Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with end-stage renal disease (ESRD) treated with dialysis have a dramatically elevated rate of cardiovascular disease (CVD) compared to the general population. Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been shown to markedly reduce cardiovascular risk in patients without renal failure, but their effect has not been fully studied in the dialysis population. In this article we will first discuss the known benefits of statin therapy in the general population and summarize the current guidelines for such therapy. We will then examine the evidence linking dyslipidemia and cardiac disease in the dialysis population and discuss possible pathophysiologic mechanisms by which statins could prevent cardiac disease in these patients. We will also review prior clinical studies of the effects of statins in patients on dialysis, with particular attention to the safety and efficacy of these drugs in this population. Finally, we will review how statins are currently being used in the care of dialysis patients and suggest whether an expanded utilization of these drugs could help reduce the enormously high rates of cardiac disease in this patient population.
Semin Dial
PMID:Are HMG-CoA reductase inhibitors underutilized in dialysis patients? 1275 74

Hemodialysis patients suffer from a high incidence of cardiovascular disease. Among the many predisposing factors, such as high blood pressure, dyslipidemia, and fluid overload, the accumulation of high molecular weight uremic toxins, the so-called middle molecules, may play an important role. Since convective therapies such as online hemodiafiltration have a better clearance profile for these compounds than standard hemodialysis, it has been suggested that these dialysis strategies may reduce cardiovascular morbidity and mortality. As reliable data on these issues are not available, the Dutch Convective Transport Study (CONTRAST) was recently initiated. This prospective randomized trial was designed to compare online hemodiafiltration with low-flux hemodialysis with respect to cardiovascular morbidity and mortality.
Semin Dial
PMID:Resolving controversies regarding hemodiafiltration versus hemodialysis: the Dutch Convective Transport Study. 1566 65

Patients undergoing chronic renal replacement therapy have a high incidence of dyslipidemia. In general, there are increased concentrations of triglyceride-rich apolipoprotein B-containing particles. These elevations lead to increased levels of non-high-density lipoprotein (HDL) levels. This pattern is further modified by the method of dialysis (peritoneal versus hemodialysis) and comorbidities such as diabetes. End-stage renal disease patients also demonstrate increased levels of lipoprotein(a) (Lp(a)) and oxidized low-density lipoprotein (LDL)both of which are highly atherogenic. This review focuses on the pathogenesis of these lipid abnormalities and their role in the atherosclerotic process.
Semin Dial
PMID:Lipid abnormalities associated with end-stage renal disease. 1642 80

Patients with advanced stages of chronic kidney disease (CKD) have an increased risk of death from cardiovascular disease (CVD). Dyslipidemias are associated with atherosclerotic vascular changes and the risk of occurrence of acute myocardial infarction in hemodialysis patients. However, management of dyslipidemia in hemodialysis patients does not appear to be actively carried out in routine practice. Presumably, there are three reasons for this reluctance to lipid-lowering in hemodialysis patients. First, there are epidemiological data showing the inverse relationship between cholesterol and mortality rate; a high cholesterol predicts a better survival. Second, lipids are not usually measured using standard fasting serum, but a non-fasting specimen. Third, although hypertriglyceridemia is the most common abnormality, fibrates are contraindicated in patients with renal failure because of a high risk of rhabdomyolysis. These issues are discussed in the current review article. Based on published work, lipid lowering would not increase the death rate if carried out without worsening malnutrition. The National Kidney Foundation K/DOQI Clinical Practice Guidelines recommend a reduction in fasting LDL-C below 100 mg/dL for the prevention of CVD in dialysis patients. Practically, however, the use of non-HDL-C measured by casual blood samples might be sufficient for the risk assessment in many hemodialysis patients. Statins are a good choice for lipid-lowering in dialysis patients. Furthermore, lipoprotein profile might be improved by an inventive use of dialyzer membranes, dialysate solutions, and other dialysis-related medications. For severe hypercholesterolemia, LDL-apheresis is another choice for consideration. Further studies are needed to clearly prove the benefit of lipid reduction in hemodialysis patients and those with CKD at earlier stages.
Ther Apher Dial 2006 Aug
PMID:Plasma lipoprotein abnormalities in hemodialysis patients--clinical implications and therapeutic guidelines. 1691 Nov 82

The management of lipid abnormalities in patients with end-stage renal disease (ESRD) remains controversial. Large, well-designed studies investigating the effects of dyslipidemia on cardiovascular (CV) morbidity and mortality and the role of cholesterol lowering drugs in reducing mortality in ESRD patients are lacking. While it seems reasonable to suspect that dyslipidemia and its treatment in ESRD patients will affect CV morbidity and mortality similar to that in the general population, recent studies have suggested that this may not be the case. Furthermore, the pharmacokinetics of lipid lowering drugs are altered in patients with ESRD and must be considered when treating this group of patients. This article reviews the major classes of drugs used to treat dyslipidemia, emphasizing their role in patients with ESRD.
Semin Dial
PMID:Management of lipid abnormalities associated with end-stage renal disease. 1697 Jul 39

Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; "remnant particles"), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition-inflammation. Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (<or=20 mg/day atorvastatin or simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large observational studies demonstrate that statin treatment is independently associated with a 30%-50% mortality reduction in patients with dialysis-dependent CKD (similar between HD- and PD-treated patients). One recent randomized controlled trial evaluated the ability of statin treatment to reduce mortality in type II diabetics treated with HD ("4D"); the primary end point of death from cardiac cause, myocardial infarction, and stroke was not significantly reduced. However, results of this trial may not apply to other end-stage renal disease populations. Two ongoing randomized controlled trials (SHARP and AURORA) are underway evaluating the effect of statins on CV events and death in patients with CKD (including patients treated with HD and PD). Recruitment to future trials should be given a high priority by nephrologists and, until more data are available, consideration should be given to following published guidelines for the treatment of dyslipidemia in CKD. Additional consideration could be given to treating all dialysis patients felt to be at risk of CV disease (irrespective of cholesterol level), given the safety and potential efficacy of statins. This is especially relevant in patients treated with PD, given their more atherogenic lipid profile and the lack of randomized controlled trials in this population.
Perit Dial Int
PMID:Statins for treatment of dyslipidemia in chronic kidney disease. 1729 64

Patients on peritoneal dialysis (PD) are at high cardiovascular risk. Although some risk factors are unmodifiable (for example, age, sex, genetics), others are exacerbated in the unfriendly uremic milieu (inflammation, oxidative stress, mineral disturbances) or contribute per se to kidney disease and cardiovascular progression (diabetes mellitus, hypertension). Moreover, several factors associated with PD therapy may both increase (by altered lipid profile, hyperinsulinemia, and formation of advanced glycation end-products) and decrease (by better blood pressure control and anemia management) cardiovascular risk. The present review discusses recent findings and therapy trends in cardiovascular research on the PD population, with emphasis on the roles of inflammation, insulin resistance, homocysteinemia, dyslipidemia, vascular calcification, and genetics/epigenetics.
Perit Dial Int 2007 Jun
PMID:Risk factors for cardiovascular disease in patients undergoing peritoneal dialysis. 1755 5

Cardiovascular complications are obviously important in the management of dialysis patients, and ultrasonography can be used to evaluate cardiac indices that can predict these complications. However, long-term longitudinal changes in ultrasonographic cardiovascular indices in dialysis patients are not well known. Also, the implications of lipid metabolism for cardiovascular change in dialysis patients is controversial. We therefore analyzed ultrasonographic cardiac parameters and laboratory data for lipid metabolism in patients who had been on peritoneal dialysis (PD) or hemodialysis (HD) for 8 years and also in patients who had been on PD for 4 years followed by another 4 years on HD. We found that lipid metabolism was worse but that cardiovascular indices were more stable over time in PD patients than in HD patients. Mean blood pressure was also better maintained in PD patients. These results indicate that cardiovascular function can be maintained in PD patients over the long term, given that blood pressure is controlled even though dyslipidemia worsens.
Adv Perit Dial 2007
PMID:Longitudinal changes in parameters of cardiovascular function in patients treated for 8 years with hemodialysis or peritoneal dialysis. 1788 5

In contrast to the associations of high body mass index (BMI) with increased mortality in the general population, high BMI is associated with better survival in dialysis patients. Nonetheless, high BMI/adiposity in chronic kidney disease (CKD)/dialysis patients is associated with insulin resistance, inflammation, dyslipidemia, atherosclerosis and coronary calcification as described in the general population. These apparently perplexing associations might be explained if (1) adiposity has dual competing effects on survival; a protective nutritional effect and a deleterious metabolic effect resulting in insulin resistance, dyslipidemia, hypertension and inflammation and (2) the level of kidney function modifies the relative importance of these effects. In this paradigm, the deleterious metabolic effects of obesity outweigh its protective nutritional effects in the non-CKD population, the deleterious metabolic effects of obesity are neutralized by its protective nutritional effects in the moderate CKD population and the deleterious metabolic effects of obesity are outweighed by its protective nutritional effects in stage V CKD on dialysis. In other words, the over-all effects of obesity on survival vary according to the level of kidney function and there is an interaction of body size and presence or absence of CKD on survival even though the metabolic effects of adiposity are not modified by the level of kidney function. Therefore, we propose that despite an association of adiposity with better survival, there is no reverse epidemiology of the associations traditional and nontraditional cardiovascular risk factors and disease with adiposity in dialysis patients.
Semin Dial
PMID:A story half untold: adiposity, adipokines and outcomes in dialysis population. 1799 Nov 93

In the general population, elevated cholesterol is associated with cardiovascular disease and mortality and lowering cholesterol is associated with improved outcomes. This reflects the predominance of isolated atherosclerotic coronary disease in the general population. In patients with renal disease, however, the relationship between serum lipids and cardiovascular outcomes is much less clear and even reversed. In our opinion, the relationship between cholesterol and coronary disease is obscured by high levels of co-morbid disease, malnutrition, inflammation, atypical dyslipidemia and the fact that myocardial infarction is not the typical presentation of cardiovascular disease in patients with renal disease. Thus, cholesterol lowering will still be effective in patients with chronic kidney diseases.
Semin Dial
PMID:The cholesterol paradox is flawed; cholesterol must be lowered in dialysis patients. 1799 Nov 95


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