Patients
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[17]. Patients were categorized according to CKD stages and Kidney Disease Outcomes Quality Initiative guidelines [17]. Patients who were categorized as CKD Stage 5D were on hemodialysis 3 times/wk (> 12 h/wk) for at least 3 months without renal transplantations. All of the participants provided prior written consents. No patients had a history of cancer, coagulation disorders, or active infection. Any patients who were unable to ambulate, either with or without assistive devices, or had insufficient cognitive function to communicate with the interviewer were excluded.
Grip Strength and Physical Performance
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 [18]. Slow walking speed was measured based on the time to walk 4 m, and the cutoff value for low gait speed was ≤ 0.8 m/s, as suggested by the AWGS [18].
Skeletal muscle mass measurement
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 [19], a squared height-adjusted ASM (ASM/ht2) less than 7.0 (kg/m2) for men and less than 5.7 (kg/m2) for women [20], or a BMI-adjusted ASM (ASM/BMI) less than 0.789 (m2) for men and less than 0.512 (m2) for women[21].
Definition of sarcopenia
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 [22].
Definition of frailty
We adopted the Fried criteria as the definition of frailty [23]. At enrollment, the five components of this frailty scale were measured: shrinking (a self-report of unintentional weight loss of more than 10 pounds in the past year based on dry weight, i.e., the weight of an individual undergoing hemodialysis without the excess fluid that builds up between dialysis treatments, which is more representative of the weight that subjects would have if they had normal kidney function), weakness (a grip-strength below an established cutoff value, based on sex), exhaustion (a self-report), low activity (kcal/wk values below an established cutoff value), and slow walking speed (the time taken to walk 4 m below an established cutoff value, according to sex) [23]. A score of 1 was given for each of the measured components. The aggregate frailty score was calculated as the sum of the component scores (range 0–5), and subjects were categorized as frail if the patients received 3 or more points [24].
Clinical variables
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 [25].
Clinical outcome: hospitalization-free survival
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.
Statistical analysis
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).