|Ahead of print publication
Assessment of uremic sarcopenia in dialysis patients: An update
Yu-Li Lin, Bang-Gee Hsu
Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; School of Medicine, Tzu Chi University, Hualien, Taiwan
|Date of Submission||02-Oct-2020|
|Date of Decision||09-Dec-2020|
|Date of Acceptance||24-Feb-2021|
|Date of Web Publication||16-Jul-2021|
Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Section 3, Chung-Yang Road, Hualien
Source of Support: None, Conflict of Interest: None
Uremic sarcopenia, which is highly prevalent in dialysis patients, leads to an increased risk of adverse outcomes, such as poor quality of life, falls, fracture, hospitalization, and even mortality. Therefore, early detection of uremic sarcopenia is crucial for administering quick and adequate multidisciplinary therapy to improve clinical outcomes. This review updates the current information about uremic sarcopenia assessment in chronic dialysis patients. We discuss the methods of assessing skeletal muscle mass, strength, and physical performance. We also discuss surrogate markers derived from serum and dialysate creatinine, in addition to emerging screening tools. The prevalence, clinical relevance, and impact of uremic sarcopenia on survival are reviewed and we discuss the limitations and challenges in applying the current working definition of sarcopenia based on the senior population to dialysis patients. The review shows that dialysis patients with skeletal muscle weakness or poor physical performance, either with or without low skeletal muscle mass, should undergo multidisciplinary therapy, included nutritional counseling, lifestyle modification, and exercise intervention, to mitigate the detrimental effects of uremic sarcopenia.
Keywords: Dialysis, Physical performance, Skeletal muscle mass, Skeletal muscle strength, Uremic sarcopenia
| Introduction|| |
Protein-energy wasting (PEW), a malnutrition status involving a progressive decline of the body's stores of protein and energy fuels, is common in patients with chronic kidney disease (CKD) ,. The prevalence of PEW increases progressively as renal function declines. Up to 75% of end-stage renal disease patients in the United States suffer from PEW . In Taiwan, the estimated prevalence of PEW in dialysis patients ranges from 44% to 58% . The development of PEW leads to a loss of skeletal muscle mass with skeletal muscle weakness or impaired physical performance. This condition is called uremic sarcopenia .
Sarcopenia is first described by Irwin Rosenberg in 1989 to define the process of age-related loss of skeletal muscle mass, which leads to poor quality of life and increased risk of adverse outcomes, such as falls, bone fractures, hospitalization, and death . In Asian community-dwelling older adults, the prevalence of sarcopenia ranges from 7% to 12% ,,,. In CKD patients, renal function deterioration is accompanied by skeletal muscle mass loss . The prevalence of sarcopenia is 6%–14% in non-dialysis CKD ,, and this risk is markedly increased in dialysis patients with end-stage renal disease ,,.
The pathogenesis of uremic sarcopenia is intricate and multifactorial. Beyond the factors commonly observed in older adults, such as the decline in exercise and protein intake, Vitamin D deficiency, growth hormone resistance, decreased sex hormones, and underlying comorbid conditions, dialysis patients are more susceptible to sarcopenia due to the loss of amino acids and other nutrients during dialysis . In addition, metabolic acidosis, insulin resistance, inflammatory status, and overexpression of angiotensin II and myostatin in dialysis patients activate the ATP-dependent ubiquitin-proteasome system, the main pathway of skeletal muscle protein degradation in CKD ,,,,. Recently, indoxyl sulfate, a poorly dialyzable gut-derived uremic toxin, is also implicated in the pathogenesis of uremic sarcopenia through inducing mitochondrial dysfunction and overexpression of two muscle atrophy-related genes, atrogin-1, and myostatin ,,,.
There is a close link between uremic sarcopenia and mortality in dialysis patients. Compared to those without sarcopenia, dialysis patients with sarcopenia have a two-to three-fold increase in the hazard ratio (HR) for mortality ,,. Therefore, accurate assessment of skeletal muscle mass and function in the clinical setting and timely detection of uremic sarcopenia in these patients is crucial for administering quick and adequate multidisciplinary therapy to improve survival. This review updates the current information about uremic sarcopenia assessment in chronic dialysis patients.
| Measurement of skeletal muscle mass|| |
Mid-arm muscle circumference
Mid-arm muscle circumference (MAMC) is a conventional anthropometric measure to evaluate skeletal muscle mass. It is calculated as follows:
MAMC (cm) = Mid-arm circumference (cm) – (3.14 × Triceps skinfold thickness [cm]) (1)
Noori et al. showed that the MAMC is well correlated with the lean body mass measured by dual-energy X-ray absorptiometry (DEXA) in hemodialysis (HD) patients; a higher MAMC was associated with a better quality of life and 5-year survival in 792 maintenance HD patients . Similarly, a median follow-up of 1709 HD patients for 2.5 years showed that a lower MAMC is associated with higher overall mortality . A low MAMC is one of the criteria for diagnosing PEW and is defined as a decrease of >10% in relation to the 50th percentile of the reference population . However, well-trained anthropometric operators should perform measurements in order to avoid measurement errors, and preferably, the same operator should monitor series changes to minimize inter-observer variability.
Computed tomography and magnetic resonance imaging
Computed tomography (CT) and magnetic resonance imaging (MRI) are gold standards for measuring regional skeletal muscle mass. In addition, they are useful for quantifying inter-and intramuscular fat infiltration ,,, which are hallmarks of skeletal muscle wasting in dialysis patients . Increased adipocyte tissue infiltration is a major factor to influences muscle quality, defined as the force generated by each volumetric unit of skeletal muscle tissue .
Unfortunately, the widespread use of CT and MRI in the clinical setting is hampered by their high cost and radiation exposure, especially for longitudinal follow-up. DEXA is an alternative low-radiation, high-precision reference standard tool for estimating skeletal muscle mass . Several current consensuses recommend using DEXA for measuring skeletal muscle mass in the assessment of sarcopenia ,,,.
Bioelectrical impedance analysis
Another widely used reliable clinical tool for evaluating the body composition, either total body or appendicular skeletal muscle mass, of dialysis patients is bioelectrical impedance analysis (BIA) . Through the evaluation of electrical characteristics (resistance and reactance), skeletal muscle mass can be estimated by predictive equations.
In dialysis patients, bioelectrical impedance has a good correlation and agreement with DEXA in the assessment of body composition ,,. In addition, several studies have confirmed its prognostic significance ,,. Moreover, phase angle, the phase difference between voltage and current sinusoidal waveforms, is regarded as an important indicator of cellular integrity and health ,. A low phase angle is associated with increased mortality in both HD and peritoneal dialysis (PD) patients ,,.
The 2020 National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines recommend BIA's clinical utility for monitoring the nutrition status . Both single-frequency BIA and multi-frequency BIA show adequate accuracy in assessing the body composition compared to DEXA . Although both of them are useful tools for longitudinal follow-up, multi-frequency BIA can provide more precise estimates of intracellular and extracellular fluid ,.
To avoid hydration effects in dialysis patients, it is recommended that measurements be performed after an HD session in HD patients and on an empty stomach in PD patients . Since different devices might show significantly different measurements, the same device should be used for a patient .
Another emerging tool for diagnosing sarcopenia is ultrasound, which is easily applicable at the bedside. Studies have shown the validity and reliability of ultrasound in older adults ,. In HD patients, the quadriceps rectus femoris and quadriceps vastus intermedius thickness is significantly correlated with the nutritional status, as assessed by the body mass index, serum albumin, and malnutrition-inflammation score . In addition, the quadriceps rectus femoris thickness is positively correlated with the phase angle and body cell mass assessed by BIA . Beyond the skeletal muscle size, echo intensity can be used as a muscle quality index to predict physical performance in non-dialysis CKD patients . Therefore, ultrasound is a promising assessment tool not only for measuring skeletal muscle mass but also for assessing skeletal muscle quality in dialysis patients. However, further studies are required to confirm these findings.
A comparison of different methods for the assessment of skeletal muscle mass is summarized in [Table 1].
|Table 1: Comparison of available clinical tools for skeletal muscle mass measurement|
Click here to view
| Measurement of skeletal muscle strength and physical performance|| |
A dialysis patient's skeletal muscle strength and physical performance depend not only on his or her skeletal muscle mass but also on his or her cardiopulmonary function, overall nutritional status, anemia degree, dialysis dose, underlying comorbidities, and nervous system coordination, which can be considered a comprehensive manifestation of multiple organ systems. Compared to healthy individuals, dialysis patients show significant deficits in skeletal muscle strength and physical performance ,.
Skeletal muscle strength
Handgrip strength measurement using a dynamometer is a simple, widely used tool for assessing skeletal muscle strength in dialysis patients, which is inversely correlated with the malnutrition-inflammation score . Studies have consistently reported the correlation between low handgrip strength and increased mortality in dialysis patients ,,,. A meta-analysis of nine prospective cohort studies by Hwang et al. showed that compared to the high-handgrip-strength group, the low-handgrip-strength group had 1.88 times higher risk of all-cause mortality, while a per kilogram unit increase in handgrip strength decreased the HR for mortality by 5% . Vogt et al. established the best cut-off to predict mortality in dialysis patients is <22.5 kg in males and <7.0 kg in females . Two studies compared the handgrip strength differences before and after HD sessions and reported a significant decrease in handgrip strength after HD sessions ,. Therefore, handgrip strength assessment of HD patients should be performed before the HD session.
The isokinetic dynamometer is a gold standard for evaluating the skeletal muscle strength of lower extremities in the general population and also in dialysis patients with good accuracy ,. However, the equipment is expensive and not widely available in clinical practice. An alternative is the portable hand-held dynamometer, whose results, which when used by well-trained operators, correlate well with those of isokinetic testing ,.
Among various physical performance assessments, the simplest method widely used in clinical practice is the usual gait speed measurement during walking for 4–6 m in a straight path at the usual speed. Gait speed is not only closely correlated with quality of life but also strongly linked to the risk of falls, hospitalization, and mortality in dialysis patients ,,,. Compared to HD patients with a gait speed of ≥0.6 m/s, the adjusted HRs for mortality are 2.17 and 6.93 for HD patients with a gait speed of <0.6 m/s and those unable to walk, respectively .
Other common tests for assessing physical performance and evaluating the effects of exercise on dialysis patients include the 6-min walk, repeated sit-to-stand, time-up-and-go, intermittent shuttle walk, stair climb, and short physical performance battery tests. The last comprises three tests: 4 m gait speed, five-time repeated sit-to-stand, and balance assessment in different standing positions. Painter and Marcus provided an excellent review of the evaluation of physical function in CKD patients .
| Working diagnosis of sarcopenia and related research in dialysis patients|| |
[Table 2] summarizes the current consensus for the operating definitions of sarcopenia. The skeletal muscle mass, measured by either DEXA or BIA, is usually divided by height squared or the BMI for adjustment. Diagnosis of sarcopenia is based on the presence of low muscle mass as an essential criterion, accompanied by either low HGS or slow gait speed.
|Table 2: Current consensus for the operational definitions of sarcopenia|
Click here to view
Although the definition of sarcopenia is well established in the older population ,,,, there is no consensus on the working diagnosis of uremic sarcopenia in dialysis patients. Most research on uremic sarcopenia applies the geriatric definition to dialysis patients, which leads to heterogenicity in the prevalence of uremic sarcopenia. For example, in older maintenance HD patients, the prevalence of uremic sarcopenia by applying different criteria widely ranges from 3.9% to 63.3% . In addition, the best indices for adjusting the skeletal muscle mass in dialysis patients are unclear. In HD patients, while adjustment by height squared is commonly adopted, the prevalence of uremic sarcopenia using four different indices for low skeletal muscle mass ranges from 3.9% to 15.9%. There is a risk of underestimating the prevalence of low muscle mass if the skeletal muscle mass is normalized to height squared, especially in overweight and obese patients. Adjustments for body size, such as the BMI and body surface area, might better define uremic sarcopenia in these patients with low muscle mass .
[Table 3] summarizes some of the recent studies on dialysis patients. Compared to HD patients, two studies showed that PD patients have a lower prevalence of sarcopenia ,. This discrepancy could be largely explained by different characteristics between HD and PD patients. Regarding the difference risk of sarcopenia between diabetes mellitus (DM) and non-DM dialysis patients, Mori et al. showed that DM has a 3.11-fold odds ratio to have sarcopenia .
| Relevance of skeletal muscle mass and strength in dialysis patients: dilemma regarding uremic sarcopenia diagnosis|| |
Although low skeletal muscle mass is well-established to be associated with poor clinical outcomes in dialysis patients, few previous studies evaluated its impacts together with muscle strength and physical performance. Isoyama et al. showed in 330 incident dialysis patients that low skeletal muscle mass alone does not increase the risk of mortality, while patients with low skeletal muscle strength are at increased risk of mortality regardless of skeletal muscle mass . Similarly, in our chronic HD patients with normal skeletal muscle mass, those with skeletal muscle weakness or slow gait speed remain at high risk of hospitalization and mortality . Kittiskulnam et al. showed that, in HD patients, slow gait speed and weak handgrip strength are independently associated with mortality, but low skeletal muscle mass is not, regardless of normalization to height squared, body weight, BMI, or body surface area . Altogether, compared to skeletal muscle mass, skeletal muscle strength and physical performance are more closely correlated with the risk of mortality in dialysis patients.
Notably, the prevalence of skeletal muscular dysfunction is considerably higher compared to low skeletal muscle mass in dialysis patients [14[,,,. Therefore, the diagnosis of uremic sarcopenia in dialysis patients by applying geriatric criteria is mainly driven by skeletal muscle mass, which is the prerequisite for diagnosing sarcopenia. This approach might overlook patients with only skeletal muscle weakness. In addition, during the muscle wasting process, the loss of skeletal muscle strength could occur earlier and be more rapid than the loss of skeletal muscle mass . Accordingly, dialysis patients diagnosed as having sarcopenia, with concurrent low skeletal muscle mass and strength, may implicate the late stage of muscle wasting. In this regard, skeletal muscle strength and physical performance measurement should be the initial step in uremic sarcopenia assessment. Dialysis patients with skeletal muscle weakness or poor physical performance should be encouraged to modify their lifestyle, diet, and exercise, even with preserved skeletal muscle mass.
Regardless of the methods and criteria used, periodic and longitudinal monitoring of the body composition, skeletal muscle strength, and physical performance changes in dialysis patients could provide a more comprehensive assessment of uremic sarcopenia, which may be more closely associated with prognostic significance compared to single measures ,.
| Surrogate markers of sarcopenia|| |
Creatinine is a breakdown product of creatine phosphate from skeletal muscle tissue and is a well-known serum surrogate for skeletal muscle wasting in dialysis patients. Low serum creatinine levels (pre-HD levels for HD patients), which indicate low skeletal muscle mass, increase the risk of mortality for dialysis patients without residual renal function ,. Creatinine kinetics, which estimates the skeletal muscle mass from pre-HD serum creatinine, 24-h dialysate, and urinary creatinine excretion with a steady status, is significantly correlated with skeletal muscle mass measured by BIA and DEXA in both HD and PD patients ,.
Given the complexity of creatinine kinetics, Noori et al. and Canaud et al. developed formulas for estimating the skeletal muscle mass of HD patients using pre-HD serum creatinine levels and routine clinical parameters ,,. The skeletal muscle mass estimated by the two formulas had a good correlation with the skeletal muscle mass measured using multifrequency BIA and near-infrared interactance. [Table 4] summarizes the skeletal muscle mass estimation formula using creatinine kinetics, the Noori formula, and the Canaud formula.
|Table 4: Skeletal muscle mass estimation equations from creatinine kinetics, Noori formula and simplified creatinine index|
Click here to view
| Clinical approach of uremic sarcopenia|| |
A proposed algorithm for the evaluation of uremic sarcopenia is shown in [Figure 1]. We suggest measurement of handgrip strength and physical performance as the initial approach. Patients with preserved handgrip strength and physical performance, who are not at increased risk of adverse outcomes, should be regularly re-evaluated, while those with either low handgrip strength or poor performance should be further evaluated through BIA or DEXA to determine the skeletal muscle mass volume. If BIA and DEXA are not available, it is reasonable to estimate skeletal muscle mass through creatinine kinetics, Noori formula, and simplified creatinine index. Multidisciplinary management should be provided for any patients with low handgrip strength or poor performance, either accompanied by low skeletal muscle mass (sarcopenia) or not (poor muscle quality).
|Figure 1: Proposed algorithm for the evaluation of uremic sarcopenia. *Creatinine kinetics, Noori formula and simplified creatinine index may be used for skeletal muscle mass estimation if BIA or DEXA is not available. STS: Sit-to-stand test, SPPB: Short Physical Performance Battery, BIA: Bioelectrical impedance analysis, DEXA: Dual-energy X-ray absorptiometry|
Click here to view
| Potential tools for screening uremic sarcopenia: SARC-F and SARC-CalF questionnaires|| |
To our knowledge, no tool has been validated for screening uremic sarcopenia. SARC-F, an easy-to-apply, semi-reported questionnaire, is recommended for initial screening of geriatric sarcopenia by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People (EWGSOP),. The SARC-F questionnaire contains five items: Sluggishness, assistance in walking, rise from a chair, climb stairs, and falls. Each item is scored as 0 (no difficulty), 1 (some difficulty), or 2 (many difficulties or inability). The total score ranges from 0 to 10, and SARC-F ≥4 is considered an increased risk of sarcopenia . [Table 5] shows details of the SARC-F questionnaire.
However, despite its high specificity for diagnosing sarcopenia, the SARC-F questionnaire yields low sensitivity in the geriatric population. To overcome this issue, the SARC-CalF questionnaire was developed, which includes an additional item, calf circumference measurement. In the SARC-CalF questionnaire, 10 points are added to the original SARC-F score if the calf circumference is ≤34 cm for males and ≤33 cm for females. SARC-CalF ≥11 is considered an increased risk of sarcopenia .
In HD patients, Yamamoto et al. first reported the use of the SARC-F questionnaire and showed good accuracy in identifying HD patients with physical limitations . However, further studies are required to determine whether the SARC-F or SARC-CalF questionnaire can be a useful tool for initial screening of dialysis patients and what the best cut-off in this population should be.
| Management of uremic sarcopenia|| |
In addition to optimal dialysis delivery and treatment of comorbidities that accelerate muscle loss (such as infection, DM, cardiovascular disease, chronic wounds, gastrointestinal disorders, depression, and malignancy), nutritional supplementation and physical exercise are the cornerstones of uremic sarcopenia management . Adequate energy (30–35 kcal/kg/day) and high protein intake (daily protein intake 1.2 g/kg/day) should be achieved to overcome the devastating process of muscle wasting . Aerobic and resistance exercise, which are feasible and safe in dialysis patients, is not only shown to improve functional capacity and quality of life but also increase muscle strength and physical performance ,.
Some other emerging and promising treatment strategies included vitamin D, androgens, growth hormone, anti-myostatin antibody, and AST-120, as well as novel strategies targeting myogenic satellite cells, epigenome, and pro-inflammatory cytokines ,,. However, more trials are warranted before firm conclusions can be drawn.
| Conclusion|| |
This review highlighted the importance of uremic sarcopenia assessment in clinical practice, which should be incorporated into the general nutritional assessment for dialysis patients. Given the relevance and clinical effects of skeletal muscle mass and function, dialysis patients with skeletal muscle weakness or poor physical performance, either with or without low skeletal muscle mass, should be identified early for nutritional counseling, lifestyle modification, and exercise intervention to mitigate the detrimental effects of uremic sarcopenia.
Financial support and sponsorship
This study was supported by a grant from Buddhist Tzu Chi Medical Foundation, Taiwan (TCMF-CP 109-01).
Conflicts of interest
Dr. Bang-Gee Hsu, an editorial board member at Tzu Chi Med J, had no role in the peer review process or decision to publish this article. The other author declared no conflict of interest in writing this paper..
| References|| |
Carrero JJ, Thomas F, Nagy K, Arogundade F, Avesani CM, Chan M, et al. Global prevalence of protein-energy wasting in kidney disease: A meta-analysis of contemporary observational studies from the international society of renal nutrition and metabolism. J Ren Nutr 2018;28:380-92.
Kopple JD. Pathophysiology of protein-energy wasting in chronic renal failure. J Nutr 1999;129:247S-251S.
Kovesdy CP, Kopple JD, Kalantar-Zadeh K. Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: Reconciling low protein intake with nutritional therapy. Am J Clin Nutr 2013;97:1163-77.
Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008;73:391-8.
Rosenberg IH. Sarcopenia: Origins and clinical relevance. J Nutr 1997;127:990S-1.
Lau EM, Lynn HS, Woo JW, Kwok TC, Melton LJ 3rd
. Prevalence of and risk factors for sarcopenia in elderly Chinese men and women. J Gerontol A Biol Sci Med Sci 2005;60:213-6.
Han P, Kang L, Guo Q, Wang J, Zhang W, Shen S, et al. Prevalence and factors associated with Sarcopenia in suburb-dwelling older Chinese using the Asian working group for Sarcopenia definition. J Gerontol A Biol Sci Med Sci 2016;71:529-35.
Wang T, Feng X, Zhou J, Gong H, Xia S, Wei Q, et al. Type 2 diabetes mellitus is associated with increased risks of sarcopenia and pre-sarcopenia in Chinese elderly. Sci Rep 2016;6:38937.
Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc 2020;21:300-700.
Zhou Y, Hellberg M, Svensson P, Höglund P, Clyne N. Sarcopenia and relationships between muscle mass, measured glomerular filtration rate and physical function in patients with chronic kidney disease stages 3-5. Nephrol Dial Transplant 2018;33:342-8.
Pereira RA, Cordeiro AC, Avesani CM, Carrero JJ, Lindholm B, Amparo FC, et al. Sarcopenia in chronic kidney disease on conservative therapy: Prevalence and association with mortality. Nephrol Dial Transplant 2015;30:1718-25.
Mori K, Nishide K, Okuno S, Shoji T, Emoto M, Tsuda A, et al. Impact of diabetes on sarcopenia and mortality in patients undergoing hemodialysis. BMC Nephrol 2019;20:105.
Isoyama N, Qureshi AR, Avesani CM, Lindholm B, Bàràny P, Heimbürger O, et al. Comparative associations of muscle mass and muscle strength with mortality in dialysis patients. Clin J Am Soc Nephrol 2014;9:1720-8.
Bataille S, Serveaux M, Carreno E, Pedinielli N, Darmon P, Robert A. The diagnosis of sarcopenia is mainly driven by muscle mass in hemodialysis patients. Clin Nutr 2017;36:1654-60.
Fahal IH. Uraemic sarcopenia: Aetiology and implications. Nephrol Dial Transplant 2014;29:1655-65.
Domanski M, Ciechanowski K. Sarcopenia: A major challenge in elderly patients with end-stage renal disease. J Aging Res 2012;2012:754739.
Gamboa JL, Billings FT, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, et al. Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiol Rep 2016;4:e12780.
Gamboa JL, Roshanravan B, Towse T, Keller CA, Falck AM, Yu C, et al. Skeletal muscle mitochondrial dysfunction is present in patients with CKD before initiation of maintenance hemodialysis. Clin J Am Soc Nephrol 2020;15:926-36.
Wang XH, Mitch WE. Mechanisms of muscle wasting in chronic kidney disease. Nat Rev Nephrol 2014;10:504-16.
Enoki Y, Watanabe H, Arake R, Sugimoto R, Imafuku T, Tominaga Y, et al. Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. Sci Rep 2016;6:32084.
Sato E, Mori T, Mishima E, Suzuki A, Sugawara S, Kurasawa N, et al. Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease. Sci Rep 2016;6:36618.
Lin YL, Liu CH, Lai YH, Wang CH, Kuo CH, Liou HH, et al. Association of serum indoxyl sulfate levels with skeletal muscle mass and strength in chronic hemodialysis patients: A 2-year longitudinal analysis. Calcif Tissue Int 2020;107:257-65.
Jheng JR, Chen YS, Ao UI, Chan DC, Huang JW, Hung KY, et al. The double-edged sword of endoplasmic reticulum stress in uremic sarcopenia through myogenesis perturbation. J Cachexia Sarcopenia Muscle 2018;9:570-84.
Giglio J, Kamimura MA, Lamarca F, Rodrigues J, Santin F, Avesani CM. Association of sarcopenia with nutritional parameters, quality of life, hospitalization, and mortality rates of elderly patients on hemodialysis. J Ren Nutr 2018;28:197-207.
Kittiskulnam P, Chertow GM, Carrero JJ, Delgado C, Kaysen GA, Johansen KL. Clinical investigation: Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis. Kidney Int 2017;92:238-47.
Noori N, Kopple JD, Kovesdy CP, Feroze U, Sim JJ, Murali SB, et al. Mid-arm muscle circumference and quality of life and survival in maintenance hemodialysis patients. Clin J Am Soc Nephrol 2010;5:2258-68.
Huang CX, Tighiouart H, Beddhu S, Cheung AK, Dwyer JT, Eknoyan G, et al. Both low muscle mass and low fat are associated with higher all-cause mortality in hemodialysis patients. Kidney Int 2010;77:624-9.
Inhuber S, Sollmann N, Schlaeger S, Dieckmeyer M, Burian E, Kohlmeyer C, et al. Associations of thigh muscle fat infiltration with isometric strength measurements based on chemical shift encoding-based water-fat magnetic resonance imaging. Eur Radiol 2019;3:45.
Therkelsen KE, Pedley A, Hoffmann U, Fox CS, Murabito JM. Intramuscular fat and physical performance at the Framingham Heart Study. Age (Dordr) 2016;38:31.
Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol (1985) 2000;89:104-10.
Wang HL, Ding TT, Lu S, Xu Y, Tian J, Hu WF, et al. Muscle mass loss and intermuscular lipid accumulation were associated with insulin resistance in patients receiving hemodialysis. Chin Med J (Engl) 2013;126:4612-7.
McGregor RA, Cameron-Smith D, Poppitt SD. It is not just muscle mass: A review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longev Healthspan 2014;3:9.
Buckinx F, Landi F, Cesari M, Fielding RA, Visser M, Engelke K, et al. Pitfalls in the measurement of muscle mass: A need for a reference standard. J Cachexia Sarcopenia Muscle 2018;9:269-78.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412-23.
Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: Consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 2014;15:95-101.
Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: An undiagnosed condition in older adults. Current consensus definition: Prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 2011;12:249-56.
Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, et al. The FNIH sarcopenia project: Rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci 2014;69:547-58.
Khalil SF, Mohktar MS, Ibrahim F. The theory and fundamentals of bioimpedance analysis in clinical status monitoring and diagnosis of diseases. Sensors (Basel) 2014;14:10895-928.
Bross R, Chandramohan G, Kovesdy CP, Oreopoulos A, Noori N, Golden S, et al. Comparing body composition assessment tests in long-term hemodialysis patients. Am J Kidney Dis 2010;55:885-96.
Fürstenberg A, Davenport A. Comparison of multifrequency bioelectrical impedance analysis and dual-energy X-ray absorptiometry assessments in outpatient hemodialysis patients. Am J Kidney Dis 2011;57:123-9.
Fürstenberg A, Davenport A. Assessment of body composition in peritoneal dialysis patients using bioelectrical impedance and dual-energy x-ray absorptiometry. Am J Nephrol 2011;33:150-6.
Castellano S, Palomares I, Moissl U, Chamney P, Carretero D, Crespo A, et al. Appropriate assessment of body composition to identify haemodialysis patients at risk. Nefrología 2016;36:268-74.
Marcelli D, Usvyat LA, Kotanko P, Bayh I, Canaud B, Etter M, et al. Body composition and survival in dialysis patients: Results from an international cohort study. Clin J Am Soc Nephrol 2015;10:1192-200.
Rosenberger J, Kissova V, Majernikova M, Straussova Z, Boldizsar J. Body composition monitor assessing malnutrition in the hemodialysis population independently predicts mortality. J Ren Nutr 2014;24:172-6.
Lukaski HC, Kyle UG, Kondrup J. Assessment of adult malnutrition and prognosis with bioelectrical impedance analysis: Phase angle and impedance ratio. Curr Opin Clin Nutr Metab Care 2017;20:330-9.
Di Vincenzo O, Marra M, Di Gregorio A, Pasanisi F, Scalfi L. Bioelectrical impedance analysis (BIA) -derived phase angle in sarcopenia: A systematic review. Clin Nutr 2020;S0261-5614(20)30594-X.
Mushnick R, Fein PA, Mittman N, Goel N, Chattopadhyay J, Avram MM. Relationship of bioelectrical impedance parameters to nutrition and survival in peritoneal dialysis patients. Kidney Int Suppl 2003;87:S53-6.
Chertow GM, Jacobs DO, Lazarus JM, Lew NL, Lowrie EG. Phase angle predicts survival in hemodialysis patients. J Ren Nutr 1997;7:204-7.
Dumler F. A low bioimpedance phase angle predicts a higher mortality and lower nutritional status in chronic dialysis patients. J Phys Conf Ser 2010;224:012104.
Ikizler TA, Burrowes JD, Byham-Gray LD, Campbell KL, Carrero JJ, Chan W, et al. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis 2020;76:S1-07.
Donadio C, Halim AB, Caprio F, Grassi G, Khedr B, Mazzantini M. Single- and multi-frequency bioelectrical impedance analyses to analyse body composition in maintenance haemodialysis patients: Comparison with dual-energy x-ray absorptiometry. Physiol Meas 2008;29:S517-24.
Raimann JG, Abbas SR, Liu L, Zhu F, Larive B, Kotanko P, et al. Agreement of single- and multi-frequency bioimpedance measurements in hemodialysis patients: An ancillary study of the Frequent Hemodialysis Network Daily Trial. Nephron Clin Pract 2014;128:115-26.
Dou Y, Liu L, Cheng X, Cao L, Zuo L. Comparison of bioimpedance methods for estimating total body water and intracellular water changes during hemodialysis. Nephrol Dial Transplant 2011;26:3319-24.
Panorchan K, Nongnuch A, El-Kateb S, Goodlad C, Davenport A. Changes in muscle and fat mass with haemodialysis detected by multi-frequency bioelectrical impedance analysis. Eur J Clin Nutr 2015;69:1109-12.
Yalin SF, Gulcicek S, Avci S, Erkalma Senates B, Altiparmak MR, Trabulus S, et al. Single-frequency and multi-frequency bioimpedance analysis: What is the difference? Nephrology (Carlton) 2018;23:438-45.
Nijholt W, Scafoglieri A, Jager-Wittenaar H, Hobbelen JSM, van der Schans CP. The reliability and validity of ultrasound to quantify muscles in older adults: A systematic review. J Cachexia Sarcopenia Muscle 2017;8:702-12.
Wang J, Hu Y, Tian G. Ultrasound measurements of gastrocnemius muscle thickness in older people with sarcopenia. Clin Interv Aging 2018;13:2193-9.
Sabatino A, Regolisti G, Delsante M, Di Motta T, Cantarelli C, Pioli S, et al. Noninvasive evaluation of muscle mass by ultrasonography of quadriceps femoris muscle in End-Stage Renal Disease patients on hemodialysis. Clin Nutr 2019;38:1232-9.
Battaglia Y, Ullo I, Massarenti S, Esposito P, Prencipe M, Ciancio G, et al. Ultrasonography of quadriceps femoris muscle and subcutaneous fat tissue and body composition by BIVA in chronic dialysis patients. Nutrients 2020;12:1388.
Wilkinson TJ, Gould DW, Nixon DG, Watson EL, Smith AC. Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease. Nephrol Dial Transplant 2019;34:1344-53.
Blake C, O'Meara YM. Subjective and objective physical limitations in high-functioning renal dialysis patients. Nephrol Dial Transplant 2004;19:3124-9.
Silva LF, Matos CM, Lopes GB, Martins MT, Martins MS, Arias LU, et al. Handgrip strength as a simple indicator of possible malnutrition and inflammation in men and women on maintenance hemodialysis. J Ren Nutr 2011;21:235-45.
Wang AY, Sea MM, Ho ZS, Lui SF, Li PK, Woo J. Evaluation of handgrip strength as a nutritional marker and prognostic indicator in peritoneal dialysis patients. Am J Clin Nutr 2005;81:79-86.
Matos CM, Silva LF, Santana LD, Santos LS, Protásio BM, Rocha MT, et al. Handgrip strength at baseline and mortality risk in a cohort of women and men on hemodialysis: A 4-year study. J Ren Nutr 2014;24:157-62.
Vogt BP, Borges MC, Goés CR, Caramori JC. Handgrip strength is an independent predictor of all-cause mortality in maintenance dialysis patients. Clin Nutr 2016;35:1429-33.
Tian ML, Zha Y, Li Q, Yuan J. Handgrip strength and mortality in maintenance hemodialysis patients. Iran Red Crescent Med J 2019;21:7.
Hwang SH, Lee DH, Min J, Jeon JY. Handgrip strength as a predictor of all-cause mortality in patients with chronic kidney disease undergoing dialysis: A meta-analysis of prospective cohort studies. J Ren Nutr 2019;29:471-9.
Pinto AP, Ramos CI, Meireles MS, Kamimura MA, Cuppari L. Impact of hemodialysis session on handgrip strength. J Bras Nefrol 2015;37:451-7.
Delanaye P, Quinonez K, Buckinx F, Krzesinski JM, Bruyère O. Hand grip strength measurement in haemodialysis patients: Before or after the session? Clin Kidney J 2018;11:555-8.
Dvir Z, Müller S. Multiple-joint isokinetic dynamometry: A critical review. J Strength Cond Res 2020;34:587-601.
Collado-Mateo D, Dominguez-Muñoz FJ, Charrua Z, Adsuar JC, Batalha N, Merellano-Navarro E, et al. Isokinetic strength in peritoneal dialysis patients: A reliability study. Appl Sci 2019:9:3542.
Matsuzawa R, Matsunaga A, Wang G, Yamamoto S, Kutsuna T, Ishii A, et al. Relationship between lower extremity muscle strength and all-cause mortality in Japanese patients undergoing dialysis. Phys Ther 2014;94:947-56.
Stark T, Walker B, Phillips JK, Fejer R, Beck R. Hand-held dynamometry correlation with the gold standard isokinetic dynamometry: A systematic review. PM R 2011;3:472-9.
Kutner NG, Zhang R, Huang Y, Wasse H. Gait speed and hospitalization among ambulatory hemodialysis patients: USRDS special study data. World J Nephrol 2014;3:101-6.
Kutner NG, Zhang R, Huang Y, Painter P. Gait speed and mortality, hospitalization, and functional status change among hemodialysis patients: A US renal data system special study. Am J Kidney Dis 2015;66:297-304.
Lee YH, Kim JS, Jung SW, Hwang HS, Moon JY, Jeong KH, et al. Gait speed and handgrip strength as predictors of all-cause mortality and cardiovascular events in hemodialysis patients. BMC Nephrol 2020;21:166.
Painter P, Marcus RL. Assessing physical function and physical activity in patients with CKD. Clin J Am Soc Nephrol 2013;8:861-72.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing 2019;48:16-31.
Lamarca F, Carrero JJ, Rodrigues JC, Bigogno FG, Fetter RL, Avesani CM. Prevalence of sarcopenia in elderly maintenance hemodialysis patients: The impact of different diagnostic criteria. J Nutr Health Aging 2014;18:710-7.
Kittiskulnam P, Carrero JJ, Chertow GM, Kaysen GA, Delgado C, Johansen KL. Sarcopenia among patients receiving hemodialysis: Weighing the evidence. J Cachexia Sarcopenia Muscle 2017;8:57-68.
Kim JK, Choi SR, Choi MJ, Kim SG, Lee YK, Noh JW, et al. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clin Nutr 2014;33:64-8.
Ren H, Gong D, Jia F, Xu B, Liu Z. Sarcopenia in patients undergoing maintenance hemodialysis: Incidence rate, risk factors and its effect on survival risk. Ren Fail 2016;38:364-71.
As'habi A, Najafi I, Tabibi H, Hedayati M. Prevalence of sarcopenia and dynapenia and their determinants in Iranian peritoneal dialysis patients. Iran J Kidney Dis 2018;12:53-60.
Lin YL, Liou HH, Wang CH, Lai YH, Kuo CH, Chen SY, et al. Impact of sarcopenia and its diagnostic criteria on hospitalization and mortality in chronic hemodialysis patients: A 3-year longitudinal study. J Formos Med Assoc 2020;119:1219-29.
Abro A, Delicata LA, Vongsanim S, Davenport A. Differences in the prevalence of sarcopenia in peritoneal dialysis patients using hand grip strength and appendicular lean mass: Depends upon guideline definitions. Eur J Clin Nutr 2018;72:993-9.
Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: The health, aging and body composition study. J Gerontol A Biol Sci Med Sci 2006;61:1059-64.
Kim C, Kim JK, Lee HS, Kim SG, Song YR. Longitudinal changes in body composition are associated with all-cause mortality in patients on peritoneal dialysis. Clin Nutr 2021;40:120-6.
Keane D, Gardiner C, Lindley E, Lines S, Woodrow G, Wright M. Changes in body composition in the two years after initiation of haemodialysis: A retrospective cohort study. Nutrients 2016;8:702.
Park J, Mehrotra R, Rhee CM, Molnar MZ, Lukowsky LR, Patel SS, et al. Serum creatinine level, a surrogate of muscle mass, predicts mortality in peritoneal dialysis patients. Nephrol Dial Transplant 2013;28:2146-55.
Patel SS, Molnar MZ, Tayek JA, Ix JH, Noori N, Benner D, et al. Serum creatinine as a marker of muscle mass in chronic kidney disease: Results of a cross-sectional study and review of literature. J Cachexia Sarcopenia Muscle 2013;4:19-29.
Keshaviah PR, Nolph KD, Moore HL, Prowant B, Emerson PF, Meyer M, et al. Lean body mass estimation by creatinine kinetics. J Am Soc Nephrol 1994;4:1475-85.
Negri AL, Barone R, Veron D, Fraga A, Arrizurieta E, Zucchini A, et al. Lean mass estimation by creatinine kinetics and dual-energy x-ray absorptiometry in peritoneal dialysis. Nephron Clin Pract 2003;95:c9-14.
Noori N, Kovesdy CP, Bross R, Lee M, Oreopoulos A, Benner D, et al. Novel equations to estimate lean body mass in maintenance hemodialysis patients. Am J Kidney Dis 2011;57:130-9.
Canaud B, Granger Vallée A, Molinari N, Chenine L, Leray-Moragues H, Rodriguez A, et al. Creatinine index as a surrogate of lean body mass derived from urea Kt/V, pre-dialysis serum levels and anthropometric characteristics of haemodialysis patients. PLoS One 2014;9:e93286.
Canaud B, Ye X, Usvyat L, Kooman J, van der Sande F, Raimann J, et al. Clinical and predictive value of simplified creatinine index used as muscle mass surrogate in end-stage kidney disease haemodialysis patients – Results from the international monitoring dialysis outcome initiative. Nephrol Dial Transplant 2020;35:2161-71.
Woo J, Leung J, Morley JE. Validating the SARC-F: A suitable community screening tool for sarcopenia? J Am Med Dir Assoc 2014;15:630-4.
Barbosa-Silva TG, Menezes AM, Bielemann RM, Malmstrom TK, Gonzalez MC, Grupo de Estudos em Composição Corporal e Nutrição (COCONUT). Enhancing SARC-F: Improving sarcopenia screening in the clinical practice. J Am Med Dir Assoc 2016;17:1136-41.
Yamamoto S, Matsuzawa R, Harada M, Watanabe T, Shimoda T, Suzuki Y, et al. SARC-F questionnaire: Rapid and easy tool for identifying physical limitations in hemodialysis patients. JCSM Clin Rep 2019;4:1-2.
Moorthi RN, Avin KG. Clinical relevance of sarcopenia in chronic kidney disease. Curr Opin Nephrol Hypertens 2017;26:219-28.
Ikizler TA, Cano NJ, Franch H, Fouque D, Himmelfarb J, Kalantar-Zadeh K, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: A consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013;84:1096-107.
Heiwe S, Jacobson SH. Exercise training in adults with CKD: A systematic review and meta-analysis. Am J Kidney Dis 2014;64:383-93.
Barcellos FC, Santos IS, Umpierre D, Bohlke M, Hallal PC. Effects of exercise in the whole spectrum of chronic kidney disease: A systematic review. Clin Kidney J 2015;8:753-65.
Stenvinkel P, Carrero JJ, von Walden F, Ikizler TA, Nader GA. Muscle wasting in end-stage renal disease promulgates premature death: Established, emerging and potential novel treatment strategies. Nephrol Dial Transplant 2016;31:1070-7.
Nishikawa M, Ishimori N, Takada S, Saito A, Kadoguchi T, Furihata T, et al. AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress. Nephrol Dial Transplant 2015;30:934-42.
Enoki Y, Watanabe H, Arake R, Fujimura R, Ishiodori K, Imafuku T, et al. Potential therapeutic interventions for chronic kidney disease-associated sarcopenia via indoxyl sulfate-induced mitochondrial dysfunction. J Cachexia Sarcopenia Muscle 2017;8:735-47.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]