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Adipose tissue is now considered an important system operating strictly in concert with other systems. The adipocyte is the main producer of two pleiotropic compounds, leptin and adiponectin, modulating inflammation and having multiple effects in disparate organs including the cardiovascular and the central nervous system. Leptin has disparate influences on various physiologic and organ systems including glucose homeostasis, hematopoiesis and the reproductive and cardiovascular systems and is a crucial hormone for the regulation of food intake and body weight. Peripherally, leptin modulates insulin sensitivity and high leptin triggers insulin resistance and vice versa. Obesity, a situation where circulating leptin attains very high levels is accompanied by increased bone mass, a phenomenon which may depend on direct stimulation of osteoblasts by leptin. However in animal models the stimulating effect of leptin on the osteoblast is counterbalanced by a strong inhibitor effect on bone formation in the central nervous system. Two recent studies reported an inverse link between leptin, bone mass and PTH in dialysis patients suggesting that leptin may be implicated in low bone turnover in these patients, likely by a mechanism involving the central nervous system. Leptin induces vascular calcifications in vitro. In uremic man leptin is unrelated to valvular calcifications but predicts incident cardiovascular events in overweight and obese dialysis patients. Leptin seems to be a relevant player in the emerging connection between bone and cardiovascular alterations in patients with end stage renal disease.
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PMID:Leptin in end stage renal disease (ESRD): a link between fat mass, bone and the cardiovascular system. 1624 56

Traditional risk factors, such as high blood pressure (BP), obesity and hypercholesterolaemia, play an important role in the development of cardiovascular disease (CVD), not only in the general population but also in patients with chronic renal disease. In recent years, it has become less clear whether these conventional risk factors are responsible for the extremely high risk of CVD in chronic haemodialysis (CHD) patients. Recent studies have shown that low BP, body mass index (BMI) and serum cholesterol are often correlated with an unfavourable clinical outcome. Thus, whereas traditional risk factors of CVD are correlated with an unfavourable outcome in the general population and patients with chronic renal failure not yet on dialysis, in CHD patients these factors appear to be protective and associated with an improved survival. Therefore, these phenomena have been referred to as 'paradoxical or reverse epidemiology'. The aetiology of this inverse relationship is not clear. Interestingly, in CHD patients, both C-reactive protein, a marker of inflammation, and (pre)albumin, a marker of nutrition, are important independent predictors of mortality. It has been speculated that what is known as the malnutritioninflammation-atherosclerosis complex underlies, at least partly, the phenomenon of reverse epidemiology, since malnutrition causes a low BMI and hypocholesterolaemia. Hence, besides care for adequate nutrition, attempts should be made to reduce inflammation. In this respect, various haemodialysis-related factors, such as the purity of the dialysate and several characteristics of the dialyser, deserve attention.
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PMID:Reverse epidemiology: paradoxical observations in haemodialysis patients. 1630 58

Either inflammation or hyperuricemia has been related with increased cardiovascular risk and mortality. A hypothetical relationship between serum uric acid levels (SUA) and inflammatory markers has never been tested in chronic kidney disease (CKD) patients. The purpose of this study was to determine the prevalence of increased C-reactive protein (CRP) levels in CKD patients, and to test the hypothesis of a relationship between SUA and CRP levels. The study group consisted of 337 patients (174 males, mean age 63 +/- 16 years) with advanced chronic renal failure not yet on dialysis. None of them had overt inflammatory or infectious diseases. High sensitivity CRP levels were analyzed as a binary (above or below median value), or continuous variable (log-transformed CRP), by multiple logistic or linear regression analysis, respectively. Demographics, clinical, and biochemical characteristics, including SUA levels, were the variables tested in these analysis. In a subset of 169 patients without diabetes, the same analysis were carried out, with the inclusion of fasting insulin levels and HOMA-IR as independent variables. Median CRP level was 3.25 mg/L, and mean SUA level was 7.59 +/- 1.94 mg/dl. Patients with CRP levels above the median had significantly higher mean SUA level than that of the rest of study patients (7.93 +/- 1.79 vs 7.24 +/- 2.03 mg/dl, p = 0.001). SUA levels correlated significantly with log-transformed CRP levels (r = 0. 16, p = 0.0022). The relationship between SUA and CRP levels remained statistically significant after adjustment for age, sex, comorbid index, obesity, residual renal function, diuretic and allopurinol treatment, in the multivariate logistic and linear regression models (OR: 1.296, p = 0.0003; and beta: 0.204, p = 0.0002). The significant association between SUA and CRP levels did not change when HOMA-IR and fasting insulin levels were included as independent variables in the subset of 169 patients without diabetes. In conclusion, SUA levels are related with CRP levels in CKD patients.
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PMID:[Serum uric acid and C-reactive protein levels in patients with chronic kidney disease]. 1651 5

Currently, due to the deficit of cadaveric tissues available for transplantation and due to the long waiting list for a kidney transplant, there is a clear tendency towards living donor kidney transplantations. Most donors are genetically related. Living donation should be considered a gift of extraordinary value, and should be made easy whenever a suitable donor is available. Worldwide, the number of patients on the waiting lists for a kidney transplantation has increased, in the last decades. Renal transplantation with living donor kidneys, is currently considered the best treatment for patients with end stage renal failure, due to the improved short and long-term survival benefits over dialysis treatment. Since considerable difference exist between countries in the evaluation and selection criteria for kidney donors, especially in selected patients such as older donors and those with associated comorbid conditions, it is necessary to discuss and establish minimal selection criteria for this cases. A common trend includes a complete clinical record, laboratory and radiologic evaluation which are described in detail in this paper. We also discuss the increasing acceptance of older kidney donors as well as the acceptance of individuals with comorbidities (such as obesity, hypertension, hyperglucemia, lithiasis and cancer) that were previously considered as not eligible for kidney donation.
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PMID:[Evaluation of the living kidney donor]. 1652 59

An increase in obesity prevalence among patients who initiate dialysis may influence the growth of the total ESRD population as a result of improved survival and decreased likelihood for transplantation. Temporal trends in mean body mass index (BMI) and obesity prevalence were examined among incident patients with ESRD by year of dialysis initiation between 1995 and 2002, and these trends were compared with those in the US population during this same period. Among incident dialysis patients, BMI was calculated with the height and estimated dry weight collected from the Centers for Medicare and Medicaid Services End-Stage Renal Disease Medical Evidence Form. In the US population, self-reported height and weight were used. Prevalence of total obesity and obesity stage > or =2 were defined as a BMI > or =30 and > or =35 kg/m(2), respectively. Among incident patients with ESRD, mean BMI increased from 25.7 to 27.5 kg/m(2), and total obesity and obesity stage > or =2 increased by 33 and 63%, respectively, among incident patients with ESRD (P < 0.0001 for obesity trends). BMI slope was approximately two-fold higher in the incident ESRD population compared with the US population for all age groups. However, temporal increases in obesity prevalence were similar between the two populations. As a result of the survival advantage associated with obesity and decreased likelihood for transplantation, these trends most likely will influence the total number of patients who receive dialysis in the next decade.
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PMID:Increasing body mass index and obesity in the incident ESRD population. 1659 82

Few large-scale epidemiologic studies have quantified the possible link between obesity and chronic renal failure (CRF). This study analyzed anthropometric data from a nationwide, population-based, case-control study of incident, moderately severe CRF. Eligible as cases were all native Swedes who were aged 18 to 74 yr and had CRF and whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women) during the study period. A total of 926 case patients and 998 control subjects, randomly drawn from the study base, were enrolled. Face-to-face interviews, supplemented with self-administered questionnaires, provided information about anthropometric measures and other lifestyle factors. Logistic regression models with adjustments for several co-factors estimated the relative risk for CRF in relation to body mass index (BMI). Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three-fold excess risk for CRF, relative to BMI<25. Obesity (BMI>or=30) among men and morbid obesity (BMI>or=35) among women anytime during lifetime was linked to three- to four-fold increases in risk. The strongest association was with diabetic nephropathy, but two- to three-fold risk elevations were observed for all major subtypes of CRF. Analyses that were confined to strata without hypertension or diabetes revealed a three-fold increased risk among patients who were overweight at age 20, whereas the two-fold observed risk elevation among those who had a highest lifetime BMI of >35 was statistically nonsignificant. Obesity seems to be an important-and potentially preventable-risk factor for CRF. Although hypertension and type 2 diabetes are important mediators, additional pathways also may exist.
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PMID:Obesity and risk for chronic renal failure. 1667 17

Ghrelin is upregulated under negative energy balance conditions, including starvation and hypoglycemia, while it is downregulated under situations of positive energy balance, such as feeding, hyperglycemia and obesity. The aims of this study were to assess potential ghrelin interactions with glucose levels in appetite control and to identify potential mechanisms involving orexigenic and anorexigenic ghrelin mediated signals by using a specific anti-ghrelin antibody. Our results confirm that peripheral ghrelin is an important signal in meal initiation and food intake stimulation. C-fos positive neurons in the PVN increased after insulin or 2-deoxyglucose administration. Moreover, we also demonstrate that peripheral ghrelin blockade with a specific anti-ghrelin antibody reduces, in part, the orexigenic signal induced by insulin and 2-DG administration. Furthermore, when we blocked peripheral ghrelin, c-fos positive CRF neurons and CART expression increased in the PVN, both under hypoglycemia or cytoglycopenia conditions, suggesting a neuronal activation (anorexigenic signalling) in this hypothalamic region. In summary, our findings imply that peripheral ghrelin plays an important role in regulatory "glucostatic" feeding mechanisms due to its role as a "hunger" signal affecting the PVN area, which may contribute to energy homeostasis through both orexigenic/anorexigenic pathways.
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PMID:Peripheral ghrelin participates in glucostatic feeding mechanisms and in the anorexigenic signalling mediated by CART and CRF neurons. 1666 99

Chronic kidney disease is fast becoming a worldwide epidemic. In the US, the prevalence of chronic kidney disease is 11%. Its increase in the recent years has mirrored the rising trend of obesity, hypertension and diabetes, which are all components of the metabolic syndrome. Metabolic syndrome comprises of 5 components: impaired fasting glucose, abdominal obesity, hypertriglyceridemia, hypertension and low high density lipoprotein cholesterol. While it is a well known cardiovascular risk factor in the general population, its effects in chronic kidney disease and dialysis populations has not been fully elucidated. While the number of people requiring renal replacement therapy is increasing globally, many of those with chronic kidney disease also suffer from cardiovascular morbidity and mortality. This review discusses the interaction between chronic kidney disease and metabolic syndrome, and the impact of the two on the cardiovascular risk in patients with chronic kidney disease.
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PMID:Metabolic syndrome and chronic kidney disease. 1676 Aug 79

In the past years, in Brazil and in developed countries, obesity has become a major public health problem. It was identified that besides DM2 and metabolic syndrome other clinical entities were associated with insulin resistance. In this review we describe some of these alterations emphasizing nonalcoholic fatty liver disease, but also including polycistic ovary disease, hyperuricemia, chronic renal failure, heart failure, cognitive decline and cancer.
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PMID:[Insulin resistance/hyperinsulinemia associated diseases not included in the metabolic syndrome]. 1676 2

ESRD incidence is much lower in Europe compared with the United States. This study investigated whether this reflects a difference in the prevalence of earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD prevalence in Norway was estimated from the population-based Health Survey of Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through 1997 (participation rate 70.4%). Data were analyzed using the same methods as two US National Health and Nutrition Examination Surveys in 1988 through 1994 (n = 15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender-specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2. ESRD rates and other relevant data were extracted from national registries. Total CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73 m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE 0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in 1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared with Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at start of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes. In conclusion, CKD prevalence in Norway was similar to that in the United States, suggesting that lower progression to ESRD rather than a smaller pool of individuals at risk accounts for the lower incidence of ESRD in Norway.
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PMID:International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. 2693 82


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