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NDT Advance Access published online on December 9, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm773
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Resistance Exercise Augments the Acute Anabolic Effects of Intradialytic Oral Nutritional Supplementation

Karen M. Majchrzak, Lara B. Pupim, Paul J. Flakoll* and T. Alp Ikizler

Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA

Correspondence and offprint requests to: T. Alp Ikizler, Division of Nephrology, Vanderbilt University Medical Center, 1161 21st Ave. South & Garland, S-3223 MCN, Nashville, TN 37232–2372, USA. Tel: +1-615-343-6104; Fax: +1-615-343-7156; E-mail: alp.ikizler{at}vanderbilt.edu



   Abstract
Top
 Abstract
Introduction
 Methods
 Calculations
 Results
 Discussion
 References
 
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 µg/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.

Keywords: haemodialysis; metabolism; protein supplementation; resistance exercise



   Introduction
Top
 Abstract
 Introduction
Methods
 Calculations
 Results
 Discussion
 References
 
A state of protein and energy depletion associated with muscle wasting, is highly prevalent in chronic haemodialysis (CHD) patients and is significantly associated with increased rates of hospitalization and death in this patient population [1–6]. Recent studies have indicated that intradialytic nutritional supplementation, administered parenterally or orally prevent haemodialysis (HD)-associated protein catabolism and results in a protein anabolic response [7–10]. An intriguing strategy to further enhance the anabolic effects of nutritional supplementation is to combine the administration of nutrients with resistance exercise. Detailed studies in healthy subjects have shown that post-exercise muscle protein accretion is increased with oral nutritional supplementation when compared to exercise performed in a fasting state [11,12]. Consistent with these findings, our laboratory has previously shown that the anabolic effect of intradialytic parenteral nutrition (IDPN) in the acute setting is augmented when combined with an aerobic exercise protocol [13]. Similar studies using oral nutritional supplementation as the primary nutrient delivery method and resistance exercise as the additional anabolic strategy have not been performed in the CHD population. Such an approach is more practical and scientifically laudable as resistance exercise is the primary mode for increasing muscle mass.

In the present study, 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 CHD patients. In order to test this hypothesis, we performed stable isotope protein kinetic studies in eight CHD patients during two separate HD sessions: with oral nutritional supplementation alone (PO) and oral nutritional supplementation combined with a single bout of resistance exercise (PO + EX).



   Methods
Top
 Abstract
 Introduction
 Methods
Calculations
 Results
 Discussion
 References
 
Study patients
Patients were recruited from the Vanderbilt University Outpatient Dialysis Unit. Inclusion criteria consisted of patients who had been on CHD for more than 3 months, with less than 100 ml/min of urine output, using a biocompatible HD membrane (Fresenius F80, Fresenius USA, Lexington, MA, USA), receiving an adequate dose of dialysis (double pool Kt/V ≥ 1.2), on a thrice-weekly HD program. Patients with active infectious disease, hospitalized within 1 month prior to the study, with recirculation in the vascular access and/or vascular access blood flow less than 500 ml/min, receiving steroids and/or immunosuppressive agents, and not capable of exercise were excluded from the study. The Institutional Review Board of Vanderbilt University approved the study protocol and written informed consent was obtained from all study patients.

Study design
This was a randomized, prospective, crossover study. After obtaining written informed consent and reviewing the inclusion and exclusion criteria, eligible patients were randomly assigned to complete the metabolic study protocols PO or PO + EX as the first protocol. All patients who participated in the study completed both protocols, with at least 4 weeks between each study, to allow for total clearance of the stable isotopes. Within a week prior to each study, dual-energy x-ray absorptiometry (DEXA) was performed to estimate lean and fat body masses, and a one-repetition maximum dual leg press exercise was performed to determine the maximum amount of weight a participant could achieve at one time.

Metabolic study
The patients were admitted to the General Clinical Research Center (GCRC) the day before the study at approximately 7 p.m., received a meal from the GCRC bio-nutrition services upon admission and remained in a fasting state hereafter. The last meal was given at least 10 h prior to the initiation of the study for all patients and consisted of 18% protein and 30% lipids. Energy intake was kept at maintenance levels based on the Harris–Benedict equation and each subject's gender, height, weight and activity levels.

A schematic diagram of the metabolic study day protocol is depicted in Figure 1. Each metabolic study consisted of a pre-HD phase (a 2-h equilibration phase followed by a 0.5-h basal sampling phase), a 1-h phase prior to dialysis to complete the intervention, a 4-h dialysis phase and a 2-h post-HD phase. Constant infusion of isotopes continued throughout the study. Blood and breath samples were collected once prior to the start of the study, three times during the basal sampling phase, six times during HD and three times during the post-HD phase. A dialysis catheter was placed at the venous site of the arteriovenous (AV) shunt of the forearm at 6 a.m. to collect a baseline blood sample (to assess baseline biochemical nutritional markers and isotopic backgrounds) and then to initiate the isotope infusion. Arterial vascular access obtained through the arterial side of the AV shunt was used to perform HD and to sample arterial blood. The venous site of the AV shunt was used to infuse the isotopes. Recirculation of the AV shunt as well as vascular access blood flow to assess stenoses in the AV shunts was checked in every patient prior to each study utilizing the ultrasound dilution technique (Transonic Systems Inc., Ithaca, NY, USA). Another catheter was placed in a deep vein (on a retrograde insertion) of the contra-lateral forearm to sample blood draining the forearm muscle bed. At the start of the infusion, subjects received a bolus injection of NaH13CO3 (0.12 mg/kg), L-(1-13C) leucine (7.2 µmol/kg), and L-(ring-2H5) phenylalanine (7.2 µmol/ kg) to prime the CO2, leucine and phenylalanine pools, respectively. A continuous infusion of leucine (0.12 µmol/ kg/min) and phenylalanine (0.12 µmol/kg/min) isotopes was then started and continued throughout the remainder of the study.


Figure 1
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  		Fig. 1. Schematic diagram of the metabolic study day protocol. Figure 1 indicate time points for blood draws, breath sample collections and muscle plasma flow measurements. A primed-constant infusion of L-(1-13C) leucine and L-(ring-2H5) phenylalanine was maintained throughout the entire study.

 
During each study, patients were dialyzed for 4 h with blood flow of 400 ml/min and dialysate flow of 500 ml/min. Ultrafiltration rates were determined by the patients’ needs and ‘estimated dry weight’ was similar during both studies. The composition of the dialysate used during the study was identical for all treatments and consisted of sodium 139 mEq/l, potassium 2 mEq/l, calcium 2.5 mEq/l, glucose 200 mg/dl and bicarbonate 39 mEq/l. The extra volume, as well as electrolytes that PO provided to the patients, was accounted for and removed during HD. Once HD was finished, dialysis lines were disconnected and the 2-h post-HD phase ensued. After the post-HD phase, all catheters were removed; the patients were given a meal and observed at the GCRC until stable, upon which they were discharged.

Anabolic interventions
Patients received the exact same type of oral nutritional supplementation during both protocols (PO and PO + EX), which consisted of a specialized nutrition for ESRD patients (NEPRO®). As shown in Figure 1, after the basal sampling phase, patients were given one can of nutrition and allowed approximately 15–25 min to consume the entire can. A second can was given 15 min after the initiation of HD. Each can provided 497 kilocalories, 16.7 g of protein, 52.8 g of carbohydrate and 22.7 g of fat. When the subjects participated in the PO + EX protocol, resistance leg press exercise was initiated after consumption of the first can of nutrition. Subjects ambulated to the dual leg press machine and performed three sets of 12 repetitions at 75% of their one-repetition maximum. Each subject performed the exercise with correct form and speed (1:3 second concentric/eccentric ratio), and a timed 1-min rest period was utilized between each set. Other than the addition of the resistance exercise, both protocols were identical in every way.

Analytical procedures
Blood samples were collected into Venoject tubes containing 15 mg Na2EDTA (Terumo Medical Corp., Elkton, MD, USA). All analytical procedures, including nutritional biochemical markers, were preformed as described previously [8,13]. Individual amino acids were also placed into groups for analysis purposes (essential amino acids: EAA—the sum of arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, theonine, tryptophan and valine; total amino acids: TAA—the sum of all individual amino acids; nonessential amino acids: NEAA—the difference between TAA and EAA). Plasma enrichments of (13C) leucine, (13C) ketoisocaproate (KIC) and (ring-2H5) phenylalanine were determined using gas chromatography/mass spectrometry (GC/MS—Hewlett-Packard 5890a GC and 5970 MS, San Fernando, CA, USA), as described previously [8,13].



   Calculations
Top
 Abstract
 Introduction
 Methods
 Calculations
Results
 Discussion
 References
 
Net skeletal muscle protein balance (synthesis-breakdown) was determined by dilution and enrichment of phenylalanine across the forearm as described by Gelfand and Barrett [14] and as previously reported [8,13]. Because phenylalanine is neither synthesized de novo nor metabolized by skeletal muscle, the rate of appearance (Ra) of unlabeled phenylalanine reflects muscle protein breakdown, whereas the rate of disappearance (Rd) of labeled phenylalanine estimates muscle protein synthesis [15]. Phenylalanine Rd was calculated by multiplying the fractional extraction of the labeled phenylalanine (based on plasma arterial and venous phenylalanine enrichments and concentrations) by the arterial phenylalanine concentration and normalized to forearm blood flow measured by plethysmography (expressed as 100 ml/min). Net phenylalanine Ra was calculated by subtracting the net AV balance of phenylalanine across the extremity from the phenylalanine Rd [16]. Rates of skeletal muscle protein breakdown and net synthesis were determined from the phenylalanine Rd and Ra, assuming that 3.8% of skeletal muscle protein comprises phenylalanine.

Endogenous leucine Ra (an estimate of whole-body protein breakdown) was determined by subtracting the rate of leucine infusion via the nutritional supplementation from the total Ra (expressed as milligram per kilogram of FFM per minute). Breath 13CO2 production was determined by multiplying the total CO2 production rate by the breath 13CO2 enrichment. The rate of whole-body leucine oxidation was calculated by dividing breath 13CO2 production by 0.8 (correction factor for the retention of 13CO2 in the bicarbonate pool) and by the plasma KIC enrichment. Leucine Rd during the dialysis phase was corrected for leucine loss into the ultrafiltration volume by measuring the ultrafiltration volume and the leucine concentration in the dialysate and by subtracting the leucine lost in the dialysate from the total Ra. The nonoxidative leucine Rd, an estimate of whole-body protein synthesis, was determined indirectly by subtracting leucine oxidation from corrected total leucine Rd [16].

The steady-state rates of total whole-body leucine appearance (Ra) were calculated by dividing the (13C)leucine infusion rate by the plasma (13C)KIC enrichment [16] and as described previously [8,13]. Steady-state conditions for KIC and phenylalanine enrichments were achieved as evidenced by slopes within each study period not significantly different from zero (Figures 2 and 3). Amino acid enrichment calculations were corrected for amino acid losses into the ultrafiltration volume by measuring the ultrafiltration volume and the amino acid concentration in the dialysate and by subtracting the amino acid lost in the dialysate from the total rate of appearance of amino acid in the plasma. Rates of whole-body protein breakdown, AA oxidation and protein synthesis were calculated from the endogenous leucine Ra, the leucine oxidation rate and the nonoxidative leucine Rd, respectively, assuming that 7.8% of whole-body protein comprises leucine [15].


Figure 2
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  		Fig. 2. KIC mass percent enrichment (MPE) during each time point for each study phase. Steady-state conditions for KIC enrichment was achieved as evidenced by slopes within each phase not significantly different than zero.

 

Figure 3
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  		Fig. 3. Phenylalanine mass percent enrichment (MPE). Steady-state conditions for phenylalanine enrichment was achieved as evidenced by slopes within each phase not significantly different than zero.

 
Statistical analysis
For each protocol, mean variables across all time points for each study phase (before, during and after HD) were averaged to represent each study phase average per patient. Values presented in the text and figures are means ± SEM, unless otherwise noted. The goal of this study was to compare PO and PO + EX at each study phase separately, rather than looking at time trends for each variable and their interaction throughout the study phases. Therefore, for comparisons of variables between study protocols at each study phase, a paired t-test for parametric distribution and the Wilcoxon signed-rank test for nonparametric distribution were used to determine which means differed. A P-value < 0.05 was required to reject the null hypothesis of no difference between the means. The software SPSS (SPSS Inc., Chicago, IL, USA) version 14 was used for all analyses.



   Results
Top
 Abstract
 Introduction
 Methods
 Calculations
 Results
Discussion
 References
 
Subject characteristics
Table 1 depicts subject characteristics, resistance exercise workload, and baseline biochemical nutritional markers for the study protocols. As can be seen, baseline biochemical nutritional markers were similar between the protocols, and there were no statistically significant differences in these variables between protocols.


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  		Table 1. Demographic, nutritional characteristics, resistance exercise and biochemical parameters of the study population (n = 8)

 
Metabolic hormones
Table 2 shows the results for glucose, metabolic hormones, and forearm plasma flow for the two study protocols. The observed changes in the hormone profiles were consistent with our previous reports and did not reveal any significant differences between PO + EX and PO protocols at any time point during the metabolic studies (before, during or after HD).


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  		Table 2. Plasma metabolic hormones, glucose concentrations and forearm plasma flow

 
Plasma amino acid concentrations and forearm amino acid uptake
There were no significant differences between study protocols for any of the plasma amino acid (AA) concentrations before, during or after HD (Table 3).


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  		Table 3. Plasma amino acid concentrations

 
The forearm uptakes of AA by functional groups are depicted in Table 4. There were no statistically significant differences between the two protocols when comparing phases before, during or after HD. PO resulted in a numerically higher positive balance in all functional groups during HD; however, during the post-HD phase, PO + EX retained a positive TAA balance (primarily due to EAA balance), while PO returned to a negative TAA balance, indicating a continuation of skeletal muscle protein accretion during the post-HD phase with the PO + EX protocol although this difference was not statistically significant.


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  		Table 4. Amino acid uptake by the forearm; individual amino acids were also placed into groups for analysis purposes

 
Whole-body protein metabolism
Table 5 shows the components of whole-body protein homeostasis for the two study protocols at phases before, during HD. There were no statistically significant differences between protocols for any of the whole-body protein turnover components.


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  		Table 5. Components of whole body protein metabolism

 
Forearm muscle protein metabolism
Table 6 and Figure 4 depict the dynamic components of the forearm muscle protein homeostasis. At baseline and during HD, there were no statistically significant differences between the study protocols. In the post-HD phase, PO + EX had significantly higher net muscle protein balance when compared to PO (P = 0.036). During the post-HD period, the PO protocol returned to pre-HD values while the PO + EX protocol remained in a positive net balance, which is consistent with the forearm AA uptake data. In other words, in the post-HD period, forearm muscle protein synthesis was higher, although not statistically significant, with addition of exercise compared to nutritional supplementation alone. Forearm protein degradation was also higher with exercise, although not statistically significant. While increased muscle proteolysis is a typical result of exercise performance, our findings indicated that protein synthesis increased to a higher extent than proteolysis, which resulted in positive net forearm muscle protein balance with exercise (muscle protein anabolism), compared to a negative net forearm muscle protein balance without exercise (muscle protein catabolism).


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  		Table 6. Components of forearm muscle protein metabolism

 

Figure 4
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  		Fig. 4. Forearm muscle protein metabolism before, during, and after HD, comparing PO ({square}) and PO + EX ({blacksquare}). Units are µg/100ml/min. * denotes P < 0.05 versus PO.

 


   Discussion
Top
 Abstract
 Introduction
 Methods
 Calculations
 Results
 Discussion
References
 
In this study, we report that the acute protein anabolic effects of intradialytic oral nutritional supplementation are further enhanced by the addition of resistance exercise. This additive beneficial effect is primarily observed in the skeletal muscle tissue and after the cessation of HD. Overall, these results provide an exciting practical nutritional strategy to improve KDW [5,17–23].

The current study has several important clinical implications. Most importantly, we provide an effective strategy to overcome a highly prevalent nutritional derangement in a very high risk patient population. There is now unequivocal evidence to indicate that nutritional status of CHD patients is the most significant predictor of their clinical outcome. Further, our intervention is practical and can be implemented in the outpatient setting with minimal logistical constraints. Specifically, the nutritional supplementation utilized in this particular study is readily available, relatively well tolerated and significantly more economical than parenteral nutrition. While we utilized a rather sophisticated device for our resistance exercise intervention, this was primarily done to appropriately quantify the amount of resistance in the research setting. A similar level of resistance could readily be implemented by utilizing bar and/or free weights [24] and performing standing leg squats.

The mechanism(s) leading to the additive anabolic effects of resistance exercise are several fold. Studies in multiple patient populations have shown that resistance exercise in general increases skeletal muscle protein synthesis, which persists for up to 48 h [25]. However, when exercise is performed in the fasted state, there is increased skeletal muscle protein turnover but often the rate of protein breakdown exceeds the rate of protein synthesis, which would result in net negative protein balance (muscle protein loss). Exercise-driven muscle anabolism requires adequate substrate availability, primarily to promote protein synthesis in excess of protein breakdown. This stipulation is especially relevant in CHD patients. More specifically, we have previously shown that AA availability is significantly decreased during HD [26], leading to significantly decreased plasma AA concentrations, hence decreased protein synthesis. Consistent with these observations are the several subsequently published studies indicating that provision of AA supplementation during HD, either parenterally or orally, counteracts the HD-associated net protein catabolism in CHD patients [7–9]. In addition, it is not uncommon for CHD patients to have an insufficient amount of dietary protein intake. It is therefore plausible that the strategy employed in this particular study would optimize separate anabolic interventions reported in several recent studies resulting in the best possible anabolic effect (i.e., maximum increase in muscle mass) [7,27–29].

The foregoing discussion should also be interpreted in the context of the choice of exercise type in this particular study. While we have previously shown that a short bout of aerobic exercise can significantly augment the protein anabolic effects of IDPN, extensive research in healthy individuals indicates that resistance rather than endurance exercise is the optimal strategy to expand skeletal muscle mass [13]. Indeed, we were able to show somewhat comparable beneficial effect to our previous report in the skeletal muscle turnover. It must also be noted that the additive effect of exercise was observed during the post-HD period as opposed to during HD, which was the case for the IDPN and aerobic exercise intervention. While the cause of this discrepancy is not clear, it is most likely related to the time needed for absorption of oral AA versus the immediate availability of AA provided by parenteral administration. Likewise, this might be the reason for our observations that oral nutritional supplementation plus resistance exercise promotes continued anabolic effects once the HD procedure is finished, likely due to the prolonged availability of substrates, whereas the anabolic effects of IDPN plus aerobic exercise seem to be limited to the period when it is being infused [7]. This is even more intriguing when one considers the relatively lower amounts of AA supplied by the oral route in the current study. It is also possible that the direct effects of each exercise intervention might be different, both on physiological and cellular levels. However, it is not clear whether this strategy will have a superior effect on accretion of muscle mass in the long-term. In a recent report by Kopple et al., it was determined that the beneficial molecular changes observed in skeletal muscle tissue are more profound in CHD patients undergoing long-term endurance exercise versus resistance exercise (abstract, ASN 2006). Needless to say, these strategies need to be tested and confirmed with future studies.

While intriguing, the results of this study should be interpreted with caution. First, our results are only applicable for measure of skeletal muscle protein metabolism in the acute setting. Clearly, long-term studies are warranted to determine if indeed resistance exercise and intradialytic oral nutritional studies can result in an increase in muscle mass over time and how a long-term intervention would affect physical activity and physical functioning. For example, Johansen et al. reported that resistance exercise during HD (without any specific concomitant nutrient supplementation) led to an increase in fat mass over 3 months rather than lean body mass in otherwise stable CHD patients [28]. The tolerability of the nutritional supplement over a long period of time should also be considered and the particular supplement administered in this study may be considered ‘rich’ especially in the elderly population. Additionally, we did not examine the mechanisms mediating these effects in the skeletal muscle tissue at the molecular level. While exploring these mechanisms are not vital to this particular report, they undoubtedly would provide novel information that could lead to newer strategies to overcome the muscle wasting which is observed in chronic disease states such as advanced uraemia. Another potential limitation of the present study is the relatively small sample size for analysis of highly variable measures, such as forearm muscle amino acid uptake. Finally, this study did not include patients with overall muscle wasting and/or with uraemic malnutrition. It is possible that the additional beneficial effects of resistance exercise to nutritional supplementation in preventing protein catabolism during the HD procedure may be different in clearly wasted and/or malnourished patients.

In summary, we report that a single bout of resistance exercise augments the protein anabolic effects of oral intradialytic nutritional supplementation on skeletal muscle protein turnover. While these results need to be confirmed with long-term studies to examine the overall somatic and visceral protein accretion overtime, they provide an intriguing strategy to prevent and/or treat uraemic wasting syndrome.



   Acknowledgments
 
The authors would like to express their appreciation to the patients and staff of Vanderbilt University Medical Center, Outpatient Dialysis Unit for their participation in the study. This study is supported in part by National Institutes of Health Grant R01-DK45604, K24-DK62849, General Clinical Research Center (GCRC) Grant M01-RR00095 and Diabetes Research Training Center Grant #DK-20593 and Satellite Health Norman Coplon Extramural Grant Program. The excellent technical assistance of Mary Sundell, Phyllis Egbert, Cindy Booker, Suzan Vaughan, Feng Sha, Mu Zheng, Wanda Snead and the nursing staff on the Vanderbilt GCRC is appreciated.

Conflict of interest statement. The authors declare no conflict of interest with regard to involvement with commercial entities that supply nutritional supplements. Lara B. Pupim is an Adjunct Professor at Vanderbilt University Medical Center and is an employee of Amgen Inc. since August of 2005, and declares no conflict of interest with the present work.



   Notes
 
* In memoriam. Back



   References
Top
 Abstract
 Introduction
 Methods
 Calculations
 Results
 Discussion
 References
 

  1. Churchill DN, Taylor DW, Cook RJ, et al. Canadian hemodialysis morbidity study. Am J Kidney Dis (1992) 19:214–234.[Web of Science][Medline]
  2. Collins AJ, Ma JZ, Umen A, et al. Urea index and other predictors of hemodialysis patient survival. Am J Kidney Dis (1993) 23:272–282.[Web of Science]
  3. Goldwasser P, Mittman M, Antignani A, et al. Predictors of mortality on hemodialysis. J Am Soc Nephrol (1993) 3:1613–1622.[Abstract]
  4. Ikizler TA, Wingard RL, Harvell J, et al. Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: a prospective study. Kidney Int (1999) 55:1945–1951.[CrossRef][Web of Science][Medline]
  5. Kopple JD. Effect of nutrition on morbidity and mortality in maintenance dialysis patients. Am J Kidney Dis (1994) 24:1002–1009.[Web of Science][Medline]
  6. Lowrie EG, Huang WH, Lew NL. The relative contribution of measured variables to death risk among hemodialysis patients. In: Death on Hemodialysis—Friedman EA, et al, eds. (1994) Amsterdam: Kluwer. 121–141.
  7. Pupim LB, Majchrzak KM, Flakoll PJ, et al. Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status. J Am Soc Nephrol (2006) 17:3149–3157.[Abstract/Free Full Text]
  8. Pupim LB, Flakoll PJ, Brouillette JR, et al. Intradialytic parenteral nutrition improves protein and energy homeostasis in chronic hemodialysis patients. J Clin Invest (2002) 110:483–492.[CrossRef][Web of Science][Medline]
  9. Veeneman JM, Kingma HA, Boer TS, et al. Protein intake during hemodialysis maintains a positive whole body protein balance in chronic hemodialysis patients. Am J Physiol Endocrinol Metab (2003) 284:E954–E965.[Abstract/Free Full Text]
  10. Cano N. Nutritional supplementation in adult patients on hemodialysis. J Ren Nutr (2007) 17:103–105.[CrossRef][Web of Science][Medline]
  11. Biolo G, Tipton KD, Klein S, et al. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol (1997) 273:E122–E129.[Web of Science][Medline]
  12. Gautsch TA, Anthony JC, Kimball SR, et al. Availability of eIF4E regulates skeletal muscle protein synthesis during recovery from exercise. Am J Physiol (1998) 274:C406–C414.[Web of Science][Medline]
  13. Pupim LB, Flakoll PJ, Levenhagen DK, et al. Exercise augments the acute anabolic effects of intradialytic parenteral nutrition in chronic hemodialysis patients. Am J Physiol Endocrinol Metab (2003) 286:E589–97.[CrossRef][Web of Science][Medline]
  14. Barrett EJ, Revkin JH, Young LH, et al. An isotopic method for measurement of muscle protein synthesis and degradation in vivo. Biochem J (1987) 245:223–228.[Web of Science][Medline]
  15. Wolfe RR. Tracers in metabolic research: radioisotope and stable isotope/mass spectrometry methods. Lab Res Methods Biol Med (1984) 9:1–287.[Medline]
  16. Wolfe RR. Radioactive and Stable Isotope Tracers in Biomedicine: Principles and Practice of Kinetic Analysis (1992) New York: Wiley-Liss. 283–316.
  17. Bergstrom J. Protein catabolic factors in patients on renal replacement therapy. Adv Exp Med Biol (1989) 260:1–9.[Medline]
  18. Bergstrom J. Nutrition and mortality in hemodialysis. J Am Soc Nephrol (1995) 6:1329–1341.[Abstract]
  19. Hakim RM, Levin N. Malnutrition in hemodialysis patients. Am J Kidney Dis (1993) 21:125–137.[Web of Science][Medline]
  20. Ikizler TA, Hakim RM. Nutrition in end-stage renal disease. Kidney Int (1996) 50:343–357.[Web of Science][Medline]
  21. Kopple JD. Causes of catabolism and wasting in acute or chronic renal failure. In: Nephrology—Robinson RR, ed. (1984) 2nd edn. New York: Springer. 1498.
  22. Mitch WE, Goldberg AL. Mechanism of muscle wasting: the role of ubiquitin-proteasome pathway. N Engl J Med (1997) 335:1897–1905.[CrossRef][Web of Science]
  23. Mitch WE, Walser M. Nutritional therapy of the uremic patient. In: The Kidney—Brenner BM, Rector FC, eds. (1991) 4th edn. Philadelphia: Saunders. 2186–2222.
  24. Cheema B, Abas H, Smith B, et al. Progressive exercise for anabolism in kidney disease (PEAK): a randomized, controlled trial of resistance training during hemodialysis. J Am Soc Nephrol (2007) 18:1594–1601.[Abstract/Free Full Text]
  25. Wolfe RR. Skeletal muscle protein metabolism and resistance exercise. J Nutr (2006) 136:525S–528S.[Abstract/Free Full Text]
  26. Ikizler TA, Pupim LB, Brouillette JR, et al. Hemodialysis stimulates muscle and whole-body protein loss and alters substrate oxidation. Am J Physiol Endocrinol Metab (2002) 282:E107–E116.[Abstract/Free Full Text]
  27. Macdonald JH, Marcora SM, Jibani M, et al. Intradialytic exercise as anabolic therapy in haemodialysis patients—a pilot study. Clin Physiol Funct Imaging (2005) 25:113–118.[CrossRef][Web of Science][Medline]
  28. Johansen KL, Painter PL, Sakkas GK, et al. Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: a randomized, controlled trial. J Am Soc Nephrol (2006) 17:2307–2314.[Abstract/Free Full Text]
  29. Headley S, Germain M, Mailloux P, et al. Resistance training improves strength and functional measures in patients with end-stage renal disease. Am J Kidney Dis (2002) 40:355–364.[CrossRef][Web of Science][Medline]
Received for publication: 7. 5.07
Accepted in revised form: 4.10.07


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Am. J. Clinical Nutrition, March 1, 2009; 89(3): 787 - 793.
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