Abstract
Introduction: Regular physical activity is beneficial for health but is often reduced in patients receiving maintenance hemodialysis treatment. Irisin is a muscle-secreted hormone that reportedly improves metabolism and slows down the progression of some chronic diseases. In this study, we aimed to investigate the relationship between physical activity capacity and serum irisin levels in hemodialysis patients. Methods: Our study included 252 patients undergoing hemodialysis at Xuanwu Hospital Capital Medical University. Enzyme-linked immunosorbent assay was used to measure blood irisin levels. Body composition was analyzed by bioelectrical impedance analysis. The International Physical Activity Questionnaire (IPAQ) was used to score physical activity ability. Results: Bivariate correlation analysis showed a positive correlation between IPAQ scores and ln irisin (the natural logarithm of irisin; r = 0.326, p < 0.001). Independent determinants of IPAQ scores were ln irisin, age, fasting glucose, and carbon dioxide combining power. Conclusion: Our findings provide the first clinical evidence that serum irisin levels are positively correlated with physical activity capacity in hemodialysis patients.
Introduction
Physical activity is any bodily movement that results in energy expenditure produced by skeletal muscles. It is generally reduced in patients with chronic kidney disease (CKD). Lack of physical activity and poor functioning are the globally acknowledged hallmarks of CKD. Increasing the intensity and duration of physical activity is beneficial for patients with CKD [1]. Observational studies have reported that exercise may provide nephroprotection and can reduce mortality in patients with CKD. In addition, randomized controlled trials have shown that regular physical activity and exercise training can improve physical function, cardiorespiratory fitness, neuromuscular function, and overall quality of life in patients with CKD [2]. The benefits of exercise for hemodialysis patients are well recognized. Aerobic exercise can improve physical fitness, muscle strength, and quality of life in CKD patients undergoing dialysis treatment [3].
Irisin is an exercise-induced myokine produced by cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC-5). Most studies have shown that irisin is associated with the health status. Irisin plays a central role in bone quality control [4]. Some studies suggest that irisin increases osteoblast survival and sclerostin production, thus potentially enhancing bone density and quality and consequently preventing bone loss [5]. Irisin reportedly stimulates brown adipose-like development, maintains glucose stabilization, and maintains bone homeostasis, while exerting an array of other effects [6]. Irisin augments liver glycogenesis and inhibits inflammatory responses, which may help reduce hepatic steatosis and fibrosis [7]. Irisin may also benefit cardiovascular health by reducing the risk of cardiovascular diseases like hypertension and atherosclerosis [8]. It is thought to alleviate several chronic non-metabolic diseases.
Studies have shown that irisin levels are lower in patients with CKD and those undergoing hemodialysis than in healthy individuals [9], and hemodialysis patients evidently tend to be less physically active. A positive correlation between irisin and skeletal muscle mass has been reported in hemodialysis patients [10]. Furthermore, it is well known that skeletal muscle wasting and atrophy characterize protein energy expenditure in patients with CKD and that malnourished patients are less physically active. Lee et al. [11] found a three-fold increase in circulating irisin levels after a moderate-intensity 1-h cycling exercise at 40% VO2max; however, there was no significant difference in plasma irisin levels in hemodialysis patients after a 6-month intradialytic resistance exercise training program [12]. Notably, circulating irisin levels are affected by several factors, and various tissues, such as muscle and adipose tissues, can secrete irisin [13]. We speculate that while resistance training may increase muscle strength, it does not necessarily significantly increase irisin secretion. Therefore, we aim to further observe the relationship between irisin levels and physical activity in hemodialysis patients in their daily state.
Methods
Study Population
From March 2020 to June 2022, a total of 380 hemodialysis patients were enrolled in Xuanwu Hospital Capital Medical University, and 252 patients were finally included (shown in Fig. 1). We included patients who had received hemodialysis treatment for at least 3 months, were older than 18 years old, and provided written informed consent to participate in this study. We excluded patients whose physical mobility was not assessed, whose serum irisin levels were not measured, and who developed or already had cancer, overt infection, stroke, acute myocardial infarction, or heart failure within 3 months before the study. The study was ethically conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Xuanwu Hospital Capital Medical University under approval number 2019 [130]. All participants signed written informed consent.
Collection of Biochemical Parameters
Routine biochemical parameters, such as hemoglobin, albumin, total protein, serum creatinine, uric acid, potassium, calcium, phosphorus, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, parathyroid hormone, and carbon dioxide combining power (CO2CP), were measured and collected according to standard methods in the laboratory of our hospital. Urea clearance (Kt/V) was calculated using the Daugirdas formula. Body mass index (BMI) was calculated as weight/height2 (kg/m2).
Measurement of Irisin
Serum irisin levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit (Phoenix Pharmaceutical, USA).
Body Composition Measurement
After 30 min of hemodialysis treatment, body composition analysis of each patient was performed using a body composition monitor (Fresenius Medical Care, AG & Co, Germany). The body composition monitor determines the whole-body impedance spectrum at 50 frequencies (from 5 kHz to 1 MHz). Electrodes were attached to the arm and ipsilateral foot without an arteriovenous fistula. Data collected included body fat (kg), lean body mass (kg), and percent body fat (%).
Physical Activity Assessment
We assessed the physical activity of the subjects based on the International Physical Activity Questionnaire (IPAQ)-long form [14]. In the IPAQ-long form, physical activity mainly comprises activity type and intensity. Activity types include work-related activities, transportation-related activities, domestic and gardening-related activities, and leisure-related activities. Activity intensity was categorized as walking, moderate intensity, and high intensity. Walking metabolic equivalent of task (MET) was calculated as 3.3 METs × walking time; moderate physical activity was calculated as 4 METs × activity time, and vigorous physical activity was calculated as 8 METs × activity time. We calculated participants’ total physical activity MET min/week as total work + total transportation + total domestic activities and gardening + total leisure time MET min/week scores.
Statistical Analysis
According to the principles of sample size estimation for cross-sectional studies [15] (the sample size should be 5–10 times the number of study variables), this study included a total of 25 variables, and the sample size was at least 138 cases, while accounting for a 10% invalid sample rate. Our study included 252 patients, which represents a large enough sample size. The distribution of the variables was tested using the Kolmogorov-Smirnov test. Results for normally distributed variables were expressed as mean ± standard deviation. Results for non-normally distributed variables and categorical variables were expressed as frequencies. Non-normally distributed variables were converted to their natural logarithm (ln). Independent Student’s t test and nonparametric tests were used to compare between-group differences. Depending on the sample distribution, correlations between variables were analyzed using the Pearson correlation test and Spearman rank correlation test. Categorical variables were compared using the Chi-square test. Multivariate logistic regression analysis was used to identify the determinants of patients’ IPAQ scores. All analyses were two tailed, and p values of <0.05 were considered statistically significant. SPSS 25.0 software (Chicago, IL, USA) was used for statistical analysis.
Results
In this study, participants’ physical activity levels were assessed using the IPAQ-long form. Participants were categorized into high and low physical activity groups on the basis of their median IPAQ score. Table 1 shows the clinical characteristics and biochemical parameters of hemodialysis patients. This study included 135 men and 117 women. The primary diseases were diabetic nephropathy (69 patients), hypertensive renal damage (27 patients), chronic interstitial nephritis (18 patients), chronic glomerulonephritis (88 patients), and others (50 patients). Irisin, serum creatinine, low-density lipoprotein cholesterol, CO2CP, body fat, and percentage of body fat were higher in patients with high physical activity levels than in those with low physical activity levels (p < 0.05). In contrast, age, systolic blood pressure, and fasting blood glucose were significantly lower in patients in the high physical activity level group than those in the low physical activity group (p < 0.05).
Clinical characteristics of subjects (comparison between the low and high activity groups)
Characteristics . | Total, n = 252 . | Low physical activity group, n = 128 . | High physical activity group, n = 124 . | p value . |
---|---|---|---|---|
Irisin | 86.40±39.30 | 74.02±41.87 | 99.19±31.89 | <0.001 |
Age, years | 60.72±14.55 | 65.75±14.41 | 55.53±12.82 | <0.001 |
Gender (M/F) | 135/117 | 66/62 | 69/55 | 0.28 |
IPAQ scores, min/week | 714.00 [221.25–1,687.50] | 222.50 [0.00–351.50] | 1,721.00 [1,245.00–3,627.00] | <0.001 |
BMI, kg/m2 | 23.77±3.55 | 24.22±3.50 | 23.37±3.57 | 0.07 |
SBP, mm Hg | 137.31±21.06 | 140.07±23.73 | 134.54±17.67 | 0.04 |
Hemoglobin, g/L | 114.26±15.67 | 112.78±15.98 | 115.79±15.24 | 0.13 |
Albumin, g/L | 38.77±4.35 | 38.89±4.28 | 38.65±4.43 | 0.66 |
Total protein, g/L | 67.87±5.72 | 67.75±5.62 | 67.99±5.84 | 0.75 |
Serum creatinine, μmol/L | 917.16±237.71 | 879.07±221.57 | 956.48±248.09 | 0.009 |
Uric acid, μmol/L | 422.67±88.82 | 427.39±93.51 | 417.95±84.00 | 0.41 |
Potassium, mmol/L | 4.62±0.73 | 4.69±0.76 | 4.55±0.70 | 0.12 |
Calcium, mmol/L | 2.41±0.25 | 2.41±0.23 | 2.41±0.27 | 0.85 |
Phosphorus, mmol/L | 1.70±0.45 | 1.72±0.42 | 1.67±0.48 | 0.46 |
Fasting blood glucose, mmol/L | 6.65±2.94 | 7.13±3.31 | 6.19±2.46 | 0.01 |
Triglyceride, mmol/L | 2.37±1.89 | 2.35±1.81 | 2.39±1.97 | 0.87 |
High-density lipoprotein cholesterol, mmol/L | 0.96±0.29 | 0.93±0.30 | 0.99±0.27 | 0.11 |
Low-density lipoprotein cholesterol, mmol/L | 2.47±0.82 | 2.35±0.88 | 2.60±0.73 | 0.02 |
Parathyroid hormone, pg/mL | 168.20 [85.32–326.50] | 173.10 [88.60–278.53] | 162.00 [70.36–336.50] | 0.45 |
Carbon dioxide combining power, mmol/L | 23.30±4.56 | 21.90±4.82 | 24.69±3.81 | <0.001 |
Kt/V (single time) | 1.41±0.25 | 1.45±0.21 | 1.30±0.28 | 0.24 |
Lean body mass, kg | 40.52±10.13 | 40.74±10.05 | 40.33±10.23 | 0.77 |
Body fat, kg | 23.08±10.0 | 21.34±10.07 | 24.78±9.67 | 0.01 |
Percentage of body fat, % | 35.21±13.04 | 32.71±12.43 | 37.64±13.22 | 0.005 |
Primary disease ratio of ESKD (1/2/3/4/5) | 69/27/18/88/50 | 42/13/8/35/30 | 27/14/10/53/20 | 0.06 |
Characteristics . | Total, n = 252 . | Low physical activity group, n = 128 . | High physical activity group, n = 124 . | p value . |
---|---|---|---|---|
Irisin | 86.40±39.30 | 74.02±41.87 | 99.19±31.89 | <0.001 |
Age, years | 60.72±14.55 | 65.75±14.41 | 55.53±12.82 | <0.001 |
Gender (M/F) | 135/117 | 66/62 | 69/55 | 0.28 |
IPAQ scores, min/week | 714.00 [221.25–1,687.50] | 222.50 [0.00–351.50] | 1,721.00 [1,245.00–3,627.00] | <0.001 |
BMI, kg/m2 | 23.77±3.55 | 24.22±3.50 | 23.37±3.57 | 0.07 |
SBP, mm Hg | 137.31±21.06 | 140.07±23.73 | 134.54±17.67 | 0.04 |
Hemoglobin, g/L | 114.26±15.67 | 112.78±15.98 | 115.79±15.24 | 0.13 |
Albumin, g/L | 38.77±4.35 | 38.89±4.28 | 38.65±4.43 | 0.66 |
Total protein, g/L | 67.87±5.72 | 67.75±5.62 | 67.99±5.84 | 0.75 |
Serum creatinine, μmol/L | 917.16±237.71 | 879.07±221.57 | 956.48±248.09 | 0.009 |
Uric acid, μmol/L | 422.67±88.82 | 427.39±93.51 | 417.95±84.00 | 0.41 |
Potassium, mmol/L | 4.62±0.73 | 4.69±0.76 | 4.55±0.70 | 0.12 |
Calcium, mmol/L | 2.41±0.25 | 2.41±0.23 | 2.41±0.27 | 0.85 |
Phosphorus, mmol/L | 1.70±0.45 | 1.72±0.42 | 1.67±0.48 | 0.46 |
Fasting blood glucose, mmol/L | 6.65±2.94 | 7.13±3.31 | 6.19±2.46 | 0.01 |
Triglyceride, mmol/L | 2.37±1.89 | 2.35±1.81 | 2.39±1.97 | 0.87 |
High-density lipoprotein cholesterol, mmol/L | 0.96±0.29 | 0.93±0.30 | 0.99±0.27 | 0.11 |
Low-density lipoprotein cholesterol, mmol/L | 2.47±0.82 | 2.35±0.88 | 2.60±0.73 | 0.02 |
Parathyroid hormone, pg/mL | 168.20 [85.32–326.50] | 173.10 [88.60–278.53] | 162.00 [70.36–336.50] | 0.45 |
Carbon dioxide combining power, mmol/L | 23.30±4.56 | 21.90±4.82 | 24.69±3.81 | <0.001 |
Kt/V (single time) | 1.41±0.25 | 1.45±0.21 | 1.30±0.28 | 0.24 |
Lean body mass, kg | 40.52±10.13 | 40.74±10.05 | 40.33±10.23 | 0.77 |
Body fat, kg | 23.08±10.0 | 21.34±10.07 | 24.78±9.67 | 0.01 |
Percentage of body fat, % | 35.21±13.04 | 32.71±12.43 | 37.64±13.22 | 0.005 |
Primary disease ratio of ESKD (1/2/3/4/5) | 69/27/18/88/50 | 42/13/8/35/30 | 27/14/10/53/20 | 0.06 |
Primary diseases of end-stage renal disease in decreasing order of occurrence were diabetic nephropathy, hypertensive renal damage, chronic interstitial nephritis, chronic glomerulonephritis, and others.
BMI, body mass index; SBP, systolic blood pressure.
In the current study, we performed bivariate correlation analysis to further investigate the relationship of IPAQ scores with irisin and other parameters, and the results showed that IPAQ scores were negatively correlated with age (r = −0.247, p < 0.001), systolic blood pressure (r = −0.162, p < 0.001), uric acid (r = −0.226, p < 0.001), phosphorus (r = −0.130, p = 0.004), and Kt/V (r = −0.164, p = 0.04) but positively correlated with ln irisin (r = 0.326, p < 0.001), hemoglobin (r = 0.161, p < 0.001), calcium (r = 0.140, p = 0.002), HDL cholesterol (r = 0.191, p < 0.001), CO2CP (r = 0.377, p < 0.001), and percentage of body fat (r = 0.193, p < 0.001). We did not find IPAQ scores to be correlated with BMI, lean body mass, albumin, total protein, serum creatinine, potassium, fasting blood glucose, triglycerides, or parathyroid hormone (all p > 0.05). Physical activity levels were lower in patients with diabetic nephropathy (Table 2).
Correlation analysis of IPAQ scores with ln irisin and other parameters
Characteristics . | IPAQ scores . |
---|---|
Ln irisin | r = 0.326, p < 0.001 |
Age (years) | r = −0.247, p < 0.001 |
Gender (M/F) | r = −0.122, p = 0.007 |
BMI (kg/m2) | r = −0.076, p = 0.11 |
Lean body mass (kg) | r = −0.093, p = 0.05 |
SBP (mm Hg) | r = −0.162, p < 0.001 |
Hemoglobin (g/L) | r = 0.161, p < 0.001 |
Albumin (g/L) | r = −0.084, p = 0.06 |
Total protein (g/L) | r = −0.005, p = 0.91 |
Serum creatinine (μmol/L) | r = −0.019, p = 0.68 |
Uric acid (mmol/L) | r = −0.226, p < 0.001 |
Potassium (mmol/L) | r = −0.075, p = 0.10 |
Calcium (mmol/L) | r = 0.140, p = 0.002 |
Phosphorus (mmol/L) | r = −0.130, p = 0.004 |
Fasting blood glucose (mmol/L) | r = −0.078, p = 0.09 |
Triglyceride (mmol/L) | r = 0.049, p = 0.28 |
High-density lipoprotein cholesterol (mmol/L) | r = 0.191, p < 0.001 |
Low-density lipoprotein cholesterol (mmol/L) | r = 0.206, p < 0.001 |
Parathyroid hormone (pg/mL) | r = −0.060, p = 0.19 |
Carbon dioxide combining power (mmol/L) | r = 0.377, p < 0.001 |
Kt/V (single time) | r = −0.164, p = 0.04 |
Body fat (kg) | r = 0.111, p = 0.02 |
Percentage of body fat (%) | r = 0.193, p < 0.001 |
Primary disease of ESKD | r = 0.145, p = 0.02 |
Characteristics . | IPAQ scores . |
---|---|
Ln irisin | r = 0.326, p < 0.001 |
Age (years) | r = −0.247, p < 0.001 |
Gender (M/F) | r = −0.122, p = 0.007 |
BMI (kg/m2) | r = −0.076, p = 0.11 |
Lean body mass (kg) | r = −0.093, p = 0.05 |
SBP (mm Hg) | r = −0.162, p < 0.001 |
Hemoglobin (g/L) | r = 0.161, p < 0.001 |
Albumin (g/L) | r = −0.084, p = 0.06 |
Total protein (g/L) | r = −0.005, p = 0.91 |
Serum creatinine (μmol/L) | r = −0.019, p = 0.68 |
Uric acid (mmol/L) | r = −0.226, p < 0.001 |
Potassium (mmol/L) | r = −0.075, p = 0.10 |
Calcium (mmol/L) | r = 0.140, p = 0.002 |
Phosphorus (mmol/L) | r = −0.130, p = 0.004 |
Fasting blood glucose (mmol/L) | r = −0.078, p = 0.09 |
Triglyceride (mmol/L) | r = 0.049, p = 0.28 |
High-density lipoprotein cholesterol (mmol/L) | r = 0.191, p < 0.001 |
Low-density lipoprotein cholesterol (mmol/L) | r = 0.206, p < 0.001 |
Parathyroid hormone (pg/mL) | r = −0.060, p = 0.19 |
Carbon dioxide combining power (mmol/L) | r = 0.377, p < 0.001 |
Kt/V (single time) | r = −0.164, p = 0.04 |
Body fat (kg) | r = 0.111, p = 0.02 |
Percentage of body fat (%) | r = 0.193, p < 0.001 |
Primary disease of ESKD | r = 0.145, p = 0.02 |
BMI, body mass index; SBP, systolic blood pressure.
Table 3 examines which clinical and biochemical factors were independently associated with physical activity levels using a multivariate logistic regression model (incorporating factors with p < 0.05 in the univariate logistic regression analysis). The results showed that ln irisin (β = 0.606, p = 0.04), age (β = −0.056, p < 0.001), fasting blood glucose (β = −0.125, p = 0.03), and CO2CP (β = 0.095, p = 0.04) were independently associated with physical activity levels in hemodialysis patients.
Univariate and multivariate logistic regression analysis of physical activity levels with the determinant factors
Variables . | Univariate . | Multivariate . | ||||
---|---|---|---|---|---|---|
B . | p value . | 95% CI for B . | B . | p value . | 95% CI for B . | |
Constant | −1.394 | 0.53 | ||||
Ln irisin | 0.774 | <0.001 | 1.486–3.166 | 0.606 | 0.04 | 1.036–3.245 |
Age (years) | −0.054 | <0.001 | 0.929–0.967 | −0.045 | <0.001 | 0.932–0.981 |
Gender (M/F) | −0.164 | 0.52 | 0.517–1.393 | Unselected | ||
BMI (kg/m2) | −0.069 | 0.07 | 0.866–1.006 | Unselected | ||
Lean body mass (kg) | −0.004 | 0.77 | 0.970–1.023 | Unselected | ||
SBP (mm Hg) | −0.013 | 0.04 | 0.975–1.000 | −0.002 | 0.76 | 0.982–1.013 |
Hemoglobin (g/L) | 0.013 | 0.13 | 0.996–1.029 | Unselected | ||
Albumin (g/L) | −0.013 | 0.66 | 0.932–1.045 | Unselected | ||
Total protein (g/L) | 0.007 | 0.75 | 0.964–1.053 | Unselected | ||
Serum creatinine (μmol/L) | 0.001 | 0.01 | 1.000–1.003 | 0.000 | 0.82 | 0.998–1.001 |
Uric acid (mmol/L) | −0.001 | 0.41 | 0.996–1.002 | Unselected | ||
Potassium (mmol/L) | −0.279 | 0.12 | 0.533–1.074 | Unselected | ||
Calcium (mmol/L) | 0.094 | 0.85 | 0.409–2.953 | Unselected | ||
Phosphorus (mmol/L) | −0.206 | 0.46 | 0.471–1.406 | Unselected | ||
Fasting blood glucose (mmol/L) | −0.119 | 0.02 | 0.804–0.980 | −0.125 | 0.03 | 0.789–0.988 |
Triglyceride (mmol/L) | 0.011 | 0.86 | 0.887–1.153 | Unselected | ||
High-density lipoprotein cholesterol (mmol/L) | 0.708 | 0.11 | 0.846–4.873 | Unselected | ||
Low-density lipoprotein cholesterol (mmol/L) | 0.385 | 0.02 | 1.073–2.014 | 0.031 | 0.88 | 0.679–1.568 |
Parathyroid hormone (pg/mL) | 0.000 | 0.46 | 0.999–1.000 | Unselected | ||
CO2CP (mmol/L) | 0.156 | <0.001 | 1.092–1.252 | 0.095 | 0.04 | 1.005–1.203 |
Kt/V (single time) | −0.992 | 0.23 | 0.073–1.887 | Unselected | ||
Body fat (kg) | 0.036 | 0.01 | 1.008–1.066 | 0.022 | 0.19 | 0.989–1.056 |
Percentage of body fat (%) | 0.030 | 0.006 | 1.009–1.053 | Unselected | ||
Primary disease of ESKD | 0.093 | 0.26 | 0.933–1.291 | Unselected |
Variables . | Univariate . | Multivariate . | ||||
---|---|---|---|---|---|---|
B . | p value . | 95% CI for B . | B . | p value . | 95% CI for B . | |
Constant | −1.394 | 0.53 | ||||
Ln irisin | 0.774 | <0.001 | 1.486–3.166 | 0.606 | 0.04 | 1.036–3.245 |
Age (years) | −0.054 | <0.001 | 0.929–0.967 | −0.045 | <0.001 | 0.932–0.981 |
Gender (M/F) | −0.164 | 0.52 | 0.517–1.393 | Unselected | ||
BMI (kg/m2) | −0.069 | 0.07 | 0.866–1.006 | Unselected | ||
Lean body mass (kg) | −0.004 | 0.77 | 0.970–1.023 | Unselected | ||
SBP (mm Hg) | −0.013 | 0.04 | 0.975–1.000 | −0.002 | 0.76 | 0.982–1.013 |
Hemoglobin (g/L) | 0.013 | 0.13 | 0.996–1.029 | Unselected | ||
Albumin (g/L) | −0.013 | 0.66 | 0.932–1.045 | Unselected | ||
Total protein (g/L) | 0.007 | 0.75 | 0.964–1.053 | Unselected | ||
Serum creatinine (μmol/L) | 0.001 | 0.01 | 1.000–1.003 | 0.000 | 0.82 | 0.998–1.001 |
Uric acid (mmol/L) | −0.001 | 0.41 | 0.996–1.002 | Unselected | ||
Potassium (mmol/L) | −0.279 | 0.12 | 0.533–1.074 | Unselected | ||
Calcium (mmol/L) | 0.094 | 0.85 | 0.409–2.953 | Unselected | ||
Phosphorus (mmol/L) | −0.206 | 0.46 | 0.471–1.406 | Unselected | ||
Fasting blood glucose (mmol/L) | −0.119 | 0.02 | 0.804–0.980 | −0.125 | 0.03 | 0.789–0.988 |
Triglyceride (mmol/L) | 0.011 | 0.86 | 0.887–1.153 | Unselected | ||
High-density lipoprotein cholesterol (mmol/L) | 0.708 | 0.11 | 0.846–4.873 | Unselected | ||
Low-density lipoprotein cholesterol (mmol/L) | 0.385 | 0.02 | 1.073–2.014 | 0.031 | 0.88 | 0.679–1.568 |
Parathyroid hormone (pg/mL) | 0.000 | 0.46 | 0.999–1.000 | Unselected | ||
CO2CP (mmol/L) | 0.156 | <0.001 | 1.092–1.252 | 0.095 | 0.04 | 1.005–1.203 |
Kt/V (single time) | −0.992 | 0.23 | 0.073–1.887 | Unselected | ||
Body fat (kg) | 0.036 | 0.01 | 1.008–1.066 | 0.022 | 0.19 | 0.989–1.056 |
Percentage of body fat (%) | 0.030 | 0.006 | 1.009–1.053 | Unselected | ||
Primary disease of ESKD | 0.093 | 0.26 | 0.933–1.291 | Unselected |
Univariate and multivariate logistic regression analysis was performed.
CO2CP, carbon dioxide combining power; BMI, body mass index; SBP, systolic blood pressure.
Discussion
Our current study demonstrated that serum irisin levels are positively correlated with physical activity in hemodialysis patients. Irisin has been proposed as a myokine that can ameliorate some chronic metabolic and non-metabolic diseases. In addition, it reportedly improves insulin resistance and regulates glucose and lipid metabolism. Studies have shown that serum irisin levels were significantly lower in patients with muscle atrophy, suggesting that irisin levels are related to physical activity capacity. Lee et al. [11] showed that exercise promotes irisin secretion in skeletal muscles. Boström et al. [16] also found that serum irisin levels were elevated after exercise. As there is currently no established consensus on optimal physical activity grouping, we herein divided the cohort into two groups based on the median IPAQ score, with a particular focus on the relationships between irisin and physical function. Our study showed that the levels of irisin were higher in individuals with higher IPAQ scores than in those with lower IPAQ scores. He et al. [10] found no correlation between physical activity and irisin levels in 128 hemodialysis patients. However, our study had a larger sample and showed a positive correlation between IPAQ scores and serum irisin levels. Our robust sample size makes our study more advantageous, enhances the generalizability of our findings, and strengthens the validity of the observed correlation between physical activity and irisin levels. We used a multilevel analysis that considered various factors that influence the relationship between physical activity and irisin levels, such as age, sex, body composition, and metabolic parameters. By taking these confounding variables into consideration, we enhanced the robustness of our findings and ensured the integrity of our conclusions. This contributes to future prospective cohort studies with the aim of validating the impact of ideal score thresholds for physical activity on patient prognosis.
The IPAQ scores provide a quantitative measure of an individual’s participation in various forms of exercise and daily sports. These scores include parameters like duration, frequency, and intensity of physical activity, providing a comprehensive assessment of overall activity levels. Low physical activity levels in patients with CKD result from a combination of factors that adversely affect their health and quality of life. The causes of physical inactivity in patients with CKD include behavioral and disease-related factors. Maintenance hemodialysis patients are less physically active than non-dialysis patients. Avesani et al. [17] found that patients’ physical activity levels were lower on hemodialysis days than on non-dialysis days, suggesting that treatment-related factors have a negative impact on physical activity. An international survey of 20,920 hemodialysis patients revealed that patients who were offered an exercise program were more likely to participate in physical activity than those who were not offered one [18]. This suggests that the development and implementation of an exercise program influences physical activity in CKD patients. In addition, depression, psychological factors, and lack of motivation may also contribute to the lack of physical activity in CKD and hemodialysis patients [19]. Serum irisin levels were previously reported to be not significantly elevated in resistance-trained hemodialysis patients [12]. In the present study, we found no significant difference in muscle mass between patients with high and low physical activity levels, while patients with high physical activity level had higher body fat levels. This suggests that daily aerobic activity, rather than resistance training, has a more elevating effect on the increase in serum irisin. It warrants further study in the future.
The results of our study showed that serum irisin levels were positively correlated with physical activity. The reasons may be as follows: physical mobility is closely related to the structure and function of bones and muscles.
Zhang et al. [20] found that 2 weeks of autonomous wheel running exercise induced high levels of irisin protein expression in mouse bone tissues. Exercise also increased the expression of several osteogenic markers, including irisin, in the bone. Intraperitoneal injection of irisin increased the thickness of bone trabeculae and bone cortex as well as the number of osteoblasts. In vitro osteoblast studies showed that irisin increased the number of osteoblasts and mineralization and inhibited osteoclast formation. In summary, active exercise increased irisin production in the bone, increased circulating irisin levels, and promoted osteogenesis in mice. In addition, the experiment by Colaianni et al. [21] demonstrated for the first time that irisin secreted by muscles during exercise has a positive regulatory effect on bone. Irisin protects bone microstructure by stimulating osteoclastogenesis and inhibiting osteoclast differentiation [22]. Deletion of irisin results in reduced bone mineral density and delayed skeletal development and mineralization in mice [23]. In summary, irisin produced by skeletal muscle during exercise can influence bone metabolism.
Low levels of circulating irisin are reportedly a sensitive indicator of muscle weakness and atrophy [24]. Zhao et al. [25] reported that patients with sarcopenia had lower levels of irisin than controls. Circulating irisin levels are positively correlated with biceps circumference and insulin-like growth factor-1 levels [26]. Irisin may serve as a potential biomarker of muscle dysfunction and help predict the onset of sarcopenia. Exercise reportedly increases irisin expression in skeletal muscle. Exercise induces FNDC5/irisin expression and promotes hypertrophy. Irisin is mainly produced in muscle tissue via the Ca2+-AMPK-PGC-1α-FNDC5 pathway. It plays a key regulatory role in muscle growth and differentiation by activating downstream ERK1/2 and IL-6 pathways and inducing muscle cell expression in an autocrine manner [27]. In addition, irisin injection reportedly induces skeletal muscle hypertrophy and enhances the regenerative capacity of skeletal muscles after muscle injury [28].
Wang et al. [29] found that intra-articular injection of irisin prevented articular cartilage loss and alleviated gait irregularity in mice. Furthermore, irisin inhibited inflammation-mediated oxidative stress and deficient production of extracellular stroma by preserving mitochondrial biosynthesis, kinetics, and autophagic programs. This revealed the protective effect of irisin on cartilage.
Our study found physical activity to be negatively correlated with age. Aging is associated with a loss of bodily functions. The complex interplay between age-related reductions in habitual physical activity and the intrinsic aging process culminates in a decline in physical function. The function of physiological systems declines with age. For example, skeletal muscles atrophy and become progressively weaker with age, and decreased bone mineral density can lead to osteoporosis. Age-related decline in lung function is an important factor contributing to the limited physical activity in the elderly. In addition, the prevalence of many chronic diseases increases with age, including cardiovascular diseases, respiratory diseases, endocrine diseases, and mental illnesses. McPhee et al. [30] found that the vast majority of septuagenarians had lower physiological function than younger adults. For example, older adults had smaller and weaker muscles, lower bone mineral density, higher BMI due to increased adiposity, and decreased cardiorespiratory and metabolic function. Piasecki et al. [31] have reported that the loss of motor neurons and remodeling of residual motor units may lead to muscle loss and dysfunction, thus limiting the way in which movement is controlled by the central nervous system. Frailty due to multiple deficits in body systems is considered a geriatric syndrome. The physical and mental function of frail patients was severely impaired, which limits physical activity.
Carbon dioxide combining power was used to reflect the correction of metabolic acidosis. Williams et al. [32] reported increased excretion of 3-methylhistidine in patients with chronic renal failure combined with metabolic acidosis. This suggests excessive catabolism of muscle proteins leading to negative nitrogen balance. Ballmer et al. [33] showed that albumin synthesis was reduced in subjects with induced acidosis and that a negative nitrogen balance soon developed. Metabolic acidosis in chronic renal failure reportedly promotes muscle protein hydrolysis by stimulating the ATP-dependent ubiquitin-proteasome pathway [34]. The development of metabolic acidosis in CKD rats leads to stimulation of muscle proteolysis and inhibition of protein synthesis. Conversely, when acidosis is corrected, muscle protein degradation decreases and protein synthesis increases [35]. Reaich et al. [36] also found a significant reduction in catabolic factors with correction of acidosis. The loss of protein leads to muscle atrophy, and athletic performance is closely associated with muscle structure and function. Therefore, the physical activity capacity of CKD patients is related to the correction of metabolic acidosis. This is consistent with our findings.
Interestingly, in our univariate analysis, we found both lean mass and fat mass to be positively correlated with IPAQ scores, which may be mainly because both fat and muscle can secrete irisin [37], suggesting the presence of a virtuous circle between irisin and muscle and adipose tissues that stimulates better motor function. It is well known that mortality in the general population is related to exercise. Exercise tolerance is reduced in hemodialysis patients, and the level of physical activity is directly related to the nutritional status. Protein-energy wasting (PEW) in hemodialysis patients is a complex clinical condition characterized by progressive depletion of the body’s protein and energy reserves. This may lead to muscle wasting, compromised immune function, and increased risk of cardiovascular disease. CKD is typically associated with a systemic inflammatory response, including overproduction of cytokines, such as C-reactive protein and interleukin-6 (IL). These factors promote proteolysis and inhibit protein synthesis, leading to wasted protein energy. Serum albumin levels decline as the inflammatory state worsens. Although epidemiology suggests that obesity is associated with increased cardiovascular risk and decreased survival, malnutrition and PEW increase mortality in patients with CKD [38]. Consequently, patients with kidney disease tend to have reduced physical activity. Furthermore, physical inactivity reportedly exacerbates the pathophysiology of PEW [39]. We have previously reported that patients with malnutrition and PEW had lower irisin levels [10], which accordingly affected their physical activity in a vicious circle.
Limitations
Our study has some limitations, such as a cross-sectional observational design, and we did not determine a causal relationship between serum irisin levels and physical activity. Further research is warranted to elucidate the mechanistic link between physical activity and irisin regulation.
Conclusion
Taken together, our study is the first to provide clinical evidence of a relationship between irisin and physical activity levels in hemodialysis patients. Understanding the interplay between physical activity and irisin secretion offers promising avenues for the development of novel therapeutic strategies aimed at improving metabolic function and physical activity capacity in CKD patients.
Acknowledgment
There are no potential conflicts of interest with respect to the research, authorship, or publication of this article. We received no external financial support for the research, authorship, or publication of this article. No copyrighted material, surveys, instruments, or tools were used in the research described in this article.
Statement of Ethics
The study was ethically conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Xuanwu Hospital Capital Medical University under Approval No. 2019 [130]. All participants signed written informed consent.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
Zhengjia Fan: conceptualization, data curation, formal analysis, investigation, methodology, validation, writing – original draft, and writing – review and editing; Feng Wu, Peixin Wang, and Leiyun Wu: validation and writing – review and editing; Jialing Zhang, Wen Li, and Qi Pang: data curation, formal analysis, methodology, and writing – review and editing; Ai-Hua Zhang: research protocol design, work coordination, and article revision.
Data Availability Statement
The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author upon reasonable request.