Association between vitamin D deficiency and exercise capacity in patients with CKD, a cross-sectional analysis.

BACKGROUND: Evidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. METHODS: This is a secondary cross-sectional analysis of previously published interventional study, with in vitro follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3 mL/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n = 20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. RESULTS: In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with V̇O2Peak was seen with total vitamin D (25OHD). in vitro, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. CONCLUSIONS: Vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.

The association of muscle size, strength and exercise capacity with all-cause mortality in non-dialysis-dependent CKD patients.

BACKGROUND/OBJECTIVE: Patients with chronic kidney disease (CKD) are commonly reported to exhibit skeletal muscle wasting, reduced strength and exercise capacity. Evidence from patients with end-stage renal disease (ESRD) demonstrates these factors are associated with mortality, but it is unclear whether this relationship exists earlier in the illness. Our objective was to determine whether muscle size, strength or exercise capacity was associated with all-cause mortality, unscheduled hospital admissions or time to ESRD in patients not requiring dialysis. METHODS: This is a prospective cohort study of 89 patients with CKD stages 3b-5 not requiring renal replacement therapy with a mean follow-up period of 3.3 years in which the contribution of predictors of rectus femoris muscle size, muscle strength, exercise capacity to all-cause mortality rates, progression to ESRD and time to first hospitalization were investigated. RESULTS: Unadjusted analysis suggested each 1 cm2 increase in quadriceps muscle size (measured by ultrasonography cross-sectional area) was associated with a 38% reduced risk for death (p = .006), and a 10 m improvement on the incremental shuttle walk test was associated with a 3% reduced risk for death (p = .04). However, this relationship was not present in analysis adjusted for age, gender and eGFR. No association was seen between any factor for the development of ESRD or time to first hospitalization. CONCLUSION: These results suggest that in this small cohort, muscle size and exercise capacity are associated with mortality when considered alone, but this relationship was not present in adjusted analyses. Further investigation in a larger patient group is warranted.

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) exhibit reduced exercise capacity, poor physical function and symptoms of fatigue. The mechanisms that contribute to this are not clearly defined but may involve reductions in mitochondrial function, mass and biogenesis. Here we report on the effect of non-dialysis dependent CKD (NDD-CKD) on mitochondrial mass and basal expression of transcription factors involved in mitochondrial biogenesis compared to a healthy control cohort (HC). In addition, we sought to investigate the effect of a 12-week exercise-training programme on these aspects of mitochondrial dysfunction in a NDD-CKD cohort.For the comparison between NDD-CKD and HC populations, skeletal muscle biopsies were collected from the vastus lateralis (VL) of n=16 non-dialysis dependent CKD patient's stage 3b-5 (NDD-CKD) and n=16 healthy controls matched for age, gender and physical activity (HC). To investigate the effect of exercise training, VL biopsies were collected from n=17 NDD-CKD patients before and after a 12-week exercise intervention that was comprised of aerobic exercise (AE) or a combination of aerobic exercise and resistance training (CE). Mitochondrial mass was analysed by citrate synthase activity and mitochondrial protein content by Porin expression, whilst the expression of transcription factors involved in mitochondrial biogenesis were quantified by real-time qPCR. NDD-CKD patients exhibited a significant reduction in mitochondrial mass when compared to HC, coupled to a reduction in PGC-1α, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression. 12-weeks of exercise training resulted in a significant increase in PGC-1α expression in both groups, with no further changes seen across indicators of mitochondrial biogenesis. No significant changes in mitochondrial mass were observed in response to either exercise programme. NDD-CKD patients exhibit reduced skeletal muscle mitochondrial mass and gene expression of transcription factors involved in mitochondrial biogenesis compared to HC. These reductions were not restored following 12-weeks of exercise training implying exercise resistance in this cohort. The reasons for this lack of improvement are currently unknown and require further investigation, as reversing the dysregulation of these processes in NDD-CKD may provide a therapeutic opportunity to improve muscle fatigue and dysfunction in this population.

Peak aerobic capacity from incremental shuttle walk test in chronic kidney disease.

BACKGROUND: Assessment of cardiorespiratory fitness is an important outcome in chronic kidney disease (CKD). We aimed to develop a predictive equation to estimate peak oxygen uptake (VO2peak ) and power output (WPeak ), as measured during a cardiopulmonary exercise test (CPET), from the distance walked (DW) during the incremental shuttle walk test (ISWT). METHODS: Thirty-six non-dialysing patients with CKD [17 male, age: 61 ± 12 years, eGFR: 25±7 ml/min/1.73 m2 , body mass index (BMI): 31 ± 6 kg/m2 ] carried out laboratory-based CPET on a cycle ergometer and ISWT on two separate occasions. RESULTS: Linear regression revealed that DW/BMI was a significant predictor of VO2Peak (r = 0.78) (VO2Peak (ml/min/kg) = [0.5688 × (DW/BMI) (m)] + 11.50). No difference (p = 0.66) between CPET VO2Peak (19.9 ± 5.5 ml/min/kg) and predicted VO2Peak (19.9 ± 4.3 ml/min/kg) was observed. DW multiplied by body mass (BM) was a significant predictor of WPeak (r = 0.80) [WPeak (W) = (0.0018 × (DW × BM)) + 50.47]. No difference (p = 0.97) between CPET WPeak (116.2 ± 38.9 W) and estimated WPeak (113.9 ± 30.1 W) was seen. CONCLUSION: The present study demonstrates that VO2Peak and WPeak can be accurately estimated using the DW during an ISWT in CKD populations.

Ultrasound assessment of muscle mass in response to exercise training in chronic kidney disease: a comparison with MRI.

BACKGROUND: Chronic kidney disease (CKD) is a catabolic condition associated with muscle wasting and dysfunction, which associates with morbidity and mortality. There is a need for simple techniques capable of monitoring changes in muscle size with disease progression and in response to interventions aiming to increase muscle mass and function. Ultrasound is one such technique; however, it is unknown how well changes in muscle cross-sectional area (CSA) measured using ultrasound relate to changes in whole muscle volume measured using magnetic resonance imaging. We tested whether rectus femoris CSA (RF-CSA) could be used as a valid indication of changes in quadriceps muscle volume as a single measure of muscle size and following a 12 week exercise intervention that resulted in muscle hypertrophy. METHODS: Secondary analysis of data was collected from the ExTra CKD study (ISRCTN 36489137). Quadriceps muscle size was assessed from 36 patients with non-dialysis CKD before and after 12 weeks of supervised exercise that resulted in muscle hypertrophy. RESULTS: Strong positive correlations were observed between RF-CSA and quadriceps volume at baseline (r2 = 0.815, CI 0.661 to 0.903; P < 0.001) and following 12 week exercise (r2 = 0.845, CI 0.700 to 0.923; P < 0.001). A moderate positive association was also observed between changes in RF-CSA and quadriceps following exercise training (rho = 0.441, CI 0.085 to 0.697; P = 0.015). Bland-Altman analysis revealed a small bias (bias 0.6% ± 12.5) between the mean percentage changes in RF-CSA and quadriceps volume but wide limits of agreement from -24 to 25. CONCLUSIONS: Rectus femoris CSA appears to be a reliable index of total quadriceps volume as a simple measure of muscle size, both as a single observation and in response to exercise training in non-dialysis CKD patients.

Twelve weeks of supervised exercise improves self-reported symptom burden and fatigue in chronic kidney disease: a secondary analysis of the 'ExTra CKD' trial.

BACKGROUND: Chronic kidney disease (CKD) patients experience a high symptom burden including fatigue, sleep difficulties, muscle weakness and pain. These symptoms reduce levels of physical function (PF) and activity, and contribute to poor health-related quality of life (HRQoL). Despite the gathering evidence of positive physiological changes following exercise in CKD, there is limited evidence on its effect on self-reported symptom burden, fatigue, HRQoL and physical activity. METHODS: Thirty-six patients [mean ± SD 61.6 ± 11.8 years, 22 (61%) females, estimated glomerular filtration rate: 25.5 ± 7.8 mL/min/1.73 m2] not requiring renal replacement therapy underwent 12 weeks (3 times/week) of supervised aerobic exercise (AE), or a combination (CE) of AE plus resistance training. Outcomes included self-reported symptom burden, fatigue, HRQoL and physical activity. RESULTS: Exercise reduced the total number of symptoms reported by 17% and had favourable effects on fatigue in both groups. AE reduced the frequency of 'itching', 'impotence' and 'shortness of breath' symptoms, and the intrusiveness for symptoms of 'sleep disturbance', 'loss of muscular strength/power', 'muscle spasm/stiffness' and 'restless legs'. The addition of resistance exercise in the CE group saw a reduction in 'loss of muscular strength/power'. No changes were seen in subjective PF or physical activity levels. AE increased self-efficacy for physical activity. CONCLUSIONS: Supervised exercise had favourable effects on symptom frequency and intrusiveness, including substantial improvements in fatigue. Although the intervention did not improve self-reported physical activity levels, AE increased patients' self-efficacy for physical activity. These favourable changes in self-reported outcomes support the important role of exercise in CKD.

Association of self-reported physical function with survival in patients with chronic kidney disease.

BACKGROUND: Reduced physical function is associated with an increased risk of mortality among patients with chronic kidney disease (CKD) not requiring renal replacement therapy (RRT). Assessments of physical performance can help to identify those at risk for adverse events. However, objective measures are not always feasible and self-reported measures may provide a suitable surrogate. METHODS: We performed a cohort study examining associations between self-reported physical function and walking behaviour with survival in patients with CKD not requiring RRT. Data were analysed from the QCKD study (Physical activity opinions in kidney disease) (ISRCTN 87066351), a prospective observational mixed methods study of physical activity in patients with CKD. A total of 450 patients with CKD not requiring RRT, ages 17-93 years, were followed up for a median of 43 months. Upon enrolment, participants completed two questionnaires: Duke Activity Status Index (DASI) (physical function) and General Practice Physical Activity Questionnaire (GPPAQ) (habitual activity). Mortality data were collected from electronic records in September 2016; RRT was considered a competing event. RESULTS: A total of 74 deaths occurred during follow-up and 101 participants were started on RRT. The adjusted subdistribution hazard ratio (SHR) of mortality in participants scoring >19.2 on the DASI was 0.51 [95% confidence interval (CI) 0.30-0.88] while a one-unit increase in the DASI was associated with an SHR of 0.97 (95% CI 0.95-0.99). The adjusted SHRs of mortality were 0.48 (95% CI 0.26-0.90), 0.25 (0.11-0.57) and 0.48 (0.23-0.80) for participants walking <1, 1-3 and ≥3 h/week, respectively, compared with no walking. A walking pace >3 mph was associated with a reduced risk of mortality [SHR 0.37 (95% CI 0.20-0.71)] compared with a walking pace <3 mph. CONCLUSIONS: Physical function and walking behaviours were independently associated with survival in CKD and may help to identify patients at risk for adverse events.

Test-retest reliability, validation, and "minimal detectable change" scores for frequently reported tests of objective physical function in patients with non-dialysis chronic kidney disease.

Physical function is an important outcome in chronic kidney disease (CKD). We aimed to establish the reliability, validity, and the "minimal detectable change" (MDC) of several common tests used in renal rehabilitation and research. In a repeated measures design, 41 patients with CKD not requiring dialysis (stage 3b to 5) were assessed at an interval of 6 weeks. The tests were the incremental shuttle walk test (ISWT), "sit-to-stand" (STS) test, estimated 1 repetition maximum for quadriceps strength (e1RM), and VO2peak by cardiopulmonary exercise testing (CPET). Reliability was assessed using intraclass correlation coefficient and Bland-Altman analysis, and absolute reliability by standard error of measurement and MDC. The ISWT, STS-60, e1RM, and CPET had "good" to "excellent" reliability (0.973, 0.927, 0.927, and 0.866), respectively. STS-5 reliability was poor (0.676). The MDC is ISWT, 20 m; STS-5, 7.5 s; STS-60, 4 reps; e1RM, 6.4 kg; VO2peak, 2.8 ml/kg/min. There was strong correlation between the ISWT and VO2peak (r = 0.73 and 0.74). While there was poor correlation between the STS-5 and e1RM (r = 0.14 and 0.47), better correlation was seen between STS-5 and ISWT (r = 0.55 and 0.74). In conclusion, the ISWT, STS-60, e1RM, and CPET are reliable tests of function in CKD. The ISWT is a valid means of exercise capacity. The MDC can help researchers and rehabilitation professionals interpret changes following an intervention.

Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is characterized by adverse changes in body composition, which are associated with poor clinical outcome and physical functioning. Whilst size is the key for muscle functioning, changes in muscle quality specifically increase in intramuscular fat infiltration (myosteatosis) and fibrosis (myofibrosis) may be important. We investigated the role of muscle quality and size on physical performance in non-dialysis CKD patients. METHODS: Ultrasound (US) images of the rectus femoris (RF) were obtained. Muscle quality was assessed using echo intensity (EI), and qualitatively using Heckmatt's visual rating scale. Muscle size was obtained from RF cross-sectional area (RF-CSA). Physical function was measured by the sit-to-stand-60s (STS-60) test, incremental (ISWT) and endurance shuttle walk tests, lower limb and handgrip strength, exercise capacity (VO2peak) and gait speed. RESULTS: A total of 61 patients (58.5 ± 14.9 years, 46% female, estimated glomerular filtration rate 31.1 ± 20.2 mL/min/1.73 m2) were recruited. Lower EI (i.e. higher muscle quality) was significantly associated with better physical performance [STS-60 (r = 0.363) and ISWT (r = 0.320)], and greater VO2peak (r = 0.439). The qualitative rating was closely associated with EI values, and significant differences in function were seen between the ratings. RF-CSA was a better predictor of performance than muscle quality. CONCLUSIONS: In CKD, increased US-derived EI was negatively correlated with physical performance; however, muscle size remains the largest predictor of physical function. Therefore, in addition to the loss of muscle size, muscle quality should be considered an important factor that may contribute to deficits in mobility and function in CKD. Interventions such as exercise could improve both of these factors.

The "Minimum Clinically Important Difference" in Frequently Reported Objective Physical Function Tests After a 12-Week Renal Rehabilitation Exercise Intervention in Nondialysis Chronic Kidney Disease.

OBJECTIVE: Chronic kidney disease patients are characterized by impaired physical function. The goal of exercise-based interventions is an improvement in functional performance. However, improvements are often determined by "statistically significant" changes. We investigated the "minimum clinically important difference," "the smallest change that is important to the patient," for commonly reported physical function tests. DESIGN: Nondialysis chronic kidney disease patients completed 12-wks of a combined aerobic (plus resistance training). The incremental shuttle walking test, sit-to-stand 5 and 60, estimated 1-repetition maximum for the knee extensors, and VO2peak were assessed. After the intervention, patients rated their perceived change in health. Both anchor- and distribution-based minimum clinically important difference approaches were calculated. RESULTS: The minimum clinically important difference was calculated as follows: incremental shuttle walking test, +45 m; sit-to-stand 5, -4.2 secs; VO2peak, +1.5 ml/kg per min. Because of comparable increases in "anchor" groups, no minimum clinically important difference was estimated for the sit-to-stand 60 or estimated 1-repetition maximum. CONCLUSIONS: We have established the minimum clinically important difference in chronic kidney disease for common tests of physical function. These values represent the minimum change required for patients to perceive noticeable and beneficial change to their health. These scores will help interpret changes after exercise interventions where these tests are used. These minimum clinically important differences can be used to power future studies to detect clinically important changes. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Define the "minimum clinically important difference"; (2) Distinguish between concepts of minimum clinically important difference, "minimal detectable change,", and "statistically significant change"; and (3) Interpret other study findings and their own results in the context of the minimum clinically important difference rather than statistically significant changes. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Characterising skeletal muscle haemoglobin saturation during exercise using near-infrared spectroscopy in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients have reduced exercise capacity. Possible contributing factors may include impaired muscle O2 utilisation through reduced mitochondria number and/or function slowing the restoration of muscle ATP concentrations via oxidative phosphorylation. Using near-infrared spectroscopy (NIRS), we explored changes in skeletal muscle haemoglobin/myoglobin O2 saturation (SMO2%) during exercise. METHODS: 24 CKD patients [58.3 (± 16.5) years, eGFR 56.4 (± 22.3) ml/min/1.73 m2] completed the incremental shuttle walk test (ISWT) as a marker of exercise capacity. Using NIRS, SMO2% was measured continuously before, during, and after (recovery) exercise. Exploratory differences were investigated between exercise capacity tertiles in CKD, and compared with six healthy controls. RESULTS: We identified two discrete phases; a decline in SMO2% during incremental exercise, followed by rapid increase upon cessation (recovery). Compared to patients with low exercise capacity [distance walked during ISWT, 269.0 (± 35.9) m], patients with a higher exercise capacity [727.1 (± 38.1) m] took 45% longer to reach their minimum SMO2% (P = .038) and recovered (half-time recovery) 79% faster (P = .046). Compared to controls, CKD patients took significantly 56% longer to recover (i.e., restore SMO2% to baseline, full recovery) (P = .014). CONCLUSIONS: Using NIRS, we have determined for the first time in CKD, that favourable SMO2% kinetics (slower deoxygenation rate, quicker recovery) are associated with greater exercise capacity. These dysfunctional kinetics may indicate reduced mitochondria capacity to perform oxidative phosphorylation-a process essential for carrying out even simple activities of daily living. Accordingly, NIRS may provide a simple, low cost, and non-invasive means to evaluate muscle O2 kinetics in CKD.

The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in nondialysis chronic kidney disease: a systematic review.

OBJECTIVE: People with nondialysis-dependent chronic kidney disease (CKD) and renal transplant recipients (RTRs) have compromised physical function and reduced physical activity (PA) levels. Whilst established in healthy older adults and other chronic diseases, this association remains underexplored in CKD. We aimed to review the existing research investigating poor physical function and PA with clinical outcome in nondialysis CKD. DATA SOURCES: Electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials) were searched until December 2017 for cohort studies reporting objective or subjective measures of PA and physical function and the associations with adverse clinical outcomes and all-cause mortality in patients with nondialysis CKD stages 1-5 and RTRs. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42016039060). REVIEW METHODS: Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare and Research Quality (AHRQ) standards. RESULTS: A total of 29 studies were included; 12 reporting on physical function and 17 on PA. Only eight studies were conducted with RTRs. The majority were classified as 'good' according to the AHRQ standards. Although not appropriate for meta-analysis due to variance in the outcome measures reported, a coherent pattern was seen with higher mortality rates or prevalence of adverse clinical events associated with lower PA and physical function levels, irrespective of the measurement tool used. Sources of bias included incomplete description of participant flow through the study and over reliance on self-report measures. CONCLUSIONS: In nondialysis CKD, survival rates correlate with greater PA and physical function levels. Further trials are required to investigate causality and the effectiveness of physical function and PA interventions in improving outcomes. Future work should identify standard assessment protocols for PA and physical function.

Twelve-week combined resistance and aerobic training confers greater benefits than aerobic training alone in nondialysis CKD.

There is a growing consensus that patients with chronic kidney disease (CKD) should engage in regular exercise, but there is a lack of formal guidelines. In this report, we determined whether combined aerobic and resistance exercise would elicit superior physiological gains, in particular muscular strength, compared with aerobic training alone in nondialysis CKD. Nondialysis patients with CKD stages 3b-5 were randomly allocated to aerobic exercise {AE, n = 21; 9 men; median age 63 [interquartile range (IQR) 58-71] yr; median estimated glomerular filtration rate (eGFR) 24 (IQR 20-30) ml·min-1·1.73 m-2} or combined exercise [CE, n = 20, 9 men, median age 63 (IQR 51-69) yr, median eGFR 27 (IQR 22-32) ml·min-1·1.73 m-2], preceded by a 6-wk run-in control period. Patients then underwent 12 wk of supervised AE (treadmill, rowing, or cycling exercise) or CE training (as AE plus leg extension and leg press exercise) performed three times per week. Outcome assessments of knee extensor muscle strength, quadriceps muscle volume, exercise capacity, and central hemodynamics were performed at baseline, following the 6-wk control period, and at the end of the intervention. AE and CE resulted in significant increases in knee extensor strength of 16 ± 19% (mean ± SD; P = 0.001) and 48 ± 37% ( P < 0.001), respectively, which were greater after CE ( P = 0.02). AE and CE resulted in 5 ± 7% ( P = 0.04) and 9 ± 7% ( P < 0.001) increases in quadriceps volume, respectively ( P < 0.001), which were greater after CE ( P = 0.01). Both AE and CE increased distance walked in the incremental shuttle walk test [28 ± 44 m ( P = 0.01) and 32 ± 45 m ( P = 0.01), respectively]. In nondialysis CKD, the addition of resistance exercise to aerobic exercise confers greater increases in muscle mass and strength than aerobic exercise alone.

Physiological benefits of exercise in pre-dialysis chronic kidney disease.

Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and muscle wasting, arising from numerous factors associated with declining renal function and lifestyle factors. Exercise has the ability to impact beneficially on the comorbidities associated with CKD and is accepted as an important intervention in the treatment, prevention and rehabilitation of other chronic diseases, however, the role of exercise in CKD is overlooked, with the provision of rehabilitation programmes well behind those of cardiology and respiratory services. Whilst there is now a large evidence base demonstrating the efficacy and safety of exercise training interventions in patients receiving dialysis, and this is now becoming incorporated into clinical guidelines for treatment of dialysis patients, there is a paucity of research evaluating the effectiveness of exercise in patients with CKD who are not on dialysis. Despite this, existing studies indicate that exercise can improve physical functioning and impact positively on the mediators of co-morbid diseases and upstream factors associated with progression of renal disease. Although preliminary evidence appears positive, more research is required to identify the best modes, frequency and intensities of exercise in order to optimise exercise prescription in pre-dialysis CKD patients. This review summarizes what is known about the main effects of exercise in pre-dialysis CKD patients, discusses the potential of exercise in the rehabilitation and treatment of disease and highlights the need for further research.

Cancer cachexia prevention via physical exercise: molecular mechanisms.

Cancer cachexia is a debilitating consequence of disease progression, characterised by the significant weight loss through the catabolism of both skeletal muscle and adipose tissue, leading to a reduced mobility and muscle function, fatigue, impaired quality of life and ultimately death occurring with 25-30 % total body weight loss. Degradation of proteins and decreased protein synthesis contributes to catabolism of skeletal muscle, while the loss of adipose tissue results mainly from enhanced lipolysis. These mechanisms appear to be at least, in part, mediated by systemic inflammation. Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia.