Application of exercise therapy in patients with chronic kidney disease-induced muscle atrophy: a scoping review

Abstract

Background

The prevalence of muscle atrophy in patients suffering from chronic kidney disease (CKD) presents a significant challenge to healthcare providers, necessitating innovative approaches to management and care. Against this backdrop, this study embarks on a comprehensive review of literature concerning the application of exercise interventions in the nursing care of these patients. Such interventions are critical in addressing the debilitating effects of the condition, which include progressive loss of muscle mass and strength, adversely affecting patient mobility, quality of life, and overall survival. This review aims to identify the specific exercise modalities, contents, outcome indicators, and application effects associated with this intervention, in the context of the complex interplay of metabolic, inflammatory, and hormonal factors contributing to muscle wasting in CKD patients. By examining the efficacy of various exercise interventions, this study seeks to elucidate optimal strategies for mitigating the impact of CKD-induced muscle atrophy, thereby informing clinical practices and improving patient outcomes.

Methods

According to the method of a scoping review, nine databases (Cochrane, PubMed, EMBASE, Web of Science, ProQuest, Ovid, CNKI, Wanfang Data, and VIP) were searched until September 28, 2023. The included literature was screened, summarized, and analyzed.

Results

A total of 20 pieces of literature were included. Some types include aerobic exercise, resistance exercise, and aerobic combined resistance exercise. The exercise intensity primarily falls within the mild to moderate range, with a recommended frequency of 2 − 3 times a week, lasting 30 − 60 min each time. The types of outcomes encompassed in this study include body composition, functional testing, strength measurements, laboratory examinations, cardiopulmonary function assessments, and patient-reported outcomes. To varying degrees, exercise intervention positively impacts the subjects' physical activity ability, body composition, and skeletal muscle status. Currently, resistance training is the primary type of intervention used for preventing and treating CKD patients induced by muscle atrophy.

Conclusion

Exercise intervention can improve muscle strength, physical function, and quality of life in patients with CKD muscle atrophy. Therefore, patients should be fully informed of the effect of exercise intervention in the treatment of chronic kidney disease-induced muscle atrophy in future, so as to promote the standardized implementation of exercise intervention.

Introduction

Chronic kidney disease (CKD) significantly impacts global health, with its management complicated by the high prevalence of sarcopenia, identified as a loss of skeletal muscle mass and strength. Duarte et al. [1] report a notable prevalence of sarcopenia in CKD patients at 24.5%, with a higher incidence observed in those undergoing dialysis. This condition, especially severe in 26.2% of dialysis patients compared to 3.0% in non-dialysis patients, underscores the critical need for early identification and intervention.Chronic Kidney Disease (CKD) is associated with various pathophysiological processes, including mitochondrial dysfunction. Studies reported that muscle atrophy in CKD patients is related to mitochondrial dysfunction [2]. Exercise intervention can reduce oxidative stress, increase mitochondrial capacity, and enhance mitochondrial function [3]. Furthermore, it is particularly noteworthy that research has identified the combination of moderate-intensity continuous exercise (MICE) with blood flow restriction (BFR) as effective in suppressing the appetite of obese adults through the promotion of Lac-Phe and ghrelin secretion [4]. This finding underscores the significant implications of exercise not only for CKD but also for diabetes management, highlighting its potential as a pivotal intervention in the treatment and prevention strategies for these conditions. Mitochondrial DNA copy number (mtDNA-CN) is considered a novel biomarker for CKD risk, as higher levels of mtDNA-CN are associated with a lower risk of CKD. This relationship is independent of traditional CKD risk factors, suggesting that mtDNA-CN could serve as an important indicator for identifying CKD progression and severity [5]. Furthermore, the onset of diabetes in patients with CKD is significant, as mitochondrial dysfunction can exacerbate metabolic dysregulation. The relationship between mitochondrial function and CKD highlights the potential for targeted interventions to improve mitochondrial health and manage CKD, particularly in the context of comorbid conditions like diabetes [6].

Recent meta-analyses showed that exercise training can increase cardiorespiratory endurance, improve muscle strength and muscle volume, reduce the risk of cardiovascular disease, delay the progression of CKD, and improve the quality of life of CKD patients [7]. Therefore, we should identify muscle atrophy in CKD patients as early as possible and implement the intervention. While patients diagnosed with CKD may participate in resistance training, flexibility exercises, and aerobic exercise [8], it is crucial to consider the diverse physical capacities and tolerances of subjects at various phases of CKD. Furthermore, the lack of clear evaluation criteria for the type, specific content, and outcomes of exercise interventions for CKD patients leads to significant heterogeneity in the type, frequency, and intensity of exercise interventions [7].

A scoping review assists researchers in elucidating their research inquiries, presenting the scope and extent of research involved, summarizing research results, identifying the limitations of existing research, and finding research progress in a particular knowledge field [9]. This study used a scoping review methodology to analyze and synthesize the application research on exercise intervention in chronic nephritis muscle atrophy. Our objective is to furnish medical and nursing professionals with a comprehensive summary of exercise intervention types, content elements, evaluation indices, and efficacy, serving as a valuable resource.

Methods

Research question

① What are the methods, intensity, frequency, and time of exercise intervention for chronic kidney disease-related muscle atrophy? ② How does the application affect the exercise intervention program?

Identifying relevant studies

Search strategy

Using a computer, a search was conducted in the Cochrane Library, PubMed, EMBASE, Ovid, ProQuest, Web of Science, CNKI, Wanfang, and VIP. The search time was covered from the establishment of the database until September 2023. The search words were combined with the MeSH words and entry terms in the PubMed database, including the search terms "Sarcopenias," "Muscle wasting," "Muscle atrophy," "Diabetes Mellitus," "Diabetes Insipidus" "Diet, Diabetic," "Prediabetic State" "Exercise Therapy" "Remedial Exercise," "Rehabilitation Exercises," "Physical Activities," "Aerobic Exercise," "Acute Exercise," "Isometric Exercise," "Exercise Training." The relevant references were tracked and noted.

Inclusion criteria and Exclusion criteria

Inclusion criteria: (1) Population: The study subjects included CKD patients with muscle atrophy or sarcopenia. (2) Intervention:Articles that employ exercise therapy as an intervention strategy are included, covering a range of modalities such as aerobic training, resistance training, and stretching exercises. Studies focusing on traditional physical therapy interventions, such as electrostimulation, and pharmacological treatments are excluded from this review. (3) Comparison: The control arm was subjected to conventional care, incorporating stretching routines or engaging in physical activities quantitatively inferior to the normative daily exertion levels. (4) Outcomes: Muscle Mass, Muscle Strength, Physical Performance, Biochemical Markers, Functional Status were measured at baseline and post-exercise. (5) Study: The literature categories comprised a variety of original research encompassing randomized controlled trials, quantitative studies, qualitative studies, and mixed studies.

Exclusion criteria: Reviews, conference abstracts, thematic summaries, protocols, duplicate publications, and full-text articles that were not accessible were excluded from the analysis. Literature that missed any discussion of the specific details regarding the execution, substance, or impact of exercise intervention in individuals afflicted with muscular atrophy due to chronic renal illness was likewise disregarded.

Study selection

Two proficient researchers conducted an exhaustive review of titles and abstracts based on the inclusion and exclusion criteria, completing preliminary literature screening. Subsequently, they reviewed the complete text to make a final selection. The screening was conducted independently, and then the results were compared. The issue was referred to the research team for discussion in a dispute.Through open dialogue and a rigorous examination of the inclusion and exclusion criteria, we reconciled differing viewpoints and reached a mutually agreed-upon selection of literature. This process highlights the critical role of collaborative discussion and meticulous scrutiny in achieving a consensus on literature screening outcomes, ensuring the integrity and quality of our research methodology.

Data extraction and synthesis

Two researchers independently extracted all the information from the included literature as follows: (1) authors, research type, country and year of publication, and sample size; (2) intervention method, intervention content and type, intervention duration of the experimental group and the control group; (3) outcome indicators, and measurement content of outcome indicators.

Results

Study characteristics

Following the initial retrieval of 875 articles, a final selection of 20 articles was made [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Figure 1 depicts the specific screening process. These included studies were conducted in China (n = 9), United Kingdom(n = 3), Brazil (n = 2), Australia (n = 1), Germany (n = 1), Italy (n = 1), South Korea (= 1), Sweden (n = 1), and the USA (n = 1). Regarding the publication years of the studies included in this article, the distribution is as follows: 2023 (n = 3), 2022 (n = 4), 2021 (n = 4), 2019 (n = 3), 2018 (n = 1), 2016 (n = 1), 2015 (n = 1), 2014 (n = 2), and 2007 (n = 1). The distribution of the studies by year and geographic location is presented in the supplementary figure. Among the 20 pieces of literature included in this study, 14 literatures described RCTs [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27] and six literatures are quantitative non-random studies [10, 11, 13, 19, 22, 29]. Table 1 lists the characteristics of the included literature and is discussed below.

Table 1 Characteristics of the included studies (n = 20)

Types of Exercise Intervention Programs

The exercise intervention scheme mainly includes resistance exercise [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28], aerobic exercise [23, 29], and aerobic exercise combined with resistance exercise [13, 15, 22, 24]. (1) Currently, resistance training is the most prevalent form of exercise intervention. The common resistance exercise intervention scheme involves strength training of the upper and lower limbs. Upper limb strength training includes biceps curl with dumbbells, elastic ball movement on the non-internal fistula side, pull-ups, and chest and shoulder compression. However, lower limb strength training focuses on the muscle groups around the knee joint, including lunge, squat, sitting leg raising, knee flexion and extension, and quadriceps strength training with elastic belts. Furthermore, there are resistance exercises for the hip joint, such as leg compression and hip flexion. (2) The aerobic exercise intervention scheme primarily consists of several modalities, such as bicycle modalities [11, 16], treadmill exercise [13], Baduanjin [29], and steady-state walking [23]. In this context, Luca et al. [23] used steady-state walking as an intervention plan for aerobic exercise and examined the impact of this simple aerobic exercise on the subjects. (3) The intervention program mostly incorporates resistance exercise with low-to-moderate intensity aerobic exercise. The three most prevalent forms of aerobic exercise are cycling, treadmill, and rowing. Liming et al. [19] used psychological theory to guide patients in resistance exercise, helping patients develop healthy behaviors through the healthy action process orientation model.

Intensity, frequency, and duration of exercise intervention

The intervention intensity and frequency varied among the studies. (1) Exercise intensity: Eight studies [10,11,12, 18, 19, 22, 24, 26] set the exercise intensity according to the scores of the subjects' perceived exertion (RPE). The intensity target of exercise training was established in two studies [14, 26] based on the patient's capacity to tolerate the quantity of exercise. The training intensity progressively escalated until the patients reached the optimal tolerance level. Two studies [21, 27] assessed the exercise intensity of the subjects based on maximum repetitions (RM) and the percentage of maximum loading (1RM) of the exercise load. Four studies [13, 15, 16, 19] set the exercise intensity based on the subjects' cardiopulmonary function indexes. This was achieved by measuring the heart rate of the patients during exercise as a reference, setting the appropriate exercise intensity after evaluating the heart rate at the maximum exercise intensity they could tolerate. Zhang Bo et al. [13] divided the exercise training into low intensity (25% ~ 44% VO_2max) and moderate intensity (45% ~ 59% VO_2max) based on the subjects' peak oxygen uptake (VO_2max). There was a gradual transition from low to moderate intensity during the intervention. This. (2) Exercise frequency: The intervention frequency of each study varied from 2 to 3 times per week, while the duration of intervention was typically set based on the subjects' tolerance level and training objectives. (3) Duration of exercise intervention: There are a total of 13 studies in which the intervention period spans 12 weeks [11,12,13, 15,16,17, 21,22,23,24,25,26,27, 29], two studies have an intervention duration of 24 weeks [14, 19], three studies have an intervention duration of 12 months [10, 18, 28], and two studies have an intervention duration of 6 months [19, 23].

Outcome indicators and measurement tools

Outcome indicators included functional tests, body composition, strength, laboratory examination, cardiopulmonary function, and strength, and functional evaluations. The principal physical activity assessments comprised a walk test, sit-to-stand test, functional reach, balance test, SPPB score, and physical activity recall. The measurement of body composition included weight, body mass index, body fat, and lean body mass. Skeletal muscle mass was assessed using dual-energy X-ray absorptiometry, anthropometry, and muscle ultrasound. Laboratory examination indicators included inflammatory markers, renal profile, and body fat. Cardiopulmonary function indicators examined forced expiratory volume in one second (FEV-1), vital capacity, forced vital capacity (FVC), maximum inspiratory pressure (MIP), and peak oxygen uptake (VO_2max). In terms of patient-reported outcomes, the primary measurement tools encompassed the Quality-of-Life Questionnaire, Pain Scale, Leicester Uremic Symptom Score, Sarcopenia Quality of Life Scale, Activities of Daily Living Scale, Barthel Index, Kidney Disease Quality of Life Scale, Dialysis Patient Quality of Life Scale, and Revised Piper Fatigue Scale.

Effects of Exercise Intervention

(1) Effects of resistance exercise intervention: The exercise intervention schemes for muscle atrophy in CKD patients in the literature included different levels of resistance exercise. A total of ten studies have documented that resistance training protocols yielded a positive impact on several aspects of the subjects' physical function [10, 11, 13, 16, 29], muscle strength [10, 13, 16, 22, 26,27,28,29], daily living ability [10, 13, 27] and renal function [19, 22]. Danielle and colleagues [12] found that a 12-week program of high-intensity progressive resistance exercise training (PRET) for hemodialysis patients led to a statistically and clinically significant increase in thigh muscle volume, with a mean difference of 193 cm³ (95% CI: 63 to 324 cm³; P = 0.007) compared to the control group. However, it did not significantly enhance the subjects' physical activity capacity or overall quality of life. (2) Aerobic exercise intervention effect: Eleven studies [11, 13, 15, 16, 22,23,24,25,26,27,28] reported the effects of different levels of aerobic exercise on subjects. Since low-intensity aerobic exercise was difficult to improve muscle strength [30] significantly, it was mostly used as an exercise intervention program for the control group [11, 13, 16, 22, 23, 26,27,28]. Furthermore, other studies showed positive impacts of aerobic exercise training interventions on the subjects. For example, Wu Qian et al. [29] found significant improvements in the intervention group's handgrip strength, daily walking speed, and physical activity level compared to the control group, with the revised Piper fatigue scale (RPFS) scores also being significantly lower (indicating less fatigue) in the intervention group. These differences were statistically significant (P < 0.05). (3) Effects of aerobic exercise combined with resistance exercise intervention: Four literatures [13, 15, 22, 24] incorporated a combination of aerobic exercise and resistance training in their physical exercise intervention program. Emma et al. [24] showed that combined resistance and aerobic training were more beneficial than aerobic training alone. Zhang Bo et al. [13] demonstrated that after 12 weeks of low and medium intensity aerobic combined with resistance exercise, elderly patients with chronic kidney disease complicated with sarcopenia showed significant improvements in appendicular skeletal muscle mass index (ASMI), grip strength index, 6-m walking speed, peak oxygen uptake (VO_2max), one-leg standing time, and reach in seat distance, with p-values indicating statistical significance (P < 0.05) for these improvements. This indicates that the exercise intervention was effective in enhancing muscle mass, muscle strength, and motor function without adversely affecting renal function.

Discussion

This study demonstrates that exercise intervention for muscle atrophy in individuals with CKD includes different modalities, mostly resistance training and a combination of aerobic exercise. Guiding patients regarding resistance training can facilitate the anabolism and metabolism of skeletal muscle, enhancing muscle quality, improving muscle strength, and effectively enhancing patients' overall quality of life [31]. Exercise intervention schemes for CKD patients are often carried out in various forms of exercise combinations. Researchers often use aerobic exercise as an important auxiliary intervention method that benefits cardiovascular health. It improves the heart and lung function of the subjects, enhances their endurance, and facilitates the development of resistance training.

There are significant differences among CKD patients at different stages, so we should comprehensively evaluate the physiological function and tolerance of CKD patients and develop individualized exercise intervention programs for patients [7]. This study showed that the exercise intervention program includes detailed pre-exercise examinations, such as preliminarily assessing the subjects’ muscle strength and cardiopulmonary function status, determining whether they can tolerate exercise intervention, and developing personalized exercise prescriptions. Jonathan [15] and colleagues completed detailed medical examinations before the intervention, measuring the subjects' cardiopulmonary function and upper and lower limb strength. Results indicated that the design of the exercise intervention program was personalized. This study showed that the exercise form of CKD patients is not a single repeat of a certain type of exercise but a combination of various exercise methods that can achieve the best effect. Despite numerous RCTs reported that resistance exercise could significantly improve muscle strength in patients with CKD [32], a meta-analysis [33] has revealed that the use of progressive resistance exercise as the sole intervention did not result in a significant improvement in the 6-min walk test, which serves as a proxy indicator of cardiopulmonary function. It indicates that resistance training alone makes it difficult to improve the cardiopulmonary function of subjects significantly. As resistance exercise training necessitates a minimum level of cardiopulmonary function as a foundation, it also imposes specific cardiopulmonary function requirements on the subjects. Low-intensity, long-duration aerobic exercise has been shown to enhance the cardiopulmonary function and exercise capacity of patients with chronic kidney disease [34]. Therefore, clinical researchers frequently combine two forms of exercise to enhance patients' quality of life by enhancing their cardiopulmonary function and muscle strength. It demonstrates the comprehensive nature of exercise intervention program design. Universality: For patients with non-maintenance dialysis CKD, regular visits to the hospital for dialysis treatment means that they cannot receive the supervision of clinical researchers throughout the process. They also face problems such as a lack of exercise equipment and professional guidance. Emma et al. [24] found that patients considered frequent visits to the hospital as a major obstacle to participating in the study. So, future research needs to design simple and feasible home training programs for different patient situations and provide feedback when patients come to the hospital for dialysis. Luca’s [23] exercise training program was designed and organized by the hospital and ultimately completed by patients at home. It improved patients' physical function significantly after six months of intervention with low-intensity exercise.

The results of this study show that exercise intervention can improve physical function, activity ability, muscle atrophy, and quality of life in patients with CKD. This viewpoint is also supported by Vanden et al.'s systematic review of exercise intervention in CKD patients [35]. Furthermore, a cross-sectional study [36] also suggested that clinical medical staff should actively implement exercise interventions for CKD patients to address adverse outcomes such as muscle atrophy and decreased quality of life caused by long-term catabolism and dialysis treatment. Although exercise intervention positively impacts CKD patients, the current studies are mainly small-sample randomized controlled trials with low quality. Therefore, larger-sample randomized controlled trials are needed to evaluate the impact of exercise intervention on muscle atrophy in CKD patients more accurately. Notably, the frequency and duration of exercise intervention are not positively correlated with the intervention effect. Excessive exercise intensity may lead to lactic acidosis in patients, and severe cases may cause acute renal failure secondary to rhabdomyolysis [37]. Therefore, exercise frequency must be determined by the patient's condition; high-intensity training should not be pursued indiscriminately. Furthermore, cardiac function in CKD patients must be matched with the intensity of exercise. A systematic review have shown that high-intensity interval exercise with passive recovery leads to a greater increase in cardiac troponin T levels compared to moderate-intensity continuous exercise [38]. To minimize cardiovascular risk during exercise, exercise prescriptions should be tailored based on individual circumstances.A unified standard regarding the exercise frequency and intervention cycle of CKD patients does not exist. The guidelines indicate that the optimal resistance exercise frequency is 2 − 3 times per week, with an interval of 24 − 48 h each time, which is consistent with the results shown in this study [39]. In the literature included in this study, only seven articles [12, 16, 17, 19, 25, 26, 29] mentioned the safety of exercise intervention, and 3 of them [12, 17, 19] reported adverse events. Danielle et al. [12] reported muscle soreness and laceration of the back wound, indicating that there is a lack of comprehensive reports regarding the safety of exercise intervention trials in CKD patients. Some researchers failed to fully consider the safety of exercise intervention based on individual differences among subjects.

Integrating insights from the studies on exercise's impact on CKD, sarcopenia in hemodialysis patients, and diabetes management through physical activity, the future perspective emphasizes a holistic approach to CKD treatment. This approach advocates for the incorporation of tailored exercise programs to address the multifaceted challenges of CKD. A study elucidates how diverse exercise modalities can significantly impact blood glucose levels, emphasizing the importance of exercise in the management of diabetes, particularly in patients with CKD. It underscores the role of physical activity in enhancing insulin sensitivity and glycemic control, offering a non-pharmacological strategy to mitigate diabetes-related complications in CKD patients [40]. Additionally, exercise has beneficial effects on mitochondrial function and diabetes management. The research emphasizes that various exercise modalities, such as resistance and endurance training, can enhance mitochondrial density, dynamics, and oxidative capacity in muscle tissues. These improvements aid in boosting glucose metabolism and insulin sensitivity, which are crucial for diabetes control. The findings indicate that structured exercise programs are an indispensable component in addressing mitochondrial dysfunction and managing diabetes, especially in populations with chronic conditions like CKD [41]. Moreover, research has identified the efficacy of exercise in alleviating fatigue among hemodialysis patients, highlighting the potential of structured exercise programs to enhance energy levels and overall health in this demographic, regular physical activity could be an essential component of comprehensive care for hemodialysis patients, thus improving their quality of life and physical function [42]. The envisioned future includes rigorous clinical trials to further validate exercise as a key adjunct therapy, potentially leading to standardized exercise recommendations that enhance patient outcomes and quality of life in CKD management.

Strengths and limitations

The strengths of this scoping review include an extensive and repeated search of the literature to capture all relevant articles and limit emissions while strictly adhering to the PRISMA reporting guidelines. Unpublished dissertations are more likely to report uncertain or negative results, which may produce a reverse publication bias and be excluded from this study. The literature included in this study lacks large-sample, multi-center, randomized controlled studies, and the methodological rigor and data quality of the included studies have not been systematically evaluated.

Conclusion

Patients with CKD face many complex issues that seriously affect their quality of life. For them, long-term dialysis treatment has produced negligible side effects, and exercise therapy is needed to improve their quality of life. Exercise intervention can improve the muscle strength, physical function, and quality of life of patients with chronic nephritis muscle atrophy, which is an effective intervention method. We are still waiting to find its potential positive effects on CKD patients. In future nursing work, we should evaluate the physiological function status of CKD patients, formulate safe and effective exercise intervention plans, and intervene early in their muscle atrophy symptoms to promote their rehabilitation and improve their clinical outcomes.