The effect of resistance exercise to augment long-term benefits of intradialytic oral nutritional supplementation in chronic hemodialysis patients.

BACKGROUND: Resistance exercise combined with intradialytic oral nutrition (IDON) supplementation improves net protein balance in the acute setting in chronic hemodialysis patients. We hypothesized that combination of long-term resistance exercise and IDON would improve markers of muscle mass and strength further compared with IDON alone. METHODS: Thirty-two participants (21 male; mean age, 43 ± 13 years) on chronic hemodialysis were randomly assigned to IDON plus resistance exercise (NS + EX), or IDON (NS) alone for 6 months. IDON consisted of a lactose-free formula consisting of protein, carbohydrate, and fat. Three sets of 12 repetitions of leg-press were completed before each dialysis session in the NS + EX arm. Primary outcome measurement was lean body mass. Muscle strength and other nutritional parameters were measured as secondary outcomes. RESULTS: Of 32 participants, 22 completed the 6-month intervention. There were no statistically significant differences between the study interventions with respect to changes in lean body mass and body weight, when comparing NS + EX to NS. There were also no statistically significant differences in any of the secondary outcomes measured in the study. Body weight (80.3 ± 16.6 kg, 81.1 ± 17.5 kg, and 80.9 ± 18.2 kg at baseline, month 3, and month 6, respectively; P = .02) and 1-repetition maximum (468 ± 148 lb, 535 ± 144 lb, and 552 ± 142 lb, respectively; P = .001) increased statistically significantly during the study for all patients combined. CONCLUSION: This study did not show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone. When both treatments groups were combined, body weight and muscle strength improved during the study.

Prospective evaluation of waist circumference and visceral adipose tissue in patients with chronic kidney disease.

BACKGROUND: Waist circumference (WC), a simple anthropometric measure, is associated with visceral adipose tissue (VAT) in cross-sectional studies, and thus has been used as a surrogate marker for VAT. However, associations between changes over time in WC and VAT have not been studied in chronic kidney disease (CKD) patients. METHODS: This prospective study included 87 nondialysis-dependent CKD patients (54 males, 56.2 +/- 10.4 years, BMI 27.3 +/- 5.1, GFR 35.9 +/- 14.6 ml/min/1.73 m(2)). VAT area was measured by computed tomography (CT) and WC was measured at the umbilicus level at baseline and after 12 months. RESULTS: Changes in WC correlated significantly but weakly with changes in VAT (r = 0.26, p = 0.016), likely due to a substantially smaller change in WC compared to changes in VAT. This was also reflected by a kappa coefficient of 0.26, i.e. indicative of poor agreement between WC and CT measurements in regards to quantification of changes in VAT. Likewise, the receiver operating characteristic curve analysis identified WC as poor predictor of changes in VAT (area under the curve = 0.62). CONCLUSION: Anthropometric measurement of WC is poorly correlated with changes in VAT measured by CT in nondialysis-dependent CKD patients. Therefore, caution should be taken when using WC as a surrogate marker of VAT changes in this population.

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.

Body composition and physical activity in end-stage renal disease.

OBJECTIVE: The study objective was to examine the relationship between visceral and somatic protein stores and physical activity in individuals with end-stage renal disease. DESIGN: This was a prospective single-center study. SETTING: The study took place at the Vanderbilt University Outpatient Dialysis Unit and General Clinical Research Center. PATIENTS: Fifty-five patients with prevalent chronic hemodialysis (CHD) were included: 33 males, 22 females, 45 African Americans, 9 Caucasians, and 1 Asian. The mean age was 47.0 +/- 1.6 years, height was 166.4 +/- 13.9 cm, and weight was 83.1 +/- 2.6 kg. METHODS: Body composition was measured by dual-energy x-ray absorptiometry. Minute-by-minute physical activity was assessed over a 7-day period with a triaxial accelerometer. Participants were interviewed by a trained registered dietitian for two 24-hour diet recalls (one from a hemodialysis day; one from a nonhemodialysis day). Laboratory values for serum concentrations of albumin, prealbumin, C-reactive protein, and creatinine were also collected. MAIN OUTCOME MEASURE: Predictors of somatic protein stores were the main outcome measure. RESULTS: Serum albumin was negatively and significantly correlated with the percentage of fat mass (P = .016) and kg of fat mass (P = .044). C-reactive protein was positively and significantly correlated with body weight (P = .006), percentage of fat mass (P = .017), kg of fat mass (P = .006), and body mass index (P = .004). Physical activity and total daily protein intake were the strongest predictors of the amount of lean body mass (P = .01 and .003, respectively). CONCLUSION: The association between somatic protein and visceral protein stores is weak in patients with CHD. Whereas increased levels of physical activity and total daily protein intake are associated with higher lean body mass in patients with CHD, higher adiposity is associated with higher C-reactive protein and lower albumin values.

Nutrition and metabolism in kidney disease.

Nutritional and metabolic derangements are highly prevalent in patients with chronic kidney disease (CKD) and patients on renal replacement therapy. These derangements, which can be termed uremic malnutrition, significantly affect the high morbidity and mortality rates observed in this patient population. Uremic malnutrition clearly is related to multiple factors encountered during the predialysis stage and during chronic dialysis therapy. Several preliminary studies suggested that interventions to improve the nutritional status and metabolic status of uremic patients actually may improve the expected outcome in these patients, although their long-term efficacy is not well established. It therefore is important to emphasize that uremic malnutrition is a major comorbid condition in CKD and renal replacement therapy patients, and that all efforts should be made to try to understand better and treat these conditions effectively to improve not only mortality but also the quality of life of chronically uremic patients. In this article we review the current state of knowledge in the field of nutrition and metabolism in all stages of CKD and renal replacement therapy, including kidney transplant. We also address questions that face investigators in this field and suggest where future research might be headed.

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.

Physical activity patterns in chronic hemodialysis patients: comparison of dialysis and nondialysis days.

OBJECTIVE: To determine physical activity patterns in chronic hemodialysis patients with a specific emphasis on the difference between dialysis and nondialysis days. Design A cross-sectional single-center study. SETTING: Vanderbilt University Outpatient Dialysis Unit. PATIENTS: Twenty current chronic hemodialysis patients: 10 male, 10 female; 15 black, 5 white; mean age, 50.1 +/- 9.9 years; height, 164.5 +/- 10.9 cm; weight, 82.5 +/- 15.4 kg; length on dialysis, 57.3 +/- 45.3 months. METHODS: Minute-by-minute physical activity was assessed over a 7-day period using a triaxial accelerometer, which consists of raw numbers or counts calculated by the 3 axes of the accelerometer (PA counts). PA counts were extrapolated on a daily and hourly basis. Physical functioning tests included: sit-to-stand, 6-minute walk, and 1-repetition maximal leg press exercise. Laboratory values for serum concentrations of albumin, prealbumin, C-reactive protein, and cholesterol were also collected. MAIN OUTCOME MEASURE: PA counts. RESULTS: Total PA counts were significantly lower on dialysis days when compared with nondialysis days (128,279 +/- 74,009 versus 168,744 +/- 95,168, respectively, P = .025). The average PA counts during the 4-hour dialysis time period were significantly lower on dialysis days when compared with nondialysis days (3,086 +/- 3,749 versus 11,070 +/- 7,695, respectively, P = .001). At postdialysis hours 1 and 2, PA counts on dialysis days were significantly higher than on nondialysis days (11,410 +/- 5,340 versus 9,082 +/- 6,646, P = .008, and 14,048 +/- 9,728 versus 8,662 +/- 6,433, P = .016, respectively). By postdialysis hour 4, PA counts on dialysis days had significantly decreased when compared with nondialysis days (6,068 +/- 6,268 versus 10,512 +/- 7,420 PA counts, P = .01, respectively). From postdialysis hours 5 to 20, there was no significant difference in PA counts between dialysis and nondialysis days. CONCLUSION: This study shows that physical activity is lower on dialysis days when compared with nondialysis days, and this decrease is caused by the lack of activity during the 4-hour hemodialysis procedure. New behavior modification strategies involving physical activity, both during hemodialysis and on nondialysis days, must be examined in this patient population.

Improvement in nutritional parameters after initiation of chronic hemodialysis.

BACKGROUND: Protein-calorie malnutrition is highly prevalent in patients with chronic renal failure and on chronic dialysis therapy. Longitudinal studies evaluating nutritional outcomes after the initiation of chronic dialysis therapy in incident dialysis patients are limited. METHODS: This prospective cohort study evaluated time-dependent changes in several well-defined markers of nutritional status before and after initiation of chronic hemodialysis therapy. Fifty incident hemodialysis (HD) patients (60% men, 38% white, 32% with insulin-dependent diabetes mellitus) were studied. Multiple nutritional markers, including biochemical parameters and analysis of body composition, were assessed before the initial outpatient CHD treatment and every 3 months thereafter for 12 months. RESULTS: At baseline, nutritional markers correlated well with each other. After the initiation of HD therapy, there were marked improvements in most nutritional parameters, including serum albumin, serum prealbumin, normalized protein catabolic rate, fat mass, reactance, and phase angle (P < 0.05 for all). Improvements in nutritional parameters were influenced by baseline nutritional status; ie, baseline nutritional parameters were predictors of their end-of-study value. CONCLUSION: Initiation of CHD therapy is associated with improvements in most nutritional markers. Nutritional benefits of increased solute clearance provided by the initiation of chronic dialysis therapy prevail over its potential catabolic effects. However, the extent of improvement was dependent on nutritional status at the time of initiation of dialysis therapy, which remained an important determinant of subsequent nutritional improvements during the first year of treatment.

Assessment and monitoring of uremic malnutrition.

Assessment and monitoring of protein and energy nutritional status are essential to prevent, diagnose, and treat uremic malnutrition, a condition highly prevalent and associated with increased morbidity and mortality in patients with advanced kidney failure. Comprehensive assessments of protein and energy nutritional status can be achieved by several measurements to quantitatively and qualitatively estimate protein content in visceral and somatic body compartments, in addition to measurements of energy balance. However, uremic malnutrition is a complex metabolic disorder in which not only net nutrient intake is lower than nutrient requirements, leading to decreased tissue function and loss of body mass, but it is also associated with many comorbid conditions. Therefore, a clinically meaningful assessment of uremic malnutrition should include methods that are able to assess clinical outcome, identify the underlying diseases, and determine whether there is potential of benefit from nutritional interventions. Such assessment usually requires using multiple measurements concomitantly, with no definitive single method that can be considered as a "gold standard." In this review, we describe the various types of methods to assess uremic malnutrition, expanding and updating data on the readily available methods, and discuss more precise techniques to estimate protein and energy homeostasis. Special considerations of specific methods related to their clinical and/or research applicability as they pertain to renal failure are also addressed.

The extent of uremic malnutrition at the time of initiation of maintenance hemodialysis is associated with subsequent hospitalization.

OBJECTIVE: End-stage renal disease (ESRD) patients with signs of uremic malnutrition at the time of initiation of maintenance hemodialysis (MHD) are likely to remain malnourished over the subsequent year. Because poor nutritional status is associated with worse clinical outcomes in MHD patients, we hypothesized that ESRD patients with evidence of uremic malnutrition at the time of initiation of MHD would have more hospitalization events compared with patients initiating MHD without signs of malnutrition during the first year of therapy. DESIGN/INTERVENTION: This was an observational cohort of incident MHD patients, with no specific nutritional intervention. SETTING: Vanderbilt University Outpatient Dialysis Unit. PATIENTS: All newly initiated MHD patients at Vanderbilt University Outpatient Dialysis Unit were recruited for study purposes. A total of 149 patients were included in the study. MAIN OUTCOME MEASURE: The following parameters were recorded at the time of initiation of MHD: age; race; gender; serum concentrations of albumin, creatinine, cholesterol, and transferrin; and whether the patient had insulin-dependent diabetes mellitus. The number of hospital admissions and length of stay in the hospital were recorded for all study patients during the first year of MHD. Associated hospital charges were obtained for a subgroup of 52 patients. RESULTS: Study variables were associated with hospitalization in the subsequent year, the number of hospital admissions, and the length of stay in the hospital. Patients who initiated MHD in the lowest quartile of serum albumin had a significantly greater average of admissions compared with patients who initiated in the highest quartile (1.77 +/- 1.82 versus 0.72 +/- 0.96 admissions, P =.002). The length of stay in the hospital was also higher in the lowest quartile of serum albumin (8.96 +/- 9.96 versus 3.83 +/- 5.68 days, P =.006). Serum creatinine was also inversely associated with greater average number of admissions (2.27 +/- 2.41 versus 0.83 +/- 1.68 admissions, P =.004) and longer length of stay (12.43 +/- 15.15 versus 4.72 +/- 11.57 days, P =.017) in lowest compared with the highest quartile. In addition, the costs associated with hospitalizations were higher in the group of patients initiating MHD with lower concentrations of serum albumin and serum creatinine. CONCLUSIONS: In this study of incident MHD patients, the concentrations of 2 nutritional parameters, serum albumin and serum creatinine at the time of initiation of MHD, were significantly and negatively associated with hospitalization events. There was also a trend for greater hospital charges in patients with lower concentrations of serum albumin and creatinine.

Early intervention improves mortality and hospitalization rates in incident hemodialysis patients: RightStart program.

BACKGROUND AND OBJECTIVES: Annualized mortality rates of chronic hemodialysis (CHD) patients in their first 90 d of treatment range from 24 to 50%. Limited studies also show high hospitalization rates. It was hypothesized that a structured quality improvement program (RightStart), focused on medical needs and patient education and support, would improve outcomes for incident CHD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 918 CHD incident patients were prospectively enrolled in a multicenter RightStart Program, and compared with a time-concurrent group of 1020 control patients from non-RightStart clinics. RightStart patients received 3 mo of intervention in management of anemia, dosage of dialysis, nutrition, and dialysis access and a comprehensive educational program. Outcomes were tracked for up to 12 mo. RESULTS: At 3 mo, RightStart patients had higher albumin and hematocrit values. Dose of dialysis and permanent access placement were not statistically significantly different from control subjects. Compared with baseline, Mental Composite Score for RightStart patients improved significantly. Mean hospitalization days per patient year were reduced with RightStart versus control subjects. Mortality rates at 3, 6, and 12 mo were 20, 18, and 17 for RightStart patients versus 39, 33, and 30 deaths per 100 patient-years for control subjects, respectively. CONCLUSIONS: A structured program of prompt medical and educational strategies in incident CHD patients results in improved morbidity and mortality that last up to 1 yr.

Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview.

BACKGROUND AND OBJECTIVES: The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population. Results from clinical trials undertaken thus far, including trials on lipid reduction, normalization of hematocrit, and increased dialysis dosage, have been unsuccessful. Available data indicate that abnormalities in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism, are associated with an increased risk for death and cardiovascular events. However, no prospective trials have evaluated whether interventions that modify these laboratory parameters result in a reduction in adverse cardiovascular outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events is a global, phase 3, double-blind, randomized, placebo-controlled trial evaluating the effects of cinacalcet on mortality and cardiovascular events in hemodialysis patients with secondary hyperparathyroidism. Approximately 3800 patients from 22 countries will be randomly assigned to cinacalcet or placebo. Flexible use of traditional therapies will be permitted. The primary end point is the composite of time to all-cause mortality or first nonfatal cardiovascular event (myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular disease, including lower extremity revascularization and nontraumatic amputation). RESULTS: The study will be event driven (terminated at 1882 events) with an anticipated duration of approximately 4 yr. CONCLUSIONS: Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events will determine whether management of secondary hyperparathyroidism with cinacalcet reduces the risk for mortality and cardiovascular events in hemodialysis patients.

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.

Accelerated lean body mass loss in incident chronic dialysis patients with diabetes mellitus.

BACKGROUND: End-stage renal disease (ESRD) patients display a higher incidence of poor nutritional status and are at high risk of hospitalization and death. Patients on renal replacement therapy (RRT) with a primary diagnosis of diabetes mellitus have the lowest survival rates along with highest hospitalization incidence. METHODS: In this study, we examined the importance of diabetes mellitus along with certain demographic and clinical variables in predicting the change in lean body mass (LBM) by dual-energy x-ray absorptiometry (DEXA), as a surrogate marker of somatic protein stores, in 142 incident ESRD patients (91 males, 52.8 +/- 1.0 years, 74.2 +/- 1.2 kg body weight) among which 34 had diabetes mellitus (19 insulin-dependent and 15 noninsulin dependent). RESULTS: Our results show that patients with diabetes mellitus had significantly accelerated loss of LBM compared to nondiabetic patients during the first year of RRT (3.4 +/- 0.6 kg vs. 1.1 +/- 0.2 kg) (P < 0.05). Multivariate linear regression analyses revealed that the presence of diabetes mellitus was the strongest predictor of LBM loss independently of several clinically-relevant variables such as age, gender, serum albumin, presence of malnutrition, presence of inflammation, and RRT modality. CONCLUSION: We conclude that the presence of diabetes mellitus is the most significant independent predictor of LBM loss in renal replacement therapy patients, providing a potential explanation as to why ESRD patients with diabetes mellitus are more prone to muscle wasting.

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.

Insulin resistance in critically ill patients with acute renal failure.

Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort (n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period (P = 0.008, adjusted P = 0.013). In the larger PICARD cohort (n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 +/- 508 vs. 234 +/- 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 +/- 30.0 vs. 11.7 +/- 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 +/- 498 vs. 1,470 +/- 581 microg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.

Uremic malnutrition: new insights into an old problem.

Uremic malnutrition is highly prevalent and is associated with poor clinical outcomes in end-stage renal disease (ESRD) patients. Inadequate diet and a state of persistent catabolism play major roles in predisposing these patients to uremic malnutrition and appear to have an additive effect on overall outcome. Recent studies highlight the existence of a complex syndrome involving chronic inflammation, metabolic abnormalities, and hormonal derangements contributing to the increased morbidity and mortality observed in ESRD patients. Novel strategies such as appetite stimulants, anti-inflammatory drugs, and anabolic hormones along with conventional nutritional supplementation may provide potential interventions to improve clinical outcome in ESRD patients.

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.