. 2021 Aug 12;110(1):1–31. doi: 10.1007/s00223-021-00898-1

Table 4.

Exercise and sarcopenia in chronic kidney disease patients: review of randomized controlled trials

Author, year	Type and duration of study	Size (n) and groups	Inclusion criteria Baseline characteristics	Primary/secondary outcomes	Results outcomes
Resistance exercises
Cheema et al., 2007 [42]	RCT 12 weeks	HD patients Progressive resistance training (PRT) (n = 24) vs. usual care (n = 25)	No inclusion criteria^a Baseline PRT group: -Total strength (kg): 98.1 ± 36.6 -6MWT (m): 496.6 ± 133.3	CSA and quality in thigh muscle by computed tomography scan Secondary: strength (peak force knee extensor, hip abductors and triceps), exercise capacity (6MWT), body circumference measures, QoL	No statistical difference in muscle CSA between groups Improvement in muscle attenuation, muscle strength, mid-thigh and mid-arm circumference
Chen et al., 2010 [43]	RCT 24 weeks	HD patients Intradialytic low-intensity strength training (n = 25) vs. stretching (n = 25)	No inclusion criteria^a Baseline: -SPPB: 6.0 ± 5.0, with 57% with SPPB score < 7 -LBM (kg): 45.8 ± 8.9 in the exercise group	Primary: SPPB Secondary: lower body strength, body composition, and QoL	Improvement in SPPB by 21.1% in strength training group vs. 0.2% in control group (p = 0.03) Knee extensor strength, self-reported physical function, and activities of daily living disability were significantly improved from baseline in exercise group compared to control group Significant improvement in change in LBM (%) (p = 0.001)
Lopes et al., 2019 [44]	RCT 12 weeks	HD patients (n = 80) HLG (high load), MLG (moderate load) vs. CG (control group: stretching)	No inclusion criteria^a Prevalence of sarcopenia: 21.4% HLG, 25% MLG, and 30% CG Baseline—HLG group: -LBM (kg): 39.1 ± 2.1 -SPPB: 11.1 ± 1.2 -Hand grip (kg): 30.0 ± 8.7	Primary: body composition (lean leg mass by DXA) Secondary: skeletal muscle mass index, sarcopenia prevalence (EWGSOP criteria), handgrip strength, functional capacity (SPPB and timed up and go), inflammatory markers, and QoL (Kidney Disease Quality of Life)	HLG was associated with increased lean leg mass compared to controls Skeletal muscle index and functional capacity increased in both HLG and MLG groups A reduction in the prevalence of sarcopenia of -14.3% in MLG group and -25% in HLG group compared to an increased prevalence (+ 10%) in the control group
Dong et al., 2019 [45]	RCT 12 weeks	HD patients Intradialytic resistance exercises with high or moderate intensity (n = 21) vs. control group (n = 20)	Inclusion criteria: patients with sarcopenia as defined by AWSG criteria	Physical activity status (maximum grip strength, daily pace, and physical activity level) Kt/V, and C-reactive protein, inflammatory factors	Significant improvement in physical activity status (maximum grip strength, daily pace, and physical activity level) in the intervention group No difference in FFMI (fat-free body mass), SMI (skeletal muscle mass index), SMM (skeletal muscle mass)
Kirkman et al., 2014 [46]	RCT 12 weeks	HD patients (n = 19) Resistance exercise training (PRET) HD (n = 9) and healthy (n = 4) vs. control group (lower body stretching) HD (n = 10) and healthy (n = 4)	No inclusion criteria^a Baseline in HD-PRET group: -Muscle volume (cm³): 2.822 ± 438 -Knee extensor strength (n): 179 ± 109 -STS (repetition): 11 ± 2 -6MWT (m): 532 ± 95	Knee extensor muscles volume by MRI Knee extensor strength (isometric dynamometer) Lower body tests of physical function	PRET increased muscle volume and increased strength in both HD and healthy patients Improvement in lower body functional capacity was only seen in the healthy participants
Song et al., 2012 [47]	RCT 12 weeks	HD patients PRT (progressive resistance training) (n = 20) vs. control group (n = 20)	Inclusion criteria^a: independent ambulation of 50 m or more, with or without an assistive device Baseline in PRT group: -SMM (kg): 21.4 ± 3.6 -Hang grip (kg): 26.3 ± 8.5 -Leg muscle strength (kg): 33.0 ± 15.3	Body composition by electrical resistance (SMM) Physical fitness (handgrip strength, lower body strength) QoL and lipid profile	Skeletal muscle mass, grip, leg muscle strength, and quality of life all improved significantly in the exercise group
Aerobic exercises
Baggetta et al., 2018 [48]	RCT (secondary analysis of EXCITE trial) 6 months	HD patients Home-based exercise (walking) (n = 53) vs. control group (n = 62)	No inclusion criteria^a Baseline exercise group: -6MWT (m): 294 ± 74 -5STS (s): 22.5 ± 5.1	6MWT and 5-time sit-to-stand test (5STS) QoL (KDQOL-SF)	Statistically significant improvement in the 6MWT and 5STS in the exercise group compared to baseline and compared to control group at 6 months
Baria et al., 2014 [49]	RCT 12 weeks	Obese CKD stages 3–4 men Aerobic center-based (n = 10), aerobic home-based (n = 9) vs. control group (n = 10)	No inclusion criteria^a Baseline center-based group: -LBM (kg): 52.5 ± 5.4 -STS (repetition): 17.7 ± 3.9 -6MWT (m): 559.1 ± 85.4	Body composition by dual-energy X-ray absorptiometry and the distribution of abdominal fat by computed tomography Physical and functional capacity including 6MWT and STS (maximal in 30 s)	In the center-based group, LBM, particularly leg lean mass increased 0.5 ± 0.4 kg (p < 0.01) after 12 weeks In both center-based and home-based exercise group, a significant improvement in 6MWT and STS were observed
Bohm et al., 2014 [50]	RCT 24 weeks	HD patients Intradialytic cycling (n = 30) vs. pedometer group (n = 30)	No inclusion criteria^a Baseline pedometer group: -STS (repetition): 10.1 ± 3.3 -6MWT: 390.2 ± 77	Primary: Aerobic capacity (VO2peak and 6MWT) Secondary: lower extremity strength (STS in 30 s), flexibility (sit-and-reach test), physical activity (accelerometer), and health-related QoL	STS testing improved significantly in both groups after 24 weeks At 12 and 24 weeks, there was no significant change in the VO2peak or 6MWT test between or within study groups
Koh et al., 2010 [51]	RCT 6 months	HD patients Intradialytic-aerobic exercise (n = 27) vs. home-based exercise (n = 21) vs. control group (n = 22)	No inclusion criteria^a Baseline intradialytic exercise: -6MWT (m): 431 ± 160 -TUG (s): 5.8 ± 1.5 -Handgrip strength (kg): 34 ± 10	Primary: 6MWT and aortic pulse wave velocity Secondary: physical activity, self-reported physical functioning, TUG, handgrip strength	No significant change in the 6MWT or in the pulse wave velocity, or any secondary outcome measures
Koufaki et al., 2002 [52]	RCT 12 weeks	HD and CAPD patients Aerobic exercise with cycle ergometer (ET) (n = 18) vs. control group (n = 15)	No inclusion criteria^a Baseline ET: -STS-5 (s): 14.7 ± 6.2 -STS-60 (s): 21.2 ± 7.2	VO2 peak, VO2–ventilatory threshold Functional capacity: sit-to-stands (STS-5, STS-60) and walk test	Significant improvement in the STS-5 were observed (ET: 14.7 ± 6.2 vs. 11.0 ± 3.3, C: 12.8 ± 4.4 vs. 12.7 ± 4.8 s) and STS-60 measurements (ET: 21.2 ± 7.2 vs. 26.9 ± 6.2, C: 23.7 ± 6.8 vs. 24.1 ± 7.2)
Resistance and/or aerobic exercises
DePaul et al., 2002 [53]	RCT 12 weeks	HD patients on EPO Aerobic + resistance exercise (n = 20) vs. range of motion exercise (n = 18)	No inclusion criteria^a Baseline exercise group: -Strength (lb): 166 ± 94 -6MWT (m): 460 ± 136	Primary: submaximal exercise test Secondary: muscle strength (combined hamstring and quadriceps), 6MWT, symptoms questionnaire, QoL (SF-36)	Improvement in the submaximal exercise test, and muscle strength but not 6MWT in favor of the combination of aerobic and resistance exercise No effect on the symptom questionnaire or SF-36
Howden et al., 2015 [54]	RCT (substudy of LANDMARK3) 12 months	CKD stages 3–4 Lifestyle intervention (aerobic + resistance exercise) (n = 36) vs. control group (n = 36)	No inclusion criteria^a Baseline intervention group: -6MWT (m): 485 ± 110 -Handgrip strength (kg): 35.3 ± 11.6 -TUG (s): 5.06 ± 1.24	Metabolic equivalent task (METs), 6MWT, TUG, handgrip strength, and anthropomorphic measures	Significant improvement in METs, 6MWT, body mass index There was no difference between groups on handgrip strength and get up and go test at 12 months
Kopple et al., 2007 [55]	RCT 20 weeks	HD patients Endurance training (ET) (n = 10), Strength training (ST) (n = 15), Strength + Endurance training (EST) (n = 12), No training (NT) (n = 14) and control (n = 20)	No inclusion criteria^a Baseline ET + NT + EST (n = 37): -FFM (kg): 53.3 ± 1.9 -FFM (%): 74.0 ± 2.2	Primary: mRNA for IGF-I, IGF-II, IGF-IR, IGF-IIR, IGFBP-2, IGFBP-3, and Myostatin in muscle biopsies Secondary: mid-arm muscle circumference, proximal-thigh and mid-thigh muscle areas, mid-calf muscle areas, Lean body mass or FFM	Anthropometry, but not dual-energy x-ray absorptiometry or bioelectrical impedance, showed a decrease in body fat and an increase in fat-free mass in all exercising patients combined
Liu et al., 2017 [56]	RCT (exploratory analysis from LIFE-P study) 12 months	CKD (eGFR < 60 mL/min/1.73 m²) (n = 105) vs. non-CKD (n = 263) Physical activity program (PA) vs. Aging education program (SA) in CKD vs. control group	Inclusion criteria: able to walk 400 m unassisted in ≤ 15 min, sedentary, and scored ≤ 9 on the SPPB Baseline: Mean SPPB in CKD 7.38 ± 1.41 and 7.59 ± 1.44 in patients without CKD (p = 0.20)	Primary: SPPB Secondary: serious adverse events and adherence to intervention Adjustment for: age, sex, diabetes, hypertension, CKD, intervention, site, visit, baseline SPPB	At 12 months, SPPBs increased In CKD PA: 8.90 (95% CI 8.82–9.47) In non-CKD PA: 8.40 (95% CI 8.01–8.79; p = 0.43) In CKD SA: 7.67 (95% CI 7.07–8.27) In non-CKD SA: 8.82 (95% CI 7.72–8.52; p = 0.86) Authors concluded there is a benefit from physical activity without any safety issues compared to patients without CKD
Rossi et al., 2014 [57]	RCT 12 weeks	CKD stages 3–4 (n = 107) Exercise (treadmill or cycling cardiovascular and weight training) (n = 59) vs. control group (n = 48)	No inclusion criteria^a Baseline Exercise group: -6MWT (ft): 1091 ± 340 -STST (% of age predicted): 67.8 ± 21.4% *Baseline gait speed test score was higher in the renal rehabilitation exercise group	Physical function: 6MWT, STS, and gait speed test QoL (SF-36)	Exercise group had significant improvement in the 6MWT and the sit-to-stand test compared to control group QoL measures of role functioning, physical functioning, energy/fatigue levels, and general health and mental measure of pain scale were better in the exercise group
Segura-Orti et al., 2009 [58]	RCT, open label 24 weeks	HD patients (n = 27) Resistance exercise (n = 19) vs Aerobic (n = 8)	No inclusion criteria^a	Primary: Physical performance (sit-to-stand to sit test, 6MWT) and knee extensor muscles strength (isometric dynamometry)	No difference between groups over time Improvement in right knee extensor muscles and physical performance tests in resistance group in intragroup analysis
van Vilsteren et al., 2005 [59]	RCT 12 weeks	HD patients Resistance exercise before HD and aerobic cycling during HD (n = 53) vs. control (n = 43)	No inclusion criteria^a Baseline Exercise group: -STS10: 26.3 ± 14.6	Behavioral change, lower extremity muscle strength (STS10) and VO2 peak Weight, blood pressure, hemoglobin and hematocrit values, cholesterol, dialysis adequacy, and health-related QoL	A significant increase in lower extremity muscle strength was noted in the exercise group compared to the control group (p = 0.05) A significant improvement in behavioral change, reaction time, dialysis adequacy, and three components of QoL was observed in the exercise group
Zhou et al., 2019 [60]	RCT (prespecified substudy of RENEXC) 12 months	CKD non-dialysis stages 3–5 Endurance + balance (n = 59) vs. Endurance + resistance (n = 53)	No inclusion criteria^a Baseline -Sarcopenia: 10%	Primary: Sarcopenia (EWGSOP criteria), physical performance Secondary: Body composition (DXA) and plasma myostatin	No change in the prevalence of sarcopenia in both group from baseline Increase of LBM in the balance group compared to baseline (+ 0.9 kg; p = 0.006). Stable LBM in the resistance group Significant increase in myostatin levels in both groups, in favor of resistance group
Other type of exercise program
Yurtkuran et al., 2007 [61]	RCT 12 weeks	HD patients Yoga-based exercise group (n = 19) vs. control group (n = 18)	No inclusion criteria^a Baseline yoga group: -Hand grip (mm Hg): 150.3 ± 40.3	Pain intensity, fatigue, sleep disturbance (VAS), and grip strength (mm Hg); biochemical variables	A significant improvement in the handgrip strength was observed in the intervention group (+ 15%)
Combination of exercise with another intervention
Dong et al., 2011 [45]	RCT 6 months	HD patients (n = 22) Intradialytic oral nutrition (IDON) (n = 12) vs. IDON + resistance exercise (n = 10)	No inclusion criteria^a Baseline: -LBM (kg) 51.4 ± 8.5 kg	LBM (DXA, BIA) and body weight	No additional benefit of resistance exercise to nutritional intervention
Castaneda et al., 2004 [62]	RCT 12 weeks	CKD patients > 50 yr (creatinine between 133 and 442 µmol/L) Resistance training + low protein diet (n = 14) vs. low protein diet (n = 12)	No inclusion criteria^a Baseline in resistance training + low protein diet group: -Knee extension (kg): 39.9 ± 17.8 -Mid-thigh muscle area (cm²): 108.9 ± 29.5	Total body potassium, mid-thigh muscle area by computerized tomography, muscle strength, type I and II muscle-fiber cross-sectional area, and protein turnover	Improvement in muscle strength was significantly greater with resistance training (28% ± 14%) than without (− 13% ± 22%) (p = 0.001) Type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training
Hristea et al., 2016 [63]	RCT 6 months	HD patients Exercise (cycling exercise) + nutrition (n = 10) vs. Nutrition only (n = 10)	Criteria of protein energy wasting^b Baseline in exercise + nutrition group -LTI (kg/m²): 11.01 ± 1.88 -6MWT (m): 284 ± 166.6 -Knee extensor maximal strength (kg): 10.22 ± 4.95	Serum albumin, prealbumin, c-reactive protein, body composition, balance and quadriceps force Physical function (6MWT), and QoL (SF-36)	No significant change in serum albumin, prealbumin, c-reactive protein, body mass index, lean and fat-tissue index, and quadriceps force Improvement in 6MWT (+ 22%) and QoL in the exercise group

Author, year

Type and duration of study

Size (n) and groups

Inclusion criteria
Baseline characteristics

Primary/secondary outcomes

Results outcomes

Resistance exercises

Cheema et al., 2007 [42]

RCT

12 weeks

HD patients

Progressive resistance training (PRT) (n = 24) vs. usual care (n = 25)

No inclusion criteria^a

Baseline PRT group:

-Total strength (kg): 98.1 ± 36.6

-6MWT (m): 496.6 ± 133.3

CSA and quality in thigh muscle by computed tomography scan

Secondary: strength (peak force knee extensor, hip abductors and triceps), exercise capacity (6MWT), body circumference measures, QoL

No statistical difference in muscle CSA between groups

Improvement in muscle attenuation, muscle strength, mid-thigh and mid-arm circumference

Chen et al., 2010 [43]

RCT

24 weeks

HD patients

Intradialytic low-intensity strength training (n = 25) vs. stretching (n = 25)

No inclusion criteria^a

Baseline:

-SPPB: 6.0 ± 5.0, with 57% with SPPB score < 7

-LBM (kg): 45.8 ± 8.9 in the exercise group

Primary: SPPB

Secondary: lower body strength, body composition, and QoL

Improvement in SPPB by 21.1% in strength training group vs. 0.2% in control group (p = 0.03)

Knee extensor strength, self-reported physical function, and activities of daily living disability were significantly improved from baseline in exercise group compared to control group

Significant improvement in change in LBM (%) (p = 0.001)

Lopes et al., 2019 [44]

RCT

12 weeks

HD patients (n = 80)

HLG (high load), MLG (moderate load) vs. CG (control group: stretching)

No inclusion criteria^a

Prevalence of sarcopenia: 21.4% HLG, 25% MLG, and 30% CG

Baseline—HLG group:

-LBM (kg): 39.1 ± 2.1

-SPPB: 11.1 ± 1.2

-Hand grip (kg): 30.0 ± 8.7

Primary: body composition (lean leg mass by DXA)

Secondary: skeletal muscle mass index, sarcopenia prevalence (EWGSOP criteria), handgrip strength, functional capacity (SPPB and timed up and go), inflammatory markers, and QoL (Kidney Disease Quality of Life)

HLG was associated with increased lean leg mass compared to controls

Skeletal muscle index and functional capacity increased in both HLG and MLG groups

A reduction in the prevalence of sarcopenia of -14.3% in MLG group and -25% in HLG group compared to an increased prevalence (+ 10%) in the control group

Dong et al., 2019 [45]

RCT

12 weeks

HD patients

Intradialytic resistance exercises with high or moderate intensity (n = 21) vs. control group (n = 20)

Inclusion criteria: patients with sarcopenia as defined by AWSG criteria

Physical activity status (maximum grip strength, daily pace, and physical

activity level)

Kt/V, and C-reactive protein, inflammatory factors

Significant improvement in physical activity status (maximum grip strength, daily pace, and physical

activity level) in the intervention group

No difference in FFMI (fat-free body mass), SMI (skeletal muscle mass index), SMM (skeletal muscle mass)

Kirkman et al., 2014 [46]

RCT

12 weeks

HD patients (n = 19)

Resistance

exercise training (PRET) HD (n = 9) and healthy (n = 4)

vs. control group (lower body stretching) HD (n = 10) and healthy (n = 4)

No inclusion criteria^a

Baseline in HD-PRET group:

-Muscle volume (cm³): 2.822 ± 438

-Knee extensor strength (n): 179 ± 109

-STS (repetition): 11 ± 2

-6MWT (m): 532 ± 95

Knee extensor muscles volume by MRI

Knee extensor

strength (isometric dynamometer)

Lower body tests of physical function

PRET increased muscle volume and increased strength in both HD and healthy patients

Improvement in lower body functional capacity was only seen in the healthy participants

Song et al., 2012 [47]

RCT

12 weeks

HD patients

PRT (progressive resistance training) (n = 20) vs. control group (n = 20)

Inclusion criteria^a: independent ambulation of 50 m or more, with or without an assistive device

Baseline in PRT group:

-SMM (kg): 21.4 ± 3.6

-Hang grip (kg): 26.3 ± 8.5

-Leg muscle strength (kg): 33.0 ± 15.3

Body composition by electrical resistance (SMM)

Physical fitness (handgrip strength, lower body strength)

QoL and lipid profile

Skeletal muscle mass, grip, leg muscle strength, and quality of life all improved significantly in the exercise group

Aerobic exercises

Baggetta et al., 2018 [48]

RCT (secondary analysis of EXCITE trial)

6 months

HD patients

Home-based exercise (walking) (n = 53) vs. control group (n = 62)

No inclusion criteria^a

Baseline exercise group:

-6MWT (m): 294 ± 74

-5STS (s): 22.5 ± 5.1

6MWT and 5-time sit-to-stand test (5STS)

QoL (KDQOL-SF)

Statistically significant improvement in the 6MWT and 5STS in the exercise group compared to baseline and compared to control group at 6 months

Baria et al., 2014 [49]

RCT

12 weeks

Obese CKD stages 3–4 men

Aerobic center-based (n = 10), aerobic home-based (n = 9) vs. control group (n = 10)

No inclusion criteria^a

Baseline center-based group:

-LBM (kg): 52.5 ± 5.4

-STS (repetition): 17.7 ± 3.9

-6MWT (m): 559.1 ± 85.4

Body composition

by dual-energy X-ray absorptiometry

and the distribution of abdominal fat by computed

tomography

Physical and functional capacity including 6MWT and STS (maximal in 30 s)

In the center-based group, LBM, particularly leg lean mass increased 0.5 ± 0.4 kg (p < 0.01) after 12 weeks

In both center-based and home-based exercise group, a significant improvement in 6MWT and STS were observed

Bohm et al., 2014 [50]

RCT

24 weeks

HD patients

Intradialytic cycling (n = 30) vs. pedometer group (n = 30)

No inclusion criteria^a

Baseline pedometer group:

-STS (repetition): 10.1 ± 3.3

-6MWT: 390.2 ± 77

Primary: Aerobic capacity (VO2peak and 6MWT)

Secondary: lower extremity strength (STS in 30 s), flexibility (sit-and-reach test), physical activity (accelerometer), and health-related QoL

STS testing improved significantly in both groups after 24 weeks

At 12 and 24 weeks, there was no significant change

in the VO2peak or 6MWT test between or within study groups

Koh et al., 2010 [51]

RCT

6 months

HD patients

Intradialytic-aerobic exercise (n = 27) vs. home-based exercise (n = 21) vs. control group (n = 22)

No inclusion criteria^a

Baseline intradialytic exercise:

-6MWT (m): 431 ± 160

-TUG (s): 5.8 ± 1.5

-Handgrip strength (kg): 34 ± 10

Primary: 6MWT and aortic pulse wave velocity

Secondary: physical activity, self-reported physical functioning, TUG, handgrip strength

No significant change in the 6MWT or in the pulse wave velocity, or any secondary outcome measures

Koufaki et al., 2002 [52]

RCT

12 weeks

HD and CAPD patients

Aerobic exercise with cycle ergometer (ET) (n = 18) vs. control group (n = 15)

No inclusion criteria^a

Baseline ET:

-STS-5 (s): 14.7 ± 6.2

-STS-60 (s): 21.2 ± 7.2

VO2 peak, VO2–ventilatory threshold

Functional capacity: sit-to-stands (STS-5, STS-60) and walk test

Significant improvement in the STS-5 were observed (ET: 14.7 ± 6.2 vs. 11.0 ± 3.3, C: 12.8 ± 4.4 vs. 12.7 ± 4.8 s) and STS-60 measurements (ET: 21.2 ± 7.2 vs. 26.9 ± 6.2, C: 23.7 ± 6.8 vs. 24.1 ± 7.2)

Resistance and/or aerobic exercises

DePaul et al., 2002 [53]

RCT

12 weeks

HD patients on EPO

Aerobic + resistance exercise (n = 20) vs. range of motion exercise (n = 18)

No inclusion criteria^a

Baseline exercise group:

-Strength (lb): 166 ± 94

-6MWT (m): 460 ± 136

Primary: submaximal exercise test

Secondary: muscle strength (combined hamstring and quadriceps), 6MWT, symptoms questionnaire, QoL (SF-36)

Improvement in the submaximal exercise test, and muscle strength but not 6MWT in favor of the combination of aerobic and resistance exercise

No effect on the symptom questionnaire or SF-36

Howden et al., 2015 [54]

RCT

(substudy of LANDMARK3)

12 months

CKD stages 3–4

Lifestyle intervention (aerobic + resistance exercise) (n = 36) vs. control group (n = 36)

No inclusion criteria^a

Baseline intervention group:

-6MWT (m): 485 ± 110

-Handgrip strength (kg): 35.3 ± 11.6

-TUG (s): 5.06 ± 1.24

Metabolic equivalent task (METs), 6MWT, TUG, handgrip strength, and anthropomorphic measures

Significant improvement in METs, 6MWT, body mass index

There was no difference between groups on handgrip strength and get up and go test at 12 months

Kopple et al., 2007 [55]

RCT

20 weeks

HD patients

Endurance training (ET) (n = 10), Strength training (ST) (n = 15), Strength + Endurance training (EST) (n = 12), No training (NT) (n = 14) and control (n = 20)

No inclusion criteria^a

Baseline ET + NT + EST (n = 37):

-FFM (kg): 53.3 ± 1.9

-FFM (%): 74.0 ± 2.2

Primary: mRNA for IGF-I, IGF-II, IGF-IR, IGF-IIR, IGFBP-2, IGFBP-3, and Myostatin in muscle biopsies

Secondary: mid-arm muscle circumference, proximal-thigh and mid-thigh muscle areas, mid-calf muscle areas, Lean body mass or FFM

Anthropometry, but not dual-energy x-ray absorptiometry or bioelectrical impedance, showed a decrease in body fat and an increase in fat-free mass in all exercising patients combined

Liu et al., 2017 [56]

RCT

(exploratory analysis from LIFE-P study)

12 months

CKD (eGFR < 60 mL/min/1.73 m²) (n = 105) vs. non-CKD (n = 263)

Physical activity program (PA) vs. Aging education program (SA) in CKD vs. control group

Inclusion criteria: able to walk 400 m unassisted in ≤ 15 min, sedentary, and scored ≤ 9 on the SPPB

Baseline:

Mean SPPB in CKD 7.38 ± 1.41 and 7.59 ± 1.44 in patients without CKD (p = 0.20)

Primary: SPPB

Secondary: serious adverse events and adherence to intervention

Adjustment for: age, sex, diabetes, hypertension, CKD, intervention, site, visit, baseline SPPB

At 12 months, SPPBs increased

In CKD PA: 8.90 (95% CI 8.82–9.47)

In non-CKD PA: 8.40 (95% CI 8.01–8.79; p = 0.43)

In CKD SA: 7.67 (95% CI 7.07–8.27)

In non-CKD SA: 8.82 (95% CI 7.72–8.52; p = 0.86)

Authors concluded there is a benefit from physical activity without any safety issues compared to patients without CKD

Rossi et al., 2014 [57]

RCT

12 weeks

CKD stages 3–4 (n = 107)

Exercise (treadmill or cycling cardiovascular and weight training) (n = 59) vs. control group (n = 48)

No inclusion criteria^a

Baseline Exercise group:

-6MWT (ft): 1091 ± 340

-STST (% of age predicted): 67.8 ± 21.4%

*Baseline gait speed test score was higher in the renal rehabilitation exercise group

Physical function: 6MWT, STS, and gait speed test

QoL (SF-36)

Exercise group had significant improvement in the 6MWT and the sit-to-stand test compared to control group

QoL measures of role functioning, physical functioning, energy/fatigue levels, and general health and mental measure of pain scale were better in the exercise group

Segura-Orti et al., 2009 [58]

RCT, open label

24 weeks

HD patients (n = 27)

Resistance exercise (n = 19) vs

Aerobic (n = 8)

No inclusion criteria^a

Primary: Physical performance (sit-to-stand to sit test, 6MWT) and knee extensor muscles strength (isometric dynamometry)

No difference between groups over time

Improvement in right knee extensor muscles and physical performance tests in resistance group in intragroup analysis

van Vilsteren et al., 2005 [59]

RCT

12 weeks

HD patients

Resistance exercise before HD and aerobic cycling during HD (n = 53) vs. control (n = 43)

No inclusion criteria^a

Baseline Exercise group:

-STS10: 26.3 ± 14.6

Behavioral change, lower extremity muscle strength (STS10) and VO2 peak

Weight, blood pressure,

hemoglobin and hematocrit values, cholesterol, dialysis adequacy, and health-related QoL

A significant increase in lower extremity muscle strength was noted in the exercise group compared to the control group (p = 0.05)

A significant improvement in behavioral change, reaction time, dialysis adequacy, and three components of QoL was observed in the exercise group

Zhou et al., 2019 [60]

RCT (prespecified substudy of RENEXC)

12 months

CKD non-dialysis stages 3–5

Endurance + balance (n = 59) vs. Endurance + resistance (n = 53)

No inclusion criteria^a

Baseline

-Sarcopenia: 10%

Primary: Sarcopenia (EWGSOP criteria), physical performance

Secondary: Body composition (DXA) and plasma myostatin

No change in the prevalence of sarcopenia in both group from baseline

Increase of LBM in the balance group compared to baseline (+ 0.9 kg; p = 0.006). Stable LBM in the resistance group

Significant increase in myostatin levels in both groups, in favor of resistance group

Other type of exercise program

Yurtkuran et al., 2007 [61]

RCT

12 weeks

HD patients

Yoga-based exercise group (n = 19) vs. control group (n = 18)

No inclusion criteria^a

Baseline yoga group:

-Hand grip (mm Hg): 150.3 ± 40.3

Pain intensity, fatigue, sleep disturbance (VAS), and grip strength (mm Hg); biochemical variables

A significant improvement in the handgrip strength was observed in the intervention group (+ 15%)

Combination of exercise with another intervention

Dong et al., 2011 [45]

RCT

6 months

HD patients (n = 22)

Intradialytic oral nutrition (IDON) (n = 12) vs. IDON + resistance exercise (n = 10)

No inclusion criteria^a

Baseline:

-LBM (kg) 51.4 ± 8.5 kg

LBM (DXA, BIA) and body weight

No additional benefit of resistance exercise to nutritional intervention

Castaneda et al., 2004 [62]

RCT

12 weeks

CKD patients > 50 yr (creatinine between 133 and 442 µmol/L)

Resistance training + low protein diet (n = 14) vs. low protein diet (n = 12)

No inclusion criteria^a

Baseline in resistance training + low protein diet group:

-Knee extension (kg): 39.9 ± 17.8

-Mid-thigh muscle area (cm²): 108.9 ± 29.5

Total body potassium, mid-thigh muscle area by computerized

tomography, muscle strength, type I and II muscle-fiber cross-sectional area, and protein turnover

Improvement in muscle strength was significantly greater with resistance training (28% ± 14%) than without (− 13% ± 22%) (p = 0.001)

Type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training

Hristea et al., 2016 [63]

RCT

6 months

HD patients

Exercise (cycling exercise) + nutrition (n = 10) vs. Nutrition only (n = 10)

Criteria of protein energy wasting^b

Baseline in exercise + nutrition group

-LTI (kg/m²): 11.01 ± 1.88

-6MWT (m): 284 ± 166.6

-Knee extensor maximal strength (kg): 10.22 ± 4.95

Serum albumin, prealbumin, c-reactive protein, body composition, balance and quadriceps force

Physical function (6MWT), and QoL (SF-36)

No significant change in serum albumin, prealbumin, c-reactive protein, body mass index, lean and fat-tissue index, and quadriceps force

Improvement in 6MWT (+ 22%) and QoL in the exercise group

6MWT 6-min walk test, aLBM appendicular lean body mass, AWSG Asian Working Group for Sarcopenia, BDI Beck Depressive Inventory, BIA Bioelectrical impedance analysis, CAPD continuous ambulatory peritoneal dialysis, CKD chronic kidney disease, CSA cross-sectional area, DXA dual-energy X-ray absorptiometry, eGFR estimated glomerular filtration rate, EPO erythropoietin, EWGSOP European Working Group on Sarcopenia in Older People, FFMI fat-free mass index, HD hemodialysis, HLG high load group, IDON intradialytic oral nutrition, KDQOL-SF Kidney Disease Quality of Life Short Form, LBM lean body mass, LTI lean tissue index, METs metabolic equivalent task, MLG moderate load group, PA physical activity program, PRET progressive resistance exercise training, PRT progressive resistance training, QoL quality of life, RCT randomized clinical trial, SA aging education program, SF-36 short form health survey 36, SMI skeletal muscle mass index, SMM skeletal muscle mass, SPEP structured physical exercise program, SPPB short physical performance battery, STS sit-to-stand, TUG timed up and go, 1RM 1 repetition maximum

^aNo inclusion criteria based on sarcopenia status, physical strength or function

^bProtein energy wasting based on Fouque D, Kalantar-Zadeh K, Kopple J et al. A proposed nomenclature and diagnostic criteria for protein energy wasting in acute and chronic kidney disease. Kidney Int. 2008; 73: 391–8