Hemodialysis (HD) patients have a decrease in physical activity and deterioration in quality of life. Muscle weakness and low impaired daily activity are in part caused by cardiovascular comorbidity, malnutrition, chronic anaemia and inflammation, alterations in mineral bone metabolism, as well as abnormal urea metabolism.1,2

Changes in urea metabolism involve an alteration of type II muscle fibres and nerve endings in the form of myopathy; and it effects on the neuronal myelin sheath. Eventually, muscular atrophy occurs and the patient has symptoms of fatigue, weakness, cramps or myoclonus.3–5

Therefore, one of the fundamental aspects of renal patient care should be physical rehabilitation to preserve functional capacity and autonomy.6,7

Several studies have reported the beneficial effects of physical exercise during HD sessions2 on functional capacity, psychological status and quality of life.8

Some patients are unable to perform physical exercise programmes in HD. Therefore, there is interest in the role of neuromuscular electrical stimulation (NMES) as an effective alternative to physical exercise in HD sessions; however studies published to date are few and limited.9–13 NMES consists in stimulating a group of muscles using a low intensity electric currents through electrodes applied to the body surface; muscles contracts, just as it would with normal muscle activity.14,15 In the healthy population, this is often used to improve of physical fitness and muscle strength. It is also applied for muscle rehabilitation mainly in populations with severe neurological or post-traumatic movement disorders.16,17

However, there is not enough evidence on the favourable effect of NMES on the impairment of muscle strength or composition in HD patients. The aim of the present study was to analyse the effect of an NMES programme on muscle strength, functional capacity and body composition in our HD patients.

From the beginning of September to the end of November 2013 (12 weeks), a prospective, single centre study was conducted, after being approved by the local Ethics Committee and in accordance with the Declaration of Helsinki guidelines. The purpose was to evaluate the effect of an exclusive NMES programme on muscle strength, functional capacity and body composition of our HD patients.

The inclusion criteria was: signed informed consent, 18 years of age or older, on regular HD for more than 3 months at our site, and clinical and haemodynamic stability during the last 3 months. The exclusion criteria was: a recent cardiovascular event, presence of vascular access for HD in the lower limbs, on a pacemaker, unable to perform body composition analysis in the lower limbs, and refusal to sign informed consent.

Our patients are distributed into 6 groups of 10–12 patients each. All patients have a pre-established fixed number. These patient undergo a 4h sessions on alternate days (M–W–F or T–T–S), in morning, noon, and afternoon shifts. Our nursing staff performed the exclusive NMES programme and assessment of body composition. Since implementation of this additional activities entailed an increase in the daily care burden, patients on the midday schedule were excluded.

There were two groups of patients. Patients from the morning and afternoon shifts with even numbers in the fixed list were included in the control group (CO), and they received routine care. Patients with odd numbers from the morning and afternoon shifts received the electrical stimulation (EMS). The patients were asked to continue their regular daily physical activity, without prescribing any additional physical exercise programme.

Neuromuscular electrical stimulation

Patients assigned to the EMS group performed an NMES programme of the quadriceps muscles of both lower limbs as previously agreed with our the Rehabilitation Department. The device used was the Compex® Rehab Theta 500i model, equipped with various rehabilitation exercise programmes with different phases, types and current intensity. The electrical stimulation programme included (total time, intensity, contraction–relaxation phase time): a toning programme in the first week (25min, 8Hz, contraction 1.5s, phase 25min, relaxation 1.5s); one week of aerobic endurance (28min, 60Hz, contraction 1.5s, phase 8s, relaxation 0.75s); 2 weeks of rehabilitation–amyotrophy (30min, 25–40Hz, contraction 2s, phase 4s, relaxation 1s); 2 weeks of rehabilitation–hypertrophy (33min, 55Hz, contraction 1.5s, phase 6s, relaxation 1s); 3 weeks of muscle strengthening (35min, 9 peaks: 2–75Hz, phase 7s, relaxation 1.5s) and finally 3 weeks of strength-endurance (38min, 90Hz, contraction 1.5s, phase 4s, relaxation 0.75s). This was performed during the first 2 hours of each HD session, with a mean duration of 30–45min. Patients were in their usual supine HD position, with full extension of the lower limbs and minimal flexion (15°) of both knees resting over a soft pillow placed in the popliteal region. Each patient always had their own electrodes (5cm×10cm). These were placed just on the motor point of the muscle heads of the quadriceps (anterior rectus, internal and external vessel), guaranteeing maximum comfort and efficiency. When the patient noticed the passage of the electric pulse, they were asked to perform a voluntary contraction to achieve the maximum contraction of the muscle. The maximum intensity was achieved by encouraging the patient to resist the highest possible level of painless stimulation energy to achieve tolerable and effective muscle contraction (Fig. 1).

Fig. 1.

Neuromuscular electrical stimulation (EMS) of the quadriceps muscles of both lower limbs. Electrodes on the motor point of the muscle heads of the quadriceps (anterior rectus, internal and external vessel). Patients in supine position, with full extension of the lower limbs and minimal flexion (15°) of both knees by means of a soft pillow placed in the popliteal region.

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Coinciding with the usual quarterly medical follow-up visits on days that patients did not have HD, the following variables were analysed both at baseline and at the end of the study.

We evaluated 41 out of the 63 patients of our dialysis unit, all were from morning and afternoon shifts. Nineteen patients were excluded. The main reasons for exclusion were: physical impossible to perform the body composition analysis in the lower limbs (5), hospitalisation (4), not giving informed consent (3), less than 3 months on our HD unit (3), vascular prostheses in lower limbs (2) and having a pacemaker (2). A total of 2 patients dropped out during the study (one death due to abdominal sepsis, one kidney transplant). Thus 20 patients completed the study. Of these, 13 were assigned to the EMS group, and 7 to the CO group. None of the patients had any relevant NMES-related adverse effects (lower limb pain, burning, or cramps) or haemodynamic instability episodes. 55% were men, with a mean age of 67.7±12.5 years and a mean HD vintage of 30.3±22.3 months. The mean Charlson index was 8.8±2.5. The etiologies of chronic kidney failure were: diabetes mellitus (35%), glomerular disease (15%), chronic pyelonephritis (15%), kidney disease of unknown origin (15%), hypertension (10%), polycystic kidney disease (5%) and others (5%).

No significant differences were found between the study groups in terms of demographic data, comorbidity and main aetiology of kidney disease at study baseline (Table 1). The data of muscle composition of the quadriceps are shown in Table 2. A significant increase in the QMA was observed only in the EMS group (128.6±30.3 vs. 144.6±22.4cm2; p 0.032). Also in EMS patients there was a significant decrease in the average value of QFA (76.5±26.9 vs. 62.1±20.1cm2; p<0.024). No significant changes were observed in QTA in any study group. The main biochemical data and dialysis parameters are shown in Table 3. No significant differences were observed in main nutritional biochemical parameters and the dialysis parameters. Medical treatment was not modified during the study, the mean dose of erythropoietic agents in EMS and CO groups were 25.6±11.6 vs. 26.2±12.4mcg darbopoietin/week and the treatment with native vitamin D (calcifediol 0.266mg/month) prescribed in any of our patients throughout the study was: 38.2 vs. 36.8% in EMS and CO groups, respectively.

Table 4 shows the results on muscle strength and functional capacity. We did not observe significant changes in muscle strength through the HG in any of groups at the end of the study. In contrast, it was observed a significant improvement in the MQES of the lower extremities in the EMS group (MQES 11.7±7.1 vs. 13.4±7.4kg, p 0.002), while in the CO group we did not observe significant changes at the end of the study (MQES 11.4±6.6 vs. 11.2±5.9kg, p 0.773).

In the 6MWT, we observed a 9.9% increase in the distance covered at the end of the study in the EMS group (293.2±163.9 vs. 325.2±176.4m, p 0.018), whereas no changes were observed for the CO group (348.7±93.4 vs. 354.3±80.4m; p=0.753). In the STS10 test, a shorter performance time was obtained in the EMS group (39.3±15.5 vs. 35.8±13.7s; p 0.310) at the end of the study, although these differences did not reach the pre-established statistical significance. In contrast, in the CO the time used to complete the test was longer but the difference was not statistically different (38.1±13.3 vs. 39.2±13.3s; p 0.299).

Regarding the body composition no significant differences were found between the study groups. In the EMS group at the end of the study, there was a moderate increase in LW (56.2±10.9 vs. 57.8kg±11.6, p 0.247), as well as a certain decrease in FW (15.4±7.8 vs. 13.9kg±7.7; p 0.278), in the percentage of abdominal fat (21.3 vs. 19.5%; p 0.262) and in TBW (36.4±4.9 vs. 35.5±6.3 l; p 0.534) (Table 5).

Patients on HD are characterised by a decrease in the physical activity and a deterioration in quality of life. High cardiovascular comorbidity, malnutrition, chronic anaemia and inflammation, HD-related sedentary lifestyle, as well as the abnormalities proper to urea metabolism could be, among others, some of the various factors that will lead to a marked muscle weakness and functional impotence throughout their permanence in HD.1,2

Metabolic abnormalities associated to uraemia mainly affect type II muscle fibres above all, and musculoskeletal nerve endings in the form of myopathy and affect the neuronal myelin sheath, that will eventually lead to significant muscular atrophy with symptoms as diverse as fatigue, weakness, cramps, or myoclonus.3–5

Some of the different strategies used in the prevention and treatment of muscle loss in these patients have been the correction of metabolic acidosis with bicarbonate supplements, the use of anabolic hormones, adequate insulin regulation and physical exercise in HD.8,26–28 An effective therapeutic alternative that may reduce the progression of muscle deterioration is not yet available. One of the fundamental aspects in the care of renal patients should be adequate physical rehabilitation to preserve their functional capacity and autonomy.6,7

The role of NMES as an alternative therapy to physical exercise during HD sessions has received considerable interest. In some cases, due to its clinical characteristics and the associated comorbidity, patients are unable to perform physical exercise programmes. The few studies published in the literature regarding the role of NMES, mainly in patients with chronic heart failure or lung disease, show favourable effects on muscle composition and functional capacity.29–31 In addition, they appear to be easy to apply and safe without serious complications.14,16,32

After a thorough review of recent literature, we found only small studies published in relation to NMES in renal patients. The first study comparing the effects of NMES with the classic effects of physical exercise was conducted by Dobsak et al.9; this was a randomised, 20-week study with 3 comparative groups (physical exercise, NMES and control), both with an exclusive NMES programme and with an aerobic physical exercise programme using cycloergometers. Patients (n=32) in HD were able to improve muscle strength in lower limbs estimated by dynamometry, functional capacity (6MWT), quality of life (SF-36 health questionnaire) as well as dialysis parameters (Kt/V, urea reduction rate) with respect to a third control group without intervention. No significant differences were observed between the 2 exercise groups (exercise vs. NMSE) in the different aspects studied.

Similarly, Farese et al.,10 evaluated the effect of NMES and physical exercise on blood pressure control and dialysis parameters. Nine patients were randomly assigned to 3 different protocols. During 9 consecutive HD sessions (3 weeks), each group underwent, on a different weekday, either a physical exercise programme using cycloergometers or a lower limb NMES programme or did not perform an intervention. The authors observed a significant increase in blood pressure and higher urea and phosphorus levels coming out in the dialysed fluid in those sessions in which patients performed NMES and physical exercise as compared to the sessions without intervention. No relevant changes were observed in plasma concentrations of these solutes or in dialysis parameters (Kt/V, urea reduction rate). The parameters of muscle strength, functional capacity and quality of life were not evaluated.

In Spain, it is worth to comment on the only 3 published studies on NMES associated with exercise. Our group obtained similar results to the mentioned in terms of muscle strength, functional capacity and quality of life after an exclusive 12-week NMES programme in 38 HD.11 Another study of 12 weeks duration, NMES associated with mainly aerobic physical exercise using cycloergometers in 11 patients in HD shows favourable results on safety, efficacy and tolerability of NMES during the HD sessions.12 Similarly, Contreras Martos et al.,13 in a group of 11 HD patients, also showed positive results after a 5-week strength-resistance programme associated with NMES of both quadriceps during HD sessions.

In the present study, we have observed an improvement in muscle strength and functional capacity in our HD patients after an exclusive NMES programme. These results can be basically superimposed to those obtained published studies; however, our study adds data of interest in relation to changes in muscle composition after the NMES programme. Our results are similar to those obtained by Dobsak et al.,9 in a population with similar demographic characteristics, through the evaluation of identical muscle strength and functional capacity tests; although in our study only both quadriceps were stimulated and it did not include stimulation of the calves. The present study did not evaluate parameters of quality of life; we, in a previous study11 observed a significant improvement in health-related quality of life through the EuroQoL-5D standardised test. As an important difference with respect to the Dobsak et al.9 and Farese et al.10 studies, it should be mentioned that our study did not specifically analyse either the blood pressure control or dialysis parameters nor the elimination of various solutes, so we cannot provide results on these matters. Nevertheless, we did not observe significant changes in the control of blood pressure, biochemical parameters, or routine parameters of dialysis adequacy. In our modest opinion, it would very unlikely to observe any changes in these parameters.

The multiple beneficial effects of physical exercise at cardiovascular, psychological, muscular or skeletal level have been widely described. At muscular level, there is an increase in strength, resistance and size of the group of muscles being exercised, this is accompanied of t changes in the body composition in the form of decrease of abdominal fat, increase of lean mass and muscle tissue, decrease of skin folds or increased muscle diameter.33,34 This muscular adaptation to physical exercise and the changes in body composition have also been described after the use of NMES globally.35,36 However, NMES is based on the application of low-frequency repetitive pulses through surface electrodes; this achieves immediate local activation and recruitment of small muscle fibres of the different muscle groups.14–16,32 Actually, this local muscle activation and recruitment could explain, in some patients with marked muscle atrophy and functional impotence, the significant improvement in muscle strength exclusively in both quadriceps (MQES) and the absence of changes in HG, a marker of upper limb muscle strength in elderly patients.7,20

Local application of NMES to certain groups of muscles, may also justify the absence of significant changes in the biochemical and nutritional parameters, as well as the absence of changes in body composition estimated by electrical bioimpedance. To produce significant changes in biochemical parameters and overall body composition it would be necessary the electrical stimulation of the upper limbs in combination with the rest of the abdominal musculature or electrical stimulation programmes combined with physical exercise, so a greater number of muscles are recruited with a more generalised effect.

The increase of muscle strength in both lower limbs was associated to a significant increase of the muscular area of the quadriceps, as well as in a significant decrease of fat. The mechanisms involved in this structural muscle change are: Increased oxygen supply to tissues, greater production of vascular endothelial growth factors (vascular endothelial growth factor), increased synthesis of some proteins related to muscle metabolism such as insulin growth factor-1 or the inhibition of myostatin, as well as the decrease in certain proinflammatory cytokines such as interferon γ or interleukin 6 caused by repeated and continuous electrical stimulationl.37–40

Despite these significant muscle findings, no significant changes were observed in the total area. These finding may be attributed, to the short duration of the specific programme of muscular hypertrophy (only 2 weeks), to the level of contraction intensity used throughout the study, as well as to the high muscle atrophy; however, we cannot either rule out errors in the measurements. Perhaps a longer-term NMES programme or perhaps the use of supplementary examinations not based on anthropometric muscle estimation formulas, such as ultrasound, computed tomography or muscle magnetic resonance imaging, intended to measure muscle and body composition changes, could more accurately detect total muscular anthropometric changes.

Both the 6MWT and the STS10 are functional tests widely used in clinical practice as indicators of quadriceps muscle strength.7,22,23 On the other hand, the quadriceps is the largest muscle in the lower limbs. Functionally, it is a powerful knee joint extender, hip flexor and knee stabiliser necessary for walking. Thus it participates in walking, running and jumping. The application of an NMES programme resulted in a significant increase in the distance covered in the walk test in the EMS group alone. This finding demonstrates the fundamental role of NMES in the strengthening of the lower limbs. Interestingly, we obtained no significant changes in the STS10 test; this could be attributed to the great variation of results obtained in the test, the difficulty in actually performing the STS10 in this particular type of patients in HD, as well as the limited number of patients. However, unlike the CO group, which used more time, the results of the EMS group showed shorter time to perform the test. This illustrates some extent, the favourable effect of the NMES programme on this functional test.

It is worth noting the efficacy, safety and the easy application and management of our NMSE programme during the HD sessions; we had no dropouts or unfavourable effects throughout the study.

Among the many limitations of our work, we should mention the absence of randomisation of the study groups, although this allocation was conditioned by the absence of external financing or additional resources, so it seemed reasonable, in the opinion of the authors, to assign the patients according to the daily nursing care burdens. Also noteworthy is the small sample size, which obliged the use of non-parametric tests, as well as the short duration of the NMES programme, although they are similar, in terms of number and duration, to those previously published. Unfortunately, we did not have more sophisticated methods (DEXA) in our unit for the evaluation of muscle composition. Thus there is still a need to perform better designed studies to establish the exclusive role of NMES in the long term and its potential beneficial effects in this type of patients.

In conclusion, intradialysis NMES of both quadriceps safely and effectively improved the muscle strength, functional capacity and muscle composition of our patients in HD. Pending future studies, NMES is a novel therapeutic alternative to improve the physical condition and muscle composition of these patients, especially in those where the performance of an intradialysis physical exercise programme is difficult or contraindicated.

The authors declare that they have no conflicts of interest.