Non-invasive Quantification of Fat Deposits in Skeletal Muscle Predicts Cardiovascular Outcome in Kidney Failure

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.

CT fatty muscle fraction as a new parameter for muscle quality assessment predicts outcome in venovenous extracorporeal membrane oxygenation

“…Also, we observed a higher rate of patients requiring continuous renal replacement therapy due to renal failure in the lowered muscle quality group. This finding is in line with a recent report, which observed decreased skeletal muscle radiation attenuation in patients with renal failure compared to healthy subjects, indicating a potential association between altered renal function and skeletal muscle fat infiltration 37 . However, as this was not the primary focus of our study, future investigations are needed to further elucidate this relationship.…”

Malnutrition Patterns in Children with Chronic Kidney Disease

“…Current clinical data highlight that apart from muscle quantity, muscle quality is also degraded in CKD, involving muscle fibrosis (myofibrosis) and intramuscular fat infiltration (myosteatosis) [ 70 ]. Experimental and longitudinal clinical adult studies have shown that kidney dysfunction promotes ectopic fat redistribution and progressive fat accumulation in skeletal muscles, inducing structural changes [ 71 , 72 ]. Uremic toxin accumulation, gut dysbiosis, and adipokine imbalance are possible incriminating factors [ 72 ].…”

“…Experimental and longitudinal clinical adult studies have shown that kidney dysfunction promotes ectopic fat redistribution and progressive fat accumulation in skeletal muscles, inducing structural changes [ 71 , 72 ]. Uremic toxin accumulation, gut dysbiosis, and adipokine imbalance are possible incriminating factors [ 72 ]. Myosteatosis contributed to decreased physical functioning and muscle strength in a cohort of pediatric patients on peritoneal dialysis [ 63 ] and was associated with poor cardiovascular outcome in adult patients [ 72 ].…”

“…Uremic toxin accumulation, gut dysbiosis, and adipokine imbalance are possible incriminating factors [ 72 ]. Myosteatosis contributed to decreased physical functioning and muscle strength in a cohort of pediatric patients on peritoneal dialysis [ 63 ] and was associated with poor cardiovascular outcome in adult patients [ 72 ].…”

Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study

“…In CKD patients not on dialysis, myosteatosis is associated with impaired physical performance 10 . In patients undergoing peritoneal dialysis, an association between myosteatosis and cardiovascular disease has recently been described 11 . Myosteatosis is now well recognized to be a risk of death in several contexts, including cancer, 12 orthotopic liver transplantation, 13 or mechanical ventilation in intensive care, 14 but no data are available concerning the impact of myosteatosis on mortality in ESRD and KT.…”