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• W3171704922 abstract "Sarcopenia and frailty are prevalent in the chronic kidney disease (CKD) population. Sarcopenia is characterised by the loss of muscle mass and function, while frailty is defined as a multi-system impairment associated with increased vulnerability to stressors. There is substantial overlap between the 2 conditions, particularly with regards to physical aspects: low grip strength, gait speed and low muscle mass. Both sarcopenia and frailty have been associated with a wide range of adverse health outcomes. Although there is no recommended pharmacological treatment as yet, it is widely accepted that exercise training and nutritional supplementation are the key interventions to maintain skeletal muscle mass and strength. This review aims to present a comprehensive overview of sarcopenia and frailty in patients with CKD. Sarcopenia and frailty are prevalent in the chronic kidney disease (CKD) population. Sarcopenia is characterised by the loss of muscle mass and function, while frailty is defined as a multi-system impairment associated with increased vulnerability to stressors. There is substantial overlap between the 2 conditions, particularly with regards to physical aspects: low grip strength, gait speed and low muscle mass. Both sarcopenia and frailty have been associated with a wide range of adverse health outcomes. Although there is no recommended pharmacological treatment as yet, it is widely accepted that exercise training and nutritional supplementation are the key interventions to maintain skeletal muscle mass and strength. This review aims to present a comprehensive overview of sarcopenia and frailty in patients with CKD. Sarcopenia is derived from Greek (sarcx for “flesh” and penia for “loss”) and was first described by Irwin Rosenberg in 1988.1Rosenberg I.H. Sarcopenia: Origins and clinical relevance.J Nutr. 1997; 127: 990S-991SCrossref PubMed Google Scholar More recent definitions include the functional loss of muscle strength and performance that occurs with aging.2Cruz-Jentoft A.J. Baeyens J.P. Bauer J.M. et al.Sarcopenia: European Consensus on Definition and Diagnosis: report of the European Working Group on Sarcopenia in Older People.Age Aging. 2010; 39: 412-423Crossref PubMed Scopus (6798) Google Scholar,3Cruz-Jentoft A.J. Bahat G. Bauer J. et al.Sarcopenia: revised European Consensus on Definition and Diagnosis.Age Aging. 2019; 48: 16-31Crossref PubMed Scopus (3240) Google Scholar Sarcopenia has only recently gained recognition as a disease entity with an International Classification of Diseases Tenth Revision Clinical Modification (ICD-10-CM) (M62.84) code in 2016.4Anker S.D. Morley J.E. von Haehling S. Welcome to the ICD-10 code for sarcopenia.J Cachexia Sarcopenia Muscle. 2016; 7: 512-514Crossref PubMed Scopus (320) Google Scholar It incurs a substantial financial burden to healthcare systems and was estimated to have a direct healthcare cost of $18.5 billion in the United States.5Janssen I. Shepard D.S. Katzmarzyk P.T. et al.The healthcare costs of sarcopenia in the United States.J Am Geriatr Soc. 2004; 52: 80-85Crossref PubMed Scopus (933) Google Scholar Frailty, a clinical condition first established by geriatricians, is a syndrome characterized by a reduction in functional reserve, with an increased susceptibility for developing adverse outcomes upon exposure to stressors.6McMillan G.J. Hubbard R.E. Frailty in older inpatients: what physicians need to know.Q J Med. 2012; 105: 1059-1065Crossref Scopus (60) Google Scholar Encompassing physical, cognitive, and social components, frailty constitutes a broader functional spectrum than sarcopenia.7Rockwood K. Mitnitski A. Frailty in relation to the accumulation of deficits.J Gerontol A Biol Sci Med Sci. 2007; 62: 722-727Crossref PubMed Scopus (1388) Google Scholar Nevertheless, there is considerable overlap between the 2 conditions, primarily the physical aspects of frailty—weak grip strength, slow walking speed, and weight loss (as a proxy for loss of muscle mass), as defined by the Fried criteria.8Fried L.P. Tangen C.M. Walston J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar Profound progress has been made in our understanding of both conditions over the past decade, and there has been an exponential growth in the number of scientific publications on sarcopenia and frailty. Furthermore, there is emerging evidence linking sarcopenia and frailty with greater mortality risk in patients with chronic kidney disease (CKD). Importantly, nephrologists frequently encounter younger patients infirmed by multiple comorbidities who present with features consistent with sarcopenia and/or frailty in clinical practice. Therefore sarcopenia and frailty are not necessarily limited to the older population. This review provides a comprehensive overview of sarcopenia and frailty in CKD and discusses the latest developments in therapeutic interventions. Sarcopenia is twice as common as frailty in the general population.9von Haehling S. Morley J.E. Anker S.D. An overview of sarcopenia: facts and numbers on prevalence and clinical impact.J Cachexia Sarcopenia Muscle. 2010; 1: 129-133Crossref PubMed Scopus (460) Google Scholar Sarcopenia may lead to frailty; however, not all patients with sarcopenia are frail. Over the age of 50, muscle mass declines by 1% to 2% per year, while muscle strength decreases at a rate of 1.5% per year, increasing to 3% after age 60 years.10von Haehling S. Morley J.E. Anker S.D. From muscle wasting to sarcopenia and myopenia: update 2012.J Cachexia Sarcopenia Muscle. 2012; 3: 213-217Crossref PubMed Scopus (115) Google Scholar In the general population, the prevalence of sarcopenia in adults aged 60 to 70 years ranges between 5% and 13%, increasing to 11% to 50% in those aged 80 years or more.9von Haehling S. Morley J.E. Anker S.D. An overview of sarcopenia: facts and numbers on prevalence and clinical impact.J Cachexia Sarcopenia Muscle. 2010; 1: 129-133Crossref PubMed Scopus (460) Google Scholar In CKD patients, the reported prevalence of sarcopenia varies markedly from 3.9% to 98.5%,11Carrero J.J. Chmielewski M. Axelsson J. et al.Muscle atrophy, inflammation and clinical outcome in incident and prevalent dialysis patients.Clin Nutr. 2008; 27: 557-564Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar, 12Greenhall G.H. Davenport A. Screening for muscle loss in patients established on peritoneal dialysis using bioimpedance.Eur J Clin Nutr. 2017; 71: 70-75Crossref PubMed Scopus (15) Google Scholar, 13Isoyama N. Qureshi A.R. Avesani C.M. et al.Comparative associations of muscle mass and muscle strength with mortality in dialysis patients.Clin J Am Soc Nephrol. 2014; 9: 1720-1728Crossref PubMed Scopus (262) Google Scholar, 14Kittiskulnam P. Chertow G.M. Carrero J.J. et al.Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis.Kidney Int. 2017; 92: 238-247Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 15Lamarca F. Carrero J.J. Rodrigues J.C. et al.Prevalence of sarcopenia in elderly maintenance hemodialysis patients: the impact of different diagnostic criteria.J Nutr Health Aging. 2014; 18: 710-717Crossref PubMed Scopus (78) Google Scholar, 16Zhou Y. Hellberg M. Svensson P. et al.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: 342-348Crossref PubMed Scopus (73) Google Scholar a variance thought due to both heterogeneous study populations and methodological inconsistencies used to evaluate sarcopenia or muscle wasting before the proposition of a unified definition and diagnostic criteria by the European and North American working groups on sarcopenia.2Cruz-Jentoft A.J. Baeyens J.P. Bauer J.M. et al.Sarcopenia: European Consensus on Definition and Diagnosis: report of the European Working Group on Sarcopenia in Older People.Age Aging. 2010; 39: 412-423Crossref PubMed Scopus (6798) Google Scholar,3Cruz-Jentoft A.J. Bahat G. Bauer J. et al.Sarcopenia: revised European Consensus on Definition and Diagnosis.Age Aging. 2019; 48: 16-31Crossref PubMed Scopus (3240) Google Scholar,17Studenski S.A. Peters K.W. Alley D.E. et al.The FNIA Sarcopenia Project: rationale, study description, conference recommendations, and final estimates.J Gerontol A Biol Sci Med Sci. 2014; 69: 547-558Crossref PubMed Scopus (1111) Google Scholar Similarly, the prevalence of frailty in CKD patients is higher than in the general population (15%−21% vs. 3%−6%),18Shlipak M.G. Stehman-Breen C. Fried L.F. et al.The presence of frailty in elderly persons with chronic renal insufficiency.Am J Kidney Dis. 2004; 43: 861-867Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar,19Wilhelm-Leen E.R. Hall Y.N. Tamura M.K. et al.Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey.Am J Med. 2009; 122: 664-671Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar and among those who are dialysis dependent, the prevalence of frailty varies between 14% and 73%.20Chowdhury R. Peel N.M. Krosch M. et al.Frailty and chronic kidney disease: a systematic review.Arch Gerontol Geriatr. 2017; 68: 135-142Crossref PubMed Scopus (129) Google Scholar In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as the presence of low appendicular lean skeletal muscle mass with low muscle strength and/or low physical performance and this was subsequently revised in 2018 to include specific cut-off points for measures to characterize sarcopenia.2Cruz-Jentoft A.J. Baeyens J.P. Bauer J.M. et al.Sarcopenia: European Consensus on Definition and Diagnosis: report of the European Working Group on Sarcopenia in Older People.Age Aging. 2010; 39: 412-423Crossref PubMed Scopus (6798) Google Scholar,3Cruz-Jentoft A.J. Bahat G. Bauer J. et al.Sarcopenia: revised European Consensus on Definition and Diagnosis.Age Aging. 2019; 48: 16-31Crossref PubMed Scopus (3240) Google Scholar Other international groups have also developed similar definitions for sarcopenia, and the cut-offs for the definitions are ethnically specific and are summarized in Table 1.21Chen L.K. Woo J. Assantachai P. et al.Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment.J Am Med Dir Assoc. 2020; 21: 300-307Abstract Full Text Full Text PDF PubMed Scopus (950) Google Scholar, 22Chen L.K. Liu L.K. Woo J. et al.Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia.J Am Med Dir Assoc. 2014; 15: 95-101Abstract Full Text Full Text PDF PubMed Scopus (2204) Google Scholar There are many techniques for evaluating muscle quantity, including bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), magnetic resonance imaging (MRI), and anthropometry measurements such as mid-arm and calf circumference. Although both CT and MRI are regarded as the criterion standards for noninvasive muscle quantity assessment,23Beaudart C. McCloskey E. Bruyere O. et al.Sarcopenia in daily practice: assessment and management.BMC Geriatr. 2016; 16: 170Crossref PubMed Scopus (266) Google Scholar they are not widely used because of high costs, requirements for highly trained personnel, and poorly established cut-off values to define low muscle mass. Both BIA and DEXA are more readily available for routine patient assessment; however, the accuracy of muscle mass estimation by these methods may possibly be affected by the fluid status of patients with CKD or end-stage kidney disease (ESKD). Nonetheless, several measures could be taken to improve the reliability and reproducibility of measurements, including performing BIA after a time interval of 15 to 20 minutes following the end of the mid-week hemodialysis session24Di Iorio B.R. Scalfi L. Terracciano V. et al.A systematic evaluation of bioelectrical impedance measurement after hemodialysis session.Kidney Int. 2004; 65: 2435-2440Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar,25Sabatino A. D'Alessandro C. Regolisti G. et al.Muscle mass assessment in renal disease: the role of imaging techniques.Quant Imaging Med Surg. 2020; 10: 1672-1686Crossref PubMed Google Scholar or when the abdomen is free of dialysate in peritoneal dialysis patients,25Sabatino A. D'Alessandro C. Regolisti G. et al.Muscle mass assessment in renal disease: the role of imaging techniques.Quant Imaging Med Surg. 2020; 10: 1672-1686Crossref PubMed Google Scholar,26Davenport A. Does peritoneal dialysate affect body composition assessments using multi-frequency bioimpedance in peritoneal dialysis patients?.Eur J Clin Nutr. 2013; 67: 223-225Crossref PubMed Scopus (46) Google Scholar to reflect a “dry-weight” state. Multi-frequency BIA (5−500 kHz) might be preferable to single-frequency BIA (50 kHz) in the assessment of muscle mass, as it is less influenced by fluid overload.27Kaysen G.A. Zhu F. Sarkar S. et al.Estimation of total-body and limb muscle mass in hemodialysis patients by using multifrequency bioimpedance spectroscopy.Am J Clin Nutr. 2005; 82: 988-995Crossref PubMed Scopus (83) Google Scholar Importantly, by recognizing the technological limits in defining muscle quantity and quality, low muscle strength has now become the primary parameter of sarcopenia in the 2018 revised European Working Group on Sarcopenia in Older People (EWGSOP2) guidelines as a more reliable measure of muscle function. It is also a better indicator than muscle mass in predicting adverse outcomes.3Cruz-Jentoft A.J. Bahat G. Bauer J. et al.Sarcopenia: revised European Consensus on Definition and Diagnosis.Age Aging. 2019; 48: 16-31Crossref PubMed Scopus (3240) Google ScholarTable 1Proposed criteria and cut-offs of measurements for different operational definitions of sarcopenia and Fried model for frailtyParameterEWGSOP (2010)2Cruz-Jentoft A.J. Baeyens J.P. Bauer J.M. et al.Sarcopenia: European Consensus on Definition and Diagnosis: report of the European Working Group on Sarcopenia in Older People.Age Aging. 2010; 39: 412-423Crossref PubMed Scopus (6798) Google ScholarEWGSOP2 (2018)3Cruz-Jentoft A.J. Bahat G. Bauer J. et al.Sarcopenia: revised European Consensus on Definition and Diagnosis.Age Aging. 2019; 48: 16-31Crossref PubMed Scopus (3240) Google ScholarFNIH (2014)17Studenski S.A. Peters K.W. Alley D.E. et al.The FNIA Sarcopenia Project: rationale, study description, conference recommendations, and final estimates.J Gerontol A Biol Sci Med Sci. 2014; 69: 547-558Crossref PubMed Scopus (1111) Google ScholarAWGS (2014)22Chen L.K. Liu L.K. Woo J. et al.Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia.J Am Med Dir Assoc. 2014; 15: 95-101Abstract Full Text Full Text PDF PubMed Scopus (2204) Google ScholarAWGS (2019)21Chen L.K. Woo J. Assantachai P. et al.Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment.J Am Med Dir Assoc. 2020; 21: 300-307Abstract Full Text Full Text PDF PubMed Scopus (950) Google ScholarFried model (2001)8Fried L.P. Tangen C.M. Walston J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google ScholarMuscle massShrinking: at least 5% unintentional weight loss in 12 monthsExhaustion: self-report using the CES-D scaleWeakness: poor grip strength, stratified by sex and BMI quartilesSlowness: gait speed, stratified by sex and heightLow physical activity: <383 kcal/wk (M) or <270 kcal/wk (F)(3 or more of the above criteria to diagnose frailty) DXA (ASM/height2)<7.26 kg/m2 (M)<7.0 kg/m2 (M)<0.789 m2 (M)aFNIH defines low lean muscle mass using appendicular skeletal muscle mass adjusted for body mass index.<7.0 kg/m2 (M)<7.0 kg/m2 (M)<5.5 kg/m2 (F)<5.5 kg/m2 (F)<0.512 m2 (F)aFNIH defines low lean muscle mass using appendicular skeletal muscle mass adjusted for body mass index.<5.4 kg/m2 (F)<5.4 kg/m2 (F) BIA (ASM/height2)<8.87 kg/m2 (M)<7.0 kg/m2 (M)<7.0 kg/m2 (M)<6.42 kg/m2 (F)<5.7 kg/m2 (F)<5.7 kg/m2 (F)Muscle strength Hand grip strength<30 kg (M)<20 kg (F)<27 kg (M)<16 kg (F)<26 kg (M)<16 kg (F)<26 kg (M)<18 kg (F)<28 kg (M)<18 kg (F) 5-Times chair stand test≥15 sMuscle performance Gait speed (4-m)<0.8 m/s≤0.8 m/s<0.8 m/s<0.8 m/s<1.0 m/sb6-Meter walk: <1.0 m/s. 400-m Walk testNon-completion or ≥6 min for completion 5-Times chair stand test≥12 sASM, appendicular skeletal muscle mass; AWGS, Asian Working Group for Sarcopenia; BIA, bioelectrical impedance analysis; BMI, body mass index; CES-D, Centre for Epidemiological Studies depression scale; DEXA, dual-energy X-ray absorptiometry; EWGSOP, European Working Group on Sarcopenia in Older People; F, female; FNIH, Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project; M, male; SM, skeletal muscle mass.a FNIH defines low lean muscle mass using appendicular skeletal muscle mass adjusted for body mass index.b 6-Meter walk: <1.0 m/s. Open table in a new tab ASM, appendicular skeletal muscle mass; AWGS, Asian Working Group for Sarcopenia; BIA, bioelectrical impedance analysis; BMI, body mass index; CES-D, Centre for Epidemiological Studies depression scale; DEXA, dual-energy X-ray absorptiometry; EWGSOP, European Working Group on Sarcopenia in Older People; F, female; FNIH, Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project; M, male; SM, skeletal muscle mass. On the other hand, at least 67 measurement scales have been used to assess frailty in population-based studies.28Harhay M.N. Rao M.K. Woodside K.J. et al.An overview of frailty in kidney transplantation: measurement, management and future considerations.Nephrol Dial Transplant. 2020; 35: 1099-1112Crossref PubMed Scopus (25) Google Scholar Broadly, there are 2 distinct models to conceptualize frailty, which has led to different measurement approaches: (i) the frailty index (FI) model, developed by Rockwood et al.,7Rockwood K. Mitnitski A. Frailty in relation to the accumulation of deficits.J Gerontol A Biol Sci Med Sci. 2007; 62: 722-727Crossref PubMed Scopus (1388) Google Scholar,29Searle S.D. Mitnitski A. Gahbauer E.A. et al.A standard procedure for creating a frailty index.BMC Geriatr. 2008; 8: 24Crossref PubMed Scopus (1518) Google Scholar defines frailty as an accumulation of deficits across multiple organ systems including cognition and mood; and (ii) the frailty phenotype (FP) model,8Fried L.P. Tangen C.M. Walston J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar also known as the Fried phenotype, which identifies sarcopenia as a critical pathophysiological feature in which frailty is defined by the presence of 3 or more of the 5 criteria comprising weakness, slowness, shrinkage, exhaustion, and low physical activity. Although the FI model is more widely accepted in the geriatrics community, the Fried phenotype is the most commonly used tool in clinical studies for frailty assessment in the CKD population (accounting for 72% of all studies).20Chowdhury R. Peel N.M. Krosch M. et al.Frailty and chronic kidney disease: a systematic review.Arch Gerontol Geriatr. 2017; 68: 135-142Crossref PubMed Scopus (129) Google Scholar Several studies have also used the modified Fried criteria for frailty assessment by substituting the measurement of grip strength and gait speed with questionnaire-based physical function assessments, probably because of the relative ease and time-efficiency of using such questionnaires. Other, simpler tools to detect frailty in clinical settings include the Short Physical Performance Battery (SPPB), which consists of 3 components (balance, gait speed and chair standing), or gait speed alone, both of which have been independently validated to predict adverse outcomes.30Abellan van Kan G. Rolland Y. Andrieu S. et al.Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) task force.J Nutr Health Aging. 2009; 13: 881-889Crossref PubMed Scopus (1190) Google Scholar,31Pavasini R. Guralnik J. Brown J.C. et al.Short physical performance battery and all-cause mortality: systematic review and meta-analysis.BMC Med. 2016; 14: 215Crossref PubMed Scopus (291) Google Scholar Although the relationship between sarcopenia and frailty has not been fully characterized, both conditions share many commonalities in the proposed underlying mechanisms involving a complex interplay between multiple systems and pathophysiologic processes,32Walston J.D. Sarcopenia in older adults.Curr Opin Rheumatol. 2012; 24: 623-627Crossref PubMed Scopus (269) Google Scholar including aging, immunosenescence, hormonal imbalance, sedentary lifestyle, and poor nutritional status, as well as other comorbidities. Specifically in CKD, metabolic acidosis, accumulation of uremic toxins, and chronic state of catabolism in clinically stable maintenance dialysis patients have been suggested to cause an imbalance of protein generation and degradation, but have not been proved to contribute to the early onset of sarcopenia. Figure 1 shows a simplified illustration of the current understanding of the proposed pathogenesis of sarcopenia and frailty. Primary sarcopenia is age-related degeneration of the lean body muscle mass and overall musculoskeletal system. The current theoretical understanding of aging suggests that it is caused by the accumulation of unrepaired molecular and cellular damage throughout life due to the limitations of the complex network of maintenance and repair functions.33Kirkwood T.B. Understanding the odd science of aging.Cell. 2005; 120: 437-447Abstract Full Text Full Text PDF PubMed Scopus (1216) Google Scholar With age, the rate of muscle injury from normal contraction exceeds that of repair and regeneration. Furthermore, a combination of decreased satellite cell (muscle stem cell) proliferative and renewal capability and accumulation of mitochondrial DNA mutations result in altered inter- and intracellular environments that sustain catabolism.34Patel H.P. White M.C. Westbury L. et al.Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS).BMC Geriatr. 2015; 15: 171Crossref PubMed Scopus (13) Google Scholar, 35Zammit P.S. Partridge T.A. Yablonka-Reuveni Z. The skeletal muscle satellite cell: the stem cell that came in from the cold.J Histochem Cytochem. 2006; 54: 1177-1191Crossref PubMed Scopus (486) Google Scholar, 36Brierley E.J. Johnson M.A. Lightowlers R.N. et al.Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle.Ann Neurol. 1998; 43: 217-223Crossref PubMed Scopus (250) Google Scholar Furthermore, the aging brain is associated with characteristic structural and physiological changes, leading to cognitive impairment and dementia. Frailty correlates with more rapid cognitive decline, and 2 extensive prospective studies have consistently demonstrated an independent association between frailty and Alzheimer’s disease. This entity has been denominated as “cognitive frailty.”37Buchman A.S. Boyle P.A. Wilson R.S. et al.Frailty is associated with incident alzheimer's disease and cognitive decline in the elderly.Psychosom Med. 2007; 69: 483-489Crossref PubMed Scopus (266) Google Scholar,38Song X. Mitnitski A. Rockwood K. Nontraditional risk factors combine to predict alzheimer disease and dementia.Neurology. 2011; 77: 227-234Crossref PubMed Scopus (148) Google Scholar Immunosenescence is defined as an age-related decline in the immune system’s ability to generate effective cellular and antibody responses, resulting in diminished responses to vaccination and increased susceptibility to infections, neoplasia, and autoimmune diseases. The hallmarks of immunosenescence include a reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells and “inflammaging,” a chronic state of low-grade inflammation.39Aiello A. Farzaneh F. Candore G. et al.Immunosenescence and its hallmarks: how to oppose aging strategically? A review of potential options for therapeutic intervention.Front Immunol. 2019; 10: 2247Crossref PubMed Scopus (189) Google Scholar In 2002, in a pilot study, Leng et al. first reported the association between elevated circulating interleukin-6 (IL-6, a pro-inflammatory cytokine) and frailty,40Leng S. Chaves P. Koenig K. et al.Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study.J Am Geriatr Soc. 2002; 50: 1268-1271Crossref PubMed Scopus (299) Google Scholar which was subsequently demonstrated in a number of studies that also investigated different inflammatory markers (neutrophils, C-reactive protein [CRP], tumor necrosis factor−α [TNFα], and CXC chemokine ligand 10 [CXCL-10]) and in CKD patients with sarcopenia.18Shlipak M.G. Stehman-Breen C. Fried L.F. et al.The presence of frailty in elderly persons with chronic renal insufficiency.Am J Kidney Dis. 2004; 43: 861-867Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar,41Bian A.L. Hu H.Y. Rong Y.D. et al.A study on relationship between elderly sarcopenia and inflammatory factors IL-6 and TNF-alpha.Eur J Med Res. 2017; 22: 25Crossref PubMed Scopus (93) Google Scholar, 42Payette H. Roubenoff R. Jacques P.F. et al.Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study.J Am Geriatr Soc. 2003; 51: 1237-1243Crossref PubMed Scopus (181) Google Scholar, 43Walston J. McBurnie M.A. Newman A. et al.Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study.Arch Intern Med. 2002; 162: 2333-2341Crossref PubMed Scopus (720) Google Scholar, 44Collerton J. Martin-Ruiz C. Davies K. et al.Frailty and the role of inflammation, immunosenescence and cellular aging in the very old: cross-sectional findings from the Newcastle 85+ Study.Mech Aging Dev. 2012; 133: 456-466Crossref PubMed Scopus (263) Google Scholar, 45Hubbard R.E. O'Mahony M.S. Savva G.M. et al.Inflammation and frailty measures in older people.J Cell Mol Med. 2009; 13: 3103-3109Crossref PubMed Scopus (252) Google Scholar, 46Qu T. Yang H. Walston J.D. et al.Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty.Cytokine. 2009; 46: 319-324Crossref PubMed Scopus (69) Google Scholar Moreover, a significant systemic inflammatory response was observed in the lipopolysaccharide-induced sepsis rat model, along with increased expressions of IL-6 and TNFα in the skeletal muscle associated with loss of muscle mass and strength,47Crossland H. Constantin-Teodosiu D. Gardiner S.M. et al.A potential role for AKT/FOXO signalling in both protein loss and the impairment of muscle carbohydrate oxidation during sepsis in rodent skeletal muscle.J Physiol. 2008; 586: 5589-5600Crossref PubMed Scopus (131) Google Scholar which were suppressed by concomitant administration of low-dose dexamethasone.48Crossland H. Constantin-Teodosiu D. Greenhaff P.L. et al.Low-dose dexamethasone prevents endotoxaemia-induced muscle protein loss and impairment of carbohydrate oxidation in rat skeletal muscle.J Physiol. 2010; 588: 1333-1347Crossref PubMed Scopus (38) Google Scholar TNFα upregulates the NF-κB pathway via Iκβ kinase (IKK) and induces MuRF-1 expression, which causes myofibril degradation via the ubiquitin−proteasome pathway.49Ladner K.J. Caligiuri M.A. Guttridge D.C. Tumor necrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products.J Biol Chem. 2003; 278: 2294-2303Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar,50Li Y.P. Reid M.B. NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes.Am J Physiol Regul Integr Comp Physiol. 2000; 279: R1165-R1170Crossref PubMed Google Scholar Similarly, secondary sarcopenia occurs in other systemic diseases that could invoke inflammatory processes: for example, malignancy, CKD, chronic obstructive pulmonary disease, and rheumatoid arthritis. Taken together, immune activation could potentially be a preceding process leading to chronic inflammation in the pathogenesis of sarcopenia and frailty. However, evidence of a direct causal relationship remains to be proved. The alterations of growth hormone (GH)/insulin growth factor−1 (IGF-1) axis, sex hormone, and cortisol have been regarded as important risk factors for sarcopenia and frailty. Substantially lower serum levels of IGF-1 and dehydroepiandrosterone sulphate (DHEA-S) have been observed in sarcopenic and frail patients.42Payette H. Roubenoff R. Jacques P.F. et al.Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study.J Am Geriatr Soc. 2003; 51: 1237-1243Crossref PubMed Scopus (181) Google Scholar,51Leng S.X. Cappola A.R. Andersen R.E. et al.Serum levels of insulin-like growth factor-1 (IFG-1) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty.Aging Clin Exp Res. 2004; 16: 153-157Crossref PubMed Scopus (196) Google Scholar Both age-related rapid decrease in estrogen in postmenopausal women and gradual decrease in testosterone in older men also led to a decline in muscle mass and strength. In CKD, abnormalities in" @default.
• W3171704922 created "2021-06-22" @default.
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• W3171704922 date "2021-10-01" @default.
• W3171704922 modified "2023-10-16" @default.
• W3171704922 title "Sarcopenia and Frailty: Challenges in Mainstream Nephrology Practice" @default.
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