Patients with chronic kidney disease (CKD) experience much more marked and earlier muscle wasting than subjects who do not have chronic illnesses. However, a few studies that have examined sarcopenia have been reported in CKD patients. We investigated the prevalence of sarcopenia in predialysis and dialysis outpatients with CKD and explored its relationship with the clinical outcomes.
Sarcopenia was defined as reduced muscle strength accompanied by decreased adjusted appendicular skeletal muscle (ASM), while those patients who exhibited only one of these characteristics were categorized as presarcopenic patients. ASM was measured by bioimpedence analysis, and muscle strength was evaluated by handgrips. ASM was adjusted by weight (ASM/wt). Patients were prospectively followed for up to 2 years.
One hundred seventy-nine patients were recruited (114 male and 65 female patients who were classified into 103 predialysis patients and 76 dialysis patients, with 44.7% having diabetes). Their mean age was 60.6 ± 13.5 years old. The prevalence of sarcopenia was 9.5%, while 55.9% of the patients were categorized as presarcopenic. The ASM/wt index showed significant correlations with age, handgrip strength, HOMA-IR and frailty scores. Multivariate Cox proportional hazards models demonstrated that the risk of hospitalization was significantly higher for patients with presarcopenia [hazard ratio (HR), 2.48; 95% confidence interval (CI), 1.180–5.230], and the risk of hospitalization was much higher for patients with sarcopenia than for patients in the nonsarcopenic group (HR, 9.11; 95% CI, 2.295–25.182)
Sarcopenia and presarcopenia, which were defined using the ASM/wt index and handgrip strength, predicted a poorer, hospitalization-free survival in CKD patients
Sarcopenia is defined as the degenerative loss of skeletal muscle mass and strength associated with aging (
Although often recognized as a comorbidity of hypertension or diabetes, chronic kidney disease (CKD) by itself contributes to global morbidity and mortality by increasing the risks related to cardiovascular diseases and infection (
Although sarcopenia has been recognized as a disease (via the classification of muscle failure with an ICD-10 code that was established in 2016 (
In this study, we investigated the prevalence of sarcopenia in predialysis and dialysis outpatients with chronic kidney disease (CKD) according to the Asian Working Group for Sarcopenia (AWGS) recommendation and explored its relationship with clinical outcomes.
One hundred three patients with CKD and 76 patients with ESRD on maintenance hemodialysis were recruited and prospectively followed for up to 2 years. The criteria for inclusion in this study included patients who were older than 20 years old with a confirmed diagnosis of CKD [defined as patients who were on dialysis or who had 2 previously estimated glomerular filtration rate (eGFR) values < 60 mL/min/1.73 m2, which was calculated according to the equation of the Modification of Diet in Renal Disease Study Group and was obtained at an interval of 3-6 months]. Patients were categorized according to CKD stages and Kidney Disease Outcomes Quality Initiative guidelines (
The patients performed three tests of maximum handgrip strength with a Jamar hand dynamometer (Sammons Preston Inc., Bolingbrook, IL). Low handgrip strength was defined as < 26 kg for men and < 18 kg for women, according to the AWGS recommendation (
Height was measured by using a stadiometer. The postdialysis weights were recorded from the last three dialysis sessions, and the average of these weights was calculated in the patients undergoing hemodialysis. To assess body composition, we used a bioimpedance analysis machine (Inbody 620, In-body, Seoul, Korea) with measuring frequencies of 5, 50, and 500 kHz. Weight-adjusted, squared height-adjusted, and body mass index (BMI)-adjusted appendicular skeletal muscle (ASM) was assessed in all of the subjects. Decreased ASM was defined as a weight-adjusted ASM (ASM/kg*100) less than 32.2% for men and less than 25.6% for women (
Sarcopenia was considered to be present when subjects had low handgrip strengths accompanied by a low adjusted ASM. Those subjects who showed low handgrip strengths or low muscle volumes were categorized as being presarcopenic (
We adopted the Fried criteria as the definition of frailty (
The patient demographic and clinical data, including age, sex, etiology of CKD (e.g., diabetes, hypertension, glomerulonephritis, polycystic kidney disease or unknown disease) and other comorbidities, were obtained via medical record reviews. Cardiac diseases were defined as patients with any medical histories of angina pectoris, a positive treadmill test, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery, or congestive heart failure. Cerebrovascular diseases were defined as patients with medical histories of a stroke, a transient ischemic attack, or an intracranial hemorrhage. Laboratory findings were collected, including serum hemoglobin, serum calcium, blood urea nitrogen, phosphate, intact parathyroid hormone (iPTH), uric acid, total cholesterol, low-density lipid (LDL) cholesterol, c-reactive protein (CRP), 25-hydroxyvitamin D (25[OH]D), and albumin levels at the time of patient enrollment. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated according to the following formula: [fasting insulin (μU/L)*fasting glucose (nmol/L)]/22.5 (
We prospectively observed all hospitalization events, mortalities, and kidney transplantations over a 2-year follow-up period. A hospitalization was defined as any hospitalization, regardless of the reason for admission, with more than 1 overnight stay. The hospitalization causes were classified as cardiac and/or cerebrovascular, infectious, or other causes via medical record reviews or telephone contacts. The outcome for this analysis was time to hospitalization from any cause.
The categorical variables were recorded as numbers and percentages. The continuous variables are presented as the mean ± standard variation or median (IQR). Student’s t-tests, Mann-Whitney U tests or ANOVAs were used to compare the continuous variables. The categorical variables were compared using χ2 tests or Fisher’s exact tests. Pearson’s correlation coefficients were used to summarize the cross-sectional relationships among age, hand grip strength, HOMA-IR, and ASM. Kaplan-Meier curves were used to estimate event times, and the distributions were compared via log-rank tests. A Cox regression model was used to analyze the independent variables that were associated with hospitalization or mortality. A p-value < 0.05 was considered to be statistically significant. Statistical analyses were performed using SPSS for Windows (version 21; SPSS, Chicago, IL, USA).
Baseline characteristics
Based on the 3 different indices (ASM/wt, ASM/ht2 and ASM/BMI;
Prevalence rate of sarcopenia in the patients with chronic kidney disease according to three different operational methods.
The analysis via the use of Pearson’s correlation coefficients revealed that the absolute value of ASM was negatively correlated with age (r = −0.432, p < 0.001) and frailty scores (r = −0.330, p < 0.001) but positively correlated with grip strength (r = 0.607, p < 0.001,
Scatterplots and correlations of appendicular skeletal muscle (ASM) or adjusted ASM indices versus age, handgrip strength, HOMA-IR or frailty scores for the patients with chronic kidney disease. ASM/BMI, body mass index adjusted ASM; ASM/ht2, height square adjusted ASM; ASM/wt, weight adjusted ASM; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; r, Pearson’s correlation coefficients;
The ASM/wt index showed the best correlations with chronological age, muscle strength, insulin resistance and geriatric syndrome, which suggests that the ASM/wt index might be the most appropriate and practical index in our subjects. In view of this contention, we divided our subjects into normal, presarcopenia, or sarcopenia groups, based on the ASM/wt index (
Comparison of clinical and laboratory characteristics according to sarcopenia status categorized by ASM/wt index.
The patients with presarcopenia were older than the normal patients, and the patients with sarcopenia were much older than the patients with presarcopenia (p < 0.001). More diabetic patients were included in the groups of presarcopenia and sarcopenia patients than were included in the normal patient group (p = 0.014). Handgrip strength and walking speed gradually decreased in the patients with presarcopenia and sarcopenia compared with those in the patients with normal skeletal muscle mass and function (p < 0.001). HOMA-IR was significantly and progressively increased in the presarcopenia and sarcopenia patients (p = 0.041), which indicates that they may have metabolic problems compared to those patients in the normal group. The patients with sarcopenia had relatively lower hemoglobin, albumin, calcium and 25(OH)D levels, but they were not statistically significantly lower. Sarcopenic patients had trends for higher phosphate, iPTH, and CRP levels, but these trends were not statistically significant.
Fifty-one patients (25 predialysis and 26 dialysis patients) were hospitalized, 6 patients died (1 predialysis and 5 dialysis patients), and 2 patients underwent kidney transplantations during the 2-year observational period. The mean observational period was 552.0 ± 252.8 days. The causes of hospitalization events included cardiac and/or cerebrovascular disease (33.3%), infection-related disease (25.5%), and initiations of dialysis (23.5%). The most common causes of death were pneumonia (50%) and cardiac arrest (20%).
The hospitalization-free survival, according to the sarcopenia status in patients with CKD, is shown in
Kaplan-Meier estimates of hospitalization-free survival probabilities of the patients with chronic kidney disease in relation to sarcopenia status and categorized by the ASM/wt index.
Univariate Cox proportional models for hospitalization. in patients with chronic kidney disease.
Multivariate Cox proportional models for hospitalization in patients with chronic kidney disease.
In our study, skeletal muscle mass was measured via a bioimpedance analysis, and the handgrip test was used in all of the participants. In terms of the adjusted ASM, the ASM/wt index showed the most favorable correlations with chronological age, muscle strength, insulin resistance, and frailty scores compared to those of other indices in these populations. When patients were categorized into normal, presarcopenia, or sarcopenia groups, the patients with presarcopenia and sarcopenia showed poor hospitalization-free survivals.
In 1974, Floyd et al. documented uremic myopathy in CKD patients (
One of the challenges in studies of sarcopenia is to determine how best to measure the amount of muscle. However, the European Working Group on Sarcopenia in Older People, as well as the AWGS, recently established a clear criterion for the diagnosis of sarcopenia (
Sarcopenia does not involve only muscle mass or strength but also involves basal metabolic rates (
Exercise interventions could be the primary treatment options for sarcopenia. Indeed, most exercise trials have shown improved muscle strength, physical performance and muscle mass in community-dwelling, elderly individuals, although these individuals were not recruited based on their sarcopenic status (
There were several limitations of our study. First, this was a small, single-center study that had a relatively short observation period. However, this study had several strengths. We used a definition of sarcopenia that included the two components of low muscle mass and muscle strength. Furthermore, we used a direct physical function test to estimate muscle strength. We compared the prevalence of sarcopenia by using three different muscle indices and explored the most appropriate muscle indices in CKD patients, which may reflect their chronological age, muscle power, metabolic derangement, and frailty. Lastly, we examined whether the selected muscle index was a good predictor for clinical prognoses in our subjects.
In conclusion, our findings showed that sarcopenia and presarcopenia can be useful for predicting hospitalization in CKD outpatients. Future studies on sarcopenia may provide new methods for gaining insights into the disease and for improving their prognoses. Therefore, we should recognize the sarcopenic and presarcopenic statuses of patients as risk factors for poor clinical outcomes and proceed with further research on the relationship between these risk factors and disease status.
This study was approved by an independent Ethics Committee at the CHA Bundang Medical Center, and written informed consent was obtained from each of the patients.
The authors have no conflicts of interest to disclose.
This work was supported by a National Research Foundation grant of Korea (NRF-2017R1D1A1B03034837), which was funded by the Korean government.
H. Y. Jeong and W. Ahn wrote the first manuscript text; J. C. Kim and Y. B. Choi prepared