Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
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Cardiovascular disease continues to be the foremost cause of morbidity and mortality in dialysis patients. Compared with the general population, dialysis patients suffer from an accelerated disease course that is, at least in part, resistant to conventional therapy. While there are a myriad of potential explanations for this resistance, derangements in lipid metabolism probably play an important role. Here, we discuss the significance of altered lipid metabolism in uremia, such as oxidative lipoprotein modification and the pathophysiology of adipose tissue; limitations of conventional approaches to dyslipidemia such as statin therapy and traditional lipid profiles; and areas of investigation with potential for new therapy, such as reverse cholesterol transport.
Semin Dial
PMID:Lipid metabolism in dialysis patients-the story gets more complicated. 1876 91

Metabolic syndrome (MetS) is defined as a cluster of risk factors for type 2 diabetes and cardiovascular disease; it is also an independent risk factor for developing chronic kidney disease (CKD) in the general population. Therefore, CKD has many similarities and associations with MetS, and the individual risk factors constituting MetS-especially insulin resistance and glucose intolerance, hypertension, dyslipidemia, and obesity-are also common features of the early stages of CKD. In the later stages of CKD, uremia per se and uremic complications such as fluid retention, protein-energy wasting, inflammation, and oxidative stress further contribute to an increase in the prevalence of MetS in CKD patients. In addition, PD patients exposed to glucose-based PD fluids have an increased risk of developing metabolic complications. The broad use of MetS in clinical research has raised the awareness of the public and of individual patients concerning the value of lifestyle interventions. However, the definition and pathogenesis of MetS are still debated, and no standardized definition nor proven prognostic value has been established for MetS as a cluster of risk factors for diabetes or cardiovascular disease in PD patients. Furthermore, considering the paradoxical associations of some of the risk factors in MetS with decreased mortality, another set of risk factors-those specific to patients with uremia (for example, inflammation and malnutrition)-and the appropriate cut-off levels to individual MetS risk factors should be taken account at the same time. Also, the benefit of interventions targeting these risk factors should be clarified in further clinical studies.
Perit Dial Int 2009 Feb
PMID:Definition of metabolic syndrome in peritoneal dialysis. 1927 Feb 3

Cardiovascular disease (CVD) is the main cause of death in peritoneal dialysis (PD) patients, a situation that can be explained by a combination of traditional and nontraditional risk factors for CVD in these patients. Glucose and insulin homeostasis are altered in chronic kidney disease (CKD) patients even in the early stages of CKD, leading to insulin resistance by various pathways. Several factors have been implicated in the pathogenesis of insulin resistance, including anemia, dyslipidemia, uremia, malnutrition, excess of parathyroid hormone, vitamin D deficiency, metabolic acidosis, and increase in plasma free fatty acids and proinflammatory cytokines. Insulin resistance and dyslipidemia are observed and increase with the progression of CKD, playing an important role in the pathogenesis of hypertension and atherosclerosis. Particularly in PD patients, exposure to glucose from dialysis fluid accentuates the foregoing metabolic abnormalities. In conclusion, insulin resistance and altered glucose metabolism are frequently observed in CKD, and although dialysis partly corrects those disturbances, the use of glucose PD solutions intensifies a series of harmful metabolic consequences. New therapeutic measures aimed at reducing metabolic disorders are urgently needed and perhaps will improve PD patient survival.
Perit Dial Int 2009 Feb
PMID:Insulin resistance and glucose homeostasis in peritoneal dialysis. 1927 Feb 4

Metabolic syndrome (MetS) occurs in about 50% of peritoneal dialysis (PD) patients. It encompasses a cluster of major risk factors for cardiovascular diseases. A modified National Cholesterol Education Program Third Adult Treatment Panel guideline for the diagnosis of MetS in PD patients has been proposed. Preliminary data suggest that PD patients with MetS in our cohort have an increased risk of cardiovascular mortality. The proinflammatory effects of adipose tissue are one of the reasons for poor outcome in obese PD patients. Lifestyle modification, including appropriate dietary restriction and exercise, especially reduction of fat mass in obese patients, has been one of the major areas proposed for managing patients with MetS. Individual therapeutic trials are treating hyperglycemia, hypertension, and dyslipidemia in dialysis patients. Evidence in PD patients that interventions targeting MetS can improve outcomes is still lacking. Large-scale studies with data on the clinical outcome for MetS intervention in PD patients are needed.
Perit Dial Int 2009 Feb
PMID:Treatment of metabolic syndrome in peritoneal dialysis patients. 1927 Feb 5

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), and one of the most prevalent microvascular complications of both type 1 and type 2 diabetes. Additionally, risk of death is increased at all stages of DKD. As early as the microalbuminuric stage, the death rate approaches 20% per year. Therefore, management strategies should address reducing risk of mortality as well as progression to ESRD. DKD is associated with multiple co-morbidities including hypertension, dyslipidemia, cardiovascular disease, anemia, and bone and mineral metabolism disorders (BMD). Anemia and BMD often occur earlier in the course of DKD than with other forms of chronic kidney disease. Pharmacological and dietary management of hyperglycemia, hypertension, dyslipidemia, anemia, and BMD pose specific challenges in DKD. However, with heightened awareness of risks and a multifactorial management approach, the impact of DKD on micro- and macrovascular complications and death can be reduced.
Semin Dial
PMID:Management of the diabetic patient with advanced chronic kidney disease. 2037 53

Dyslipidemia, a prominent feature of end-stage renal disease, is considered a risk factor for premature atherosclerosis in hemodialysis (HD) patients. Dyslipidemia is related to loss of kidney function as well as use of low-flux cellulosic dialyzer membranes, but the effects of dialysate purity are unknown. Forty-eight incident HD patients started high-flux polysulfone maintenance HD, either with conventional (potentially contaminated) or with on-line produced ultrapure dialysate. The quality of the dialysis fluid (CFU/mL, endotoxin concentration), markers of inflammation (C-reactive protein, Il-6), and parameters of the lipid profile and oxidative stress (oxidized low-density lipoprotein) were measured before initiation of HD, and after 6, 12 and 24 months on HD. Compared to baseline, treatment with conventional (mildly contaminated) dialysate significantly increased the uremic low-grade systemic inflammatory response syndrome (SIRS), augmented uremic dyslipidemia (triglycerides by +21%, and high-density lipoprotein (HDL) cholesterol by -10%) and enhanced oxidative stress. In contrast, the use of ultrapure dialysate significantly decreased uremia-associated SIRS, dyslipidemia (triglycerides -7% and HDL cholesterol +11%) and oxidative stress. Ultrapure dialysis fluid improves potential parameters of cardiovascular risk by decreasing inflammatory reactions, improving uremic dyslipidemia and lowering oxidative stress.
Ther Apher Dial 2010 Feb
PMID:Effects of dialysis purity on uremic dyslipidemia. 2043 14

A retrospective study--the Italian Multicenter Study on Low-density Lipoprotein Apheresis (IMS-LDLa)--was carried out, which involved 19 centers for LDLa in Italy, distributed all over the country--in the north, center, south, and the major islands. The survey was conducted through two consecutive questionnaires, which can be downloaded online from a dedicated site. The total number of procedures performed until 2007 was 31 012, and the number of patients undergoing treatment until 2007 were 229. The treated patients still surviving consisted of 136 (74 males and 62 females); those surviving but not treated numbered 95, and those deceased numbered 14. The techniques utilized, listed by frequency of use, were the following: dextran sulfate cellulose adsorption, direct adsorption of lipids (DALI), heparin extracorporeal LDL precipitation, immunoadsorption, plasma-exchange, cascade filtration, and Lipocollect 200. The mean treated plasma and blood volumes per session were 3916.5 mL and 8735.1 mL, respectively. The most frequently utilized vascular access points were: venous 84.4% and arteriovenous fistula 15.5%. Hematoma by venipuncture (230 episodes), low outlet flow (125 episodes), and circuit coagulation (44 episodes) were reported as to be the most frequent side effects. In the second questionnaire (filled in by 19 centers) the centers were asked to report their data on: quality diagnosis of dyslipidemia and referents for genetic-molecular and clinical diagnosis, cholesterol-lowering drugs and dosages, typology of cardiovascular check-ups at the beginning of treatment and in follow-up, non-cholesterol-lowering drugs with priority for cardiologic drugs, including oral anti-coagulants, and, lastly, information related to the appropriateness of curing patients still under treatment with LDLa and, where possible, news on patients no longer under treatment.
Ther Apher Dial 2010 Feb
PMID:Italian Multicenter Study on Low-Density Lipoprotein Apheresis: retrospective analysis (2007). 2043 22

Clinical observations revealed an increased prevalence of iron deficiency anemia without chronic bleeding in patients treated with serial low-density lipoprotein (LDL) apheresis. Since several different proteins are adsorbed by LDL apheresis beside pro-atherogenic lipoproteins, we examined the modification of the full blood count, plasma iron, vitamin B12, folic acid, and hemolysis by LDL apheresis. Nineteen patients (55 (50-59) years, 4 female, 15 male) undergoing chronic LDL apheresis due to mixed dyslipidemia (N = 17), homozygous familiar hypercholesterolemia (N = 1) or isolated elevated lipoprotein(a) (N = 1) were included in this study. They were treated with direct adsorption of lipoproteins (DALI; N = 6), heparin-induced LDL-precipitation (HELP; N = 7) or double filtration plasmapheresis (DFPP; N = 6). The patients' full blood count, iron metabolism (plasma iron, ferritin, transferrin, transferrin saturation), vitamins involved in erythropoiesis (vitamin B12 and folic acid), and markers of hemolysis (haptoglobin and free hemoglobin) were analyzed directly before and after LDL apheresis. A single LDL apheresis session significantly decreased the levels (reduction in the median [25(th)-75(th) percentiles] of: ferritin 9.8 [1.3-18] %; P = 0.004), transferrin (12.1 [10.0-15.96] %; P = 0.0005), and vitamin B12 (17.8 [16.2-20.8] %; P = 0.0005). Thereby, transferrin and vitamin B12 were decreased in all (N = 19) and ferritin in 74% (N = 14) of the patients. Twelve out of 19 patients (63.2%) had mild anemia despite iron administration in 14 out of 19 patients (73.7%). LDL apheresis had no significant influence on full blood count, plasma iron, transferrin saturation, folic acid, or hemolysis. Similar changes were observed in all LDL apheresis methods used. LDL apheresis significantly decreases ferritin, transferrin, and vitamin B12, suggesting an influence of serial LDL apheresis on erythropoiesis.
Ther Apher Dial 2010 Apr
PMID:Low-density lipoprotein apheresis decreases ferritin, transferrin and vitamin B12, which may cause anemia in serially treated patients. 2043 34

Atherosclerosis is a major cause of mortality and morbidity among hemodialysis patients, but whether it is more severe in hemodialysis patients than in cardiovascular disease patients without chronic kidney disease is unclear. We examined 46 autopsy patients who had undergone hemodialysis, and age and sex-matched 46 patients with cardiovascular disease and an eGFR of >60 mL/min/1.73 m(2). There was no difference in the prevalence of diabetes or hypertension between the groups. We divided the aorta into four segments: A, ascending artery to arch; B, descending artery to diaphragm; C, suprarenal; and D, infrarenal. We used the classification of the American Heart Association to evaluate atherosclerosis progression. Distribution was scored by the extent to which each segment was damaged: 0, none; 1, less than 1/3; 2, more than 1/3 to less than 2/3; 3, more than 2/3. Histological examination revealed that the progression score (P < 0.05) and distribution score (P<0.005) were more severe in the hemodialysis group, especially in segment A. Regression analysis showed that atherosclerosis of segment A was related to age, gender, dyslipidemia, smoking, hemodialysis therapy, and hemodialysis duration. In hemodialysis patients, atherosclerotic changes in the aorta were more severe than in cardiovascular disease patients with an eGFR of >60 mL/min/1.73 m(2). Aortic atherosclerosis was aggravated by traditional and chronic kidney disease-related risk factors.
Ther Apher Dial 2011 Feb
PMID:Evidence for severe atherosclerotic changes in chronic hemodialysis patients: comparative autopsy study against cardiovascular disease patients without chronic kidney disease. 2127 53

We previously reported that the level of low-density lipoprotein cholesterol (LDL-C) was higher in patients receiving continuous ambulatory peritoneal dialysis (CAPD) than in patients on hemodialysis (HD). One of the problems associated with reaching the LDL-C target during statin treatment of patients on CAPD is the emergence of laboratory or clinical side effects. The present study evaluated the efficacy and tolerability of daily combined treatment with ezetimibe 10 mg and simvastatin 10 mg in patients receiving CAPD. Our study enrolled 12 CAPD patients who were experiencing adverse effects from statin therapy. Their existing statin therapy was suspended for 1 month ("washout period"), and the patients were then shifted to treatment with the ezetimibe-simvastatin combination. The patients were again monitored for adverse events such as asthenia and myalgia during the subsequent 12 months. Body mass index and levels of glycated hemoglobin, fasting plasma glucose, total cholesterol, LDL-C, triglycerides, alanine amino-transferase, aspartate aminotransferase, and creatinine phosphokinase were also assessed. The combination of ezetimibe and low-dose simvastatin significantly reduced levels of total cholesterol (by a mean of 27%), triglycerides (by 9%), and LDL-C (by 33%) and increased levels of high-density lipoprotein cholesterol (by 15%). In 11 patients (92%), the target LDL-C level of less than 100 mg/dL was reached. No significant change in weekly creatinine clearance occurred, and no serious adverse effects were observed. No patient developed muscle pain or weakness, and no increase in creatinine kinase was found. Residual renal function declined, although not significantly when compared with initial values. In conclusion, the present study suggests that combined ezetimibe and low-dose statin treatment is a promising approach for safe and effective primary treatment of dyslipidemia in CAPD patients.
Adv Perit Dial 2010
PMID:Efficacy and safety of ezetimibe and low-dose simvastatin as primary treatment for dyslipidemia in peritoneal dialysis patients. 2134 80


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