Original ResearchThe Associations of Muscle Strength, Muscle Mass, and Adiposity With Clinical Outcomes and Quality of Life in Prevalent Kidney Transplant Recipients
Introduction
Sarcopenia was formerly defined as age-related loss of muscle mass1, 2 but has recently been redefined as loss of both skeletal muscle strength and mass.1, 3, 4, 5 It is associated with inferior outcomes in quality of life (QoL),6, 7, 8, 9 morbidity and mortality in aging, and chronic kidney disease (CKD) populations.10, 11, 12 Although muscle strength is commonly associated with muscle mass,13 there may be a discordant relationship between the two muscular indices.14 Studies on aging and CKD populations suggest that muscle strength represents a more powerful prognostic index than muscle mass.15, 16 Indeed, data available in the general and dialysis populations concluded that muscle strength per se is an important prognostic marker.17, 18, 19, 20, 21
Studies on individual muscular indices (i.e., muscle strength or mass) either in isolation or in combination (i.e., sarcopenia) remain scarce in kidney transplantation. The limited literature concludes that muscle strength is impaired in kidney transplant recipients (KTRs) compared with healthy individuals.13 One study revealed that low muscle strength was found in 20.5% of KTRs, possibly a consequence of decreased vitamin D levels and aging.22 On the other hand, decreased muscle mass is a common feature in KTRs, variably attributed to the use of corticosteroid therapy,23, 24 presence of diabetes,23 and suboptimal renal function.13 Low muscle mass at the end of the first year posttransplantation was found to associate with prior episodes of delayed graft function and acute rejection.24 Furthermore, decreased urinary creatinine excretion, a surrogate marker of low muscle mass, predicts subsequent graft loss and mortality in KTRs.23 However, no studies to date have scrutinized the relationships between directly-measured muscular derangement categories (i.e., low muscle strength, low muscle mass, and sarcopenia) and clinical outcomes of kidney transplantation.
Of relevance, deranged muscular indices may coexist with obesity and weight gain, as both entities are highly prevalent in KTRs.25 The combination of obesity and sarcopenia is termed as the “sarcopenic obesity” phenotype. Associations of sarcopenic obesity with increased mortality and inferior QoL have been verified in general and CKD populations26, 27 but not in kidney transplantation. Obesity among KTRs is known to be associated with worsened QoL, cardiovascular risk profiles, and graft and overall survival.25 It is therefore possible that the coexistence of obesity and muscular derangements (i.e., sarcopenic obesity) may aggravate these inferior outcomes.
Therapeutic measures targeting muscle strength, muscle mass, sarcopenia, and sarcopenic obesity individually are not necessarily identical. Therefore, greater insight into each entity and their clinical impacts is prerequisites for developing specific nutritional and physical activity interventions in KTRs. As such, the primary objective of this study was to investigate the associations of muscle strength, muscle mass, sarcopenia, and sarcopenic obesity with a composite endpoint of all-cause mortality and acute hospitalization, and secondly, with health-related QoL, in clinically stable KTRs.
Section snippets
Study Population, Study Design, and Clinical Outcome
Adult KTRs beyond 1-year posttransplantation with stable graft function (i.e., defined as <10% increase in serum creatinine over the preceding 6 months) were consecutively recruited from renal transplant clinic to this single-centre prospective longitudinal study between April 2010 and April 2013. Written informed consent was obtained from all participants. Detailed biochemical, clinical, anthropometric, dietary, lifestyle, and health-related QoL assessments were performed at initial study
Population Characteristics
Of 138 patients approached, 10 did not participate because of work commitment (93% consent rate). Mean age was 49 ± 15 years; 56% was men; 78% was Caucasian; median time posttransplantation was 5 (2–11) years; and mean eGFR was 45 ± 18 mL/min/1.73 m2. Table 1 indicates the baseline characteristics of the entire study population and stratified according to normal or low muscle strength. KTRs with low muscle strength were older (P = .008), presented with longer transplant (P = .005) and dialysis (
Discussion
This study revealed that low muscle strength is common among a prevalent cohort of clinically stable KTRs. Importantly, only decreased muscle strength was identified as an independent risk factor for a composite endpoint of all-cause mortality and morbidity, as well as health-related QoL. Muscle mass, sarcopenia, and sarcopenic obesity did not demonstrate meaningful prognostic impact in this study.
This study addresses two important phenomena. Firstly, muscle strength per se was found to be an
Practical Application
This study presents the first compelling independent association between decreased muscle strength and adverse clinical outcomes in kidney transplantation. Muscle strength assessment in routine clinical practice may serve as a novel tool for improving risk stratification in prevalent KTRs, setting the scene for future interventional research and therapeutic strategies.
Acknowledgments
The research was carried out at the National Institute of Health Research (NIHR)/Wellcome Trust Clinical Research Facility based at University Hospitals Birmingham NHS Foundation Trust and University of Birmingham. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The authors would like to thank the staff in the Renal Outpatients Department and the Wellcome Trust Clinical Research Facility for supporting this study. In
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Author Contributions: Winnie Chan, David Jones, Jos A Bosch, and Richard Borrows designed the research. Winnie Chan, Shui Hao Chin, Anna C Whittaker, Jos A Bosch, and Richard Borrows wrote the manuscript. Winnie Chan, Okdeep Kaur, and Richard Borrows conducted the research. Winnie Chan, Jos A Bosch, and Richard Borrows analyzed the data and performed the statistical analysis. Winnie Chan and Richard Borrows had primary responsibility for the final content.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Support: Winnie Chan received a research grant from the British Renal Society and was awarded a PhD research training fellowship from the National Health Service (NHS) West Midlands Strategic Healthy Authority.