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      Role of Interleukin-1β in the Development of Malnutrition in Chronic Renal Failure Patients

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          Protein-energy malnutrition and wasting are common among patients with end-stage renal disease (ESRD) and these complications are strongly associated with poor survival in these patients. Whereas both under- and overweight predict in increased mortality risk in the general population, a high body mass index is associated with better outcome in ESRD patients. Circulating levels of pro-inflammatory cytokines are markedly elevated in uremia and also predictor of a poor clinical outcome in ESRD patients. Interleukin-1β (IL-1β), which is a major pro-inflammatory cytokine, may further amplify inflammation and lead to malnutrition, through inducing anorexia, and muscle wasting due to increased protein breakdown. Several clinical studies have shown that the circulating level of IL-1β may affect nutritional status, especially body composition. Several IL-1 gene cluster polymorphisms were reported, and they may affect the prevalence of cytokine-mediated diseases. Although a number of factors are related to malnutrition and wasting in ESRD, pro-inflammatory cytokines, such as IL-1β, may play an important role. This could in part be due to genetic factors. Further research, especially regarding the IL-1 gene cluster polymorphisms, is necessary to determine this hypothesis.

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          Most cited references 42

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          Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms.

          Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1 beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o) IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were not associated with any of the cancers studied. A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.
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            Accelerated atherosclerosis in prolonged maintenance hemodialysis.

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              Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

              Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                September 2005
                04 October 2005
                : 23
                : 4
                : 275-281
                Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
                86012 Blood Purif 2005;23:275–281
                © 2005 S. Karger AG, Basel

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                Figures: 1, Tables: 2, References: 67, Pages: 7
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