Improving Physical Functioning for People on Long-Term Dialysis: What Does the Evidence Show?

The maintenance dialysis population continues to grow, and over the next decade, it is projected that over half will be over the age of 65 years.1 Due to the systemic effects of aging and kidney failure and its treatment, individuals receiving dialysis experience the loss of muscle strength, balance, and coordination at an accelerated rate. Consequently, individuals receiving dialysis have physical function levels that are 30%–60% lower than age- and sex-matched controls.2 Physical function declines over time on dialysis, and low physical function is associated with decreased life participation, high symptom burden, poor quality of life, and higher risk of falls, hospitalization, mortality, and institutionalization.2,3 Physical function is a multidimensional construct that can be summarized as the capacity of an individual to carry out the physical activities required for their daily lives. Objective tests of physical performance are often used to measure physical function. These tests are typically timed, are performed under standardized conditions, and can either evaluate a single domain of physical function (e.g., measuring strength with hand grip strength) or integrate different domains (e.g., the Timed Up and Go Test incorporates power, balance, and walking speed). Physical function can also be assessed by self-report. Importantly, life participation is a priority outcome for individuals receiving dialysis. To date, a range of interventions aimed at improving either self-reported or objective physical function measures have been tested in trials including erythropoiesis-stimulating agents,4 more frequent hemodialysis,5 and exercise,6 with overall moderate benefits. Given the uncertain and complex pathophysiology of functional impairment in individuals receiving dialysis, its association with adverse outcomes, and concerns regarding feasibility and adherence with exercise training in the dialysis population, it is important to test alternative interventions to address this common problem. Whole-body vibration is one such novel intervention with the potential to improve physical function by providing a mechanical stimulus in the form of vibratory oscillations to the muscles.7 Although the exact mechanisms are unclear, studies have shown higher muscle blood volume and flow with whole-body vibration as well as neuromuscular activation via muscle-stretch reflex contractions, resulting in increased strength and power. With reported improvements in physical function that are similar to low-level/mild intensity exercise in elderly individuals with low physical function,7 whole-body vibration may be helpful in improving physical function in individuals receiving dialysis who are extremely impaired and whose limitations prohibit more intense exercise programming. In this issue of CJASN, Asahina et al.8 report the results of a randomized clinical trial comparing 12 weeks of thrice-weekly whole-body vibration versus standard care for improving the primary outcome of the Timed Up and Go Test in maintenance hemodialysis patients. Additional outcomes included balance testing (single-leg stand test) and strength endurance (30-second chair stand). All measures were taken at baseline and follow-up. The investigators randomized 98 participants aged 65 years and older from three centers in Japan. Whole-body vibration was delivered over 3 minutes before each hemodialysis session using a vibration platform designed to deliver a side-side movement similar to walking. The vibration frequency progressed from 18 Hz to a maximum of 26 Hz at an amplitude of 2–3 mm. The difference in Timed Up and Go Test times between groups, however, was not significant (0.3 seconds [95% confidence interval, −1.4 to 2.0]), and no significant changes were detected in secondary outcomes. Although not defined, adherence was reported as “high” and overall study dropout was 9% (12% and 6% in whole-body vibration and control groups, respectively), which is acceptable. The authors also reported that there were no adverse musculoskeletal events, although how this was monitored and reported was not clearly specified. Asahina et al. should be commended for addressing an important outcome and examining a novel intervention to improve physical function that demonstrated feasibility in this small trial. They chose an appropriate primary outcome measure to assess neuromuscular fitness, an aspect of physical function for which whole-body vibration has biological plausibility and demonstrated efficacy in other populations.7 The authors offer several explanations for the equivocal findings, such as the short duration of the intervention and small sample size, although this was only marginally lower than what was specified in their sample size calculation. It is important to note that the sample size calculation did not account for minimal clinically important difference of the Timed Up and Go Test, which is unknown in the dialysis population, and the mean change used for sample size calculation was below the threshold of minimal detectable change identified for the Timed Up and Go Test in the CKD population (e.g., approximately 3 seconds).9 Critically, baseline Timed Up and Go Test times were comparable with normative values for community-dwelling older adults, suggesting that study participants were relatively high functioning.10 This is an important observation considering that the benefits of whole-body vibration alone have mainly been demonstrated in older, frail adults.7 Furthermore, there is uncertainty regarding appropriate dose of whole-body vibration, but study dose seemed relatively low compared with studies in other populations. Finally, the muscular response to whole-body vibration is maximal when the vibration stimulus is comparable to the inherent frequency of the target tissue.7 Therefore, the intrinsic properties of the tissue (muscle stiffness, posture, and anthropometrics) will affect the response, suggesting that successful implementation of whole-body vibration may require more protocolization and supervision than proposed by the authors and provided in the current study. The equivocal results of this study contribute to the uncertainty regarding the role of whole-body vibration in addressing physical function impairment in individuals receiving dialysis. Such ambiguity is common in trials investigating the effects of candidate therapies on physical function. Heterogeneity and uncertainty regarding validity and reliability for the outcome measures used, lack of specificity between the intervention and the component of physical function being measured, and the timing of these measures in relation to the intervention make comparisons between studies and different interventions addressing physical function extremely difficult.11 Despite this, a recent Cochrane systematic review and meta-analysis in maintenance dialysis populations demonstrated that any exercise (aerobic or resistance) was shown to improve physical function and functional capacity with moderate certainty.6 It is important to note that the majority of those studies included some form of direct supervision and were delivered in the hemodialysis unit. Although, as Asahina et al. state, feasibility of an intervention is a critical feature, poor physical function is a complex problem and multidimensional problems often require more than a single, simple solution for sustainable benefit. To obtain clinically meaningful improvements in physical function, we may have to reframe our criteria for feasibility for these interventions. For example, the feasibility of intradialytic exercise programs has been reported across a range of settings; however, the key feature of “success” across these programs is the allocation of resources (e.g., exercise specialists or dedicated champions, equipment, and administrative support). An additional challenge to improving physical function is that although modification of contributing factors (e.g., optimizing clearance through more frequent dialysis), may result in modest gains, to enhance efficacy, physical function interventions need to have greater specificity for specific patient goals. Plainly stated, if we want people to be able to carry out everyday physical activity to maintain independence, the intervention should target and measure outcomes required to perform those daily activities. Yet, as Asahina et al. point out, adherence and sustainability are major challenges to exercise-based interventions, and consequently, our search for simpler solutions continues. This approach is perhaps why most exercise trials in the maintenance dialysis population have tested intradialytic cycling to minimize loss to follow-up and nonparticipation. However, exercise training strictly in a seated position may explain why even greater gains in objective physical performance have not been demonstrated with intradialytic cycling, especially for multicomponent tests that integrate different domains of fitness, such as the Timed Up and Go Test. In conclusion, on the basis of current evidence and the principles of specificity, aerobic and/or resistance exercise are the most promising interventions to address physical function with the potential for novel strategies, including whole-body vibration as useful adjuncts. Future research should therefore test combinations of candidate interventions (e.g., exercise, nutritional interventions, and whole-body vibration) using novel trial methodologies including adaptive, platform designs that can accommodate multiple interventions within one trial. An important aspect of any future research study would be to include outcomes that are prioritized by and validated in individuals receiving dialysis while ensuring that the trial is powered for minimally clinically important difference or minimal detectable change in its chosen primary outcome. Importantly, whole-body vibration has demonstrated efficacy for outcomes that may also influence physical function (e.g., pain) in other populations,7 and the effect of this intervention on this and other patient-important outcomes should be further evaluated. Finally, if the ultimate goal of improving physical function is to maintain patients' independence and decrease the risk of institutionalization, a multidisciplinary solution that includes exercise (in addition to optimizing disease and treatment-related factors) will be needed. It will therefore ultimately be left to the nephrology community and the collective values of individual kidney programs to decide whether to allocate the necessary resources to achieve this.

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