Resistance exercise augments the acute anabolic effects of intradialytic oral nutritional supplementation.

BACKGROUND: An intriguing strategy to further enhance the anabolic effects of nutritional supplementation is to combine the administration of nutrients with resistance exercise. We hypothesized that the addition of resistance exercise to oral nutrition supplementation would lead to further increases in skeletal muscle protein accretion when compared to nutritional supplementation alone in chronic haemodialysis (CHD) patients. METHODS: We performed stable isotope protein kinetic studies in eight CHD patients during two separate settings: with oral nutritional supplementation alone (PO) and oral nutritional supplementation combined with a single bout of resistance exercise (PO + EX). Metabolic assessment was performed before, during and after haemodialysis. Both interventions resulted in robust protein anabolic response. RESULTS: There were no differences in metabolic hormones, plasma amino acid and whole-body protein balance between the interventions. During the post-HD phase, PO + EX retained a positive total amino acid (TAA) balance (primarily due to essential amino acid) while PO returned to a negative TAA balance although this difference did not reach statistical significance (78 +/- 109 versus -128 +/- 72 nmol/100 ml/min, respectively; P = 0.69). In the post-HD phase, PO + EX had significantly higher net muscle protein balance when compared to PO (19 +/- 16 versus -24 +/- 10 microg/100 ml/min, respectively; P = 0.036) We conclude that a single bout of resistance exercise augments the protein anabolic effects of oral intradialytic nutritional supplementation when examining skeletal muscle protein turnover.

Intradialytic parenteral nutrition improves protein and energy homeostasis in chronic hemodialysis patients.

Decreased dietary protein intake and hemodialysis-associated protein catabolism are among several factors that predispose chronic hemodialysis (CHD) patients to protein calorie malnutrition. Since attempts to increase protein intake by dietary counseling are usually ineffective, intradialytic parenteral nutrition (IDPN) has been proposed as a potential therapeutic approach in malnourished CHD patients. In this study, we examined protein and energy homeostasis during hemodialysis in seven CHD patients at two separate hemodialysis sessions, with and without IDPN administration. Patients were studied 2 hours before, during, and 2 hours following a hemodialysis session, using a primed constant infusion of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. Our results showed that IPDN promoted a large increase in whole-body protein synthesis and a significant decrease in whole-body proteolysis, along with a significant increase in forearm muscle protein synthesis. The net result was a change from an essentially catabolic state to a highly positive protein balance, both in whole-body and forearm muscle compartments. We conclude that the provision of calories and amino acids during hemodialysis with IDPN acutely reverses the net negative whole-body and forearm muscle protein balances, demonstrating a need for long-term clinical trials evaluating IDPN in malnourished CHD patients.

Defects in postabsorptive plasma homeostasis of fatty acids in sickle cell disease.

BACKGROUND: The chronic hemolytic anemia experienced by sickle cell disease (SCD) patients leads to adverse effects on oxygen transport by the blood and to a decrease in oxygen availability for peripheral tissues. Limited tissue oxygen availability has the potential to modify events of intracellular metabolism and, thus, alter lipid homeostasis. METHODS: The impact of SCD on plasma fatty acid homeostasis was determined in 8 African American SCD patients and in 6 healthy African American control subjects under postabsorptive conditions and during a 3-hour IV infusion of a nutrient solution containing lipid, glucose, and amino acids. RESULTS: SCD patients had higher fasting levels of plasma nonesterified fatty acids (NEFA), triglycerides, and phospholipids than healthy controls. Similarly, SCD patients had higher fasting levels of fatty acids in plasma triglycerides and phospholipids than healthy controls. Infusion of nutrients resulted in equivalent plasma NEFA profiles, total NEFA, and triglycerides in SCD patients and controls. However, the plasma phospholipid concentrations and fatty acid composition of plasma triglycerides and phospholipids were significantly higher in SCD patients; in particular, plasma pools of oleic acid were consistently increased in SCD. Plasma free oleic acid levels were elevated basally, leading to increased oleic acid content in triglycerides and phospholipids both post absorptively and during nutrient infusion. CONCLUSIONS: There is an underlying defect in lipid metabolism associated with SCD best manifested during the fasting state. This abnormality in lipid homeostasis has the potential to alter red blood cell (RBC) membrane fluidity and function in SCD patients.

Glutamine supplementation increases postprandial energy expenditure and fat oxidation in humans.

BACKGROUND: Glutamine interacts with insulin-mediated glucose disposal, which is a component of the increase in energy expenditure (EE) after a meal. The study aim was to examine if glutamine supplementation alters postmeal nutrient oxidation. METHODS: Ten healthy young adults consumed a mixed meal (6.5 kcal/kg, 14%:22%:64% = protein:fat:carbohydrate) containing either glutamine (GLN:1.05 kcal/kg) or an isocaloric amino acid mixture (alanine: glycine:serine = 2:1:0.5; CON). GLN and CON treatments were administered on separate days in random order for each subject. EE, nonprotein respiratory quotient (RQ), and fat and carbohydrate oxidation rates were assessed using indirect calorimetry for 30 minutes before and for 360 minutes after meal ingestion. RESULTS: Premeal EE and RQ were similar between treatments. The increase in EE above basal during both early (0-180 minutes) and late (180-360 minutes) postmeal phases was greater in GLN than in CON (p < .05), resulting in postmeal EE being 49% greater during the total postmeal phase (p < .05). Net change of carbohydrate oxidation was 38% higher during the early phase with GLN (p < .05), whereas it was 71% lower during the later phase (p < .05). GLN enhanced fat oxidation by approximately 42 kcal compared with CON during the late phase (p < .05). CONCLUSIONS: Glutamine supplementation with a mixed meal alters nutrient metabolism to increase postmeal EE by increasing carbohydrate oxidation during the early postmeal phase and fat oxidation during the late postmeal phase. Consideration must be given to the potential that these postprandial changes in EE are related to glutamine-mediated changes in insulin action and consequently glucose disposal.

The use of a handheld calorimetry unit to estimate energy expenditure during different physiological conditions.

BACKGROUND: Accurately determining rates of energy expenditure (EE) under free-living conditions is important in understanding the mechanisms involved in the development and prevention of obesity. Metabolic carts are not portable enough for most free-living situations. The purpose of this study was to compare a portable, handheld indirect calorimetry device (HealtheTech Incorporated, Golden, CO) to a metabolic cart (Physio-Dyne Instrument Corporation, Quogue, NY) during 3 different physiologic states. METHODS: EE was measured by both the handheld calorimeter (5-10 minutes) and the metabolic cart (15-20 minutes) in 20 healthy subjects (18-35 years of age). Measurements were made during 3 physiologic states: (1) postabsorptive rest (REE), (2) postprandial rest (fed energy expenditure, FEE), and (3) while walking in place (activity energy expenditure, AEE). RESULTS: There were no significant differences between the means of the cart vs the hand-held device for REE (mean +/- SE; kcal/d; 1552 +/- 64 vs 1551 +/- 63), FEE (1875 +/- 99 vs 1825 +/- 86), and AEE (3333 +/- 218 vs 3489 +/- 152). The range over which the techniques were tested was 1300-5000 kcal/d. The agreement between the 2 methods was excellent for REE (0.80, p < .0001), FEE (0.89, p < .0001), and AEE (0.75, p < .0002). CONCLUSIONS: Compared with the metabolic cart, the handheld device provided similar estimates of energy expenditure during resting, postprandial, and physically active states. This suggests that portable indirect calorimetry devices can provide reliable and valuable information in free-living research situations for which maximal energy expenditure is <5000 kcal/d.

Recombinant human growth hormone improves muscle amino acid uptake and whole-body protein metabolism in chronic hemodialysis patients.

BACKGROUND: Intradialytic parenteral nutrition (IDPN), with or without exercise, has been shown to reverse the net negative whole-body and forearm muscle protein balances observed during hemodialysis. Pharmacologic doses of recombinant human growth hormone (rhGH) constitute another potential anabolic therapy in chronic hemodialysis patients. OBJECTIVE: Our goal was to examine the potential additive anabolic effects of rhGH compared with IDPN and exercise on protein and energy homeostasis. DESIGN: We studied 7 chronic hemodialysis patients in a crossover design study in which each subject participated in 2 protocols: GH (rhGH + IDPN + exercise) and no GH (IDPN + exercise). During the GH protocol, the subjects were studied after 3 daily doses of rhGH. Each subject was studied 2 h before, 4 h during, and 2 h after a hemodialysis session with the use of a primed, constant infusion of l-[1-(13)C]leucine. RESULTS: Whole-body net protein balance was -0.50 +/- 0.07 mg x kg fat-free mass(-1) x min(-1) when the patients did not receive rhGH and -0.39 +/- 0.04 mg x kg fat-free mass(-1) x min(-1) when the patients received rhGH, a 22% improvement in prehemodialysis whole-body protein homeostasis (P < 0.05). Essential amino acid muscle loss was also significantly less during the prehemodialysis period when rhGH was administered (-18 +/- 23 compared with -71 +/- 20 mmol/L; P < 0.05). The whole-body anabolic effects of rhGH observed during the prehemodialysis period persisted throughout the entire study, as evidenced by a lack of significant interaction or main effect of treatment during hemodialysis and in the posthemodialysis period. CONCLUSION: rhGH improves whole-body protein homeostasis in chronic hemodialysis patients.

Impact of glutamine supplementation on glucose homeostasis during and after exercise.

The interaction of glutamine availability and glucose homeostasis during and after exercise was investigated, measuring whole body glucose kinetics with [3-3H]glucose and net organ balances of glucose and amino acids (AA) during basal, exercise, and postexercise hyperinsulinemic-euglycemic clamp periods in six multicatheterized dogs. Dogs were studied twice in random treatment order: once with glutamine (12 micromol.kg(-1).min(-1); Gln) and once with saline (Con) infused intravenously during and after exercise. Plasma glucose fell by 7 mg/dl with exercise in Con (P < 0.05), but it did not fall with Gln. Gln further stimulated whole body glucose production and utilization an additional 24% above a normal exercise response (P < 0.05). Net hepatic uptake of glutamine and alanine was greater with Gln than Con during exercise (P < 0.05). Net hepatic glucose output was increased sevenfold during exercise with Gln (P < 0.05) but not with Con. Net hindlimb glucose uptake was increased similarly during exercise in both groups (P < 0.05). During the postexercise hyperinsulinemic-euglycemic period, glucose production decreased to near zero with Con, but it did not decrease below basal levels with Gln. Gln increased glucose utilization by 16% compared with Con after exercise (P < 0.05). Furthermore, net hindlimb glucose uptake in the postexercise period was increased approximately twofold vs. basal with Gln (P < 0.05) but not with Con. Net hepatic uptake of glutamine during the postexercise period was threefold greater for Gln than Con (P < 0.05). In conclusion, glutamine availability modulates glucose homeostasis during and after exercise, which may have implications for postexercise recovery.

Postexercise protein supplementation improves health and muscle soreness during basic military training in Marine recruits.

Elevated postexercise amino acid availability has been demonstrated to enhance muscle protein synthesis acutely, but the long-term impact of postexercise protein supplementation on variables such as health, muscle soreness, and function are unclear. Healthy male US Marine recruits from six platoons (US Marine Corps Base, Parris Island, SC; n = 387; 18.9 +/- 0.1 yr, 74.7 +/- 1.1 kg, 13.8 +/- 0.4% body fat) were randomly assigned to three treatments within each platoon. Nutrients supplemented immediately postexercise during the 54-day basic training were either placebo (0 g carbohydrate, 0 g protein, 0 g fat), control (8, 0, 3), or protein supplement (8, 10, 3). Subjects and observers making measurements and data analysis were blinded to subject groupings. Compared with placebo and control groups, the protein-supplemented group had an average of 33% fewer total medical visits, 28% fewer visits due to bacterial/viral infections, 37% fewer visits due to muscle/joint problems, and 83% fewer visits due to heat exhaustion. Recruits experiencing heat exhaustion had greater body mass, lean, fat, and water losses. Muscle soreness immediately postexercise was reduced by protein supplementation vs. placebo and control groups on both days 34 and 54. Postexercise protein supplementation may not only enhance muscle protein deposition but it also has significant potential to positively impact health, muscle soreness, and tissue hydration during prolonged intense exercise training, suggesting a potential therapeutic approach for the prevention of health problems in severely stressed exercising populations.

Postexercise protein intake enhances whole-body and leg protein accretion in humans.

PURPOSE: Exercise increases the use of amino acids for glucose production and stimulates the oxidation of amino acids and other substrates to provide ATP for muscular contraction, and thus the availability of amino acids and energy for postexercise muscle protein synthesis may be limiting. The purpose of this study was to determine the potential of postexercise nutrient intake to enhance the recovery of whole-body and skeletal muscle protein homeostasis in humans. METHODS: Primed-continuous infusions of L-[1-13C]leucine and L-[ring-2H5]phenylalanine were initiated in the antecubital vein and blood was sampled from a femoral vein and a heated (arterialized) hand vein. Each study consisted of a 30-min basal, a 60-min exercise (bicycle at 60% VO2max), and a 180-min recovery period. Five men and five women were studied three times with an oral supplement administered immediately following exercise in random order: NO = 0, 0, 0; SUPP = 0, 8, 3; or SUPP+PRO = 10, 8, 3 g of protein, carbohydrate, and lipid, respectively. RESULTS: Compared to NO, SUPP did not alter leg or whole-body protein homeostasis during the recovery period. In contrast, SUPP+PRO increased plasma essential amino acids 33%, leg fractional extraction of phenylalanine 4-fold, leg uptake of glucose 3.5-fold, and leg and whole-body protein synthesis 6-fold and 15%, respectively. Whereas postexercise intake of either NO or SUPP resulted in a net leg release of essential amino acids and net loss of whole-body and leg protein, SUPP+PRO resulted in a net leg uptake of essential amino acids and net whole-body and leg protein gain. CONCLUSIONS: These findings suggest that the availability of amino acids is more important than the availability of energy for postexercise repair and synthesis of muscle proteins.

Bioelectrical impedance vs air displacement plethysmography and dual-energy X-ray absorptiometry to determine body composition in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have significant shifts in fluid homeostasis that may impair measurements of body composition using methods based upon determinations of body water. Estimates of body water are fundamental for bioelectrical impedance analysis (BIA), which measures electrical resistance to estimate total body water and body composition. METHODS: BIA was compared with 2 other techniques: (1) air displacement plethysmography (ADP), which relies on measurements of body density to estimate body fat and fat-free masses; and (2) dual-energy x-ray absorptiometry (DXA), which depends on the relative attenuation of an x-ray beam to produce images of body fat and bone mineral. In study 1, BIA and ADP were performed on 38 ESRD patients (21 men and 17 women; age 51.3 +/- 2.2 years; weight 79.8 +/- 2.9 kg; body mass index [BMI] 27.4 +/- 0.9 kg/m2). In study 2, BIA and DXA were performed on 47 patients (22 men and 25 women; age 52.7 +/- 2.3 years; weight 73.6 +/- 2.9 kg; BMI 25.9 +/- 1.0 kg/m2). RESULTS: The ranges of percent body fat using BIA in studies 1 and 2 were from 7% to 57% and from 6% to 52%, respectively. Percent body fat measurements were significantly (p < .0001) correlated for BIA vs ADP (r = .74) and for BIA vs DXA (r = .84). Mean body fat as determined by BIA and ADP in study 1 was 31.8 +/- 2.0% and 36.3 +/- 1.8%* and by BIA and DXA in study 2 was 29.6 +/- 1.5% and 31.8 +/- 1.8%*, respectively (*p < .05 vs BIA). All 3 methods had similar variability associated with their measurements (coefficients of variation approximately 5%). The average body fat measured by BIA was less than ADP or DXA, regardless of gender or race. Furthermore, the variation was not greater at lower or higher body fat values. CONCLUSIONS: Body fat measurements using ADP and DXA were correlated with those using BIA across a relatively wide range of body fat levels in adults with ESRD. However, BIA appeared to underestimate body fat and overestimate fat-free mass, possibly because of increased measurements of body water. Because ADP is convenient and does not use body water content in determination of body density and body composition, it has very good potential as a relatively new technique to estimate percent body fat in adults with ESRD.

Differences in daily energy expenditure in lean and obese women: the role of posture allocation.

OBJECTIVE: A low resting metabolic rate (RMR) is considered a risk factor for weight gain and obesity; however, due to the greater fat-free mass (FFM) found in obesity, detecting an impairment in RMR is difficult. The purposes of this study were to determine the RMR in lean and obese women controlling for FFM and investigate activity energy expenditure (AEE) and daily activity patterns in the two groups. METHODS AND PROCEDURES: Twenty healthy, non-smoking, pre-menopausal women (10 lean and 10 obese) participated in this 14-day observational study on free-living energy balance. RMR was measured by indirect calorimetry; AEE and total energy expenditure (TEE) were calculated using doubly labeled water (DLW), and activity patterns were investigated using monitors. Body composition including FFM and fat mass (FM) was measured by dual energy X-ray absorptiometry (DXA). RESULTS: RMR was similar in the obese vs. lean women (1601 +/- 109 vs. 1505 +/- 109 kcal/day, respectively, P = 0.12, adjusting for FFM and FM). Obese women sat 2.5 h more each day (12.7 +/- 3.2 h vs. 10.1 +/- 2.0 h, P < 0.05), stood 2 h less (2.7 +/- 1.0 h vs. 4.7 +/- 2.2 h, P = 0.02) and spent half as much time in activity than lean women (2.6 +/- 1.5 h vs. 5.4 +/- 1.9 h, P = 0.002). DISCUSSION: RMR was not lower in the obese women; however, they were more sedentary and expended less energy in activity than the lean women. If the obese women adopted the activity patterns of the lean women, including a modification of posture allocation, an additional 300 kcal could be expended every day.

Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status.

Decreased dietary protein intake and hemodialysis (HD)-associated protein catabolism predispose chronic HD (CHD) patients to deranged nutritional status, which is associated with poor clinical outcome in this population. Intradialytic parenteral nutrition (IDPN) reverses the net negative whole-body and skeletal muscle protein balance during HD. IDPN is costly and restricted by Medicare and other payers. Oral supplementation (PO) is a more promising, physiologic, and affordable intervention in CHD patients. Protein turnover studies were performed by primed-constant infusion of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine in eight CHD patients with deranged nutritional status before, during, and after HD on three separate occasions: (1) with IDPN infusion, (2) with PO administration, and (3) with no intervention (control). Results showed highly positive whole-body net balance during HD for both IDPN and PO (4.43 +/- 0.7 and 5.71 +/- 1.2 mg/kg fat-free mass per min, respectively), compared with a neutral balance with control (0.25 +/- 0.5 mg/kg fat-free mass per min; P = 0.002 and <0.001 for IDPN versus control and PO versus control, respectively). Skeletal muscle protein homeostasis during HD also improved with both IDPN and PO (50 +/- 19 and 42 +/- 17 microg/100 ml per min) versus control (-27 +/- 13 microg/100 ml per min; P = 0.005 and 0.009 for IDPN versus control and PO versus control, respectively). PO resulted in persistent anabolic benefits in the post-HD phase for muscle protein metabolism, when anabolic benefits of IDPN dissipated (-53 +/- 25 microg/100 ml per min for control, 47 +/- 41 microg/100 ml per min for PO [P = 0.039 versus control], and -53 +/- 24 microg/100 ml per min for IDPN [P = 1.000 versus control and 0.039 versus PO]). Long-term studies using intradialytic oral supplementation are needed for CHD patients with deranged nutritional status.

Increased muscle protein breakdown in chronic hemodialysis patients with type 2 diabetes mellitus.

BACKGROUND: The presence of diabetes mellitus (DM) in chronic hemodialysis (CHD) patients has potential to increase body protein losses and muscle wasting. METHODS: In this study, we examined whole-body and skeletal muscle protein metabolism in 6 CHD patients with type 2 (T2) DM (2 male, 44.4 +/- 6.1 years old, 2 white/4 African American HbA(1)C = 9.5 +/- 1.1%), and 6 non-DM CHD patients (2 male, 43.3 +/- 6.7 years old, 2 white/4 African American) in a fasting state, using a primed-constant infusion of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. RESULTS: CHD patients with T2DM had significantly increased (83%) skeletal muscle protein breakdown (137 +/- 27 vs. 75 +/- 25 microg/100 mL/min). There was no significant difference in muscle protein synthesis between groups (78 +/- 27 vs. 66 +/- 21 microg/100 mL/min, for DM and non-DM respectively), resulting in significantly more negative net protein balance in the muscle compartment in the DM group (-59 +/- 4 vs. -9 +/- 6 microg/100 mL/min, P < 0.05). A similar trend was observed in whole-body protein synthesis and breakdown. Plasma glucose levels were 113 +/- 16 and 71 +/- 2 mg/dL, P < 0.05, and insulin levels were 25.3 +/- 9.6 and 7.3 +/- 1.0 uU/mL, for DM versus non-DM, respectively, P < 0.05. No significant differences between DM and non-DM were found in other metabolic hormones. CONCLUSION: The results of this study demonstrate that CHD patients with T2DM under a suboptimal metabolic control display accelerated muscle protein loss compared with a matched group of non-DM CHD patients.

Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans.

Acute increases of the key counterregulatory hormone epinephrine can be modified by a number of physiological and pathological conditions in type 1 diabetic patients (T1DM). However, it is undecided whether the physiological effects of epinephrine are also reduced in T1DM. Therefore, the aim of this study was to determine whether target organ (liver, muscle, adipose tissue, pancreas, cardiovascular) responses to epinephrine differ between healthy subjects and T1DM patients. Thirty-four age- and weight-matched T1DM (n = 17) and healthy subjects (n = 17) underwent two randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (Epi) and without epinephrine infusion. Muscle biopsy was performed at the end of each study. Epinephrine levels during Epi were similar in all groups (4,039 +/- 384 pmol/l). Glucose (5.3 +/- 0.06 mmol/l) and insulin levels (462 +/- 18 pmol/l) were also similar in all groups during the glucose clamps. Glucagon responses to Epi were absent in T1DM and significantly reduced compared with healthy subjects. Endogenous glucose production during the final 30 min was significantly greater during Epi in healthy subjects compared with T1DM (8.4 +/- 1.3 vs. 4.4 +/- 0.6 micromol.kg(-1).min(-1), P = 0.041). Glucose uptake showed almost a twofold greater decrease with Epi in healthy subjects vs. T1DM (Delta31 +/- 2 vs. Delta17 +/- 2 nmol.kg(-1).min(-1), respectively, P = 0.026). Glycerol, beta-hydroxybutyrate, and nonesterified fatty acid (NEFA) all increased significantly more in T1DM compared with healthy subjects. Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi. Reduction of glycogen synthase was significantly greater during epinephrine infusion in T1DM vs. healthy subjects. In summary, despite equivalent epinephrine, insulin, and glucose levels, changes in glucose flux, glucagon, and cardiovascular responses were greater in healthy subjects compared with T1DM. However, T1DM patients had greater lipolytic responses (glycerol and NEFA) during Epi. Thus we conclude that there is a spectrum of significant in vivo physiological differences of epinephrine action at the liver, muscle, adipose tissue, pancreas, and cardiovascular system between T1DM and healthy subjects.

Nutritional supplementation acutely increases albumin fractional synthetic rate in chronic hemodialysis patients.

Uremic malnutrition is associated with increased risk of hospitalization and death in chronic hemodialysis (CHD) patients. Most nutritional intervention studies in CHD patients traditionally have used concentrations of serum albumin as the primary outcome measure and showed slight or no significant improvements. A recent study showed that intradialytic parenteral nutrition (IDPN) improves whole-body protein synthesis in CHD patients. On the basis of this observation, it was hypothesized that the anabolic effects of IDPN are associated with increases in the fractional synthetic rate of albumin, a direct estimate of acute changes in hepatic albumin synthesis. Seven CHD patients were studied during two hemodialysis (HD) sessions, with and without IDPN, using primed-constant infusion of (13C) leucine 2 h before, during, and 2 h after HD. Plasma enrichments of (13C) leucine and (13C) ketoisocaproate were examined to determine the fractional synthetic rate of albumin. The results indicate that administration of IDPN significantly improves the fractional synthetic rate of albumin during HD (16.2 +/- 1.5%/d versus 12.8 +/- 1.7%/d; P < 0.05) in CHD patients in parallel with significant improvements in whole-body protein synthesis (5.05 +/- 1.3 mg/kg fat-free mass/min versus 3.22 +/- 0.3 mg/kg fat-free mass/min; P < 0.05). IDPN is protein anabolic in the acute setting in CHD patients, as evidenced by significant concomitant increases in the fractional synthetic rate of albumin and whole-body protein synthesis.

Protein homeostasis in chronic hemodialysis patients.

PURPOSE OF REVIEW: Nutritional status is an important predictor of clinical outcome in chronic hemodialysis patients, as uremic malnutrition is strongly associated with an increased risk of death and hospitalization events. Decreased muscle mass is the most significant predictor of morbidity and mortality in these patients. Several factors that influence protein metabolism predispose chronic hemodialysis patients to increased catabolism and the loss of lean body mass. The purpose of this review is to discuss recent advances in the understanding of abnormalities in protein homeostasis in chronic hemodialysis patients. RECENT FINDINGS: It has long been suspected that the hemodialysis procedure is a net catabolic event. Recent studies have indeed shown that the hemodialysis procedure induces a net protein catabolic state at the whole-body level as well as in skeletal muscle. There is evidence to suggest that these undesirable effects are caused by decreased protein synthesis and increased proteolysis. The provision of nutrients, either in the form of intradialytic parenteral nutrition or oral feeding during hemodialysis, can adequately compensate the catabolic effects of the hemodialysis procedure. Whereas the mechanisms of these effects have not been studied in detail, changes in extracellular amino acid concentrations and certain anabolic hormones such as insulin are important mediators of these actions. SUMMARY: There is now indisputable evidence to suggest that the hemodialysis procedure leads to a highly catabolic state. Despite this, chronic hemodialysis patients can still achieve anabolism when given adequate protein supplementation to meet the metabolic requirements of hemodialysis, and when adequate insulin is present.

Exercise augments the acute anabolic effects of intradialytic parenteral nutrition in chronic hemodialysis patients.

Decreased dietary protein intake and hemodialysis (HD)-associated protein catabolism are among several factors that predispose chronic hemodialysis (CHD) patients to uremic malnutrition and associated muscle wasting. Intradialytic parenteral nutrition (IDPN) acutely reverses the net negative whole body and forearm muscle protein balances observed during the HD procedure. Exercise has been shown to improve muscle protein homeostasis, especially if performed with adequately available intramuscular amino acids. We hypothesized that exercise performance would provide additive anabolic effects to the beneficial effects of IDPN. We studied six CHD patients at two separate HD sessions: 1) IDPN administration only and 2) IDPN + exercise. Patients were studied 2 h before, during, and 2 h after an HD session by use of a primed constant infusion of l-[1-(13)C]leucine and l-[ring-(2)H(5)] phenylalanine. Exercise combined with IDPN promoted additive twofold increases in forearm muscle essential amino acid uptake (455 +/- 105 vs. 229 +/- 38 nmol.100 ml(-1).min(-1), P < 0.05) and net muscle protein accretion (125 +/- 37 vs. 56 +/- 30 microg.100 ml(-1).min(-1), P < 0.05) during HD compared with IDPN alone. Measurements of whole body protein homeostasis and energy expenditure were not altered by exercise treatment. In conclusion, exercise in the presence of adequate nutritional supplementation has potential as a therapeutic intervention to blunt the loss of muscle mass in CHD patients.

Inflammatory signals associated with hemodialysis.

BACKGROUND: Inflammation is highly prevalent in chronic hemodialysis patients. Because hemodialysis involves the contact of blood with "foreign" surfaces, and the documented activation of several humoral and cellular pathways during the procedure, the hemodialysis procedure has been suggested as a potential source of inflammation in this patient population. Earlier studies did not provide clear-cut evidence of the potential contribution of the hemodialysis procedure to inflammation, as assessed by markers of inflammation such as cytokine levels and acute-phase protein production. METHODS: Nine patients were studied using primed-constant infusion of l-(l-13C) leucine 2 hours before, during, and 2 hours after a single hemodialysis session. We evaluated the effects of hemodialysis on induction of interleukin-6 (IL-6) production as well as the fractional synthetic rates (FSR) of albumin and fibrinogen, two well-known acute-phase proteins. RESULTS: During hemodialysis, albumin FSR and fibrinogen FSR increased significantly compared to the measurements obtained during baseline period. During this period, albumin and fibrinogen FSR increased 64% and 34%, respectively, compared to baseline (P < 0.05). While the increase in IL-6 concentration was modest during hemodialysis (14%), the levels further increased at the end of the 2-hour post-hemodialysis period (68% higher compared to baseline, P < 0.05). Fibrinogen FSR also demonstrated a further increase during the post-dialysis period (17% higher compared to the intradialytic period and 58% higher compared to baseline), while albumin FSR stabilized during this period. CONCLUSIONS: The results provide clear evidence of hemodialysis-induced inflammatory response. The process is most notable during the 2-hour post-hemodialysis period.

Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation.

The hemodialysis (HD) procedure has been implicated as a potential catabolic factor predisposing the chronic HD (CHD) patients to protein calorie malnutrition. To assess the potential effects of HD on protein and energy metabolism, we studied 11 CHD patients 2 h before, during, and 2 h after HD by use of primed constant infusion of L-[1-13C]leucine and L-[ring-2H5]phenylalanine. Our results showed that HD led to increased whole body (10%) and muscle protein (133%) proteolysis. Simultaneously, whole body protein synthesis did not change, and forearm synthesis increased (120%). The net result was increased net whole body protein loss (96%) and net forearm protein loss (164%). During the 2-h post-HD period, the muscle protein breakdown trended toward baseline, whereas whole body protein breakdown increased further. Substrate oxidation during the post-HD was significantly altered, with diminished carbohydrate and accelerated lipid and amino acid oxidation. These data demonstrate that hemodialysis is an overall catabolic event, decreasing the circulating amino acids, accelerating rates of whole body and muscle proteolysis, stimulating muscle release of amino acids, and elevating net whole body and muscle protein loss.

Urea space and total body water measurements by stable isotopes in patients with acute renal failure.

BACKGROUND: Knowledge of urea volume of distribution (Vurea) in patients with acute renal failure (ARF) is critical in order to prescribe and monitor appropriate dialytic treatment. We have recently shown that in ARF patients, Vurea estimation by urea kinetic modeling is significantly higher than total body water (TBW) by anthropometric estimation. However, these estimates of Vurea and TBW have not been validated by isotopic methods, considered as reference measurement standards. METHODS: In this study, we measured Vurea by [13C]urea and TBW by deuterium oxide (D2O) in 21 patients with ARF (14 males, 7 females, age 62.0 +/- 10.6 years old, 83% Caucasian, 17% African American) at three different centers. These measurements were compared to TBW estimates from anthropometric and bioelectrical impedance (BIA) measurements. RESULTS: Our results show that Vurea by [13C]urea (51.0 +/- 11.7 L) is significantly higher than TBW estimated by all other methods (TBW by D2O: 38.3 +/- 9.8 L, P < 0.001; TBW by BIA: 45.7 +/- 15.7 L, P= 0.08; TBW by Watson formula: 38.3 +/- 7.3 L, P < 0.001; TBW by Chertow formula: 39.3 +/- 7.8 L, P= 0.002, all versus Vurea). Despite significant overestimation of the absolute value and considerable variation, Vurea significantly correlated with TBW by BIA (r= 0.66, P < 0.01) and TBW by D2O (r= 0.5, P= 0.04). There was also significant correlation between D2O and BIA determined TBW (r= 0.8, P < 0.001). CONCLUSION: In terms of useful guidelines to prescribe a specific dose of dialysis in patients with ARF, conventional estimates of TBW as surrogates for Vurea should be used with caution. We propose that these conventional estimates of TBW should be increased by approximately 20% (a factor of 1.2) to avoid significant underdialysis.