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Published ahead of print on April 19, 2006
Clin J Am Soc Nephrol 1: 488-495, 2006
© 2006 American Society of Nephrology
doi: 10.2215/CJN.01501005
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Clinical Nephrology

Exercise Performance Falls over Time in Patients with Chronic Kidney Disease Despite Maintenance of Hemoglobin Concentration

Murray J. Leikis*,{dagger}, Michael J. McKenna{ddagger}, Aaron C. Petersen{ddagger}, Annette B. Kent*, Kate T. Murphy{ddagger}, James A. Leppik{ddagger}, Xiaofei Gong{ddagger}, and Lawrence P. McMahon*,{dagger}

* Department of Nephrology, Royal Melbourne Hospital and Western Hospital; {dagger} Department of Medicine, University of Melbourne; and {ddagger} School of Human Movement, Recreation & Performance, Centre for Ageing, Rehabilitation, Exercise and Sport, Victoria University, Melbourne, Australia

Address correspondence to: Dr. Murray Leikis, Wellington Hospital, Department of Renal Medicine, Private Bag 7902, Wellington 6001, New Zealand. Phone: +4-385-5696; Fax: +4-385-5521; E-mail: murray.leikis{at}ccdhb.org.nz


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Physical function is limited in patients with kidney disease, although previous studies have been confounded by anemia. What is not clear is how physical performance changes over time as renal function deteriorates. A cohort of 12 patients (10 male, two female; mean ± SD age 49 ± 11 yr) who had stages 3 to 4 chronic kidney disease without previous anemia were examined, and nine were followed for a 2-yr period. Assessments were made of peak oxygen consumption (VO2peak) by cycle ergometry, leg extension strength, and fatigue on an isokinetic dynamometer and thigh muscle cross-sectional area (TMCSA) by computed tomography. At baseline, creatinine clearance was 31 ± 13 ml/min and hemoglobin concentration ([Hb]) was 129 ± 9g/L. VO2peak was low (1.88 L/min, 82% of predicted), and maximal isometric voluntary contraction was 188 ± 42 Nm, with a TMCSA of 144 ± 27 cm2. VO2peak correlated with creatinine clearance corrected for body surface area (r = 0.613, P = 0.034) but not to [Hb]. VO2peak adjusted for patient weight correlated with leg fatigue (r = –0.693, P = 0.012). For those with follow-up tests, there were falls in renal function by 28% (P = 0.007) and VO2peak by 9% (P = 0.03), whereas [Hb] did not change. Leg strength fell across a range of isokinetic speeds (P = 0.04), whereas no change in TMCSA was observed. In conclusion, exercise performance as measured by aerobic (VO2peak) and leg strength tests were reduced in patients with stages 3 to 4 chronic kidney disease. As renal function declined over time, there was a corresponding decline in exercise performance even when [Hb] was maintained.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
It is well recognized that patients with chronic kidney disease (CKD) have limited physical function. This has been shown both subjectively in quality-of-life surveys (1) and objectively by measures of exercise such as walking times/distances (2), treadmill (3) and cycle ergometry tests (4–6), and measures of strength (3,6–8). A reduced ability to exercise has significance not only on quality of life but also on morbidity and mortality. Using the Short Form 36 (SF-36) quality-of-life questionnaire, low scores for self-reported physical function in patients who initiated dialysis are independently associated with a higher mortality risk (to a level similar to that of low albumin) (9).

Why exercise performance is limited remains unclear. In patients with CKD, there is an independent association with exercise performance across a wide range of renal function (5) that can be improved significantly after renal transplantation (10). However, despite good kidney function and exercise training programs, the level of exercise performance does not return to expected "normal" values up to 1 yr after transplantation (11). The most significant feature that confounds many of these studies is anemia, which, when treated in both patients with CKD (12) and hemodialysis patients (13–17), has resulted in improved exercise performance. Unfortunately, the absolute rise in hemoglobin (Hb) has not been matched by similar improvements in exercise.

We also previously found impaired potassium (K+) regulation during exercise in hemodialysis patients compared with healthy control subjects (18). Because muscle K+ disturbances are linked with muscle fatigue (19), this was suggested to contribute to reduced exercise capacity in hemodialysis patients (18). When Hb concentration ([Hb]) was corrected, the change in plasma [K+] to work performed ({Delta}[K+]/work) ratio (as a marker of K+ regulation during exercise) was inversely related to [Hb] (15). This has not been studied in patients who have CKD and are not on dialysis.

We therefore studied patients who have CKD and have not had a history of anemia to assess the relationships of aerobic exercise performance, muscular strength, and fatigability with renal function and muscle mass. We then followed the cohort for up to 2 yr to examine the relative impact of changes in kidney function and [Hb] with respect to exercise performance. In addition, we studied aerobic performance with respect to K+ regulation.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Patients with CKD were recruited from the Royal Melbourne and Western Hospitals (Victoria, Australia) and followed for 2 yr or until they commenced dialysis if renal function deteriorated. The research was carried out under the principles of the Declaration of Helsinki. All patients gave written informed consent after approval from the human research ethics committees of the Royal Melbourne Hospital and Victoria University (Melbourne, Australia).

Inclusion criteria were age between 18 and 70 yr, a calculated creatinine clearance (Cockcroft-Gault) between 15 and 50 ml/min, and [Hb] ≥120 g/L with satisfactory iron stores. Exclusion criteria were a history of [Hb] <120 g/L at any time, expected to commence dialysis within 12 mo, body mass index >40 kg/m2, significant history of left ventricular failure or ischemic heart disease, peripheral vascular or cerebrovascular disease, uncontrolled hypertension, severe hyperparathyroidism, pregnancy, active malignancy, or renal transplant.

Data were collected on patients’ age, gender, and body size. Hematology and biochemistry tests were performed at baseline and every 3 mo during the course of the study. Creatinine clearance was calculated as per Cockcroft and Gault (20). Medications and medical and social history were noted at each exercise test visit.

Tests
The following tests were performed at both baseline and end of study. Cycle ergometry and leg strength tests were performed on different days separated by a minimum of 48 h.

Cycle Ergometry and Peak Oxygen Consumption.  All tests were performed on an electronically braked cycle ergometer (Lode Excalibur, Groningen, Netherlands) with seat and handlebar positions kept constant for each patient upon repeated testing. An incremental exercise test was performed according to a protocol of 2 min seated rest followed by cycling with a pedal cadence of 60 to 70 rpm. An initial resistance of 15 W was applied and increased by 15 W each minute until fatigue, defined as the inability to maintain pedal cadence >60 rpm. Expired air was collected via a two-way nonrebreathing valve (Hans-Rudolph Co., Kansas City, MO) and a 6-L mixing chamber. Expired volume was measured using a flow transducer (KL Engineering, Sunnydale, CA), and mixed expired oxygen and carbon dioxide were analyzed by rapid responding gas analyzers (model S-3A; Amtek, Pittsburgh, PA). Ventilatory gas data were calculated over 15 s, and VO2 was calculated (TurboFit, Ventura, CA). Recordings were taken every 15 s, and the VO2peak was taken as the highest recorded mean of two consecutive results. All patients had 12-lead cardiac telemetry monitoring during the test and for 30 min after fatigue. Predicted VO2peak was calculated using the formula of Wasserman for sedentary, healthy individuals (21).

Blood Sampling.  A 20-G intravenous cannula was inserted into a dorsal hand vein or distal forearm vein for blood sampling during the test. The venous blood was arterialized by placing the hand in a water bath (45°C) for 10 min before exercise testing and sustained until 10 min into recovery (22). Samples were taken at rest; at the end of each minute of exercise until fatigue; at fatigue; and then at 1, 2, 5, and 10 min into recovery. A 4-ml sample was collected in a plain tube. A 0.5-ml whole-blood aliquot was removed and stored on ice for duplicate measures of [Hb] and hematocrit (Sysmex, K-800, Kobe, Japan). The remaining portion was centrifuged for 3 min at 4500 rpm. The plasma then was analyzed in duplicate for [K+] (Ciba Corning 865pH/Blood Gas Analyzer; Bayer, Norwood, MA). Fluid shifts were calculated according to changes in [Hb] and hematocrit (23). Change in plasma volume ({Delta}PV) from baseline allowed the calculation of net K+ change at each time point.

Leg Strength and Fatigue Tests.  Isometric and dynamic leg strengths were assessed on an isokinetic dynamometer (Cybex Norm 770; Henley HealthCare, Medway, MA). The patients were seated in a chair with the back set at 90 degrees. Straps secured the patient across the chest, hips, and dominant thigh and ankle, with the axis of rotation centered to the femoral condyles, allowing assessment of dominant leg extension. The dynamometer was calibrated before every testing session, and torque data were adjusted for gravity. After a warm-up of 1.5 min, gentle extension and flexion and isometric strength (maximal voluntary contraction [MVC]) was assessed at a 60-degree knee extension, in triplicate. Isokinetic leg strength was performed at speeds of 60, 120, 180, 240, 300, and 360 degrees/s in triplicate through a range of 0 to 90 degrees. Each patient had a familiarization test. Formal tests then were conducted on 3 separate days, with the mean of the three tests recorded.

Muscle fatigue also was assessed on the dynamometer for the dominant leg. The patient performed 30 maximal extensions at an isokinetic speed of 180 degrees/s at a frequency of 0.5 Hz. The fatigue index (FI) was calculated as the percentage of force drop over the 30 repetition using the following formula:

Formula 1(1)

Each patient had a familiarization test. Formal tests then were conducted on 3 separate days, with the mean of the three tests recorded.

Thigh Muscle Cross-Sectional Area.  Thigh muscle cross-sectional area (TMCSA) was measured by computed tomography (CT) scan (16 Channel Scanner, GE Medical Systems, Waukesha, WI). An initial anterior–posterior scout film was taken of the thigh, and then a single transverse image was taken of the dominant leg 20 cm above the medial femoral condyle. Muscle area was calculated as the total area of the muscle compartment minus the femur area.

Statistical Analyses
All data are presented as mean ± SD unless specified. Pearson correlation coefficients are used for baseline data, and a backward stepwise regression analysis model was used for multiple variables where stated. Paired t test was used to compare baseline and end-of-study results. All tests were performed using Sigma Stat software (version 2.03; SPSS Inc., Chicago, IL) with significance taken as {alpha} < 0.05.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Patient Characteristics
Twelve patients were enrolled (10 male, two female). No patients were undertaking any form of regular exercise. Baseline characteristics, cause of renal failure, biochemistry, and hematology are shown in Table 1. Although all patients completed the baseline set of tests, three patients subsequently withdrew. One deteriorated quickly and commenced dialysis 3 mo after baseline testing. One was unable to do further tests because of knee pain, and one withdrew because of poor recovery after major surgery. Therefore, nine patients had follow-up tests, and seven completed a full 2 yr.


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  		Table 1. Patient characteristics at baselinea

 
For those with follow-up, calculated creatinine clearance fell (35 ± 13 versus 25 ± 11 ml/min; P = 0.007). During the same period, [Hb] did not change (131 ± 10 versus 126 ± 11 g/L; P = 0.21). There were no other changes from baseline characteristics for patient size and blood biochemistry (data not shown).

Medications varied greatly between patients. ß Blockers were used by four patients, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were used by 11, calcium channel blockers were used by four, diuretics were used by six, vitamin D was used by four, and insulin was used by one. During the trial, ß blocker therapy did not change; 6 patients had alterations in vitamin D therapy and phosphate binders.

Cycle Ergometry and VO2peak
All patients cycled to volitional fatigue, eventually stopping as a result of leg weakness (n = 8), shortness of breath (n = 1), or both (n = 3). Satisfactory test performance was indicated by the mean respiratory exchange ratio (RER) of 1.14 ± 0.05 at peak exercise (Table 2). Heart rate at fatigue was 93 ± 9% of maximum predicted (220 – age bpm for those who were not on ß blockers compared with 63 ± 11% for those who were treated with ß blockers; P < 0.001). There were no adverse events and, in particular, no significant adverse electrocardiogram changes during the tests or in recovery.


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  		Table 2. Results for incremental cycle ergometry test to volitional exhaustion (baseline test)a

 
Results for VO2peak achieved and predicted, peak work rate, total work achieved, and heart rate for the baseline test are shown in Table 2. Only two patients were able to achieve a VO2peak >100% of predicted. Other than maximum heart rate, treatment with a ß blocker had no impact on exercise results. From rest to volitional fatigue, plasma volume fell by a mean of 11 ± 5%, and plasma [K+] rose (4.97 ± 0.42 versus 6.21 ± 0.51 mmol/L). This represents a rise in plasma [K+] of 1.09 ± 0.25 mmol/L when corrected for the change in plasma volume and a corresponding {Delta}[K+]/work ratio of 25.9 ± 10.7 µmol/L per J.

From a reduced baseline VO2peak, there was a further decline in VO2peak with follow-up testing over 2 yr, matched by a reduced time to fatigue and total cumulative work performed (Table 3, Figure 1). The tests were comparable in peak RER and heart rates. There were no differences between baseline and follow-up tests in the relative decline in plasma volume (–10.5 ± 3.3 versus –9.1 ± 4.5%; P = 0.39) or increase in [K+] (1.08 ± 0.18 versus 1.00 ± 0.22 mmol/L; P = 0.36) during exercise.


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  		Table 3. Comparative baseline and follow-up tests (n = 9) for cycle ergometry, leg strength and fatigue index, and TMCSAa

 

Figure 1
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  		Figure 1. Mean (±SD) oxygen consumption (VO2) during incremental cycle ergometry test to volitional exhaustion at Baseline (•) and end of study ({circ}; n = 9). *Peak VO2 (VO2peak) was lower at fatigue for the end-of-study tests (P = 0.03), and the test duration was shorter (P = 0.04).

 
Leg Strength and Fatigue Tests
MVC was 188 ± 42 Nm (n = 12) at baseline and for those with follow-up testing did not change over time (Table 3). Dynamic strengths are demonstrated in Figure 2. The follow-up tests found significantly lower peak torque (P < 0.05) for isokinetic speeds of 60, 120, 180, and 240 degrees/s. Across the entire torque-velocity curve, including MVC, there was a main effect for time, with baseline greater than follow-up values (P = 0.04). When torque is expressed relative to weight (Nm/kg), follow-up tests had a lower peak torque (P < 0.05) for isokinetic speeds of 120, 180, and 240 degrees/s. When torque was expressed relative to the TMCSA, there were no statistical differences between baseline and follow-up tests. The calculated FI was 22 ± 7% at baseline. For the nine patients with follow-up tests, it did not change (21 ± 6 versus 19 ± 6%; P = 0.62).


Figure 2
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  		Figure 2. Mean (±SD) isometric and isokinetic peak muscle strengths at baseline (•) and end of study ({circ}) measured on Cybex Norm 770 dynamometer (n = 9; *P < 0.05). ANOVA across speeds between groups (P = 0.04).

 
TMCSA
The TMCSA at baseline measured 144 ± 27 cm2 (n = 12). For the nine patients who were followed for 2 yr, this did not change (P = 0.66; Table 3).

Correlations
As with the normal healthy population, a strong linear relationship was seen between VO2peak and the total work performed (r = 0.98, P < 0.001; Figure 3). Baseline VO2peak had a number of correlates on univariate analysis (Table 4), including creatinine clearance when adjusted for BSA (Figure 4). There was no relationship between VO2peak and [Hb]. The change in creatinine clearance and the change in VO2peak during the study period did not correlate. VO2peak adjusted for weight correlated inversely with the thigh muscle FI (r = –0.693, P = 0.012; Figure 5). Baseline MVC correlated with weight (r = 0.668, P = 0.0176) and height (r = 0.827, P < 0.001) but not TMCSA, [Hb], or renal function (n = 12).


Figure 3
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  		Figure 3. Correlation between VO2peak for incremental cycle ergometry test and total cumulative work performed during the test for 12 patients at baseline. Regression line is shown with 95% confidence intervals (CI; r = 0.98, P < 0.001).

 

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  		Table 4. Univariate correlations with VO2peak at baseline tests (n = 12)

 

Figure 4
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  		Figure 4. VO2peak versus creatinine clearance (Cockcroft-Gault, corrected for BSA) for baseline tests. Regression line ± 95% CI (r = 0.613, P = 0.034; n = 12).

 

Figure 5
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  		Figure 5. VO2peak (adjusted for body weight) versus fatigue index (% force fall over 30 leg extensions performed at 0.5 Hz, 180 degrees/s; n = 12; r = –0.693, P = 0.012). Regression line ± 95% confidence interval.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
This study examined patients who had moderate to severe CKD (stages 3 to 4) yet have maintained a near-normal [Hb] without a history of anemia. We found that exercise performance that was measured by VO2peak on a cycle ergometer was significantly below that predicted for healthy, sedentary individuals of the same age and gender (21) and inversely correlated to thigh muscle fatigue. We also found that despite the maintenance of [Hb], VO2peak declined a further 9% as mean creatinine clearance fell by 28%. This was also associated with a decline in muscle strength, despite maintenance of muscle cross-sectional area.

Measured either by peak work rate or VO2, numerous exercise studies have demonstrated that patients with CKD underperform compared with predicted performance capabilities (24) or with healthy control subjects (8); however, the relationship between renal function and exercise capacity usually is confounded by the associated anemia that occurs with CKD. Anemia per se is well established as a factor that limits exercise in the normal population (25,26), and a direct relationship between Hb and VO2 also has been demonstrated in patients with CKD (5,6). Furthermore, when anemic patients with CKD are treated with erythropoietin to increase [Hb], exercise capacity (12) and VO2peak (27) have been shown to improve, although only modestly compared with the increase in [Hb]. The patients in this study had not previously been anemic, and they maintained a near-normal [Hb] throughout; however, of note is that these patients already had a reduced VO2peak at entry to the study despite the preserved [Hb]. During 2 yr of follow-up, we found a further 9% fall in VO2peak without a change in [Hb], suggesting that, at least in this cohort of patients, factors other than a decline in oxygen-carrying capacity influence the deterioration in exercise performance.

Our findings support a strong relationship between renal function and VO2peak in those with moderate CKD even when [Hb] has been maintained. It seems that at least moderate renal dysfunction is required before this relationship is observed. Previously, Clyne et al. (5) demonstrated a correlation between reduced GFR (<30 ml/min) and maximal exercise capacity when controlled for Hb, and a post hoc analysis of the Heart and Estrogen/Progestin Replacement Study (HERS) found poor subjective physical function correlated with renal function beginning when the GFR fell below 60 ml/min (CKD stage 3) (28). This also is supported by a study of young adults with mild renal impairment (29) and another in the elderly (30), which had similar exercise performances to their control groups.

One factor that is known to affect aerobic performance is muscular strength. For this cohort of patients, we found a relationship between VO2peak and strength (MVC). This relationship has previously been noted by Diesel et al. (31), who found in hemodialysis patients that strength was a better predictor of exercise capacity than [Hb]. Kettner-Melsheimer et al. (6) earlier had found a marked reduction in isometric leg extension strength in patients with CKD, being only two thirds that of healthy control subjects in men and one quarter in women. The patients in this study exhibited a mean MVC of only 85% of a comparative sedentary control group from our laboratory (unpublished data), a similar reduction to that from the predicted VO2peak. Corresponding with the decline in aerobic performance over 2 yr was a fall in muscle strength parameters across the dynamic range of isokinetic strength tests.

The parallel reductions in both VO2peak and muscle strength without a change in [Hb] suggest that intrinsic muscle changes such as enzymatic defects or alterations in fiber type and structure contribute more to poor performances than do limitations in oxygen supply. Underscoring this is our finding that the short isokinetic fatigue test correlated inversely with the longer aerobic VO2peak results. This relationship also is suggested by a study that showed that strength training alone can improve VO2peak (7) even when thigh muscle area does not change (3).

One enzymatic abnormality that potentially could affect exercise performance relates to the regulation of muscle intracellular K+ by the sodium-potassium ATPase. Intracellular K+ is reduced in renal failure (32), and resting muscle membrane potential has been found to change linearly in association with renal function (33). Disturbances in muscle K+ homeostasis also have been linked with muscular fatigue (19). Together with a more recent study demonstrating a relatively higher plasma K+ rise with exercise in hemodialysis patients (18), this suggests that abnormalities in muscle K+ regulation may be a factor that limits exercise performance. Although the patients in this study had a relatively high plasma [K+] before exercise testing (5.0 ± 0.4 mmol/L), we found that the {Delta}K+/work performed ratio was similar to that in the control subjects reported by Sangkabutra et al. (18), which was significantly lower than that in hemodialysis patients. Between baseline and follow-up tests in this study, however, there was no difference in the [K+] rise with exercise. We also found no correlation between the change in plasma [K+] and renal function, [Hb], or VO2peak, suggesting that, in this cohort at least, [K+] increases did not restrict muscle performance and thus incremental exercise. The normal {Delta}K+/work ratio found here is consistent with findings of McMahon et al. (15) in hemodialysis patients, in whom [Hb] raised from 100 to 140 g/L resulted in a lower {Delta}K+/work ratio.

Histologic muscle changes that are found in CKD also may influence muscle function. Grossly altered muscle fiber size and fiber type distribution are seen in both patients with CKD (34,35) and hemodialysis patients (36,37). It is interesting that these can be improved not only with exercise training (38,39) but also when [Hb] is increased with erythropoietin treatment (40). In addition to fiber changes, the amount of contractile tissue will have an impact on exercise performance. We used CT scanning for cross-sectional area as a measure of index of muscle size and therefore were unable to determine fat content of the muscle. CT scanning has been validated as a reliable indicator of nutrition in hemodialysis patients (41); however a magnetic resonance scan is more sensitive. Magnetic resonance scanning previously found that the proportion of muscle contractile tissue is reduced in hemodialysis patients compared with healthy control subjects despite similar muscle size (42).

There are limitations to this study. The small sample size highlights the difficulties of enrolling patients with CKD in studies that require a long follow-up and a number of assessments. This was compounded by the relative difficulty of finding nonanemic patients with CKD. Selection bias was an additional potential limitation because the enrolled patients were likely to be healthier and well motivated. This, however, only highlights the very limited exercise capacity of patients with CKD in general as others are likely to have an even poorer performance. Another factor with the potential to limit VO2peak could be the multiple medications that are required by patients with CKD. The most significant is ß blocker therapy. Fortunately, this was not translated into a reduced exercise performance in this study. Although the four patients in this study had significantly lower heart rates at fatigue, there was no difference in any other parameter measured either before exercise or at fatigue, including the RER, consistent with previous studies (5).


   Conclusion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
Exercise performance was reduced in CKD stages 3 to 4 even in the absence of anemia. Whether measured by oxygen consumption or leg strength, exercise performance progressively fell as renal function deteriorated. The likely causes are myriad, although, in this study, intrinsic muscle changes that result in reduced muscle strength and fatigue, and aerobic performance are likely to be dominant. To maintain the well-being and functional capacity of patients with CKD, therefore, attention should be directed toward maintaining strength and aerobic fitness as well as focusing on renal function and anemia.


   Acknowledgments
 
This study was supported by a research grant from Janssen-Cilag Pty Ltd, Australia, and M.J.L. is supported by a National Health and Medical Research Council Scholarship.

We sincerely thank all the patients who gave up their time to participate in this project and our other colleagues, Rob Aughey, Ivan Medved, Ian Mullis, and Simon Sostaric, for assisting with the cycle ergometry testing.


   Footnotes
 
Published online ahead of print. Publication date available at www.cjasn.org.

Received October 28, 2005. Accepted March 1, 2006.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Kutner NG, Zhang R, McClellan WM: Patient-reported quality of life early in dialysis treatment: Effects associated with usual exercise activity. Nephrol Nurs J27 :357 –367, discussion 368, 424,2000[Medline]
  2. Fitts SS, Guthrie MR, Blagg CR: Exercise coaching and rehabilitation counseling improve quality of life for predialysis and dialysis patients. Nephron82 :115 –121,1999[Medline]
  3. Castaneda C, Gordon PL, Uhlin KL, Levey AS, Kehayias JJ, Dwyer JT, Fielding RA, Roubenoff R, Singh MF: Resistance training to counteract the catabolism of a low-protein diet in patients with chronic renal insufficiency. A randomized, controlled trial. Ann Intern Med135 :965 –976,2001[Abstract/Free Full Text]
  4. Clyne N, Jogestrand T, Lins LE, Pehrsson SK, Ekelund LG: Factors limiting physical working capacity in predialytic uraemic patients. Acta Med Scand222 :183 –190,1987[Medline]
  5. Clyne N, Jogestrand T, Lins LE, Pehrsson SK: Progressive decline in renal function induces a gradual decrease in total hemoglobin and exercise capacity. Nephron67 :322 –326,1994[Medline]
  6. Kettner-Melsheimer A, Weiss M, Huber W: Physical work capacity in chronic renal disease. Int J Artif Organs10 :23 –30,1987[Medline]
  7. Boyce ML, Robergs RA, Avasthi PS, Roldan C, Foster A, Montner P, Stark D, Nelson C: Exercise training by individuals with predialysis renal failure: Cardiorespiratory endurance, hypertension, and renal function. Am J Kidney Dis30 :180 –192,1997[Medline]
  8. Cupisti A, Licitra R, Chisari C, Stampacchia G, D’Alessandro C, Galetta F, Rossi B, Barsotti G: Skeletal muscle and nutritional assessment in chronic renal failure patients on a protein-restricted diet. J Intern Med255 :115 –124,2004[Medline]
  9. Knight EL, Ofsthun N, Teng M, Lazarus JM, Curhan GC: The association between mental health, physical function, and hemodialysis mortality. Kidney Int63 :1843 –1851,2003[CrossRef][Medline]
  10. Painter P, Hanson P, Messer-Rehak D, Zimmerman SW, Glass NR: Exercise tolerance changes following renal transplantation. Am J Kidney Dis10 :452 –456,1987[Medline]
  11. Painter PL, Hector L, Ray K, Lynes L, Dibble S, Paul SM, Tomlanovich SL, Ascher NL: A randomized trial of exercise training after renal transplantation. Transplantation74 :42 –48,2002[CrossRef][Medline]
  12. Clyne N, Jogestrand T: Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients. Nephron60 :390 –396,1992[Medline]
  13. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. Canadian Erythropoietin Study Group. BMJ300 :573 –578,1990[Medline]
  14. McMahon LP, Johns JA, McKenzie A, Austin M, Fowler R, Dawborn JK: Haemodynamic changes and physical performance at comparative levels of haemoglobin after long-term treatment with recombinant erythropoietin. Nephrol Dial Transplant7 :1199 –1206,1992[Abstract/Free Full Text]
  15. McMahon LP, McKenna MJ, Sangkabutra T, Mason K, Sostaric S, Skinner SL, Burge C, Murphy B, Crankshaw D: Physical performance and associated electrolyte changes after haemoglobin normalization: A comparative study in haemodialysis patients. Nephrol Dial Transplant14 :1182 –1187,1999[Abstract/Free Full Text]
  16. Lundin AP, Akerman MJ, Chesler RM, Delano BG, Goldberg N, Stein RA, Friedman EA: Exercise in hemodialysis patients after treatment with recombinant human erythropoietin. Nephron58 :315 –319,1991[Medline]
  17. Robertson HT, Haley NR, Guthrie M, Cardenas D, Eschbach JW, Adamson JW: Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients. Am J Kidney Dis15 :325 –332,1990
  18. Sangkabutra T, Crankshaw DP, Schneider C, Fraser SF, Sostaric S, Mason K, Burge CM, Skinner SL, McMahon LP, McKenna MJ: Impaired K+ regulation contributes to exercise limitation in end-stage renal failure. Kidney Int63 :283 –290,2003[CrossRef][Medline]
  19. Sejersted OM, Sjogaard G: Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiol Rev80 :1411 –1481,2000[Abstract/Free Full Text]
  20. Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron16 :31 –41,1976[Medline]
  21. Wasserman K, Hansen JE, Sue Dy, Whipp BJ, Casaburi R: Principles of Exercise Testing and Interpretation, Philadelphia, Williams & Wilkins,1994
  22. McKenna MJ, Schmidt TA, Hargreaves M, Cameron L, Skinner SL, Kjeldsen K: Sprint training increases human skeletal muscle Na(+)-K(+)-ATPase concentration and improves K+ regulation. J Appl Physiol75 :173 –180,1993[Abstract/Free Full Text]
  23. Harrison MH: Effects on thermal stress and exercise on blood volume in humans. Physiol Rev65 :149 –209,1985[Abstract/Free Full Text]
  24. Clyne N, Ekholm J, Jogestrand T, Lins LE, Pehrsson SK: Effects of exercise training in predialytic uremic patients. Nephron59 :84 –89,1991[Medline]
  25. Woodson RD, Wills RE, Lenfant C: Effect of acute and established anemia on O2 transport at rest, submaximal and maximal work. J Appl Physiol44 :36 –43,1978[Abstract/Free Full Text]
  26. Celsing F, Svedenhag J, Pihlstedt P, Ekblom B: Effects of anaemia and stepwise-induced polycythaemia on maximal aerobic power in individuals with high and low haemoglobin concentrations. Acta Physiol Scand129 :47 –54,1987[Medline]
  27. Lim VS, DeGowin RL, Zavala D, Kirchner PT, Abels R, Perry P, Fangman J: Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial. Ann Intern Med110 :108 –114,1989[Medline]
  28. Kurella M, Ireland C, Hlatky MA, Shlipak MG, Yaffe K, Hulley SB, Chertow GM: Physical and sexual function in women with chronic kidney disease. Am J Kidney Dis43 :868 –876,2004
  29. Parrish AE, Zikria M, Kenney RA: Oxygen uptake in exercising subjects with minimal renal disease. Nephron40 :455 –457,1985[Medline]
  30. Heiwe S, Tollback A, Clyne N: Twelve weeks of exercise training increases muscle function and walking capacity in elderly predialysis patients and healthy subjects. Nephron88 :48 –56,2001[CrossRef][Medline]
  31. Diesel W, Noakes TD, Swanepoel C, Lambert M: Isokinetic muscle strength predicts maximum exercise tolerance in renal patients on chronic hemodialysis. Am J Kidney Dis16 :109 –114,1990
  32. Bergstrom J, Alvestrand A, Furst P, Hultman E, Widstam-Attorps U: Muscle intracellular electrolytes in patients with chronic uremia. Kidney Int Suppl16 :S153 –S160,1983[Medline]
  33. Cotton JR, Woodard T, Carter NW, Knochel JP: Resting skeletal muscle membrane potential as an index of uremic toxicity. A proposed new method to assess adequacy of hemodialysis. J Clin Invest63 :501 –506,1979[Medline]
  34. Clyne N, Esbjornsson M, Jansson E, Jogestrand T, Lins LE, Pehrsson SK: Effects of renal failure on skeletal muscle. Nephron63 :395 –399,1993[Medline]
  35. Sakkas GK, Ball D, Mercer TH, Sargeant AJ, Tolfrey K, Naish PF: Atrophy of non-locomotor muscle in patients with end-stage renal failure. Nephrol Dial Transplant18 :2074 –2081,2003[Abstract/Free Full Text]
  36. Diesel W, Emms M, Knight BK, Noakes TD, Swanepoel CR, van Zyl Smit R, Kaschula RO, Sinclair-Smith CC: Morphologic features of the myopathy associated with chronic renal failure. Am J Kidney Dis22 :677 –684,1993
  37. Fahal IH, Bell GM, Bone JM, Edwards RH: Physiological abnormalities of skeletal muscle in dialysis patients. Nephrol Dial Transplant12 :119 –127,1997[Abstract/Free Full Text]
  38. Sakkas GK, Sargeant AJ, Mercer TH, Ball D, Koufaki P, Karatzaferi C, Naish PF: Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training. Nephrol Dial Transplant18 :1854 –1861,2003[Abstract/Free Full Text]
  39. Kouidi E, Albani M, Natsis K, Megalopoulos A, Gigis P, Guiba-Tziampiri O, Tourkantonis A, Deligiannis A: The effects of exercise training on muscle atrophy in haemodialysis patients. Nephrol Dial Transplant13 :685 –699,1998[Abstract/Free Full Text]
  40. Davenport A, King RF, Ironside JW, Will EJ, Davison AM: The effect of treatment with recombinant human erythropoietin on the histological appearance and glycogen content of skeletal muscle in patients with chronic renal failure treated by regular hospital haemodialysis. Nephron64 :89 –94,1993[Medline]
  41. Ohkawa S, Odamaki M, Yoneyama T, Hibi I, Miyaji K, Kumagai H: Standardized thigh muscle area measured by computed axial tomography as an alternate muscle mass index for nutritional assessment of hemodialysis patients. Am J Clin Nutr71 :485 –490,2000[Abstract/Free Full Text]
  42. Johansen KL, Shubert T, Doyle J, Soher B, Sakkas GK, Kent-Braun JA: Muscle atrophy in patients receiving hemodialysis: Effects on muscle strength, muscle quality, and physical function. Kidney Int63 :291 –297,2003[CrossRef][Medline]




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