Interaction between nutrition and inflammation in end-stage renal disease.
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Biomedical subjects
Publications and source records attributed to B R Bistrian.
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Since many end stage renal disease (ESRD) patients experi inflammation, malnutrition, and anemia, the interplay of these processes should be considered in the approach to patients treated with erythropoietin (EPO). This article reviews the interrelationship between these factors. The systemic inflammatory response caused by exposure to inflammatory stimuli results in anorexia and metabolic disturbances leading to protein calorie malnut tion as well as sequestration of iron and hyporesponsiveness to EPO. The implications of these effects and possible strategies to optimize anemia management in the presence of these conditions are discussed.
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The objective of this study was to determine if the positional structure of dietary triacylglycerol affected lipidemic responses. Thirty healthy adults (16 men and 14 postmenopausal women) with low-density lipoprotein cholesterol (LDL-C) concentrations >3.37 mM (130 mg/dL) enrolled in a prospective, single-blind, cross-over outpatient clinical trial that consisted of two 5-wk dietary phases. After baseline screening, subjects were instructed to follow individualized meal plans (weight maintenance diets with 36% of total energy from fat, half of which was from a test oil) and randomized to receive either butter (B) or an interesterified mixture (IM) of butter, medium-chain triacylglycerol (MCT), and safflower oils. Blood drawn during weeks 5 and 10 of feeding was analyzed for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C),LDL-C, and triacylglycerols (TAG). Mean plasma levels of TC (B, 6.98+/-1.06 mM; IM, 7.09+/-1.20 mM), HDL-C (B,1.30+/-0.35 mM; IM, 1.29+/-0.34 mM), and LDL-C (B, 4.91+/-0.95 mM; IM, 4.92+/-1.10 mM) were not significantly different between the two dietary treatments. Mean TAG levels were higher for the interesterified B-MCT mixture (B, 1.75+/-0.72 mM; IM, 1.96+/-0.86 mM, P < 0.05). We conclude that an IM of B, MCT, and safflower oils as compared to native B has no appreciable effect on plasma cholesterol concentrations but is associated with a modest rise in plasma TAG.
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Patients with end-stage liver disease (ESLD) manifest a wide variety of functional abnormalities that lead eventually to their death. Such patients also often have low levels of long-chain polyunsaturated fatty acids (PUFA) of carbon length 20 or greater in plasma total lipids, triacylglycerols, cholesterol esters, and phospholipids. We hypothesize that, due to hepatic damage, there is an impairment in de novo synthesis of very long-chain (20-22) carbon PUFA from their essential fatty acid 18 carbon dietary precursors that normally takes place principally in the liver. This results in a "conditional" essential fatty acid deficiency that may, in fact, be responsible for some of the pathophysiologic effects in ESLD. We propose that direct supplementation with very long-chain PUFA will provide a unique advantage in the correction of this "conditional" essential fatty acid deficiency in patients with ESLD and lead to improvements in their clinical condition.
A prospective trial was conducted with 14 hospitalized patients who were severely underweight with a mean weight of 40.9+/-5.1 kg and 70.7+/-7.8% of ideal body weight, to compare estimates of resting energy expenditure (REE) with measured values. The 9 women and 3 men, whose mean age was 66.5+/-13.9 y, underwent nutritional assessment and measurement of their REE by indirect calorimetry using the Sensormedics Deltatrac MBM100 indirect calorimeter. Their REE was also estimated by the Harris-Benedict formula (mean 1032+/-66 kcal/d) as well as a previously established empirical formula where REE = 25 x body weight in kg (mean 1023+/-129 kcal/d). Results by both estimates were significantly lower than the measured resting energy expenditure (MREE) in this group of patients (P<0.0001). The percentage difference between MREE and estimated REE by the Harris-Benedict formula was 18.4+/-9.4% and 20.9+/-7.5% by the empirical formula. The MREE exceeded the estimated REE in each individual. The correlation between MREE and body weight (r2 = 0.558, r = 0.005) was better than that between MREE and estimated REE by Harris-Benedict formula (r2 = 0.275, P = 0.08) suggesting that weight was the principal determinant rather than the other components (height, age, sex) of the Harris-Benedict formula. Our data shows that commonly employed formulae routinely underestimate the energy needs of severely underweight patients below 50 kg in body weight. The Harris-Benedict equation had limited predictive value for the individual, explaining approximately 25% of the variance in energy expenditure. Given the particular importance of matching energy intake to needs in this group of patients with limited reserves, many of whom are critically ill, we suggest an empirical equation using 30-32 kcal/kg be used to estimate the energy requirements of severely underweight patients when direct measurements are unavailable or clinically less imperative.
The indications for initiating total parenteral nutrition (TPN) were prospectively evaluated in 100 consecutive patients at a tertiary referral hospital with a long-standing Nutritional Support Service to illustrate the reasons why the parenteral route was chosen at this unique institution in terms of patient population. Sixty male and 40 female patients, average age 59 +/- 17 years (range 22-86 years), were classified a priori as to the underlying reasons for initiation of TPN. The study was conducted by a Nutrition Support Service at this hospital without pediatric, trauma, or burn services specializing in the care of patients with diabetes mellitus. Of the 100 patients, 63% were from the surgical service; 24% had diabetes mellitus. Their mean weight (118 +/- 29% of ideal), body mass index (25 +/- 6 kg/m(2)), and serum albumin (2.8 +/- 0.7 g/dL) indicated a reasonable body composition with a moderate systemic inflammatory response. Six patients received preoperative TPN for an average of 5 +/- 3 days with a variety of diagnoses including malignancy, Crohn's disease, bowel obstruction, and gastrointestinal bleeding. The underlying reasons for initiating nutritional support were related to three factors that largely determine the need for involuntary feeding: preexisting protein calorie malnutrition, actual or anticipated semistarvation for a prolonged period, and the presence of a systemic inflammatory response. The choice of TPN was based on anticipated or proven intolerance to full enteral feeding. The duration of time before initiation of TPN postoperatively was 6 +/- 5 days, which reflects our policy that initially well-nourished patients who are experiencing a systemic inflammatory response should not undergo more than 5 to 7 days of inadequate feeding. The duration of TPN overall was 11 +/- 10 days, which primarily illustrates the dramatic reduction in length of hospital stay that has occurred throughout the health care system and the willingness to provide TPN in alternative settings including transitional care units, rehabilitation hospitals, and for short-term care, the patient's home. The most common specific reasons identified for initiating TPN rather than enteral nutrition were ileus (25%), an underlying acid-base or electrolyte/mineral disorder (13%) requiring correction, and the convenience of TPN because a central venous catheter was in place (12%). The usual indication for nutritional support at this tertiary referral and specialty hospital was actual or impending protein calorie malnutrition. TPN was chosen for a variety of reasons related to actual or anticipated tolerance to enteral feeding. This audit demonstrates that our TPN practice has evolved in relation to time of initiation and duration of feeding, which reflect a clearer appreciation of the risks and benefits of TPN.
The purpose of this study was to determine the plasma triglyceride and phospholipid fatty acid (FA) composition of severely malnourished patients with chronic liver disease and to examine the effects of parenteral nutrition with a total nutrient admixture (TNA) on these profiles. Nine consecutive patients with end-stage chronic liver disease were compared with 35 patients admitted for elective surgery of upper gastrointestinal malignancy. Baseline laboratory values and the FA profiles of the plasma triglyceride and phospholipids were analyzed. FA profiles were also performed after infusion of a TNA including 33+/-7 g of lipid/24 hr for 7.9+/-4 days in the patients with chronic liver disease. Compared with control patients, the plasma phospholipid fatty acid analysis results (relative mole percentage) of patients with chronic liver disease were significantly lower in the two essential FA, linoleic acid (15.4+/-3.4% vs. 20.8+/-2.9%, P<0.001) and alpha-linolenic acid (0.02+/-0.05% vs. 0.08+/-0.10%, P<0.001). Similar changes were demonstrated in the FA composition of the triglyceride fraction. Short-term infusion of intravenous lipid resulted in a significant increase in linoleic acid in the triglyceride fraction (9.9+/-2.8% before supplementation vs. 20.7+/-9.4% after supplementation, P<0.01) and a decrease in oleic acid (38.7+/-5.2% before supplementation vs. 29.3+/-7.5 after supplementation, P<0.01). In conclusion, acute and chronic deficiencies of essential FA occurs in patients with chronic liver disease. The clinical significance of these deficiencies is unknown, but they potentially may impact on eicosanoid metabolism. Short-term supplementation with modest amounts of intravenous lipid has only a minimal effect on normalization of longer-chain fatty acids.
In most chronic disease conditions, the systemic inflammatory response and its mediators play an essential pathogenic role. Protein calorie malnutrition, a prominent feature of end-stage renal disease (ESRD), also develops, largely as a consequence of the systemic inflammatory response. ESRD (uremia), dialysis, systemic metabolic acidosis, and infections activate the systemic inflammatory response. Elevations in C-reactive protein and depressions of serum albumin below 4 g/dL are found in more than 50% of ESRD patients undergoing dialysis. In many patients receiving dialysis, the impact of this acute-phase response on measures of iron metabolism limits the ability to diagnose iron deficiency. Furthermore, there are risks to iron administration, although data linking iron overload to risk of infection in dialysis patients is suggestive, not definitive. It seems reasonable to hypothesize that the greatest risk of iron administration is in patents who are already infected, and the greater risk would be to raise the serum iron level and transferrin saturation precipitously. The total-dose infusion method, which provides all iron required to correct deficiency in 1 dose, is more likely to produce side effects and rapidly raise serum iron levels and transferrin saturation. The use of low-dose intravenous iron supplementation (10 to 20 mg per dialysis treatment or 100 mg every second week) avoids iron overtreatment and should reduce adverse events. In ESRD patients receiving dialysis, the importance of the systemic inflammatory response in the development of protein calorie malnutrition, the impact of the acute-phase response on iron nutriture, and the response to erythropoietin therapy must be considered to achieve an understanding of the altered responses to nutritional therapy in this setting.
BACKGROUND: Elevations in liver function tests have been reported in patients receiving total parenteral nutrition (TPN). The clinical aspects of end-stage liver disease (ESLD) associated with the prolonged use of home TPN have not been fully clarified. In previous series patients with duodenocolostomies appeared to be at higher risk than persons with some jejunum or ileum remaining in situ. METHODS: The records of 42 patients treated with home TPN for more than 1 year were examined. This constituted 283 person-years of home TPN. Patients with duodenocolostomies were examined as a separate group on the basis of the literature experience. RESULTS: Six of 42 patients who received chronic home TPN had ESLD with 100% subsequent mortality, at an average of 10.8 +/- 7.1 months after the initial bilirubin elevation. Thirteen of 42 patients had superior mesenteric artery or vein thrombosis (SMT) leading to duodenocolostomy. In 8 of these 13 patients with SMT and underlying inflammatory or malignant disorder, 2 had ESLD. The remaining 5 SMT patients who had only minimal liver enzyme elevation over 13.6 +/- 6.7 (range 3 to 19) years of home TPN were significantly younger (36 +/- 7 years vs 64 +/- 13 years) and did not have underlying inflammation either by clinical diagnosis or as reflected in the high normal serum albumin level (> or = 4.0 g/dL). Despite their extreme short bowel syndrome and long exposure to home TPN, ESLD did not develop. CONCLUSIONS: Approximately 15% of patients who receive prolonged TPN have ESLD with a high rate of morbidity and mortality. The combination of chronic inflammation and the short bowel syndrome appears to be necessary for the development of ESLD with prolonged home TPN.
Heart disease is the leading cause of death in the U.S. One way to reduce the risk of developing the disease is to lower serum cholesterol levels by making dietary changes. In addition to reducing intake of total fat, saturated fat, and dietary cholesterol, serum cholesterol can be further reduced by added fiber, especially from sources rich in beta-glucan. In this review, two sources of beta-glucan are described; one source is oats and the other yeast. Their chemical structures and physical properties are compared, and their effect on serum lipid levels is described. Oat beta-glucans are found in various breakfast cereals and snacks. Usually, several servings of these products are required to meet the Food and Drug Administration's claim of reducing the risk of heart disease. The yeast-derived fiber is a more concentrated source of beta-glucan than the oat product. It is currently being tested in a wide variety of food products.
BACKGROUND: Dietary fiber has been shown to improve blood lipids. OBJECTIVE: The purpose of this study was to evaluate the effect on serum lipids of a yeast-derived beta-glucan fiber in 15 free-living, obese, hypercholesterolemic men. DESIGN: After a 3-wk period in which subjects ate their usual diet, 15 g fiber/d was added to the diet for 8 wk and then stopped for 4 wk. Plasma lipids were measured weekly during baseline and at week 7 and 8 of fiber consumption, and again at week 12. RESULTS: Compared with baseline, fiber consumption significantly reduced plasma total cholesterol (by 8% at week 7 and 6% at week 8; P < 0.05 using Bonferroni correction); week 12 values did not differ from baseline. No significant differences were noted between baseline LDL cholesterol and values at weeks 7, 8, or 12 when comparing individual groups by using Bonferroni correction, even though the overall one-way analysis of variance with repeated measures was highly significant (P < 0.001). LDL-cholesterol concentrations did decline by 8% at week 8 compared with baseline. There was a significant effect of diet on plasma HDL-cholesterol concentrations (P < 0.005 by one-way ANOVA with repeated measures). However, a group difference was observed only between baseline and week 12 (16% increase; P < 0.05 by Bonferroni correction). Triacylglycerol concentrations did not change. CONCLUSIONS: The yeast-derived beta-glucan fiber significantly lowered total cholesterol concentrations and was well tolerated; HDL-cholesterol concentrations rose, but only 4 wk after the fiber was stopped.
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OBJECTIVES: Because vasoactive eicosanoids derived from arachidonic acid present in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid from fish oil and gamma-linolenic acid from borage oil have been designed to limit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. The present study determined whether short-term enteral feeding with diets enriched with either eicosapentaenoic acid alone or in combination with gamma-linolenic acid would modulate alveolar macrophage eicosanoid synthesis without compromising bactericidal function. DESIGN: Prospective, randomized, controlled, blinded study. SETTING: University medical center. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats underwent surgical placement of a gastroduodenal feeding catheter and were randomly assigned to receive one of three high-fat (55.2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, whereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma-linolenic acid. Alveolar macrophages were then procured to assess phospholipid fatty acid composition, eicosanoid synthesis after stimulation with endotoxin, superoxide formation and phagocytosis by flow cytometry, and killing of Staphylococcus aureus MEASUREMENTS AND MAIN RESULTS: Alveolar macrophage levels of arachidonic acid were significantly (p < .01) lower and levels of eicosapentaenoic and dihomo-gamma-linolenic acids were higher after feeding the eicosapentaenoic and gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thromboxane B2,/B3, leukotriene B4/B5, and prostaglandin E2/E1 were reduced in the macrophages from rats given either the eicosapentaenoic acid or eicosapentaenoic acid with gamma-linolenic acid diet compared with ratios from rats given the linoleic acid diet. Macrophages from rats given the eicosapentaenoic with gamma-linolenic acid diet released 35% or 24% more prostaglandin E1 than macrophages from rats given either the linoleic acid or the eicosapentaenoic acid diet, respectively. Macrophage superoxide generation, phagocytosis of opsonized zymosan, and killing of S. aureus were similar irrespective of dietary treatment. CONCLUSION: Short-term enteral feeding with an eicosapentaenoic acid-enriched or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modulated the fatty acid composition of alveolar macrophage phospholipids, promoted a shift toward formation of less inflammatory eicosanoids by stimulated macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.