A structured exercise programme during haemodialysis for patients with chronic kidney disease: clinical benefit and long-term adherence.

OBJECTIVE: Long-term studies regarding the effect of a structured physical exercise programme (SPEP) during haemodialysis (HD) assessing compliance and clinical benefit are scarce. STUDY
DESIGN: A single-centre clinical trial, non-randomised, investigating 46 patients with HD (63.2 ± 16.3 years, male/female 24/22, dialysis vintage 4.4 years) performing an SPEP over 5 years. The SPEP (twice/week for 60 min during haemodialysis) consisted of a combined resistance (8 muscle groups) and endurance (supine bicycle ergometry) training. Exercise intensity was continuously adjusted to improvements of performance testing. Changes in endurance and resistance capacity, physical functioning and quality of life (QoL) were analysed over 1 year in addition to long-term adherence and economics of the programme over 5 years. Average power per training session, maximal strength tests (maximal exercise repetitions/min), three performance-based tests for physical function, SF36 for QoL were assessed in the beginning and every 6 months thereafter.
RESULTS: 78% of the patients completed the programme after 1 year and 43% after 5 years. Participants were divided--according to adherence to the programme--into three groups: (1) high adherence group (HA, >80% of 104 training sessions within 12 months), (2) moderate adherence (MA, 60-80%), and 3. Low adherence group (LA, <60%)) with HA and MA evaluated quantitatively. One-year follow-up data revealed significant (p<0.05) improvement for both groups in all measured parameters: exercise capacity (HA: 55%, MA: 45%), strength (HA: >120%, MA: 40-50%), QoL in three scores of SF36 subscales and physical function in the three tests taken between 11% and 31%. Moreover, a quantitative correlation analysis revealed a close association (r=0.8) between large improvement of endurance capacity and weak physical condition (HA).
CONCLUSIONS: The exercise programme described improves physical function significantly and can be integrated into a HD routine with a high long-term adherence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

This study shows for the first time that a structured, individual combined cardiovascular and resistance exercise programme during dialysis, suitable also for older and frail patients, can be permanently integrated into the dialysis routine of a standard dialysis unit.

With patients’ adherence maintained at the 80% level, the improvement of strength and endurance as well as quality of life over 1 year was significant and largest in very weak patients.

With declining health status and sample size reduction due to death or transplantation, the size of the cohort was too small for quantitative analysis after 5 years.

Owing to its study design with patient motivation being a key element, this single centre study did not allow for randomisation and a control group.

Introduction

Patients with end stage renal disease (ESRD) are characterised by low levels of physical activity and a continuous decline in physical function. Observational studies1–3 have revealed that physical inactivity is associated with increased mortality in these patients. Patients have a substantial and sustained decline in functional status, especially during the period before and after initiation of dialysis, in addition to a dramatically high mortality.4

Among the many reasons for low levels of physical activity in ESRD, three factors contribute most: (1) Reduced muscle strength caused by muscle catabolism and wasting,5–7 (2) a substantially increased cardiovascular risk in combination with a high prevalence of comorbid disorders,8 both leading to a reduced health related quality of life (QoL),9 10 which is in itself part of a vicious cycle further impairing physical activity with subsequently (3) reduced physical fitness.

All these factors can be improved by exercise training: Aerobic endurance exercise training in patients with ESRD has been shown to improve physical functioning and QoL,11–21 data which have been previously reviewed.22–24 Also, resistance training has been proven to increase muscle strength and physical functioning in these patients.22 25–27 Moreover, exercise training improves cardiovascular risk factors such as blood pressure28 29 and lipid profiles30 as well as dialysis efficacy.31–33

Despite these proven benefits, a structured physical exercise programme (SPEP) for patients with dialysis is rarely performed on a routine basis. Even more scarce is regular exercise training during haemodialysis. This is surprising, as this approach offers a supervised setting for the patients, is time sparing as patients will not have to attend additional exercise sessions and even improves dialysis efficacy.

Therefore, empirical data on short-term and long-term follow-up including adherence and clinical benefit are mandatory to implement this approach in routine clinical practice.34–36 In our present study, we could demonstrate that this approach is indeed feasible and can be implemented in the daily dialysis routine. This, together with the quantitative evaluation of all data taken over the first year, constitutes the primary outcomes of the study, while the detailed adherence data after 5 years form the secondary outcome, allowing for an informed estimate for the boundary conditions of a future 5-year quantitative study (see online supplementary material).

Participants and methods

Participants

Participants for the study were recruited from an outpatient haemodialysis unit (KfH, Bischofswerda, Germany), where they had been on maintenance haemodialysis for at least 3 months when starting the study. Patients were dialysed three times a week for 4–5 h and had to be in a stable medical condition (see table 1 for patient characteristics). Patients suffering from symptomatic ischaemic heart disease, orthopaedic or musculoskeletal problems interfering with exercise training were excluded. Forty six patients (61% of all 72 patients in the unit at the beginning of the study, 24 male) were included.

Table 1

Patient characteristics

Variable	Group HAn=19	Group MAn=12	Group LA and dropoutsn=15	Totaln=46
Age (years)	63.4±13.8	62.1±18.8	63.9±18	63.2±16.3
Gender, male/female	11/8	6/6	7/8	24/22
Comorbidities n (percentage)
Diabetes (%)	6 (32)	2 (17)	9 (60)	17 (37)
Hypertension (%)	17 (89)	11 (92)	15 (100)	43 (94)
Coronary artery disease (%)	7 (37)	3 (25)	7 (47)	17 (37)
Peripheral artery disease (%)	5 (26)	3 (25)	8 (53)	16 (35)
Cerebrovascular disease (%)	2 (11)	1 (8)	5 (33)	8 (17)
Heart failure (%)	3 (16)	3 (27)	7 (47)	13 (28)
Cancer (%)	4 (21)	2 (18)	3 (20)	9 (20)
Leg amputation	1 (5%)	0	2 (13%)	3 (7%)
BMI (kg/m2)	24.8±4.7	27.6±7.0	27.7±6.6	27.1±5.6
Kt/V	1.47±0.27	1.58±0.3	1.58±0.33	1.54±0.3
Dialysis vintage (years)*	4 (0.3,13)	4.5 (0.3,14)	4 (1,10)	4.4 (0.3,14)
Haemoglobin (g/dL)	11.52±1.14	10.78±1.71	11.3±1.42	11.28±1.4
Albumin (g/dL)	39.93±4.82	40.55±2.28	38.24±3.77	39.53±4.03

The groups characterise the degree of training participation, HA: 80–100%, MA: 60–80%, LA: <60%. Data with a range represent mean±SD except if noted otherwise at the beginning of the study. Kt/V, dialysis adequacy.

*Results are reported as median (minimum, maximum) because of the non-normal distribution.

BMI, body mass index; HA, high adherence; LA, low adherence; MA moderate adherence.

Study design

The programme of combined endurance and resistance training (30 min each per training session, design is shown in figure 1) started after a 5 min warm-up and was performed twice a week during the first 2 h of dialysis under the direct supervision of an experienced exercise specialist. Regular maximal exercise tests provided new individual baseline parameters for the next training interval, namely maximal training heart and repetition rate for endurance and resistance, respectively.

Figure 1

Scheme for our individual structured training to improve endurance and strength in patients with dialysis including a feedback loop. (A) The eight exercises refer to the muscle groups biceps, triceps, abductor, adductor, abdomen, back, leg extensor and leg curl. Theraband resistance and weights were increased in relation to the patient's training success; for details, see text. (B) The training was performed with letto2 Reck MOTOmed cycle ergometers which record automatically the exercise data; see text.

Endurance training

Endurance training was performed with bed-cycle ergometers (MOTOmed letto2, Reck MOTOmed, Germany) positioned in front of the patients’ chairs. Average power, total work and distance cycled, as well as the duration of each training session, were stored on a personalised memory card.

All patients were connected to a heart rate monitor with continuous registration during exercise. Each patient's target heart rate was calculated by Karvonen's method37 from maximal exercise stress testing before inclusion in the study and stored on the memory card. The target heart rate was derived (see figure 1) from the maximum heart rate determined during the maximum exercise test: participants underwent maximal incremental exercise on a non-dialysis day using standard methodology by cycling ≥50 rpm on an electrically braked ergometer (Ergo bike therapie 2000 pc; Daum electronic, Germany) with a three-lead ECG and blood pressure monitoring. The test starts with a workload of 10 W, increasing by 10 W every 2 min. Participants continue until muscular fatigue, pathological ECG criteria or new clinical symptoms appear.

Resistance training

Eight muscle groups were trained with an individual target repetition rate (R) (see figure 1) of appropriate exercises in two sets of 1 min each with a 1 min break according to table 2. Biceps and triceps were trained with weights of 0.5, 1.0, 2.0 and 4.0 kg according to the patient’s strength. Similarly, for the abductor, elastic bands (theraband) with different resistances were used. Patients started with weights/therabands inducing a subjectively perceived intensity of ‘somewhat hard’. For illustration, two short training videos are available as online supplementary material.

Table 2

Strength improvement through resistance training

	Exercise
(R12/R0-1)±SE (%)	leg extensor	legcurl	Back	adductor	abdomen	biceps	triceps	abductor
Group HA	89±15	34±10	112±31	100±21	140±32	33±7.9	47±11	129±29
p Value (ANOVA)	<0.0001	0.001	0.0004	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Group MA	74±22	48±30	79±58	61±32	74±32	16±15	5.6±11	43±16
p Value (ANOVA)	0.002	0.09	0.19	0.045	0.033	0.28	0.59	0.0007

Strength improvement R12/R0−1 in per cent measured in maximum training tests of all muscles trained after 12 months with respect to initial strength. Groups characterise the degree of training participation, HA: 80–100%, MA: 60–80%. The significance level p is also given. The exercises consisted of pressing one's legs against a big ball at the end of the chair/bed (leg extensor); positioning a big ball under the knees and squeezing it with one's heels (leg curl); hip bridge (back); pressing with a ball (adductor); crunches (abdomen); biceps curl (only non-shunt arm, patients were motivated to train the shunt arm between dialysis sessions); triceps extensions (non-shunt arm) with weights; abductors pulling with a theraband.

ANOVA, analysis of variance; HA, high adherence; MA moderate adherence.

The target repetition rate was derived from the maximal repetition rate (MRR) in a maximum strength test for all eight muscle groups: Patients were asked to perform as many repetitions as possible in 1 min.

Since we observed a faster increase in the patients’ strength, in modification of the training programme according to figure 1, maximum strength tests for new baseline parameters and the corresponding training adaption were initiated after 3, 5, 7 and 9 months. If the MRR exceeded 50 rpm, a heavier weight or a more rigid theraband with more resistance was used for the biceps/triceps or abductor exercise.

Clinical tests of physical mobility and capacity

The improvement of physical function was assessed with three performance-based tests at baseline and subsequently every 6 months:

The 6 min walking test measures walking distance as a rough measure of maximal exercise capacity and was performed according to the American Thoracic Society.38

The timed up and go test is a short test which measures basic mobility skills.39

The sit to stand test (STS60) measures functional lower extremity strength during 60 s.40

Quality of life

QoL was assessed with the SF-36 survey41 at baseline and after 6 and 12 months.

Motivation strategies

Patients were exercising together during dialysis and were permanently motivated by the trainer, medical staff and physicians. The individual development of exercise capacity and training data was discussed every 3 months with the patient as part of the treatment which also included the adaption of the prescribed exercise intensity.

Statistics

Quantitative analysis over 1 year was performed for patients who completed more than 60% of the 104 target training sessions of the first year. They were divided into high adherence (HA) and moderate adherence (MA) adherence groups with more than 80% and 60–80% of the sessions completed, respectively. These groups were evaluated separately to investigate the effect of high and moderate compliance on physical functions.

The third group, the low adherence group (LA, <60% session participation), consisted of five members only, precluding follow-up evaluation due to very different comorbidities, for example, diabetes, peripheral artery disease, cardiovascular disease, chronic heart failure and leg amputation.

The effect of the resistance training was quantified by recording the repetitions RN of each exercise from the maximum exercise tests for each patient at the beginning of training and after 3, 5, 7, 9 and 12 months. The normalised data RN/R0 were compared statistically among patients to the initial value for N=0, which is by construction unity. Results including the respective p values (analysis of variance, ANOVA) are summarised for patient groups HA and MA in table 2.

The success of the endurance training was assessed according to the power achieved in each training session, which was averaged over 1 month to give 12 data points PN over a year for each patient. The normalised power data PN/P1 were compared statistically among patients to the initial value for N=1. Resulting curves including the p values (ANOVA) are given for groups HA and MA in figure 2.

Figure 2

Endurance built through training on the cycle ergometer according to the scheme of figure 1. The power PN achieved on average in month N is shown normalised to the power P1 in month N=1. Data are taken from groups HA (>80% training participation) and MA (60–80% training participation) for parts (A) and (B), respectively. The standard error is given for each data point as well as the significance p(ANOVA) of PN/P1 being different from the initial value 1 at N=1 with the scale on the right side. After month 3, roughly the maximum average increase is reached (55% and 45% in groups HA and MA, respectively). This corresponds to an average power of =22.1±2.0 W in group HA (=19.4±3.2 W in group MA) increased from an initial average power of =17.5±1.8 W and =16.0±3.0 W in groups HA and MA, respectively. ANOVA, analysis of variance; HA, high adherence; MA moderate adherence.

Additional analysis aimed at revealing a possible correlation between the change of power from 1 month to the next one, ΔP/Δt, and the power P itself. In a typical saturation behaviour for the power, characterised by a logistic equation, ΔP/Δt is given by ΔP/Δt=α P(P∞−P), where α (in units of inverse Megajoule, MJ−1) characterises the patient's relative improvement in power for work done, while P∞ specifies the maximally reachable power. The relative change Y(P)=P−1⋅ΔP/Δt fits a linear regression curve (with different slope −α) for each patient (figure 3). The (linear) correlation of the slopes with the average patients’ power