Effect of a home based, low intensity, physical exercise program in older adults dialysis patients: a secondary analysis of the EXCITE trial

Sedentary lifestyle and reduced physical performance are hallmarks of dialysis patients [1] and both these conditions negatively impact upon general health status and quality of life in this patient-population [2, 3]. NKF-KDOQI Guidelines formally recommend patients on dialysis be encouraged to increase their level of physical activity [4] and a recent randomized, controlled, multicenter, clinical trial (Clinicaltrials.​gov identifier: NCT01255969) demonstrated that a personalized, low intensity, home-based, exercise program improved physical performance and had a favourable impact on cognitive function and quality of social interaction (as assessed by KDQOL-SF) in dialysis patients [5]. Furthermore, a corollary analysis of the EXCITE trial showed that a poor physical performance, as assessed by the 6-min walking distance [6], predicted a high risk of mortality, cardiovascular events and hospitalizations in the dialysis population [7].

Patients over 65 years of age constitute the fastest growing segment of ESRD population worldwide [8] and although dialysis treatment increases life expectancy among older patients on chronic dialysis, many uremic patients suffer from distressing physical limitations [9]. Since aging is associated with a decline in muscle mass and performance [10], physical exercise is one of the potential methods to counterbalance age-related worsening in muscle mass and function [11]. Notwithstanding, to date very few studies investigated the effect of physical exercise on clinical outcomes in older patients on dialysis.

With this background in mind we specifically designed a secondary analysis of the Exercise Introduction to Enhance Performance in Dialysis (EXCITE) trial [5] by investigating the efficacy and safety of a low intensity exercise program on physical performance and quality of life in the subgroup of patients of the EXCITE trial aged > 65 years.

The CONSORT diagram describing the flow of patients through the trial is shown in Fig. 1. The source population was composed by 714 patients and among these 418 patients were excluded for various reasons (Fig. 1). Thus, 296 patients were randomized to walking exercise (n = 151) or to usual care/normal physical activity (n = 145). As depicted in Figs. 1, 160 patients of 296 (54%) fulfilled the criterion to have an age over 65 years (active arm, n = 83; control arm, n = 77) and were considered in this secondary analysis. Older adults patients (i.e. patients aged > 65 years) who completed the study at 6 months (active arm, n = 53; control arm, n = 62) in the two study arms were quite similar as for demographic, clinical, and biochemical data (Table 1) but differed for BMI, systolic BP, hemoglobin, and albumin (Additional file 1: Table S1) which were higher in patients in the active than in those in the control arm. Patients in the active arm had also less frequently stroke/TIA in their clinical history (Table 1). Moreover, age tended to be lower and diastolic BP to be higher (P = 0.06 and P = 0.07, respectively) in patients allocated to the active arm than in those to the control arm (Table 1). Among patients allocated to the active arm, 26 had low (49%) and 27 high (51%) adherence to the physical exercise program.

This secondary analysis of the EXCITE trial generates the hypothesis that a low intensity, home-based, personalized, physical exercise program improves physical performance and stabilizes cognitive function in dialysis patients aged > 65 years.

Dialysis patients have extremely low levels of physical functioning and exercise capacity, and are often physically inactive [15, 16]. NKF-KDOQI Guidelines formally recommend that all dialysis patients should be counselled and regularly encouraged by nephrology and dialysis staff to increase their level of physical activity and that physical functioning assessment and encouragement for participation in physical activity should be part of the routine patient care plan [4]. On the basis of this recommendation, we designed and performed a multicenter, randomized, controlled clinical trial, the EXerCise Introduction To Enhance performance in dialysis patients trial (EXCITE -NCT01255969), testing whether a personalized, home-based, low-intensity, physical exercise program improves the degree of fitness and quality of life in dialysis patients [5, 7, 17]. In the primary analysis of the EXCITE trial, i.e. in a dialysis population with a wide spectrum of age (from 25 to 91 years), we already documented that a home-based exercise program managed by dialysis staff improves physical performance and quality of life in dialysis patients [5]. In particular, over a 6-month time period we found that the 6MWD improved by 39 m in the exercise group and only by 3 m in the control group and the between groups difference was highly significant (P < 0.001). Similarly, the 5STS test time improved in the active arm (− 2.3 s) whereas it remained virtually unchanged in the control arm of the same trial (− 0.7 s) and again the between groups difference was statistically significant (P = 0.001). In the present analysis restricted to ESRD patients aged > 65 years, we found that in patients of the active arm the improvements in 6MWD (+ 33 m) and in 5STS test time (− 2.7 s) were of similar magnitude to those found in patients of the exercise arm of the primary analysis of the EXCITE trial (Δ 6MWD: + 39 m; Δ 5STS: -2.3 s) whereas no improvement in physical performance was observed in older adults patients of the control arm (Δ 6MWD: -1 m, Δ 5STS test time: − 0.8 s). These findings are of interest because for the first time we demonstrate that a low intensity, home-based, physical exercise program has an effect in older adults dialysis patients which is comparable to that observed in the general ESRD population with a wide age range (from 25 to 91 years).

The EXCITE trial also contemplated the assessment of quality of life in patients of the active and control arm over a 6-month time period. Cognitive function is an important component of quality of life and general health status which pertains attention, memory, language, perception, decision making, and problem solving [18‐20]. The burden of cognitive impairment is higher in dialysis patients than in the general population and represents a disabling condition because it compromises quality of life, increases resource utilization, and results in suboptimal medical care [21‐23]. In this secondary analysis of the EXCITE trial, we found that cognitive function significantly reduced in patients of the control arm (P = 0.04) while it remained substantially unchanged in those of the active arm (P = 0.78) and the between-arms difference was of borderline significance (P = 0.05). This result suggests that regular physical activity over a 6-month time period may stabilize the cognitive decline in older adults dialysis patients and generates the hypothesis that physical exercise may counterbalance the age-related worsening in cognitive function in the dialysis population. However, this latter hypothesis demands to be specifically investigated in an appropriately designed randomized clinical trial.

The effect of physical exercise on clinical outcomes in dialysis patients represents a tantalizing research area and various exercise programmes have been proposed. Koh et al., in a pilot study in older dialysis patients [24], found no significant differences between intradialytic or home-based exercise training and usual care for physical function as assessed by 6MWD. The results emerged in our study do not contrast with those of Koh et al. In the Koh’s study, over a 6 month period, the increase in 6MWD in patients of the home-based exercise arm was more than double than that found in patients of the usual care arm (11% versus 5%) and the lack of a significant difference between the magnitude of these effects most likely depends on the extremely low sample size of the Koh’s study (from an initial population of 70 patients, the 6 month data were only available in 15 patients of the home-based exercise arm and in 16 patients of the usual care arm).

Another novel finding of our study is that the physical exercise program is safe and well tolerated in older adults ESRD patients. Moderate intensity symptoms such as moderate fatigue, leg pain, dyspnea and joint pain were recorded in 54% of session performed by 38 patients and only 5 phone calls for problems related with exercise tolerance were received by the rehabilitation team that supervised the training of patients and the safety of the intervention. Furthermore, no episodes of angina or other major symptoms have been reported in either of the two analyzed groups.

Major limitations of our study are that it is a post-hoc analysis of a randomized clinical trial which did not aim to examine a geriatric population and the fact that the number of patients considered here is about one half of that of the original trial (115 versus 227). Thus, our findings need to be interpreted very cautiously and formally confirmed in a randomized clinical trial specifically enrolling older adult patients on dialysis. Another limitation of our study is that the protocol did not contemplate frailty assessment, dietary change or dietary diary and other physical assessment.

In conclusion, this secondary analysis of the EXCITE trial generates the hypothesis that a simple, home-based, personalized exercise program is well tolerated and improves physical performance and stabilizes cognitive function in older adults dialysis patients. Our trial represents a stimulus to nephrologists for beginning long term trials testing whether a simple exercise training could reduce the risk of many adverse health conditions and increase life expectancy and quality of life in a very high-risk population such as older adults patients on chronic dialysis.