Objective-We tested the hypothesis that long-term resistance exercise combined with intradialytic oral nutrition (IDON) supplementation will improve markers of muscle mass and strength further compared to IDON alone in chronic hemodialysis (CHD) patients. Design-Randomized controlled trial.Setting-Outpatient Dialysis Unit at an academic center.Main outcome measure-Lean body mass (LBM). Muscle strength and other nutritional parameters were measured as secondary outcomes.Patients-Thirty-two participants (age 43±13 yrs, 21 male) on CHD Design-Subjects 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 prior to each dialysis session in the NS+EX arm.Results-22 out of 32 participants completed the 6-month intervention. There were no statistically significant differences between the study interventions with respect to changes in LBM 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=0.02) and 1-Repetition Maximum (468±148 lb, 535±144 lb, 552±142 lb, respectively, P=0.001) increased statistically significantly during the study for all patients combined.Conclusion-This study did not show further benefits of additional resistance exercise on longterm somatic protein accretion above and beyond nutritional supplementation alone. When both treatments groups were combined, body weight and muscle strength improved during the study.

SummaryBackground Insulin resistance (IR) is highly prevalent in chronic hemodialysis (CHD) patients and is associated with poor cardiovascular outcomes. Hyperinsulinemic euglycemic glucose clamp (HEGC) is the gold standard for measuring IR. The comparison of commonly-used indirect indices of IR to HEGC has not been adequately performed in this population. Furthermore, the validity of newly proposed adipokine-based IR indices has not been explored. Design, setting, participants, & measurementsThis is an observational study performed in a single center, involving 12 prevalent CHD patients (50 Ϯ 9 years old, 100% African American, 33% women, body mass index of 34.4 Ϯ 7.6 kg/m 2 ) who were studied three consecutive times. IR was assessed by HEGC (glucosedisposal rate [GDR]), homeostatic model assessment of IR (HOMA-IR), HOMA-IR corrected by adiponectin (HOMA-AD), leptin adiponectin ratio (LAR), QUICKI, and the McAuley's index at each time point.Results Eighty-three percent of the subjects displayed either glucose intolerance or overt insulin resistance by HEGC (GDR median, 5.71; interquartile range [IQR], 4.16, 6.81). LAR and HOMA-AD were the best correlates of IR measured by HEGC (r ϭ Ϫ0.72, P Ͻ 0.001, and Ϫ0.67, P Ͻ 0.001), respectively. Fat percentage, interleukin-6, and adipokines (leptin, adiponectin, and resistin) were strongly associated with GDR. HEGC, LAR, and HOMA-AD had the best intraclass correlation coefficients.Conclusion IR is common in CHD patients. Adipokine-based indices are the best correlates of IR measurements by HEGC. HOMA-IR and QUICKI are reasonable alternatives. Use of these indices may allow better detection of alterations in insulin sensitivity in CHD patients.

BackgroundCoenzyme Q10 (CoQ10) supplementation improves mitochondrial coupling of respiration to oxidative phosphorylation, decreases superoxide production in endothelial cells, and may improve functional cardiac capacity in patients with congestive heart failure. There are no studies evaluating the safety, tolerability and efficacy of varying doses of CoQ10 in chronic hemodialysis patients, a population subject to increased oxidative stress.MethodsWe performed a dose escalation study to test the hypothesis that CoQ10 therapy is safe, well-tolerated, and improves biomarkers of oxidative stress in patients receiving hemodialysis therapy. Plasma concentrations of F2-isoprostanes and isofurans were measured to assess systemic oxidative stress and plasma CoQ10 concentrations were measured to determine dose, concentration and response relationships.ResultsFifteen of the 20 subjects completed the entire dose escalation sequence. Mean CoQ10 levels increased in a linear fashion from 704 ± 286 ng/mL at baseline to 4033 ± 1637 ng/mL, and plasma isofuran concentrations decreased from 141 ± 67.5 pg/mL at baseline to 72.2 ± 37.5 pg/mL at the completion of the study (P = 0.003 vs. baseline and P < 0.001 for the effect of dose escalation on isofurans). Plasma F2-isoprostane concentrations did not change during the study.ConclusionsCoQ10 supplementation at doses as high as 1800 mg per day was safe in all subjects and well-tolerated in most. Short-term daily CoQ10 supplementation decreased plasma isofuran concentrations in a dose dependent manner. CoQ10 supplementation may improve mitochondrial function and decrease oxidative stress in patients receiving hemodialysis.Trial RegistrationThis clinical trial was registered on clinicaltrials.gov [NCT00908297] on May 21, 2009.

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Objective-We examined the protein anabolic effects of Pro-Stat 64, a high nitrogen-containing, enzyme-hydrolyzed, tryptophan-fortified, collagen protein supplement administrated during hemodialysis, at two different dosing regimens.Design-This was a randomized, controlled, prospective study with 3 different groups: control, single dose of supplementation, and double dose of supplementation. Setting-This study was performed at a clinical research center.Patients-Six prevalent chronic hemodialysis (HD) patients were enrolled: 5 males, 1 female, 4 African Americans, and 2 Caucasians. Their mean age was 45 ± 11 years. Two patients were diabetic.Methods-Protein turnover studies were performed using amino-acid (AA) balance and primed constant infusion of L-(1-13 C) leucine.Main Outcome Measure-Whole-body protein balance was determined according to substrate kinetics.Results-There were no statistically significant difference at any time point between protocols for blood chemistries and hormonal markers, except for minor variations in plasma glucose. All plasma AA groups displayed decreases during control. Compared with the control group, plasma nonessential AA and total AA concentrations were statistically significantly higher during HD after both single and double doses of supplementation. The forearm arteriovenous AA balance was statistically significantly better for essential, nonessential, and total AA uptake after both single-dose and double-dose supplementation compared with the control group, except for nonessential AA, which was significantly better only after a double dose. Whole-body protein breakdown and net protein balance were statistically significantly better during HD with a double-dose administration in a dose-dependent manner, compared with the control and single-dose groups.Conclusions-Oral AA supplementation alone improves whole-body and skeletal muscle protein anabolism in a dose-dependent manner in chronic HD patients. These data should be taken into NUTRITIONAL SUPPLEMENTATION has been an effective strategy to overcome overt uremic protein-energy wasting, a state of metabolic and nutritional derangements known to be strongly associated with major adverse clinical outcomes in chronic hemodialysis (CHD) patients. 1,2 Several studies showed that parenteral and oral nutritional supplementation administered during hemodialysis led to a protein anabolic response in CHD patients. [3][4][5] In all these studies, the nutritional supplementation, oral or parenteral, contained variable amounts of protein, carbohydrate, and fat. A very limited number of studies examined the efficacy and feasibility of more selective protein supplementation in CHD patients.Amino acids are considered the most physiologically active substrate for promoting net protein anabolism. 6 Amino-acid administration enhances protein synthesis primarily via increased delivery to the muscle tissue. On the other hand, concurrent carbohydrate intake may be necessary to promote net anabolism, insofar as this would lead to increased in...