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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

The homocysteine (Hcy) theory states that total homocysteine (tHcy) is a risk factor for atherosclerosis. Chronic kidney disease (CKD) is one of the most frequent causes of hyperhomocysteinemia in the presence of high prevalence of cardiovascular disease (CVD). However, there is not yet any conclusive answer to the question whether Hcy may contribute to, or predict, cardiovascular events or mortality in CKD patients or whether it is just an innocent bystander biologically related to other potential risk factors for CVD. Moreover, tHcy levels in CKD are influenced by several commonly occurring confounding factors, such as inflammation and protein-energy wasting (PEW). These factors are also associated with morbidity and mortality and altogether this may explain why Hcy does not show up as a cardiovascular risk but in fact is reversely associated with clinical outcome. Thorough evaluation of such reverse association may not necessarily imply that the principles of Hcy being a contributor to vascular pathophysiology are different in CKD patients but rather indicate that other superimposed factors, such as PEW and inflammation, are more important. These confounders contribute significantly to the unacceptably high mortality rate in this patient population and may require nutritional and anti-inflammatory interventions to improve clinical outcome. So far, the results of recent folic acid intervention trials do not support the use of folic acid supplementation for lowering tHcy and improving survival in CKD patients. Although we are still waiting for the results from several ongoing controlled randomized trials in this area, future studies are needed to evaluate if thiol-exchange agents, besides folic acid, as part of a future multifactorial intervention regime targeting inflammation, PEW, oxidative stress as well as hyperhomocysteinemia may decrease CVD risk in this high-risk patient population.
Semin Dial
PMID:Homocysteine-lowering is not a primary target for cardiovascular disease prevention in chronic kidney disease patients. 1799 Nov 98

The risk of atherosclerosis and cancer is high in patients on hemodialysis. A breakdown in the natural balance between the activity of the body's antioxidant system and the production of oxidizing agents is suggested to be involved. To investigate the oxidative stress status in Iranian hemodialytic patients, in this study we evaluated plasma vitamin E, malondialdehyde (MDA), reduced glutathione (GSH), and ferric reducing antioxidant power (FRAP) levels in these patients. Twenty-four hemodialytic patients and 24 control subjects (age and sex matched) were included in this study. Each patient was under dialysis, three times per week, four hours in each session. Before and after dialysis, blood was taken for biochemical measurements as well as oxidative stress tests. There was a significant decrease in FRAP and GSH levels after dialysis comparing to before treatment levels. MDA was increased by dialysis and vitamin E levels were less in dialytic patients, both before and after treatment, compared to controls. This study indicates that there is a significant level of oxidative stress in chronic renal patients and this stress is augmented by dialysis. Antioxidant therapy could be considered in these patients.
Ther Apher Dial 2008 Apr
PMID:Assessment of plasma antioxidant status in hemodialysis patients. 1838 64

Cardiovascular accidents related to atherosclerosis are the leading cause of death among hemodialysis patients, which makes continuous monitoring of their cardiovascular status crucial. Recently, a handy device for monitoring the augmentation index (AIx) in the radial artery was introduced in Japan, enabling the use of the AIx in addition to pulse wave velocity (PWV) in the management of hemodialysis patients. In this study the AIx, PWV, abdominal aortic calcification index (ACI), and left ventricular mass index (LVMI) were serially assessed in 108 hemodialysis patients. The radial AIx was monitored using a newly introduced tonometer (HEM-9010AI), and the interrelationships among the measured parameters and their contributions to the risk of cardiovascular accidents were evaluated. The radial AIx was significantly higher in hemodialysis patients than in healthy subjects (N = 50) and was well correlated with risk markers such as LVMI (r = 0.30, P = 0.019) and ACI (r = 0.38, P < 0.001), but not with PWV. Multiregression analysis showed that radial AIx was also significantly associated with LVMI, ACI and blood pressure; PWV was associated with other parameters such as age, blood pressure, and ACI. The AIx and ACI were both significantly increased in patients with cardiovascular complications. Although PWV was strongly increased in the hemodialysis patients, it failed to discriminate between these subgroups of high-risk patients. The radial AIx is closely associated with aortic calcification, cardiac hypertrophy, and a history of cardiovascular accidents in hemodialysis patients, and could be a useful marker for management of these patients.
Ther Apher Dial 2008 Apr
PMID:Radial augmentation index is related to cardiovascular risk in hemodialysis patients. 1838 66

In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has biocompatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.
Perit Dial Int 2008 Jun
PMID:Peritoneal dialysis solutions low in glucose degradation products--evidence for clinical benefits. 1855 41

The recent introduction of calcimimetics, a novel class of therapeutic agents, has led to a change in the treatment strategy of secondary hyperparathyroidism in patients with end-stage renal disease. In initial acute studies in chronic hemodialysis patients, the calcimimetic cinacalcet was shown to reduce plasma intact parathyroid hormone within hours, followed by a rapid, profound decrease in plasma calcium and a minor decrease in plasma phosphorus. Subsequent reports showed that the long-term administration of cinacalcet to such patients proved to be superior to standard therapy in controlling secondary uremic hyperparathyroidism, in that it was able to induce a decrease in both plasma intact parathyroid hormone and the calcium x phosphorus product, in contrast to the effects of active vitamin D sterols. This allowed the achievement of the guideline treatment targets proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative in a much larger proportion of dialysis patients than standard therapy did. Moreover, the effect of cinacalcet is long-lasting. An important question is that of cinacalcet's effects on patient outcomes, which is still lacking. A similar lack of information exists for most other treatment modalities given to correct the mineral and bone disorder of chronic kidney disease. A post-hoc analysis of four clinical trials combined done in hemodialysis patients showed that randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization. To obtain a definitive answer to this question, including patient survival, we will have to wait for the results of prospective, randomized controlled trials. In pre-clinical studies performed in rats with chronic renal failure, the administration of the calcimimetic NPS R-568 at the time of uremia induction allowed the prevention of parathyroid hyperplasia, and the reversal of already established hyperplasia as well. Perhaps more important from the clinical point of view, NPS R-568 also appeared to allow reversal of osteitis fibrosa in uremic rats and reduction of aortic calcification and atherosclerosis in uremic rats and mice. In conclusion, the clinical introduction of cinacalcet allows for better control of secondary hyperparathyroidism in dialysis patients as compared to standard therapy, based on surrogate biochemical markers. Hopefully, in the future, this improvement will be shown to be associated with better patient outcomes for the treatment of fractures and cardiovascular morbidity and mortality.
Ther Apher Dial 2008 Oct
PMID:Cinacalcet treatment in dialysis patients with secondary hyperparathyroidism: effects and open issues. 1903 22

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

Mortality from cardiovascular or cerebrovascular disease due to atherosclerosis is increased in patients on chronic hemodialysis. Monocyte chemoattractant protein-1 and its receptor, C-C chemokine receptor 2, play an important role in recruiting monocytes to atherosclerotic lesions. The relationship between atherosclerosis in hemodialysis patients and C-C chemokine receptor 2 expression is unknown. Fifty-six patients on chronic hemodialysis and 27 age- and sex-matched controls were enrolled. Serum levels of monocyte chemoattractant protein-1 and expression of C-C chemokine receptor 2 by circulating monocytes were determined. Atherosclerosis was evaluated from the carotid intima-media thickness and cardio-ankle vascular index. Serum levels of monocyte chemoattractant protein-1 and expression of C-C chemokine receptor 2 by monocytes were significantly higher in the hemodialysis patients than the controls. Multiple regression analysis showed a positive correlation between receptor expression and both indexes of atherosclerosis. C-C chemokine receptor 2 expression by circulating monocytes influences atherosclerosis in patients on chronic hemodialysis.
Ther Apher Dial 2009 Jun
PMID:C-C chemokine receptor 2 expression by circulating monocytes influences atherosclerosis in patients on chronic hemodialysis. 1952 67

In hemodialysis (HD) patients, routine dialysis center blood pressure (BP) measurements may be a poor indicator of BP control. Ambulatory blood pressure monitoring (ABPM) improves the predictability of BP as a risk factor for target organ damage. Carotid intima-media thickness (IMT) is an important indicator of asymptomatic atherosclerosis and a predictor of cardiovascular events. The purpose of our study was to evaluate the possible association between different BP measurements and carotid IMT in HD patients. Eighty-five HD patients were included in our study. BP was measured with a standard mercury sphygmomanometer before and after each HD session. The average one-monthly values of routine BP measurements were also analyzed. 24- and 48-h ABPM was performed after the end of each HD session using non-invasive ABPM. The average values of systolic and diastolic BP were analyzed separately for the first (HD) and second (interdialytic) days ABPM, and for both days together. Using B-mode ultrasonography, carotid IMT was measured and plaque occurrence investigated. We found a statistically significant correlation between carotid IMT and the average one-monthly pre-HD diastolic BP (P < 0.05), diastolic BP on the HD-day ABPM, the interdialytic-day ABPM, and during 48-h ABPM (P < 0.05). By multiple regression analysis, we found a statistically significant correlation only between carotid IMT and diastolic BP on the HD-day ABPM, the interdialytic-day ABPM, and during 48-h ABPM (P < 0.05). Only longer BP measurements (24- and 48-h ABPM) were associated with carotid IMT in HD patients.
Ther Apher Dial 2009 Aug
PMID:Blood pressure measurements and carotid intima media thickness in hemodialysis patients. 1969 61

The purpose of our study was to evaluate the intima-media thickness (IMT) of the carotid and brachial arteries, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilatation (NMD) in diabetic and non-diabetic hemodialysis patients. We also examined the effects of traditional and other risk factors on carotid and brachial IMT, FMD and NMD in all hemodialysis patients. Fifty-eight adult hemodialysis patients, 14 of whom had diabetes, were studied. They had been on hemodialysis for 1-340 months. Using B-mode ultrasonography, we measured the carotid and brachial IMT, FMD and NMD, and correlated the values with cardiovascular risk factors. FMD and NMD were significantly lower in diabetic patients (FMD 4.01 +/- 0.99 vs. 6.69 +/- 2.37 mm; NMD 9.1 +/- 1.95 vs. 11.23 +/- 2.86 mm), while no such differences were found between the two groups with respect to carotid or brachial IMT. In all patients with respect to age a positive correlation was found with carotid and brachial IMT, and a negative one with FMD and NMD. With respect to hypertension as well as diabetes, a negative correlation was found with FMD and NMD. Age is the most important factor that significantly affected all studied markers of atherosclerosis in hemodialysis patients. The endothelial and smooth vascular functions are significantly impaired in diabetic and hypertensive hemodialysis patients, and hypertension is shown to be an independent risk factor for smooth vascular dysfunction in hemodialysis patients. According to our results, intensive antihypertensive treatment is recommended in hypertensive chronic hemodialysis patients.
Ther Apher Dial 2009 Aug
PMID:Intima media thickness and endothelial function in chronic hemodialysis patients. 1969 62


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