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Appropriate initiation of dialysis is of an outstanding importance in the treatment of patients with end-stage renal disease. It prevents development of irreversible uremic complication and enables selection of the most appropriate dialysis modality for the individual patient. The major causes of morbidity and mortality in dialysis patients are cardiovascular diseases. Hypertension and hyperlipidemia are commonly found in dialysis patients as well as anemia, chronic inflammation and fluid overload, all of which are found to be risk factors for the development of cardiovascular diseases. Arterial hypertension is the main risk factor for left ventricular hypertrophy, and there is clear evidence that control of hypertension has a beneficial effect on left ventricular hypertrophy. It is best achieved by correction of overhydration and maintenance of dry weight. Modern dialysis machines are capable of changing electrolyte concentrations, which reduces intradialytic cardiovascular complications, incidence of cardiac arrhythmias and hypotension. Correction of anemia with erythropoietin results in regression of left ventricular hypertrophy and improvement of the quality of life and defense against microorganisms. Chronic inflammation can be prevented with the use of biocompatible high-flux dialysis membranes and sterile dialysate, which are also important for the prevention of oxidative stress involved in the increase of LDL oxygenation and incorporation into the intimal layer of the vessels. Low molecular weight heparins by their action on lipoprotein lipase serve as an additional factor that suppresses development of atherosclerotic plaque in dialysis patients. Optimal dialysis dose decreases the mortality and morbidity rates. High-flux membranes or prolongation of dialysis session are modalities for dialysis dose improvement. Individualized approach to preparation of dialysis solutions has resulted in better control of fluid overload and intradialytic hyper- or hypotension, reduction in the incidence of arrhythmias, improvement of hemodynamic stability, and delay of renal osteodystrophy. Malnutrition is a relatively common problem in dialysis patients that may be secondary to poor nutritional intake, inadequate amount of dialysis, lack of appetite, acidosis, associated disease, and/or increase in protein catabolism. The most appropriate approach includes individualization of dietary prescription according to the nutritionist's advice, increase of dialysis dose with biocompatible membranes, and use of sterile bicarbonate dialysate with glucose and erythropoietin. The major goal of adequate dialysis is not just improvement in survival of dialysis patients, but also improvement in the quality of their lives.
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PMID:[Biological adequacy--what does it mean?]. 1512 86

About 1,000 children develop end-stage renal disease (ESRD) each year in the United States and about 5,000 children are currently receiving dialysis. Children who develop ESRD are eligible to receive renal replacement therapy, including renal transplantation. There are inherent risks associated with transplantation, including renal insufficiency, infections, post-transplant lymphoproliferative disorder, and cardiovascular disease (CVD). Potential risk factors for CVD in pediatric renal transplant recipients include renal insufficiency, hyperlipidemia, hyperhomocysteinemia, inflammation, malnutrition, anemia, and hyperglycemia/insulin resistance. Despite evidence that many children may possess various risk factors for CVD post-renal transplantation, there are very few studies that have attempted to assess the link between these risk factors and CVD in pediatric renal transplant recipients.
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PMID:Risk factors for cardiovascular disease in pediatric renal transplant recipients. 1526 67

The metabolic syndrome (MetS) is a huge public health problem worldwide, being one of the major causes of cardiovascular disease, responsible for a growing number of premature deaths throughout the world. MetS includes a cluster of anomalies, such as: abdominal obesity, insulin resistance, hyperinsulinemia, hypertension, type 2 diabetes mellitus or glucose intolerance, hypertriglyceridemia etc. The number of people with MetS increases with age, affecting more than 40% of people in their 60s and 70s. About 30% of European people over 50 have MetS. Some experts estimate that as many as two thirds of Americans may be suffering from MetS. The exact cause of MetS is not known: genetics play a minor role, acquired in-utero factors also play a role (prenatal malnutrition, toxin exposure, exposure to high levels of maternal cortisol). For most people, the MetS results primarily from lifestyle factors, such as: chronic stress, inadequate exercise. The MetS can be avoided and reversed in most cases. Weight loss is both a treatment and goal for MetS patients. Moderate weight loss, in the range of 5-10% of body weight, can help restore body's ability to recognize insulin and greatly reduce the chance that the syndrome will evolve into a more serious illness. In most people weight loss will lower blood pressure and improve triglyceride levels. Increased activity alone can improve insulin levels. Physical activity result in a weight loss, improved blood pressure, improved cholesterol and triglyceride level and reduced risk of developing diabetes. It is also important to treat: hyperlipidemia, hypertension, prothrombotic state.
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PMID:The metabolic syndrome--a multifaced disease. 1552 15

The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.
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PMID:[Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome]. 1572 52

Programming is an epigenetic phenomena by which nutritional, hormonal, physical psychological and other stressful events acting in a critical period of life, such as gestation and lactation, modifies in a prolonged way certain physiological functions. This process was preserved by natural selection as an important adaptive tool for survival of organisms living in nutritional impaired areas. So, malnutrition during gestation and lactation turns on different genes that provide the organism with a thrifty phenotype. In the case of an abundant supply of nutrients after this period, those organisms that were adapted to a low metabolic waste and higher energy utilization will be in a higher risk of developing metabolic diseases, such as obesity, hyperlipidemia, diabetes mellitus and hypertension. The kind of malnutrition, duration and intensity are important for the type of programming obtained. We discuss some of the hormonal and metabolic changes that occur in gestation or lactation, when malnutrition is applied to the mothers and their offspring. Some of these changes, such as an increase of maternal triiodothyronine (T(3)), leptin and glucocorticoids (GC) and decrease in prolactin are by itself potential programming factors. Most of these hormones can be transfer through the milk that has other important macronutrients composition changes in malnourished dams. We discuss the programming effects of some of these hormones upon body weight and composition, leptin, thyroid and adrenal functions, and their effects on liver, muscle and adipose tissue metabolism and the consequences on thermogenesis.
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PMID:Neonatal programming of body weight regulation and energetic metabolism. 1628 56

Since the introduction of peritoneal dialysis (PD) into clinical nephrology at the end of the 1970s, many improvements have led to acceptance of this method as renal replacement therapy equivalent to hemodialysis. It is unclear whether the diabetic patient is the ideal candidate for PD and if this procedure should be the preferred method of treatment of renal failure in these patients, especially when kidney transplantation cannot be performed. PD may provide several advantages for diabetic patients with end-stage renal failure; for example, better hemodynamic stability is achieved during peritoneal ultrafiltration and vascular access surgery becomes unnecessary. On the other hand, the continuous glucose absorption may lead to increased insulin requirements, obesity and hyperlipidemia. Furthermore, peritoneal protein loss may aggravate malnutrition, which is frequently present in these patients. However, for a differentiated assessment of outcome in PD, the individual history (diabetes type 1 or type 2) and accompanying comorbidity of diabetic patients have to be considered. Nowadays nephrologists have to be aware of the concept of individualized therapy, which is integrated into an overall plan and takes into account the different conditions of diabetic patients and their treatment options. By improving removal of sodium and water, as well as improving quality of metabolic control, new dialysis solutions (icodextrin, neutral-pH solutions) and automated PD could have a positive impact on outcome in diabetic patients. In contrast, from retrospective studies on PD there is evidence of higher long-term mortality rates in elderly women with diabetes and in patients with cardiac insufficiency than in those on hemodialysis. Further research is necessary in order to optimize individualized therapy for diabetic patients with end-stage renal disease in the future.
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PMID:[Peritoneal dialysis in patients with diabetic nephropathy]. 1643 30

Protein-energetic malnutrition, characterized by both lean mass and fat depletion, was common in the pre-HAART era, and was associated with shortened survival and diminished quality of life. The pathogenesis of protein-energy malnutrition was multifactorial, and nutritional treatments were largely ineffective in the absence of disease stabilization. The introduction of HAART brought markedly improved outcomes, including a decrease in the incidence of malnutrition. However, other nutritional and metabolic alterations were noticed, and included changes in body shape, both lipoatrophy and lipohypertrophy, as well as changes in metabolism, notably hyperlipidemia and insulin resistance. These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. Several mechanisms have been hypothesized, including impairment to adipocyte differentiation and adipokine regulation, production of proinflammatory cytokines and mitochondrial toxicity. The role of the single drug class is still unclear, because both PI and NRTI have been associated with the syndrome, and the therapeutic protocols include both groups. Most of the medical therapies proposed for lipodystrophy are ineffective, and even if surgery remains an alternative, it is not associated with long lasting outcomes.
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PMID:[Effect of anti-retroviral therapy on body composition changes: a literature review]. 1679 74

Epidemiological studies in humans suggest that maternal undernutrition, obesity and diabetes during gestation and lactation can all produce obesity in offspring. Animal models have allowed us to investigate the independent consequences of altering the pre- versus post-natal environments on a variety of metabolic, physiological and neuroendocrine functions as they effect the development in the offspring of obesity, diabetes, hypertension and hyperlipidemia (the 'metabolic syndrome'). During gestation, maternal malnutrition, obesity, type 1 and type 2 diabetes and psychological, immunological and pharmacological stressors can all promote offspring obesity. Normal post-natal nutrition can reduce the adverse impact of some of these pre-natal factors but maternal high-fat diets, diabetes and increased neonatal access to food all enhance the development of obesity and the metabolic syndrome in offspring. The outcome of these perturbations of the perinatal environmental is also highly dependent upon the genetic background of the individual. Those with an obesity-prone genotype are more likely to be affected by factors such as maternal obesity and high-fat diets than are obesity-resistant individuals. Many perinatal manipulations appear to promote offspring obesity by permanently altering the development of central neural pathways, which regulate food intake, energy expenditure and storage. Given their strong neurotrophic properties, either excess or an absence of insulin and leptin during the perinatal period are likely to be effectors of these developmental changes. Because obesity is associated with an increased morbidity and mortality and because of its resistance to treatment, prevention is likely to be the best strategy for stemming the tide of the obesity epidemic. Such prevention should begin in the perinatal period with the identification and avoidance of factors which produce permanent, adverse alterations in neural pathways which control energy homeostasis.
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PMID:Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis. 1681 95

Despite the enormous cardiovascular disease epidemic among maintenance hemodialysis (MHD) patients, total hypercholesterolemia seems paradoxically to be associated with better survival. It was hypothesized that similar paradoxic associations also exist for serum LDL, HDL, and triglycerides. A 3-yr (July 2001 through June 2004) cohort of 15,859 MHD patients was studied in the United States from DaVita dialysis clinics where lipid profile was measured in at least 50% of all outpatients during a given calendar quarter. Cox proportional hazard models were adjusted for case mix and surrogates of malnutrition-inflammation complex. Both total and LDL hypercholesterolemia showed a paradoxic association with better survival. Hypertriglyceridemia (>200 mg/dl) also showed a similar trend, but serum HDL cholesterol did not have any clear association with survival. The association between a low serum LDL <70 mg/dl, which was prevalent among almost 50% of all MHD patients, and a higher all-cause death risk was robust to multivariate adjustment. In the subgroup analyses, these paradoxic associations persisted among most subgroups, although they tended to be stronger among hypoalbuminemic (<3.8 mg/dl) patients and those with a lower dietary protein intake (<1 g/kg per d). However, in black patients, a high serum LDL (>100 mg/ml) was associated with adjusted cardiovascular death hazard ratio of 1.94 (95% confidence interval 1.12 to 2.38; P = 0.02). Despite inverse associations between hyperlipidemia and survival, black MHD patients with high LDL show almost two-fold increase in cardiovascular death risk. Although these associations may not be causal, they call into question whether specific subgroups of dialysis patients are better targets for cholesterol-lowering therapy.
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PMID:Association between serum lipids and survival in hemodialysis patients and impact of race. 1716 13

Traditional cardiovascular disease risk factors including hyperlipidemia and obesity are paradoxically associated with improved survival in individuals with advanced chronic kidney disease. Such paradoxes underscore the important role of malnutrition-inflammation-cachexia syndrome in chronic kidney disease mortality and highlight the urgent need for comprehensive but practical nutritional assessment tools. In this Practice Point commentary, Rambod and colleagues discuss a recent paper by Yamada et al. that used the Malnutrition-Inflammation Score (MIS) as the 'reference standard' to validate five simplified nutritional screening tools in 422 Japanese patients on hemodialysis. The study found the Geriatric Nutritional Risk Index to be the most accurate of the simplified tools for identifying those patients on dialysis who are at nutritional risk. The commentary authors discuss Yamada et al.'s study and conclude that although the MIS has been widely used in patients undergoing maintenance dialysis, its wide utility does not automatically make it the ultimate reference standard for assessing other nutritional scoring tools.
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PMID:Malnutrition-Inflammation Score for risk stratification of patients with CKD: is it the promised gold standard? 1817 43


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