%, P: < 0.001; RLP cholesterol r(2) = 58%, P: < 0.005). Serum creatinine increased with fenofibrate treatment (14%, P: < 0.01); however, creatinine clearance was unchanged. LDLIII concentration was 187 +/- 85 mg/dl after cerivastatin treatment and 133 +/- 95 mg/dl after fenofibrate treatment. Cerivastatin and fenofibrate reduce LDLIII concentration in nephrotic-range proteinuria. However, atherogenic concentrations of LDLIII remain prevalent after either treatment. Fenofibrate but not cerivastatin reduces remnant lipoproteins. The two treatments seem to reduce LDLIII by different mechanisms, suggesting a potential role for combination therapy to optimize lowering of LDLIII and RLP.     

Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome

The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d(3)-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL(2) cholesterol (P < 0.001), HDL(3) cholesterol (P < 0.01), apoAI (P = 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.     

Are lipid‐dependent indicators of cardiovascular risk affected by renal transplantation?

Hyperlipoproteinemia has been reported to frequently occur in kidney transplanted patients, thus possibly explaining, at least in part, the increased incidence of cardiovascular disease in this population. To evaluate the impact of renal transplantation (Tx), and related immunosuppressive therapy, on plasma lipoprotein and Lp(a) profile, we selected a cohort of kidney transplanted patients (36 M/14 F; age 33.8 + 12.0 yr, range 13-62) lacking significant causes of hyperlipidemia. All patients received a triple immunosuppressive regimen and showed a stable renal function after Tx (plasma creatinine: 1.36 +/- 0.35 mg/dL). One year after Tx, we found a significant increase of total cholesterol (TC), LDL, HDL, ApoB and ApoA-I (p < 0.005), while plasma triglyceride levels remained unmodified. Lp(a) plasma levels after Tx were within the normal range and displayed a significant inverse relationship with apo(a) size. Noteworthy, LDL/HDL ratio and ApoB/ ApoA-I ratio in kidney transplanted patients were almost superimposable with those of normal controls. Specifically, LDL/HDL ratio significantly decreased in 64% of patients after Tx, due to a prevalent increase of HDL, and was associated with a moderate amelioration of plasma TG. In a multiple linear regression model, post-Tx HDL level was significantly related to recipient's age, gender, BMI and cyclosporine (CyA) trough levels (Adj-R2 = 0.35, p = 0.0002), with gender and CyA trough levels being the better predictors of HDL. In conclusion, immunosuppressive regimens, in themselves, do not appear to significantly increase the atherogenic risk related to lipoproteins. Rather, other factors can affect the lipoprotein profile and its vascular effects in renal transplant recipients.     

Is dietary intervention effective in post-transplant hyperlipidaemia?

Current therapies for hyperlipidaemia following renal transplantationinclude modification of dietary fat. We examined the effectof dietary intervention according to the American Heart AssociationStep One diet on serum lipids and lipoproteins among 26 menand women with post-transplant hyperlipidaemia. Weighed dietaryrecords showed that the intake of total fat decreased from 30to 27% and the intake of saturated fat decreased from 12 to8% of total calories. Body-weight remained stable throughoutthe study. Serum total, LDL and HDL cholesterol levels wereunchanged following 12 weeks of therapy. Serum tri-glyceridelevels decreased slightly. The decrease was seen only in participantswith a body mass index < 26 kg/m², compared to those whosebody mass index was 26 kg/m² (0.4 versus 0 mmol/l; P = 0.03).Serum LDL cholesterol and triglyceride levels were significantlycorrelated with serum creatinine levels. In conclusion, amongrenal transplant recipients, hyperlipidaemia appears to be partlyrelated to impairment of renal function, and may not be responsiveto modification of dietary fat without weight reduction attemptedon an outpatient basis.     

Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease

BACKGROUND: There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin. METHODS: After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients. RESULTS: Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups. CONCLUSIONS: Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.     

Low-Density Lipoprotein Oxidizability and the Alteration of Its Fatty Acid Content in Renal Transplant Recipients Treated With Cyclosporine/Tacrolimus

Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclerosis is an important posttransplantation risk factor for renal transplant recipients. Subsequent to transplantation low-density lipoprotein (LDL) particles become susceptible to oxidative modification, which results in atherosclerosis. Therefore, the aim of our study was to investigate differences in the susceptibility of LDL particles to oxidation by analyzing LDL fatty acid levels among renal transplant recipients. The changes in lag phases and fatty acid levels of LDL were observed over 4 months among renal transplant recipients treated with Cyclosporine (CsA; n = 7) or Tacrolimus (FK-506; n = 9). We also analyzed cholesterol and triglyceride levels of patients and healthy controls. The lag phase at the 60th day after transplantation was significantly shorter than the results either before transplantation or among control subjects. In conclusion, a similar decrease in lag phase was observed in both above groups, but the FK-506-treated group showed a better lipid profile than the CsA-treated group.     

Randomized Controlled Trial of Sirolimus Conversion in Cardiac Transplant Recipients With Renal Insufficiency

This randomized, comparative, multinational phase 3b/4 study of patients 1–8 years postcardiac transplantation (mean 3.9 years) evaluated the effect of conversion from a calcineurin inhibitor (CNI) to sirolimus on renal function in patients with renal insufficiency. In total, 116 patients on CNI therapy with GFR 40–90 mL/min/1.73m² were randomized (1:1) to sirolimus (n = 57) or CNI (n = 59). Intent‐to‐treat analysis showed the 1‐year adjusted mean change from baseline in creatinine clearance (Cockcroft‐Gault) was significantly higher with sirolimus versus CNI treatment (+3.0 vs. ?1.4 mL/min/1.73 m², respectively; p = 0.004). By on‐therapy analysis, values were +4.7 and –2.1, respectively (p < 0.001). Acute rejection (AR) rates were numerically higher in the sirolimus group; 1 AR with hemodynamic compromise occurred in each group. A significantly higher treatment discontinuation rate due to adverse events (AEs; 33.3% vs. 0%; p < 0.001) occurred in the sirolimus group. Most common treatment‐emergent AEs significantly higher in the sirolimus group were diarrhea (28.1%), rash (28.1%) and infection (47.4%). Conversion to sirolimus from CNI therapy improved renal function in cardiac transplant recipients with renal impairment, but was associated with an attendant AR risk and higher discontinuation rate attributable to AEs.     

Renal protective effects of pitavastatin on spontaneously hypercholesterolaemic Imai Rats.

BACKGROUND: Independent of their lipid-lowering effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have renal protective effects on various models of progressive renal diseases, therefore, additional therapeutic advantages have been considered. In the present study, using spontaneously hypercholesterolaemic Imai rats, we examined the protective effects of pitavastatin on renal injuries and the oxidative modification of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), since oxidized lipoproteins are speculated to be involved in the mechanism of this rat strain's renal injuries. METHODS: Male Imai rats were treated with pitavastatin (n = 11) at a dose of 100 mg/kg diet or received no specific therapy as controls (n = 11) from 10 to 22 weeks of age. Body weight, urinary protein excretion and serum constituents were evaluated every 4 weeks. At the end of the study, the effects of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, and renal histology were examined. RESULTS: Pitavastatin treatment did not affect hyperlipidaemia, but significantly reduced proteinuria and preserved creatinine clearance deterioration. At the end of the study, lag times for LDL and HDL oxidation were prolonged by the treatment of pitavastatin to 126 and 153%, respectively, compared with the controlled group. The glomerulosclerosis index (SI) for untreated controlled rats was significantly higher than that for the pitavastatin-treated group. An immunohistochemistry study showed significantly lower numbers of ED-1 positive macrophages in the glomeruli and interstitium in pitavastatin-treated rats compared with those controlled. CONCLUSION: Pitavastatin treatment prevented renal injuries in Imai rats independent of lipid-lowering effects. Prevention of oxidative modification of LDL and HDL may play an important role on the beneficial effects of pitavastatin treatment.     

Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency

BACKGROUND: Although cardiovascular disease and low high-density lipoprotein (HDL) cholesterol are common in people with renal insufficiency, data addressing the cardiovascular benefits of fibric acid derivatives in this population are sparse. We conducted a post hoc subgroup analysis of a randomized double-blind, placebo-controlled trial to determine whether gemfibrozil is effective and safe for secondary prevention of cardiovascular events in individuals with chronic renal insufficiency (CRI). METHODS: Using an analysis plan that was developed a priori, we analyzed data from the Veterans' Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) study; a randomized trial of gemfibrozil versus placebo in 2531 men with established coronary disease, an HDL cholesterol level of 40 mg/dL (1.0 mmol/L) or less, and a low-density lipoprotein (LDL) cholesterol level of 140 mg/dL (3.6 mmol/L) or less. Of these, 1046 men had CRI as defined by creatinine clearance 相似文献   

Impact of nutrition on outcome: a prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy

BACKGROUND: We aimed to determine the effect of dietary counseling or oral supplements on outcome for patients with cancer, specifically, nutritional outcome, morbidity, and quality of life (QOL), during and 3 months after radiotherapy. METHODS: Seventy-five patients with head and neck cancer who were referred for radiotherapy (RT) were randomized to the following groups: group 1 (n = 25), patients who received dietary counseling with regular foods; group 2 (n = 25), patients who maintained usual diet plus supplements; and group 3 (n = 25), patients who maintained intake ad lib. Nutritional intake (determined by diet history) and status (determined by Ottery's Subjective Global Assessment), and QOL (determined by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 [EORTC QLQ-C30]) were evaluated at baseline, at the end of RT, and at 3 months. RESULTS: Energy intake after RT increased in both groups 1 and 2 (p < or = .05). Protein intake also increased in both groups 1 and 2 (p < or = .006). Both energy and protein intake decreased significantly in group 3 (p < .01). At 3 months, group 1 maintained intakes, whereas groups 2 and 3 returned to or below baseline levels. After RT, >90% of patients experienced RT toxicity; this was not significantly different between groups, with a trend for reduced symptomatology in group 1 versus group 2/group 3 (p < .07). At 3 months, the reduction of incidence/severity of grade 1+2 anorexia, nausea/vomiting, xerostomia, and dysgeusia was different: 90% of the patients improved in group 1 versus 67% in group 2 versus 51% in group 3 (p < .0001). After RT, QOL function scores improved (p < .003) proportionally with improved nutritional intake and status in group 1/group 2 (p < .05) and worsened in group 3 (p < .05); at 3 months, patients in group 1 maintained or improved overall QOL, whereas patients in groups 2 and 3 maintained or worsened overall QOL. CONCLUSIONS: During RT, nutritional interventions positively influenced outcomes, and counseling was of similar/higher benefit; in the medium term, only counseling exerted a significant impact on patient outcomes.     

Effect of cerivastatin on urinary albumin excretion and plasma endothelin-1 concentrations in type 2 diabetes patients with microalbuminuria and dyslipidemia.

BACKGROUND/AIMS: To determine whether cerivastatin, a newly developed novel synthetic potent statin, exerts a renoprotective effect, we assessed urinary albumin excretion (UAE) and plasma and urinary endothelin (ET)-1 concentrations in normotensive microalbuminuric type 2 diabetes patients with dyslipidemia. METHODS: Sixty normotensive type 2 diabetic patients (38 men and 22 women; mean age 56.5 years) with microalbuminuria (20-200 microg/min) and dyslipidemia (total cholesterol >200 mg/dl, LDL cholesterol >160 mg/dl, HDL cholesterol <35 mg/dl, and triglyceride >150 mg/dl) were enrolled in a double-blind study for 6 months, receiving either cerivastatin (0.15 mg/day) or placebo. Plasma and urinary ET-1 concentrations were measured by radioimmunoassay. RESULTS: Cerivastatin did not affect serum creatinine and HbA(1c) levels, and reduced systolic blood pressure slightly, but not significantly. Plasma levels of total cholesterol and LDL cholesterol were significantly reduced (p < 0.01), and plasma triglyceride levels were also reduced significantly (p < 0.05) after 6 months of cerivastatin treatment. A concomitant significant decrease in UAE (p < 0.01), and urinary and plasma ET-1 concentrations (p < 0.01) were found during this period. CONCLUSION: The use of cerivastatin is associated with decreased microalbuminuria and plasma and urinary ET-1 levels in microalbuminuric patients with type 2 diabetic mellitus and speculate that this may represent an amelioration of renal injury.     

Efficacy and safety of atorvastatin after pediatric heart transplantation.

BACKGROUND: Lipid abnormalities are prevalent after pediatric and adult heart transplantation. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are efficacious and safe and can lower the incidence of graft coronary artery disease after heart transplantation in adults. Given the high prevalence of lipid abnormalities and the increased recognition of graft coronary disease in children, we retrospectively investigated the efficacy and safety of atorvastatin among pediatric heart transplant recipients. METHODS: Thirty-eight patients were started on atorvastatin 48.2 +/- 54.4 months after transplantation. Atorvastatin dosage was 0.2 +/- 0.1 mg/kg per day. No patient had changes in drug dose unless there was evidence for rhabdomyolysis, myositis or an asymptomatic rise in creatine kinase above normal. Laboratory studies included total cholesterol, triglycerides; high, low and very low-density lipoproteins (HDL, LDL and VLDL, respectively); creatine kinase; creatine; and serum alanine transaminase. RESULTS: Significant declines in total cholesterol (20%), triglyceride (18%) and LDL (26%) were observed after starting atorvastatin therapy. There were no significant changes in HDL or VLDL compared with baseline. There were also no differences in alanine transaminase pre- vs post-atorvastatin therapy. Complications included muscle pain (n = 2) and asymptomatic elevations in creatine kinase (n = 2). Two of these 4 patients developed rhabdomyolysis. Excluding these 4 patients, creatine kinase did not rise compared with baseline. No patient developed alterations in renal function. CONCLUSIONS: Use of atorvastatin in pediatric heart transplant recipients is effective in lowering total cholesterol, triglyceride and LDL without altering HDL levels. Complications included rhabdomyolysis, seen in 5%. Baseline and routine screening of creatine kinase should be employed in all pediatric patients undergoing HMG-CoA reductase inhibitor therapy.     

Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients.

AIM: Oxidative stress and susceptibility of low-density lipoproteins (LDL) to oxidation are increased in renal transplant recipients. The aim of this study was to determine the effect of dietary supplementation with tomato juice on plasma levels of the antioxidant lycopene, serum indices of lipid peroxidation (fluorescent lipid oxidation products (FLOP) and thiobarbituric acid-reacting substances (TBARS)) and the resistance of isolated low-density lipoprotein (LDL) to oxidation (lag time) in patients with a kidney graft. SUBJECTS AND METHODS: Fifteen patients were randomized to daily consumption of either tomato juice or synthetic orange drink for 4 weeks in a crossover study. Plasma lycopene levels were significantly higher (1.57 micromol/l versus 0.91 micromol/l, p = 0.015) while serum FLOP and TBARS and resistance of LDL to oxidation were not significantly different during supplementation with tomato juice compared with orange drink. At baseline, serum levels of lycopene and FLOP were abnormally high and serum FLOP was correlated significantly with plasma cyclosporine levels (r = 0.646, p = 0.016). CONCLUSION: In conclusion, these data suggest that increased oxidative stress and susceptibility of LDL to oxidation may not be reduced by increasing plasma lycopene levels with regular consumption of tomato juice in renal transplant recipients.     

Lipid profile in chronic allograft nephropathy

Chronic allograft nephropathy (CAN) represents the cumulative and incremental damage to nephrons by time-dependent immunologic and nonimmunologic causes. Hyperlipidemia is one nonimmunologic mechanism that promotes injury and poor function in a renal transplant. The aim of our study was to determine the effect of lipid profiles on CAN among renal transplant recipients. We retrospectively evaluated 53 renal transplant recipients who were classified according to the presence of CAN: CAN+ = 28 (18 males, 10 females) constituted the study group, whereas those with stable graft function CAN- = 25 (14 males, 11 females) were the control group. Biochemical parameters included serum urea, creatinine, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a), homocysteine, and high-sensitive CRP (hs CRP). Angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) use was significantly greater among the CAN+ group compared with the controls (P = .02, P = .04). Also, higher serum creatinine levels were observed in the CAN+ group (1.49 vs 1.22 mg/dL, P = .002), whereas serum levels of total cholesterol, triglyceride, hs CRP, and albumin were similar in both groups. The levels of ApoA1, ApoB, and lipoprotein (a) were similar, whereas the LDL/HDL cholesterol ratio and homocysteine levels were significantly higher in the CAN+ group (P = .04, P = .04). In conclusion, the LDL/HDL ratio may have a positive impact on CAN and may be used as a parameter during patient follow-up.     

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.     

Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial.

BACKGROUND: Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts. METHODS: A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation. RESULTS: Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%). CONCLUSIONS: Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.