Abstract
Fat accumulation in skeletal muscle was recently established as a major risk factor for cardiovascular disease (CVD) in the general population, but its relevance for patients with kidney failure is unknown. Here we examined the potential association between muscle radiation attenuation (MRA), a non-invasive indicator of fat deposits in muscle, and cardiovascular events in patients with kidney failure treated with peritoneal dialysis (PD) and investigated dynamic changes and determinants of MRA in this population. We retrospectively assessed MRA on computed tomography images collected yearly in 101 incident patients with kidney failure starting PD between January 2006 and December 2015. After a median of 21 months on dialysis, 34 patients had 58 non-fatal cardiovascular events, and 22 patients had died. Baseline MRA was associated with cardiovascular events during time on dialysis, and patients with higher MRA (reflecting lower amounts of fat in muscle) showed a reduced incidence of CVD, independently of traditional risk factors (adjusted HR, 0.91; 95% CI, 0.86–0.97, P = 0.006). Multivariate regression analysis identified old age, female gender, visceral fat area, and low residual urine volume as independent determinants of MRA. As compared with reference values from a healthy population, patients with kidney failure had lower MRA (i.e., increased fat accumulation), independently of age, gender, and body-mass index. The subset of patients who underwent kidney transplantation showed a significant increase in MRA after restoration of kidney function. These observations expand the association between ectopic fat accumulation and CVD to the population on dialysis, and suggest that kidney failure is reversibly associated with fatty muscle infiltration.
Highlights
Chronic kidney disease (CKD) dramatically increases the risk of cardiovascular disease (CVD), which culminates in patients with kidney failure in a 10- to 20-fold increased hazard as compared with age- and gender-matched controls (Go et al, 2004; Gansevoort et al, 2013)
Ectopic fat accumulation, which refers to an increased amount of lipids around and within non-adipose tissue organs such as the skeletal muscle, liver, and heart, is recognized as a major risk factor for metabolic alterations and CVD
The development of highly sensitive imaging-based methods to quantify fat distribution, and their application to large cohorts of non-CKD individuals uncovered a strong association between ectopic fat accumulation and insulin resistance, atherogenic dyslipidemia, hypertension, and CVD (Neeland et al, 2018, 2019)
Summary
Chronic kidney disease (CKD) dramatically increases the risk of cardiovascular disease (CVD), which culminates in patients with kidney failure in a 10- to 20-fold increased hazard as compared with age- and gender-matched controls (Go et al, 2004; Gansevoort et al, 2013). The unacceptably high CVD risk in this population is related to a high prevalence of traditional risk factors, such as hypertension and diabetes, and to nontraditional, kidney-specific mechanisms (Gansevoort et al, 2013) Among the latter, metabolic disturbances represent an established feature of CKD, and are independently associated with CVD morbidity and mortality in patients with ESKD (DeFronzo et al, 1981; de Boer et al, 2012, 2016; Spoto et al, 2016). Ectopic fat accumulation, which refers to an increased amount of lipids around and within non-adipose tissue organs such as the skeletal muscle, liver, and heart, is recognized as a major risk factor for metabolic alterations and CVD. Decreased muscle radiation attenuation (MRA) on computed tomography reflects excessive fat deposition in the tissue and is associated with poor cardiovascular outcome (Brumbaugh et al, 2012; Therkelsen et al, 2013; Lim and Meigs, 2014; Miljkovic et al, 2015; Zhao et al, 2016; Sugai et al, 2018)
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