Association of sarcopenia with mortality and end‐stage renal disease in those with chronic kidney disease: a UK Biobank study

Abstract

Background Sarcopenia, a degenerative and generalized skeletal muscle disorder involving the loss of muscle function and mass, is an under‐recognized problem in clinical practice, particularly in chronic kidney disease (CKD). We aimed to investigate the prevalence of sarcopenia in individuals with CKD, its risk factors, and its association with all‐cause mortality and progression to end‐stage renal disease (ESRD). Methods UK Biobank participants were grouped according to the presence of CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2) and as having probable (low handgrip strength), confirmed (plus low muscle mass), and severe sarcopenia (plus poor physical performance) based on the 2019 European Working Group of Sarcopenia in Older People and Foundation for the National Institutes of Health criteria. Risk factors were explored using logistic regression analysis. Survival models were applied to estimate risk of mortality and ESRD. Results A total of 428 320 participants, of which 8767 individuals with CKD (46% male, aged 62.8 (standard deviation 6.8) years, median estimated glomerular filtration rate 54.5 (interquartile range 49.0–57.7) mL/min/1.72 m2) were included. Probable sarcopenia was present in 9.7% of individuals with CKD compared with 5.0% in those without (P < 0.001). Sarcopenia was associated with being older; inflammation; poorer renal function; and lower serum albumin, total testosterone, and haemoglobin. The largest risk factors for sarcopenia were having three or more comorbidities (odds ratio: 2.30; 95% confidence interval: 1.62 to 3.29; P < 0.001) and physical inactivity: participants in the highest quartile of weekly activity were 43% less likely to have sarcopenia compared to the lowest quartile (odds ratio: 0.57; 0.42 to 0.76; P < 0.001). Participants with CKD and sarcopenia had a 33% (7% to 66%; P = 0.011) higher hazard of mortality compared with individuals without. Sarcopenic CKD individuals had a 10 year survival probability of 0.85 (0.82 to 0.88) compared with 0.89 (0.88 to 0.30) in those without sarcopenia, an absolute difference of 4%. Those with sarcopenia were twice as likely to develop ESRD (hazard ratio: 1.98; 1.45 to 2.70; P < 0.001). Conclusions Participants with reduced kidney function are at an increased risk of premature mortality. The presence of sarcopenia increases the risk of mortality and ESRD. Appropriate measurement of sarcopenia should be used to identify at‐risk individuals. Interventions such as physical activity should be encouraged to mitigate sarcopenia.

Primary skeletal muscle cells from chronic kidney disease patients retain hallmarks of cachexia in vitro

“…Understanding the causal mechanisms that underpin uraemic cachexia is key for the development of therapeutic interventions to combat this debilitating co‐morbidity in people with kidney disease. Research conducted within this patient population has shown that uraemic cachexia manifests early in the disease process 29 and as such, targeting patients in stages G1–4 may allow for a preventative approach to management. 30 Progress in understanding such uraemic skeletal muscle cachexia has predominantly been conducted in patient populations, 2 , 3 , 6 , 7 , 31 with any cellular work to this point using immortalised cells lines.…”

Sarcopenia in the setting of nonalcoholic fatty liver

“…In a retrospective study of 225 Italian adults of both genders diagnosed with NAFLD, sarcopenia prevalence increases progressively with the severity of liver fibrosis. It rises from 22.2% in the absence of fibrosis to 60.0% in patients with stage 4 fibrosis [24] .…”

“…Sarcopenia is predominantly a geriatric condition, but young and middle-aged people are at risk of developing it due to multiple factors that are not primarily related to aging per se. Malnutrition, diabetes, hormonal imbalances, low physical activity, or comorbidities such as cancer [21] , chronic respiratory diseases [22] , mental diseases [23] , hepatic diseases [24] , renal failure [25] , Cushing's syndrome [26] , genetic predisposition, and the effects of environment in early development are all associated with the development of muscle wasting [27,28] .…”

Potential implications of blood flow restriction exercise on patients with chronic kidney disease: a brief review

“…Markers of muscle mass, strength, and functional capacity are important predictors of outcomes in this patient population subjected to a catabolic protein-energy wasting (PEW) syndrome and consequently, muscle atrophy ( Chatzipetrou et al, 2022 ; Sabatino et al, 2021 ). Importantly, assessment of muscle functionality may provide additional diagnostic and prognostic information to clinical outcomes, quality of life, and mortality rates ( Wilkinson et al, 2021 ).…”